Sept 2009

 
BJMP 2009:2(2) 4-5
Obesity and Pulmonary Hypertension. What’s the Link?
Roop Kaw.
 
In the second paragraph of the left column on page 5, the second sentence must have read

"The most direct evidence comes from observations that treatment of OSA with continious positive airway pressure (CPAP) may lower daytime PAP"
 

 
BJMP 2009:2(1) 38 - 40
The ‘Lost’ Mirena: What Investigations Are Required ? An Intraperitoneal Levonorgestrel-Releasing Intrauterine System Following Uterine Perforation: Case Report
Shambhu S and Pappas M 
 
The correct name of the author must have read Pappas A on pages 4,39, 41
 

ANAESTHESIOLOGY
 
REFRESHER DAY ON OBSTETRIC ANAESTHESIA AND ANALGESIA
Contact: Obstetric Anaesthetists' Association Secretariat Tel: 011-44-20-8741-1311 Fax: 011-44-20-8741-0611 Email: available through webpage Website: www.oaa-anaes.ac.uk
Anesthesiology
October 07, 2009 United Kingdom / London
 
UPPER & LOWER LIMB PERIPHERAL NERVE BLOCK WORKSHOP
Contact: Aynsley Pix, B. Braun Medical Limited Email: aynsley.pix@bbraun.com Website: www.aesculap-academy.com
Anesthesiology / Pain Management
October 08, 2009 United Kingdom / Sheffield 
 
2009 DIFFICULT AIRWAY SOCIETY ANNUAL MEETING
Contact: Anne Griffin, Abbey Conference & Corporate Tel: 011-353-1-648-6130 Fax: 011-353-1-648-6197 Email: das2009@abbey.ie Website: www.das2009.co.uk/cms/
Anesthesiology
November 04-06, 2009 United Kingdom / Perth 
 
ASSOCIATION OF CARDIOTHORACIC ANAESTHETISTS AUTUMN MEETING 2009
Contact: Mrs. Andrea Reid, Secretary to Cardiac Anaesthetists Tel: 011-44-125-365-7789 Fax: 011-44-125-365-7134 Email: andrea.reid@bfwhospitals.nhs.uk Website: www.actablackpool2009.nhs.uk
Anesthesiology
November 05-06, 2009 United Kingdom / Blackpool 
 
2009 THREE-DAY COURSE ON OBSTETRIC ANAESTHESIA AND ANALGESIA
Contact: Obstetric Anaesthetists' Association Secretariat Tel: 011-44-20-8741-1311 Fax: 011-44-20-8741-0611 Email: available through webpage Website: www.oaa-anaes.ac.uk
Anesthesiology
November 09-11, 2009 United Kingdom / London 
 
GENERAL MEDICINE
 
DIABETES & ENDOCRINOLOGY: CLINICAL CHALLENGES & EXPERT ADVICE
Contact: Christine Berwick Tel: 011-44-131-247-3634 Fax: 011-44-131-220-4393 Email: c.berwick@rcpe.ac.uk Website: www.rcpe.ac.uk
Endocrinology / Family Medicine / General Medicine / Geriatrics / Internal Medicine
October 01, 2009 United Kingdom / Edinburgh 
 
2ND NATIONAL CONFERENCE: ANXIETY & DEPRESSION
Contact: Mark Allen Group Tel: 011-44-20-7501-6762 Fax: 011-44-20-7733-8174 Email: conferences@markallengroup.co.uk Website: www.mahealthcareevents.co.uk
Family Medicine / General Medicine / Psychiatry
October 01-02, 2009 United Kingdom / London 
 
3RD ROYAL COLLEGE OF GENERAL PRACTITIONERS (RCGP) ANNUAL NATIONAL PRIMARY CARE CONFERENCE
Contact: Terri Myers, RCGP Tel: 011-44-20-7581-3232 Fax: 011-44-20-7225-3047 Email: courses@rcgp.org.uk Website: www.rcgpannualconference.org.uk
Family Medicine / General Medicine
November 05-07, 2009 United Kingdom / Glasgow 
 
NEW CLINICAL SOLUTIONS IN DIABETES CARE CONFERENCE: OPPORTUNITIES & CHALLENGES
Contact: Alison Bone, Diabetes UK Tel: 011-44-1325-488-606 Email: alison.bone@diabetes.org.uk Website: www.diabetes.org.uk
Family Medicine / General Medicine
November 05, 2009 United Kingdom / York 
 
INNOVATIONS AND PROGRESS IN HEALTHCARE FOR WOMEN
Contact: Confab Consulting, Conference Organisers Tel: 011-44-20-8906-7778 Fax: 011-44-20-8906-7790 Email: IPHW09@confab-consulting.co.uk Website: www.womenshealth.uk.com
Family Medicine / General Medicine / Obstetrics/Gynecology / Oncology
November 09-11, 2009 United Kingdom / London 
 
GYNAE & OBSTETRICS
 
TRAINING THE TRAINERS
Contact: Royal College of Obstetricians & Gynaecologists Tel: 011-44-20-7772-6245 Fax: 011-44-20-7772-6388 Email: conference@rcog.org.uk Website: www.rcog.org.uk/events
Obstetrics/Gynecology
October 01-02, 2009 United Kingdom / London 
 
POSTMENOPAUSAL HEALTH
Contact: Royal College of Obstetricians & Gynaecologists Tel: 011-44-20-7772-6245 Fax: 011-44-20-7772-6388 Email: conference@rcog.org.uk Website: www.rcog.org.uk/events
Obstetrics/Gynecology
October 12-13, 2009 United Kingdom / London 
 
ADVANCED TECHNIQUES IN VAGINAL HYSTERECTOMY
Contact: Therese Eleftheriou, Course Secretary Tel: 011-44-20-7795-0500 ext. 33863 Fax: 011-44-20-7431-1321 Email: courses@gynendo.com Website: www.gynendo.com/dates.htm
Obstetrics/Gynecology / Surgery
October 15, 2009 United Kingdom / London 
 
BASIC PRACTICAL SKILLS IN OBSTETRICS AND GYNAECOLOGY
Contact: Royal College of Obstetricians & Gynaecologists Tel: 011-44-20-7772-6245 Fax: 011-44-20-7772-6388 Email: conference@rcog.org.uk Website: www.rcog.org.uk/events
Obstetrics/Gynecology
October 26-28, 2009 United Kingdom / London 
 
ADVANCE LABOUR WARD PRACTICE
Contact: Royal College of Obstetricians & Gynaecologists Tel: 011-44-20-7772-6245 Fax: 011-44-20-7772-6388 Email: conference@rcog.org.uk Website: www.rcog.org.uk/events
Obstetrics/Gynecology
November 02-04, 2009 United Kingdom / London 
 
BRITISH SOCIETY OF UROGYNAECOLOGY / ROYAL COLLEGE OF OBSTETRICIANS & GYNAECOLOGISTS JOINT MEETING
Contact: Royal College of Obstetricians & Gynaecologists Tel: 011-44-20-7772-6245 Fax: 011-44-20-7772-6388 Email: conference@rcog.org.uk Website: www.rcog.org.uk/events
Obstetrics/Gynecology
November 05-06, 2009 United Kingdom / London 
 
MEDICAL COMPLICATIONS IN PREGNANCY
Contact: Symposium Office, Imperial College London Tel: 011-44-20-7594-2150 Fax: 011-44-20-7594-2155 Email: sympreg@imperial.ac.uk Website: www.prossl.com/symposiassl/events.asp
Obstetrics/Gynecology
November 11-13, 2009 United Kingdom / London 
 
PROMPT (PRACTICAL OBSTETRICS MULTI-PROFESSIONAL TRAINING) COURSE: TRAINING THE TRAINERS
Contact: Conference Office, Royal College of Obstetricians and Gynaecologists Tel: 011-44-20-7772-6245 Fax: 011-44-20-7772-6388 Email: conference@rcog.org.uk Website: www.rcog.org.uk/meetings
Obstetrics/Gynecology
November 12, 2009 United Kingdom / London 
 
PROMPT (PRACTICAL OBSTETRICS MULTI-PROFESSIONAL TRAINING) COURSE: TRAINING THE TRAINERS
Contact: Conference Office, Royal College of Obstetricians and Gynaecologists Tel: 011-44-20-7772-6245 Fax: 011-44-20-7772-6388 Email: conference@rcog.org.uk Website: www.rcog.org.uk/meetings
Obstetrics/Gynecology
November 13, 2009 United Kingdom / London 
 
NEONATAL UPDATE 2009
Contact: Symposium Office, Imperial College London Tel: 011-44-20-7594-2150 Fax: 011-44-20-7594-2155 Email: sympreg@imperial.ac.uk Website: www.prossl.com/symposiassl/events.asp
Obstetrics/Gynecology
November 16-20, 2009 United Kingdom / London 
 
QUALITY MANAGEMENT OF A FERTILITY SERVICE STUDY DAY 2009
Contact: British Fertility Society Tel: 011-44-14-5464-2217 Fax: 011-44-14-5464-2222 Email: bfs@bioscientifica.com Website: www.britishfertilitysociety.org.uk
Obstetrics/Gynecology / Other Specialties / Urology
November 17, 2009 United Kingdom / London 
 
REPRODUCTIVE GENETICS
Contact: Royal College of Obstetricians & Gynaecologists Tel: 011-44-20-7772-6245 Fax: 011-44-20-7772-6388 Email: conference@rcog.org.uk Website: www.rcog.org.uk/events
Obstetrics/Gynecology
November 19, 2009 United Kingdom / London 
 
LAPAROSCOPIC SURGERY
Contact: Royal College of Obstetricians & Gynaecologists Tel: 011-44-20-7772-6245 Fax: 011-44-20-7772-6388 Email: conference@rcog.org.uk/events Website: www.rcog.org.uk/events
Obstetrics/Gynecology / Surgery
December 02, 2009 United Kingdom / London 
 
RECENT ADVANCES IN GYNAECOLOGICAL SURGERY
Contact: Royal College of Obstetricians & Gynaecologists Tel: 011-44-20-7772-6245 Fax: 011-44-20-7772-6388 Email: conference@rcog.org.uk Website: www.rcog.org.uk/events
Obstetrics/Gynecology / Surgery
December 03-04, 2009 United Kingdom / London 
 
HANDS ON LAPAROSCOPIC HYSTERECTOMY WORKSHOP
Contact: Therese Eleftheriou, Course Secretary Tel: 011-44-20-7795-0500 ext. 33863 Fax: 011-44-20-7431-1321 Email: courses@gynendo.com Website: www.gynendo.com/dates.htm
Obstetrics/Gynecology / Surgery
December 03, 2009 United Kingdom / London 
 
BASIC PRACTICAL SKILLS IN OBSTETRICS & GYNAECOLOGY
Contact: Royal College of Obstetricians & Gynaecologists Tel: 011-44-20-7772-6245 Fax: 011-44-20-7772-6388 Email: conference@rcog.org.uk Website: www.rcog.org.uk/events
Obstetrics/Gynecology
December 07-09, 2009 United Kingdom / London 
 
PAEDIATRICS
 
EUROPEAN SYMPOSIUM ON LATE COMPLICATIONS AFTER CHILDHOOD CANCER
Contact: Margaret Falconer, Event Co-ordinator Tel: 011-44-131-226-0821 Fax: 011-44-131-226-0801 Email: eslccc2009@colpitts.co.uk Website: www.eslccc2009.com
Oncology / Pediatrics
October 29-30, 2009 United Kingdom / Edinburgh 
 
3RD NATIONAL CONFERENCE: PAEDIATRICS ASTHMA & ALLERGY
Contact: Mark Allen Group Tel: 011-44-20-7501-6762 Fax: 011-44-20-7733-8174 Email: conferences@markallengroup.co.uk Website: www.mahealthcareevents.co.uk
Immunology/Allergy / Pediatrics
November 09-10, 2009 United Kingdom / London 
 
PSYCHIATRY
 
2ND NATIONAL CONFERENCE: ANXIETY & DEPRESSION
Contact: Mark Allen Group Tel: 011-44-20-7501-6762 Fax: 011-44-20-7733-8174 Email: conferences@markallengroup.co.uk Website: www.mahealthcareevents.co.uk
Family Medicine / General Medicine / Psychiatry
October 01-02, 2009 United Kingdom / London 
 
DRUG TREATMENTS IN AFFECTIVE DISORDERS
Contact: Mrs. Susan Chandler, British Association for Psychopharmacology Tel: 011-44-1223-358-428 Email: susan@bap.org.uk Website: www.bap.org.uk
Psychiatry
October 08-09, 2009 United Kingdom / Manchester 
 
DRUG TREATMENTS IN OLD AGE PSYCHIATRY
Contact: Mrs. Susan Chandler, British Association for Psychopharmacology Tel: 011-44-1223-358-428 Email: susan@bap.org.uk Website: www.bap.org.uk
Psychiatry
November 11-13, 2009 United Kingdom / London 
 
BRITISH ASSOCIATION FOR PSYCHOPHARMACOLOGY (BAP) MASTERCLASSES IN CLINICAL PSYCHOPHARMACOLOGY
Contact: Lynne Harmer, BAP Tel: 011-44-1223-358-421 Email: lynne@bap.org.uk Website: www.bap.org.uk
Clinical Pharmacology / Psychiatry
November 11, 2009 United Kingdom / London 
 
CAREIF 2009 INTERNATIONAL CONFERENCE*
Contact: Hampton Medical Conferences Tel: 011-44-20-8979-8300 Fax: 011-44-20-8979-6700 Email: careif@hmconline.co.uk Website: www.careif.ukevents.org
Other Specialties / Psychiatry
December 04, 2009 United Kingdom / London 
 
7TH NATIONAL CONFERENCE: BIPOLAR DISORDERS
Contact: Mark Allen Group Tel: 011-44-20-7501-6762 Fax: 011-44-20-7733-8174 Email: conferences@markallengroup.co.uk Website: www.mahealthcareevents.co.uk
Psychiatry
December 10, 2009 United Kingdom / London 
 
SLEEP DISORDERS
Contact: Mark Allen Group Tel: 011-44-20-7501-6762 Fax: 011-44-20-7733-8174 Email: conferences@markallengroup.co.uk Website: www.mahealthcareevents.co.uk
Psychiatry / Respirology
 
RADIOLOGY
 
ECHOCARDIOGRAPHY
Contact: Robina, Intensive Care Society Tel: 011-44-20-7280-4350 Email: events@ics.ac.uk Website: www.ics.ac.uk
Internal Medicine / Radiology/Imaging
September 04, 2009 United Kingdom / London 
 
PET / CT COURSE
Contact: British Institute of Radiology Tel: 011-44-20-7307-1400 Email: available through website Website: www.bir.org.uk
Radiology/Imaging
October 01, 2009 United Kingdom / Glasgow 
 
WELSH BRANCH, BRITISH INSTITUTE OF RADIOLOGY, AUTUMN MEETING
Contact: British Institute of Radiology Tel: 011-44-20-7307-1400 Email: available through website Website: www.bir.org.uk
Radiology/Imaging
October 16-17, 2009 United Kingdom / Llantrisant 
 
OBESITY: THE CHALLENGES & SOLUTIONS IN IMAGING
Contact: British Institute of Radiology Tel: 011-44-20-7307-1400 Email: available through website Website: www.bir.org.uk
Radiology/Imaging
October 19, 2009 United Kingdom / London 
 
ROYAL COLLEGE OF RADIOLOGISTS BREAST GROUP MEETING*
Contact: Hampton Medical Conferences, Conference Manager Tel: 011-44-20-8979-8300 Fax: 011-44-20-8979-6700 Email: hmc@hamptonmedical.com Website: www.hamptonmedical.com
Radiology/Imaging
November 02, 2009 United Kingdom / Belfast 
 
CONTROLLING RADIATION RISKS IN DIAGNOSTIC RADIOLOGY
Contact: British Institute of Radiology Tel: 011-44-20-7307-1400 Email: available through website Website: www.bir.org.uk
Radiology/Imaging
November 24, 2009 United Kingdom / London 
 
RPS UPDATE TRAINING SESSION
Contact: British Institute of Radiology Tel: 011-44-20-7307-1400 Email: available through website Website: www.bir.org.uk
Radiology/Imaging
November 25, 2009 United Kingdom / London 
 
BRITISH SOCIETY OF THORACIC IMAGING AUTUMN MEETING
Contact: British Institute of Radiology Tel: 011-44-20-7307-1400 Email: available through website Website: www.bir.org.uk
Radiology/Imaging
November 27, 2009 United Kingdom / London 
 
7TH ANNUAL CONFERENCE OF UK & IRELAND NEUROENDOCRINE TUMOUR SOCIETY (UKI NETS)
Contact: UKI NETS Secretariat Tel: 011-44-145-464-2277 Fax: 011-44-145-464-2222 Email: enquiries@ukinets.org Website: www.ukinets.org
Endocrinology / Gastroenterology / Oncology / Other Specialties / Pathology / Radiology/Imaging / Surgery
November 30, 2009 United Kingdom / London 
 
SURGERY
 
2ND ANNUAL ROYAL MARSDEN BREAST CANCER MEETING: HOT TOPICS IN BREAST CANCER
Contact: The Royal Marsden Tel: 011-44-20-7808-2921 Fax: 011-44-20-7808-2334 Email: conferencecentre@rmh.nhs.uk Website: www.royalmarsden.nhs.uk
Oncology / Pathology / Radiology/Imaging / Surgery
October 02, 2009 United Kingdom / London 
 
CURRENT CONCEPTS IN EXTERNAL FIXATION IN TRAUMA
Contact: Jean Fretwell Tel: 011-44-113-392-3819 Email: jean.fretwell@leedsth.nhs.uk Website: www.rcseng.ac.uk
Orthopedics / Surgery
October 05, 2009 United Kingdom / Leeds 
 
ADVANCED TECHNIQUES IN VAGINAL HYSTERECTOMY
Contact: Therese Eleftheriou, Course Secretary Tel: 011-44-20-7795-0500 ext. 33863 Fax: 011-44-20-7431-1321 Email: courses@gynendo.com Website: www.gynendo.com/dates.htm
Obstetrics/Gynecology / Surgery
October 15, 2009 United Kingdom / London 
 
CARE OF THE CRITICALLY ILL SURGICAL PATIENT INSTRUCTOR COURSE
Contact: Royal College of Surgeons of England Tel: 011-44-20-7869-6311 Email: ccrisp@rcseng.ac.uk Website: www.rcseng.ac.uk/education/courses/course_list.html
Other Specialties / Surgery
October 26-27, 2009 United Kingdom / London 
 
21ST CENTURY DECONTAMINATION: SHARING EXPERTISE
Contact: Aynsley Pix, B. Braun Medical Limited Email: aynsley.pix@bbraun.com Website: www.aesculap-academy.com
Surgery
November 03-04, 2009 United Kingdom / Sheffield 
 
CORE SKILLS IN OPERATIVE ORTHOPAEDIC SURGERY
Contact: Mrs. Kelly Westlake Tel: 011-44-29-2068-2129 Email: westlakekm@cardiff.ac.uk Website: www.rcseng.ac.uk/education/courses/course_list.html
Surgery
November 04-06, 2009 United Kingdom / Cardiff 
 
CORE SKILLS IN OPERATIVE ORTHOPAEDIC SURGERY
Contact: Lesley Izzard Tel: 011-44-114-271-4027 Email: Lesley.izzrd@sth.nhs.uk Website: www.rcseng.ac.uk/education/courses/course_list.html
Surgery
November 04-06, 2009 United Kingdom / Sheffield 
 
HANDS ON GYNAECOLOGICAL ENDOSCOPY SKILLS WORKSHOP
Contact: Therese Eleftheriou, Course Secretary Tel: 011-44-20-7795-0500 ext. 33863 Fax: 011-44-20-7431-1321 Email: courses@gynendo.com Website: www.gynendo.com/dates.htm
Obstetrics/Gynecology / Surgery
November 11-13, 2009 United Kingdom / London 
 
ONEHEALTH STUDY DAY
Contact: Aynsley Pix, B. Braun Medical Limited Email: aynsley.pix@bbraun.com Website: www.aesculap-academy.com
Surgery
November 11, 2009 United Kingdom / Tankersley
 

Introduction:

According to The National Kidney Foundation of The United States of America ¹ CKD is defined as (1) evidence of kidney damage based on abnormal urinalysis results (e.g., proteinuria, hematuria) or structural abnormalities observed on ultrasound images or (2) an absolute GFR of less than 60 mL/min for 3 or more months. Based on this definition there are five stages. See Table 1. Anemia affects 60% to 80% of patients with chronic kidney disease (CKD) and reduces their quality of life. Treatment options are blood transfusion, epoietin alfa and darbepoetin alfa ^2 . Anemia of CKD is, in most patients, normocytic and normochromic and primarily caused by depressed production of erythropoietin (EPO), oxidative stress and inflammation, erythropoiesis inhibition and reduction in red blood cell survival ^3,4,5 . The other cause of anemia is deficiency of iron. The dialysis patient is in a state of continuous iron loss from gastrointestinal bleeding, blood drawing, and/or, most important with hemodialysis (HD), the dialysis treatment itself. HD patients lose an average of 2 g of iron per year. Thus, iron deficiency will develop in virtually all dialysis patients receiving EPO unless supplemental iron therapy is given orally or intravenously. DRIVE study, a randomized trial study, adds direct evidence that administration of intravenous iron to patients with functional iron deficiency who were on supplemental EPO therapy results in increase in the hemoglobin level ⁶. The aim of this review is to assess that whether Erythropoietin (EPO) treatment is beneficial or harmful in the management of anemia associated with CKD. To address these issues, we have analyzed randomized controlled trials, observational studies and meta-analyses.
 
Table 1: Stages of CKD according to NKF.

 
Methods:

Search strategy: The search strategy was designed to capture the patient population, suffering from CKD on supplemental erythropoietin (EPO) therapy. Literature search (1989 to 2008) was carried out using MEDLINE, PubMed as well as other electronic databases and in online journals using the keywords "Kidney failure, chronic and "erythropoietin" for studies up to 1996, and "epoetin alfa" for subsequent years.
 
Selection of studies: All papers identified were English-language, full text papers. In addition, the reference lists of identified relevant articles were also searched. The search was not limited to any specific study design, and we searched for randomized controlled trials (RCTs), observational studies, systemic review and meta-analysis. Citations identified in the literature search were independently screened by author to select potentially relevant articles. The full articles from this list were retrieved and subsequently reviewed by author for inclusion in the systematic review. During selection preference was given to articles published within last five years. Articles were included if they met the following inclusion criteria 1) published in a peer reviewed journal; 2) written in English; 3) reported randomized controlled trials of EPO; 4) observational studies regarding EPO and quality of life; 5) Review articles and meta-analyses about EPO therapy in CKD patients.
 
Results:
470 citations were identified in search from PubMed, Medline and from other online journals. Of these 470 citations, 444 did not meet the selection criteria and were excluded, leaving 26. Out of 26 citations 11 were RCTs, 10 were observational studies and 5 were reviews and meta-analysis.
 
Five studies (Parfrey et al⁷, Foley et al⁸, Furuland et al⁹, Drüeke et al¹⁰, and Canadian Erythropoietin Study Group¹¹) showed that correction of anemia result in improvement of quality of life, although the singh et al¹² showed such improvement with partial correction of anemia, and no detectable difference in the quality of life was evident in Roger et al¹³ study. Five studies Parfrey et al⁷, Foley et al⁸ and Levin et al¹⁴ and McMahon et al¹⁵ and Roger et al¹³ showed that normalization of hemoglobin does not lead to regression of established concentric LV hypertrophy or LV dilation. It may, however, prevent the development of LV dilation. In McMahon et al¹⁵ study the only factor that seemed to predict normalization of LV mass in patients who had LV hypertrophy at study entry was a lower pulse pressure. One study Sikole et al¹⁶ correction of renal anemia can normalize heart morphology and improve heart function. Three studies Besarab et al¹⁷, Drüeke et al¹⁰ and Singh et al¹² demonstrated increased cardiovascular events whereas two studies Drüeke et al¹⁰ and Singh et al¹² also showed progression to dialysis in patients assigned to the highest hemoglobin targets (>13.0 g/dL), compared with <12 g/dL, trial design of three studies was same in respect that both arms were on EPO. In comparison to Drüeke et al¹⁰ and Singh et al¹² studies, in Roger et al¹³ study the renal function was not adversely affected in the group randomized to the higher Hb. (Table 2).
 
Table 2: Randomized controlled trials (RCTs)

 
Both Phrommintikul et al¹⁸andGiovanni et al¹⁹ addressed the similar issues, to evaluate the benefits and harms of different hemoglobin (Hb) targets in CKD in their meta-analyses. They reached to similar conclusion, increase in the risk of all-cause mortality in anemic patients with CKD in whom a higher Hb target (in the normal physiological range) is aimed for with treatment with EPO. Such patients are also at an increased risk of arteriovenous access thrombosis and poorly controlled hypertension, which could contribute to the increased risk of mortality. Furthermore, there seems to be no beneficial effect on left ventricular mass in such patients. There were similarities and differences in inclusion criteria. Both used the trials targeting different Hb concentrations in patients with anemia caused by CKD, majority of trials analyzed were different except 4 trials which were same in both. The difference in inclusion criteria was that Giovanni et. al analyzed two groups of studies: The first group contained studies in which the intervention was to achieve different Hb targets compared (higher versus lower Hb targets), both arms were on EPO and trials included individuals with clinical cardiovascular disease. The second group compared EPO treatment with no EPO treatment. The results of these two groups of studies were analyzed separately. In Phrommintikul only one group of studies “EPO treatment with no EPO treatment” was analyzed. Meta-analysis by Phrommintikul et alincludes nine RCTs, which enrolled 5143 patients.
 
In Jones et al²⁰ meta-analysis both randomized controlled trials and uncontrolled trial were analyzed, all studies were of the “pre/post” design, in that measurements of anemia, quality of life, hospitalizations, and transfusions were taken before and after initiation of EPO therapy. They drew these conclusions from 16 published studies of which 5 were randomized clinical trials. He found that treatment with EPO raised hemoglobin levels, reduced transfusion requirements and improved quality of life. For quality of life outcome in these meta-analysis please review Table 3.
 
Table: 3 Meta-analysis.

Discussion:
Erythropoietin (EPO) has become an essential part of the management of anemic patients with CKD. It is also used to treat the anemia associated with chemotherapy and other diseases, and it improves quality of life ^21,22 . The introduction of EPO in 1989 significantly improved the clinical management of anemia of CKD. By 2005, 99% of incenter hemodialysis patients received EPO treatment for their anemia. EPO dosing has changed dramatically in the past decade and a half; between 1991 and 2005, the mean dose of EPO increased about 4-fold in dialysis patients. Today, EPO therapy is the largest single Medicare drug expenditure totaling $1.8 billion in 2004 (an increase of 17% from 2003) and EPO comprised 11% of all Medicare ESRD costs ²³
 
EPO and left ventricular hypertrophy. Randomized vs. Observational studies. Anemia is a contributing factor in many of the symptoms associated with reduced kidney function. These include fatigue, depression, reduced exercise tolerance, dyspnea. Data from observational studies shows that severe anemia may results in cardiovascular consequences, such as left ventricular hypertrophy (LVH) and left ventricular systolic dysfunction ²⁴. Left ventricular hypertrophy (LVH) is present in nearly 80% of dialysis patients and is associated with higher rates of cardiovascular events ^25. It is also associated with an increased risk of morbidity and mortality principally due to cardiac disease and stroke ^26,27. As a result, patients with anemia due to CKD are at increased risk of hospitalization, hospital length of stay, reduced quality of life and mortality ^28. Uncontrolled studies suggested that partial correction of anemia with EPO therapy may result in prevention or regression of CHF ²⁹ and LVH ^30,31. Several randomized controlled trials showed that left ventricular hypertrophy was not further improved by a complete correction of anemia compared to only partial correction ^{7,13,14,15,17.} Robert N Foley et al. randomly assigned 146 patients with either concentric LV hypertrophy or LV dilation to receive EPO to achieve hemoglobin levels of 10 or 13.5 g/dL. He concluded that normalization of hemoglobin does not lead to regression of established concentric LV hypertrophy or LV dilation. It may, however, prevent the development of LV dilation, and it leads to improved quality of life ^8. Partial correction of severe anemia <8 or 9g/dl to mild anemia (10-11 g/dL) likely reduces mortality, but further treatment to higher Hb levels has not been shown to further reduce mortality, and has actually increased mortality. Controlled studies with quality of life (QOL) and left ventricular mass as end points support partial correction of hemoglobin in dialysis patients ^11,13,16,32,  The fact that anemic renal failure patients have more LVH than non-anemic renal failure patients does not prove that anemia causes LVH. Vaziri et al in a review mentioned that the real culprits are oxidative stress, inflammation and diminished biological capacity that simultaneously cause treatment-resistant anemia and adverse cardiovascular and other outcomes ^33.
 
EPO and quality of life:Numerous randomized, controlled trials have demonstrated that EPO significantly raises hemoglobin levels, reduces transfusion requirements, and improves quality of life in anemic patients with chronic renal failure. Lefebvre et al conducted an analysis on data from a multicenter, open-label, prospective study of EPO for anemia in patients with CKD not on dialysis to evaluate the relationship between Hb level and quality of life (QOL). The results showed that the maximal incremental gain in QOL occurred when Hb reached 11 to 12 g/dL. This suggests that treating anemic patients with non-dialysis CKD until their Hb level reaches 12 g/dL will result in the greatest QOL improvement per Hb unit increase ^34.
 
Randomized vs. Observational studies. Many randomized controlled trials suggest an association between higher hemoglobin level and improved quality of life, physical function, and exercise capacity ^7,8,9,35 but the association with survival is less clear. Whereas observational studies have generally shown increased survival with higher hemoglobin level ^{36,37,38,39,40} randomized trials have not shown such benefits. The extent anemia of inflammation varies between patients with renal failure. It is this factor that likely explains the following paradox: in observational studies, higher hemoglobin associates with better survival in CKD, while in controlled trials, higher hemoglobin achieved by escalated EPO dosing decreases survival. In the observational studies, those with the higher Hb levels were likely those patients who had the least component of anemia of inflammation, and therefore less resistant to EPO supplementation; they survived better not because they had better hemoglobin, but because they had less burden of inflammatory disease. Anemia of chronic disease is a highly conserved response that is mediated by multiple mechanisms acting in concert to lower the hemoglobin in the face of inflammation, and should be presumed until proven otherwise to be adaptive for most patients who exhibit it. That this is so is supported by the observation that the correction of anemia confers lower survival not only in renal failure, but also in cancer patients and in patients in the critical care unit.
 
Jones et al. in their very thorough meta-analysis ²⁰ indeed found that treatment with EPO raised hemoglobin levels, reduced transfusion requirements and improved quality of life. Studies have demonstrated that morbidity and mortality rates are lower when hematocrit values are within the Disease Outcomes Quality Initiative (DOQI) target range (33 to 36%) ⁴⁰. Ernesto Paoletti et alin their review of observational and randomized studies concluded from the results of observational studies that normalization of Hb in renal patients seems to be associated with further improvement in quality of life and physical activity but with no significant differences in mortality rate, hospitalization rate, and the extent of LVH regression, but the results of randomized trials show that achieving near-normal Hb did not reduce the risk for death from all causes or the risk for cardiac death. The latter risk actually increased slightly, in the group of dialysis patients with normalized Hb concentration ⁴¹. For CKD stage 3 and 4 patients, no improvement seen in CHOIR, but improvements reported in CREATE. There may be reporting bias in CREATE as it was an open label study, and the low target arm had to develop worsening anemia prior to initiating EPO therapy ^10,12
 
EPO and Cardiovascular Events:Anemia is a common complication of chronic kidney disease. Determination of the appropriate target hematocrit level for patients undergoing hemodialysis continues to be a controversial area ⁴⁰. The National Kidney Foundation Dialysis Outcomes Quality Initiative (K/DOQI) states when a decision to use EPO is made, some Hgb value in the range of 11 to 12, but no higher than 13 should generally be chosen. ⁴². The European Best Practice Guidelines (EBPGs) recommend that most patients with CKD achieve a target hemoglobin (Hb) 11 g/dl to reduce the risk of adverse outcomes ^43. Randomized vs. Observational studies. Observational studies have shown a strong  association between severity of anemia and risk of morbidity and mortality from cardiovascular disease and other causes in CKD patients ^{36,37,38,39,40}. These findings have been interpreted as evidence for the causal role of anemia in the pathogenesis of adverse outcomes in these patients. On the hand, randomized clinical trials of anemia management revealed either no effect or increased morbidity and mortality in patients assigned to normal hemoglobin Hb targets ^10,12,17. Meta- analyses of randomized clinical trials have shown a significant increase in cardiovascular and all-cause mortality and arteriovenous access thrombosis among patients assigned to the higher than those randomized to the lower Hb targets ^18,19. Meta-analysis of Phrommintikul shows a significantly higher risk of all-cause mortality (targeting a Hb level higher than 12 g/dL results in a 17% increased risk of death compared with target hemoglobin levels less than 12 g/dL), arteriovenous access thrombosis and higher risk of poorly controlled blood pressure in the higher Hb target group than in the lower target Hb. The incidence of myocardial infarction was much the same in the two groups ¹⁸. Meta-analysis of Giovanni F.M et al shows that on the basis of available randomized, controlled trials, Hb targets of <12.0 g/dL are associated with a lower risk of death in the population with cardiovascular disease and CKD compared with Hb targets of >13.0 g/dL. For every 30 patients treated to an Hb target of <12.0 g/dL compared with an Hb target of >13.0 g/dL, approximately one death is avoided ¹⁹. Two large randomized controlled trials; CREATE ^[38] and CHOIR ^[39] demonstrated increased cardiovascular events and progression to dialysis in patients assigned to the highest hemoglobin targets (>13.0 g/dL), compared with <12 g/dL. US Food and Drug Administration (FDA) warned that use of erythropoiesis-stimulating agents (ESAs) increases mortality and morbidity risk. The warning follows publication of studies suggesting that correction of anemia in patients with CKD did not reduce the risk of cardiovascular events and that reaching a target Hb level of >13 g/dL, compared with a target level of 11.3 g/dL, was associated with increased risk of cardiovascular events. FDA said recent studies had found increased risk of death, blood clots, strokes, and myocardial infarctions in patients with chronic renal disease who received ESAs at higher-than-recommended doses that maintained their hemoglobin levels at more than 12 g/dL ^44.
 
EPO and kidney:EPO has been found to interact with its receptor in a large variety of non-haematopoietic tissues, which result into cytoprotective cellular responses, like mitogenesis, angiogenesis, inhibition of apoptosis and promotion of vascular repair through mobilization of endothelial progenitor cells from the bone marrow. In experimental ischaemic and toxic acute renal failure administration of EPO, promotes renoprotection. Preliminary experimental and clinical evidence also indicates that EPO may be renoprotective in chronic kidney disease²² .EPO is used widely to treat anemia in patients with CKD, but the benefits of EPO use in patients with acute renal failure (ARF) are unclear. In vitro and animal studies suggest that EPO may promote renal recovery and decrease mortality in ARF ^45. Partial amelioration of anemia with low doses of EPO was reported to slow the rate of progression to ESRD in a group of CKD patients ^46. These cellular protection from EPO observed in animal models has not been confirmed in humans, and has been specifically addressed and disproven in large randomized trial. The CREATE study found as a secondary endpoint that early treatment with EPO increased the likelihood of starting dialysis. CHOIR found no reduction in the rate of progression of CKD in patients given more EPO (the higher target arm) compared to the lower target arm ^10,12.
 
EPO for other Indications:In recent years, studies in animals and humans have focused on the use of EPO for other indications. It has been found to play a role in both cardioprotection and neuroprotection. It has effects on the immune system, and can cause regression in hematologic diseases such as multiple myeloma. It may also improve the response of solid tumors to chemotherapy and radiation therapy ^21. Again the cellular protection from EPO observed in animal models has not been confirmed in humans.
 
EPO and Seizures:Seizures are reported to be a complication of EPO in the product information. However, in a meta-analysis conducted by Giovanni et alshowed that treating with EPO may be protective against seizures Lower Hb targets of <95 g/L in individuals who are not treated with EPO are associated with a significantly increased risk of seizures compared with treatment with EPO and Hb values of >100 g/L ¹⁹.
 
EPO and Hypertension:Administration of ESA may be associated with exacerbation of
hypertension in about 5% of patients. Robert N. Foley et alin his analysis of observational and randomized studies found that most of the trials that have been reported to date have shown that higher hemoglobin targets lead to higher BP levels and/or greater requirements for antihypertensive therapy, he drew this conclusion from nine randomized trials ^47. The mechanism of ESA induced hypertension is thought to be related to stimulation of the vascular endothelium by ESA resulting in increased circulating levels of endothelin. Furthermore the increase in hemoglobin associated with ESA therapy may increase blood viscosity resulting in vasospasm. As such routine monitoring of blood pressure is essential in patients treated with ESA ⁴⁸. Meta-analysis of Phrommintikul et al showed a significantly higher risk of poorly controlled blood pressure in the higher haemoglobin target group than in the lower target hemoglobin ¹⁸ . Giovanni et almeta-analysis showed lower Hb levels of <95 g/L with no EPO treatment are associated with a reduced risk of patients who present with hypertensive episodes. In absolute terms, the risk of developing hypertensive episodes is 16% lower with Hb values <95 g/L compared with Hb >100 g/L. For every seven patients treated to obtain an Hb >100 g/L, one patient will require additional antihypertensive medication ¹⁹
 
EPO and Access:Normalizing hemoglobin has been associated with a higher incidence of vascular access clotting ^40. Randomized, prospective, open-label trial study of Besarab et al, showed a significantly higher risk of access thrombosis with the higher Hb targe¹⁷. Meta-analysis of Phrommintikul et alshowed a significantly higher arteriovenous access thrombosis in the higher Hb target group than in the lower target Hb ^18.
 
EPO and Pure Red Cell Aplasia (PRCA):Although rare, administration of ESA may result in formation of anti-erythropoietin antibodies, thereby leading to pure red cell aplasia and erythropoietin resistance ⁴⁹ In patients in whom ESA doses have been maximized without effect and no other causes can be identified, serum anti-erythropoietin levels and bone marrow biopsy should be performed. If confirmed, erythropoietin administration should be ceased and the patient treated with periodic blood transfusions.
 
Conclusion: Achieving hemoglobin control over time is a major challenge because of the various physiological factors that influence the response in individual patients and the potential risk for increased mortality, particularly for patients with co morbidities ⁵⁰. The association data led to several hypotheses about what anemia was causing e.g. LVH, fatigue, and increased mortality. These hypotheses have been tested in RCT's and in most cases anemia is associated with but does not cause the outcome, such as LVH or mortality. Fatigue is improved somewhat by anemia treatment with EPO, and transfusion frequency is reduced, though the cost is high. In the case of EPO balance is critical. Too little treatment and patients with chronic kidney disease are subjected to a lifetime of exhaustion and blood transfusions. Too much and they could be threatened with an increased risk of death. The overall quality of life is improved when anemia is treated with EPO, but aiming for a target value of 13.5 g of hemoglobin per deciliter provided no additional quality-of-life benefit ¹².
 

Key Points:

1. Anemia is associated with bad outcomes; Anemia is nearly universal in advanced renal disease. In these patients, anemia is associated with increased cardiovascular morbidity and mortality, reduced quality of life, and accelerated renal disease progression, though those associations do not necessarily establish causation.
2. Treatment of anemia reduces transfusion requirements and improves quality of life in anemic patients with CKD.
3. Mortality increases with treatment to higher targets; Recent studies have found an increased risk of death, blood clots, strokes, and myocardial infarctions in patients with chronic renal disease who received ESAs at doses that maintained their hemoglobin levels at more than 12g/dL, leading the Food and Drug Administration to apply a 'black box' warning to the product monographs of licensed ESAs.
4. Recent studies support partial correction, not normalization of hemoglobin.
5. Current guidelines recommend target of 10-12g/dL. 

INTRODUCTION:

Implantation of prosthetic mesh in repair of different hernias has gained a global acceptance and popularity. It is thought to be a potent safeguard against recurrence of hernias ^{1, 2}.The use of prosthetic mesh in different types of hernias has brought a phenomenal change in the out look of hernia patients all over the world ³. Today, an ever increasing number of hernias are repaired by implanting prosthetic meshes either by conventional open method or by laparoscopic approach ⁴. Beside its well known advantages and global acceptance in every day hernia surgery, a number of complications are thought to be associated with the use of mesh in different types of hernias ^5-15. We present our experience of mesh related complications in different open hernia repairs and their management in this study. MARERIALS AND METHODS It’s a descriptive observational study over 5 years during which a total number of 1008 patients with different types of hernias were repaired electively    in a teaching hospital as well as in private hospitals by the same surgical team. Of these, 638 (63.29 %) hernias were repaired by implanting prolene mesh of different sizes depending on the size of the defect. A drain was left in place in selected cases .The patients were followed up to a period of three years after discharge from the hospital. The follow up visits were scheduled at 1 month, 6 months, and then yearly. Of the total patients , 432(67.71%) were followed up to three years while 159 (26%) patients were lost in the follow up from day of discharge from the hospital. Another 47 patients attended follow up up to 2 years only and then disappeared. Sixteen of these patients continued to complain about chronic pain and foreign body sensation up to two years and then they did not return while 4 of these patients developed recurrent hernia in one year time but they were lost in follow up. The data of every patient is recorded on a proforma and their follow up records are maintained. The variables studied included immediate, early and late post-operative complications in addition to the demographic details. The statistical analysis of the data is done on SPSS version 12. RESULTS The mean age of the patients is 41 years with a range of 73 years and a STD of 19.089. There is a male dominance (N=531, 83%) over females (N=107, 17 %). The commonest type of hernia in this series is inguinal hernia (n=518, 81%) followed by Para-umbilical hernia (n=83, 13 %). Distribution of different varieties of hernias among male and female study population is shown inTable-I. Table-1. Frequency of hernias and distribution among males and females 

  Of the total number, 34 (5 %) hernias were recurrent hernias including 21 inguinal hernias, 11 Para-umbilical hernias and 2 Incisional hernias. The patients were operated after preliminary investigations and medical fitness. All the patients were operated by open conventional technique regardless of the type of hernia. Total duration of operation is shown in Figure -I with maximum patients (467, 73%) operated with in 60 minutes.  Figure-I.   Total duration of operation: Various early complications during the same admission occurred in 9 % (n=55) of the patients. Their distribution according to the type of hernia is displayed inTable- II. Table-II   Type of hernia * Complications during same hospitalization Cross tabulation 

 Wound infection has an alarmingly high incidence in our series (n=19, 3 %). Most of these infections are superficial and effectively controlled by intensive antibiotic therapy so that the failure of repair is saved and mesh rejection prevented effectively. Four of recurrences occurred during 2 years follow up but patient discontinued follow up afterwards. Remaining 07 recurrences occurred between 24 to 36 weeks. The complications observed during the follow up period of up to three years in different hernias are shown in Table-III.  Table-III    Type of hernia * Late Complications after discharge Cross tabulation 

 A remarkably low incidence of wound infection in para-umbilical and incisional hernia is attributable to the placement of suction drain which prevents hematoma formation and secondary infection. Seven (2%) recurrences occurred in para-umbilical hernias where suction drain did not work. Mesh infection with massive reaction , although, treated conservatively in 5 patients with vigorous antibiotic therapy led to the formation of a weaker scar which later on gave way and recurrence of hernia occurred. Follow up was not 100% and about 26% patients were lost in the follow up. Majority of the patients (n=457, 90 %) were discharged within 4 days while patients who were complicated had a longer stay up to 15 days (P <0.001). Late complications were mostly chronic pain and foreign body sensations with 2 cases of unilateral testicular atrophy. DISCUSSION A number of non-infectious and infectious complications are attributed to the use of mesh in the repair of most of the hernias^{5, 13, 16}. The type of mesh as well as their composition seems to affect complications following their use and specific materials are related to specific complications. We present 638 patients of different types of hernias repaired by implanting polypropylene mesh of varying sizes depending upon the size of defect. Prolene meshes are monofilaments, non-absorbable, inert, sterile and porous synthetic materials commonly used for this purpose. The use of mesh in hernia repair has brought a phenomenal change in the overall outcome of hernia repair especially in terms of recurrence of hernia ¹⁷. We experienced wound infection as the commonest complication in our series (n=19, 3%) and this was more so in the inguinal hernias. Most of the wound infections are superficial and very easy to control on conservative measures. On the contrary deep seated mesh infections are always dreaded complications and if not treated vigorously can lead to total failure and rejection of prosthetic mesh. A number of similar studies have reported an increased infection rate in mesh hernia repair testifying our results ^18-28. Grant AM ²⁹, however claims no difference in the incidence of infection between mesh and non-mesh repair of groin hernias. A severe local reaction occurred in 4 (0.62%) patients which resolved in few days without any consequences. Seroma and hematoma occurred in 11(2 %) and 7(1.09%) patients respectively. Only 3 seromas and one hematoma needed evacuation. We report a recurrence of 11(2 %) hernias of which 4 are inguinal and 7 are para-umbilical hernias. All of the recurrent para-umbilical hernias had severe reaction and wound infection in the post-operative period which was effectively controlled by vigorous antibiotic therapy and local wound care. There is probably a weaker scar after resolution of the infective process which resulted in recurrence. A significantly low recurrence rate in inguinal hernias in our study (0.77%) is consistent with the results of other similar reports ^30-32. Chronic pain and a foreign body sensation poses a real problem and though it occurred in only two cases but a similar study by Bay-Nielsen M ³³ claims 22.9% study population having chronic pain and more so in the adult males. CONCLUSION Although mesh repair is an efficient method of hernia repair, a number of complications may be associated and can lead to failure. An aggressive antibiotic therapy and wound care may control even massive infections.

Leg ulcers are defined as discontinuity of the epidermis and dermis in the lower limb of more than 6 weeks duration ^{1, 2}. They are a common presentation in the elderly population and are associated with a negative impact on the quality of life of patients and they also cause a substantial burden on the health budget ³. Pathogenesis of leg ulceration is heterogeneous ⁴. Prevention strategies, early identification and proper management are paramount in improving quality of life of patients and reducing costs on an already strained health budget. In this article we review the prevalence of leg ulcers in the elderly people, its common causes and management.

Prevalence                          The estimated prevalence of leg ulcers in the UK is between 1.5 and 3 per 1,000 population ³.A studies by Moffat et al 2004 showed a prevalence of 0.45 per 1000 which is less than the previously reported figures ⁵. In the same study leg ulceration was found to be more common in females than males  ⁵. In a systematic review of prevalence studies for leg ulcer, the authors also reported an increase in prevalence of leg ulcers with age and in women ⁶.The overall prevalence of ulcers is not affected by social class although ulcers tend to take longer to heal in lower socio economic classes ⁷. Quality of life Several studies have shown that patients with leg ulcers have a poor quality of life compared to age matched controls ^{8, 9.A} systematic review of studies measuring quality of life of patients with leg ulcers showed a negative impact on several domains of quality of life ⁸. In most of the studies pain was shown to be the major complaint among leg ulcer patients compared to controls, with males experiencing greater pain intensity than female patients. ^{10, 11} Restricted mobility and sleep disturbance due to pain was also reported in other studies.¹² Leg ulcer patients often complain of itchiness, odour and leg swelling ⁸.  In one study, unpleasant odour was reported as causing social embarrassment leading to higher anxiety and depression scores as well as altered body image ¹².Reduced mobility due to leg ulceration can restrict working capacity in younger patients¹³.A negative emotional impact on life with symptoms such as anger, depression, and social isolation was reported by 68% of patients in another study looking at impact of leg ulcers on quality of life ¹⁴. Aetiology Several factors contribute to the development of leg ulcers. However majority of ulcers are due to venous insufficiency which accounts for about 80-85% of all cases. ^{15, 16.} Frequency of venous ulcers increases with age as a result of several factors such as immobility and venous disease¹⁵.  Other risk factors for venous ulceration include obesity, previous deep vein thrombosis, thrombophlebitis, previous fracture, and varicose veins ¹⁷.Venous ulcers(also referred to as varicose or stasis ulcer)are commonly found between the malleoli and lower calf and are associated with a shallow base covered with granulation tissue and fibrinoid material, and have irregular margins ^16,17. The mechanism of venous ulceration involves initial damage to valves as a result of thrombosis or valve incompetence in varicose veins leading to pooling of blood in lower limbs. Extravasation of red blood cells then follows which causes a local inflammatory reaction and collagen deposition. This impairs the healing process eventually resulting in tissue breakdown and hence ulceration¹⁶. Venous ulcers are also associated with symptoms such as oedema, eczema.Arterial ulcers form the second largest group of leg ulcers and account for about 20% of leg ulcers. Atherosclerosis and diabetes are the commonest causes of this group of ulcers. Thrombotic episodes secondary to vasculitis, thromboangitis, and sickle cell disease can also result in arterial ulcers¹⁷.Arterial insufficiency causes hypoxia, ischaemia, tissue necrosis and consequently ulceration ¹⁸.Arterial ulcers are usually found below the ankle especially on the toes. The ulcers are characteristically small, have steep edges and a dry base. Risk factors for arterial ulcers include conditions that predispose to peripheral vascular disease such as smoking, diabetes, hypertension, hyperlipidaemia and obesity ¹⁷. It is worth mentioning that diabetes causes foot ulcers via two mechanisms: ischemia and neuropathy. Neuropathic ulcers are usually found on the plantar surface of metatarsal heads or on the toes. They are a consequence of poor glycaemic control¹⁹. The risk of malignancy in chronic leg ulcers is generally believed to be small, but a study by Yang et al 1997 showed a rate of 4.4% in chronic leg ulcers. The diagnosis should be considered in patients with non healing ulcers despite optimum management ²⁰.  Chronic inflammatory conditions such as rheumatoid arthritis, inflammatory bowel diseases are also associated with leg ulceration. Rare causes of leg ulceration such as ill fitting shoes have also been reported in literature. In a study looking at complications of ill fitting footwear among 65 elderly patients, foot ulceration was reported by 15% of the patients ²¹. Although small, this study showed that simple measures such as appropriate foot wear may be useful in preventing foot ulcers. Table 1: summarises causes of ulcers and main characteristics of leg ulcers ^{16, 17}

 Management  Like all medical conditions, management of leg ulcer should include a detailed history of the onset of the problem (as well as past medical history), examination of the legs and skin, investigations and modalities of treatments. The underlying causes need to be identified as this has crucial implications for management. A medical history suggestive of venous and arterial ulcers have been mentioned above but other factors to consider while assessing leg ulcer are: general health status, cigarette smoking, nutrition, limitation to self care, pedal pulses, Ankle Brachial Pressure Index (ABPI), oedema, limb size and shape, sensation and pain (Table 2). Table 2: Assessment of lower limb ulcers 

Examination of the legs and skin identifies markers of underlying pathology. Venous disease may present with some or all of the following: brawny skin, haemosiderin staining, lipodermatosclerosis, atrophie blanche (patchy areas of ischemia),and stasis eczema, while the skin of patients with arterial disease is often shiny, hairless, pale and cool; with thickened nails and changes in foot structure. The absence of venous or arterial signs and symptoms raises the possibility of less common causes of ulceration like: Sun damaged skin, Bowen disease or a history of previous skin cancer treatment is an alert to a malignant lesion.                                                                    Site & Appearance: Most venous ulcer occur in the “gaiter” area of the leg (i.e. area extending from just above the ankle to below the knee and tends to occur on both lateral and medial aspect of the leg), they are usually superficial with poorly defined margins. The base of the wound is usually red granulation tissue with moderate to high levels of exudates. Arterial ulcers can occur anywhere on the lower leg and may appear in the gaiter region, especially with coexisting venous disease. Many arterial/ischaemic ulcers occur over bony prominences and have a history of pressure related cause. They are often deeper with a punched out appearance and may involve structures such as muscles, tendon and bone in the base. They have sloughy, devitalized tissue in the wound base and low levels of wound exudates. Ulcers occurring in atypical site with an atypical appearance require further investigation to determine the cause. Ulcers with a violaceous (purple) border, inflammation, and extreme pain, may be related to vasculitis problem or underlying connective tissue disorder. Size: Dimensions of the ulcer should be taken at first presentation and fortnightly thereafter and recorded in the notes. This is important as it gives an objective assessment of the effectiveness of the current treatment plan, and modify as necessary²².There are a range of techniques available such as digital photography, ruler based vertical, horizontal and depth measurements and circumferential tracings of wound margins using acetate sheets over cling film .The system chosen needs to reflect consistency, accuracy, and reduced operator error, and also provide visual feedback to the patient. Pain: The level of pain associated with ulcer must be assessed on presentation and at each visit thereafter using a standardized pain scale (0-10). Pain may suggest infection or arterial disease, so careful assessment is required.Surrounding skin area should be observed for the presence of eczema, hyperkeratosis skin, maceration, cellulitis, signs of irritation and scratching which are signs and symptoms associated with underlying venous disease.Assessment should also include palpation of peripheral pulses, regular blood pressure measurement, weight (with reference to a Body Mass Index chart) as well as routine urinalysis (to screen for diabetes). Vascular Assessment: This is mainly carried out by the use of Doppler ultrasound to measure the Ankle Brachial Pressure Index (ABPI).This is mandatory and must be repeated every 3 months. All patients with a non healing wound on the leg of greater than 4-6weeks should have a vascular assessment to eliminate any underlying ischaemic disease²².The result of ABPI are used to determine the likelihood of arterial insufficiency and can be used to guide the management plan, especially in relation to healing potential, referral for vascular assessment and use of appropriate compression bandages. ²³ The normal range for ABPI is 0.8-1.2. An ABPI of less than 0.5 or greater than 1.2 needs vascular opinion. Treating the ulcer Many dressing materials are available for the treatment of leg ulcers and there is no adequate evidence from clinical trials to recommend one dressing type over another, but we have to bear in mind few criteria in choosing a particular dressing. The dressing should be low adherent, cost effective and must also be comfortable as well as acceptable for the service user. The choice of product should be determined by   the level of exudate. Products which commonly cause skin sensitivity such as those containing lanolin and topical antibiotics should not be used on any service user²². The use of white soft paraffin has been identified as a potential fire hazard risk, hence a water based emollient should be considered as an alternative to a paraffin emollients e.g aqueous cream. Please note water based emollients are not as effective in providing sustained emollient therapy as an ointment and also contain preservatives, which are known potential irritants. Other modalities of treatments of leg ulcers are described below.  Compression Therapy The mainstay of treatment of any venous component to ulceration is the application of sustained, graduated compression at therapeutic level ²⁴ .Graduated compression increases venous flow, decreases valvular reflux while walking and increases the effectiveness of the calf muscle pump resulting in a “thinning leg”. The most effective level of compression to overcome venous hypertension has been determined to be around 40mmHg at the ankle ²⁵. Correct application of bandages is essential to avoid pressure ulceration over the bony high points and along the anterior border of the tibia. It is acknowledged that the application of compression bandaging is a specialized skill traditionally undertaken by nurses. The combination of compression bandages used to achieve compression of 40mmHg at the ankle will depend on ankle circumference, according to Laplace’s law, which states that the sub bandage pressure is inversely proportional to the circumference of the limb. A modified compression regimen is necessary when pain is present. This may be achieved by providing periods of relief until pain is controlled or removing the bandage at night when the leg is elevated. Patients with mixed arterial and venous disease may only tolerate up to 20mmHg compression to treat oedema. Bandage choices include short stretch, long stretch, multilayer systems and stockings. A Cochrane Review of compression regimens identified increased healing rates with compression compared to no compression²⁶ . A high compression bandages were better than moderate compression bandages, and that multi-layered bandages were better than single layered bandages. Comparisons between various high compression bandages systems, e.g. 4 layer and short stretch bandages, were unable to find any difference in effectiveness. For venous ulcer with ABPI > 0.8, use 4 layer bandages as per ankle circumference below (Table 3) Ulcers with ABPI between 0.6-0.8: Reduced compression is achieved by omitting the outer cohesive bandage (e.g. Coban) Table 3: Multilayered bandage regime in relation to ankle circumference. 

Once the ulcer site is well healed, continue with the compression bandages for at least 4 weeks and then maintain compression at a slightly lower level indefinitely as tolerated. It must be replaced annually. Other factors to consider and deal with include: Infection This requires regular cleansing, more frequent changes of dressing (especially if exudates levels are high), topical antimicrobial dressings or systemic antibiotics. Pain Ranging from simple analgesia to potent opioid (depending on severity of pain), non steroidal anti inflammatory drugs may be beneficial. For neuropathic pain, amitriptyline can be started which can be replaced by gabapentin if no improvement. The dose can be titrated upwards. Pressure: Requires pressure relief for the ulcer to heal especially over bony prominences. Larval Therapy Larval therapy has been used for debridement of wounds for many years.²⁷ Debridement is an essential component of wound care as the presence of devitalized tissue can impede the healing process. While the exact mechanism of larval therapy remains unknown, it encompasses three processes: debridement, disinfection and promotion of healing. The beneficial effects of larval therapy were first observed during the Napoleonic war by Larrey, who noted that soldiers whose wounds had become infested with maggots had an improved prognosis ²⁷. During the First World War, Baer documented the successful treatment of leg ulcers and osteomyelitis using larval therapy, and paved the way for further use of it by doctors of that time. However, the development of antibiotics and improvements in surgical techniques reduced larval therapy to a “treatment of last resort”, reserved for the most intractable wounds ²⁸. The emergence of antibiotic- resistant strains of bacteria such as methicillin resistant staphylococcus aureus (MRSA) and the curiosity of researchers has prompted a resurgence of interest in larval therapy. Larval therapy has been employed effectively to treat a wide spectrum of wounds including venous and arterial leg ulcers²⁹.Some of the benefits of larval therapy include: reduction in wound pain and odour, and promoting healing process with relatively few side effects³⁰ .Larval therapy is also reported as being cost-effective in comparison with conventional wound dressings. The use of larval therapy often resulted in quicker healing, and a subsequent reduction of nursing time and materials³⁰. A further advantage of larval therapy is that, as larvae are typically applied for 3 days, wounds are disturbed less frequently than conventional dressings that require changing every 1-2days.In addition to this, a further advantage is that treatment can usually be carried out in outpatient and community settings. A study   at an outpatient wound clinic on chronic wounds, of varying aetiologies reported that using larval therapy resulted in a 62% decrease in need of amputation ³¹. Larvae offer the benefit of eliminating bacteria from the wound through ingestion and subsequent degradation within their intestinal tract. They also act to reduce bacterial activity through the production of inhibitory secretions. The most commonly mentioned disadvantage of larval therapy is the negative perception with which it is regarded by both patients and practitioners because of the unpleasant appearance. The use of “Biobags”, which completely enclose the larvae within a polyvinyl alcohol membrane, has become a popular method of improving the application of this treatment, as larvae are able to feed freely through the open cell polymer. Pain has occasionally been reported by patients, the cause may be the sharp mouth hooks and spicules with which larvae anchor themselves onto tissue. A case history has suggested larval therapy to be contraindicated with fistulae, exposed wounds connecting to vital organs³²  because bloodstream infections have been reported with some larvae³³.Alteration of the disinfection process appeared to eliminate this problem, and with no further cases of sepsis occurring during the subsequent 12 months The risk of cross-infection by escaped larvae may be greatly reduced through careful dressing. Vacuum Assisted Closure therapy Vacuum Assisted Closure (VAC) therapy involves the application of controlled negative pressure to wounds ³⁴. Negative pressure, as a method of management for difficult to heal wounds, was initially explored in 1970, with the first wound drainage system being introduced in 1989. The use of negative pressure to heal wounds, however, is more commonly associated with the work of Argenta and Morykwas in 1997.³⁵ VAC therapy was designed with the aim of improving healing, decreasing morbidity, and decreasing the cost and length of hospital stay in patients with chronic, non healing wounds. VAC therapy promotes healing in several ways. Firstly, the foam dressing, in combination with adhesive tape, creates an occlusive dressing. This alone prevents dessication and increases the rate at which epithelial tissue is developed, therefore aiding healing times. Occlusive dressing prevents an increase in infection. Secondly, the suction effect and the mechanical forces generated at the interface of the foam work to decrease interstitial fluid accumulation, control wound exudates, stimulate granulation tissue formation, reverse tissue expansion, decrease bacterial colonisation and increase blood flow and dermal perfusion. In summary, VAC therapy aids wound healing by:       Maintaining a moist environment       Increasing local blood flow       Removing wound exudates       Promoting granulation tissue formation       Reducing infection       Exerting mechanical pressuresVAC therapy is suitable for the following wound types/processes ³⁶        Acute   (trauma, burns)        Chronic (pressure sores, leg ulcers, diabetic ulcers)        Surgical (skin grafts, flap surgery, wound bed preparation)        Salvage (wound dehiscence, wound infection, post operative sternum infections) Contraindications to the use of vacuum therapy include: wounds with untreated osteomyelitis, grossly infected wounds, when necrotic tissue is present or when there is unspecified disorder of the blood. VAC therapy should also not be used in wounds with malignancy .Dressings should not be placed over any exposed vessels or organs and VAC therapy should be used with caution in patients with active bleeding, difficult wound haemostasis and in patients taking anticoagulants. Skin grafting Skin grafting is the transplanting of skin, and, occasionally, other underlying tissues to another location of the body. It is the only means of reconstructing a defect in the skin, regardless of the cause of the defect ³⁷. Generally, skin grafting is used when, in the opinion of the reconstructive surgeon, other methods of reconstruction such as primary closure, secondary intention healing, or local skin flap are inappropriate, are unavailable or would produce a suboptimal result. Skingraft are divided into 2 major categories: full thickness skin graft (FTSGs) and split thickness skin graft ( STSGs).STSGs may be subdivided into thin (0.008-0.012mm),medium(0.012-0.018mm) and thick (0.018-0.030mm)grafts ³⁷. STSGs are the one used in covering chronic unhealing cutaneous ulcer. Split skin grafting is technically demanding and requires hospital admission²⁵. The discharge from the surface of venous ulcers tends to dislodge continuous sheets of split skin, leaving a choice between mesh and pinch skin grafting. Pinch skin grafting provides epithelial islands, from which epithelial growth may spread outwards as well as inwards from the ulcer margin. Pinch skin grafting has been done by district nurses in the community and has been found to be cost effective accelerating healing when used with multilayer compression bandaging.²⁵ Some contraindications to the use of skin graft generally include: vascular tissues such as exposed bone or cartilage (as this will lead to graft necrosis), uncontrolled bleeding of the recipient because of haematoma and/or seroma formation under the graft compromises graft survival. Venous Surgery Superficial venous surgery has been shown to improve ulcer healing in patients with only superficial venous incompetence³⁸. In patients with no deep reflux on duplex imaging, superficial venous surgery has been shown to reduce long term ulcer recurrence²⁵ . Indications for superficial venous surgery are:

•  Patient fit for surgery
•  Sufficient mobility to activate calf muscle pump
•  Prepared to attend hospital for investigation and surgery
•  Obesity controlled (BMI <30)
•  Superficial venous incompetence

 There are few other modalities of treatment of leg ulcers currently in use, although no strong evidence has been found to show they really improve healing. Intermittent Pneumatic Compression Intermittent pneumatic compression (IPC) is a mechanical method of delivering compression to swollen limbs that can be used to treat venous leg ulcers and limb swelling due to lymphoedema.It uses an air pump to inflate and deflate an airtight bag wrapped around the leg.³⁹ However, review of trials found conflicting evidence about whether it is better than compression bandages. It may increase healing compared with no compression but it is unclear whether it improves healing when added to treatment with bandages. Electromagnetic Therapy  Electromagnetic therapy involves the use of electromagnetic, microwave, or infrared energy to diagnose or treat an illness by detecting and correcting imbalances in the body's energy fields. Electronic devices that emit some form of low-voltage electrical current or radio frequency are often involved. It has been used in the treatment of chronic diseases like venous leg ulcers. Cochrane wound group conducted trials on several occasions comparing electromagnetic therapy with other treatments and up till now, there is no reliable evidence of benefit of electromagnetic therapy in the healing of venous leg ulcers.⁴⁰ Further research is still needed.  Oral Zinc Supplement Leg ulcers may take long time to heal despite good wound care. This may be due to poor nutrition which reduces the ability of the body to repair itself. Minerals such as zinc are necessary for good healing and so it has been thought that taking zinc sulphate tablets might aid healing of ulcers especially if patients were found to have low baseline Zinc level. Few trials were found where zinc was used to treat leg ulcers but all were too small to pick up on any benefit, if such a benefit exists. In addition, the quality of those trials was mediocre. On the basis of the evidence available so far, it appears that taking zinc tablets does not improve leg ulcer healing, however more good quality trials are needed.⁴¹ Laser Therapy Low level laser therapy (LLLT) refers to the use of red beam or near infrared laser with a wavelength between 600and 1000nm power from 5-500 milliwatts.It is also referred to as cold laser therapy, low power laser therapy (LPLT), low intensity laser and low energy laser therapy. The exact effect of its mechanism is unknown; however, hypotheses have included improved cellular repair and stimulation of the immune, lymphatic and vascular system. Several randomised controlled trials involving patients with venous ulcers failed to demonstrate any significant benefits of LLLT when compared to standard treatment methods or placebos.⁴² Hyperbaric Oxygen Therapy Oxygen is one of the most versatile and powerful agents available to the modern medical practitioner. The therapeutic use of oxygen under pressure is known as hyperbaric oxygen therapy (HBO₂) and has been used to assist wound healing for almost 40 years. HBO₂ has several specific biological actions which can enhance wound healing processes .These include: Hyper-oxygenation of tissue, vasoconstriction, down regulation of inflammatory cytokines, up-regulation of growth factors, antibacterial effects, potentiation of antibiotics, and leukocyte effects.⁴³ Systemic oxygen can be administered via 2 basic chambers: Type A( multiplace) and Type B(monoplace). Both types can be used for routine wound care, treatment of most dive injuries, and treatment of patients who are ventilated or in critical care.HBO₂ is a relatively safe non-invasive therapy. Side effects include middle ear and pulmonary barotraumas and myopia. Contraindications include poor cardiac output and severe obstructive pulmonary disease. Conclusion In this article, we have been able to show that leg ulcers are a common presentation in the elderly population and have negative impact on the quality of life of affected patients. It has been found to be more common in females. Most leg ulcers (about 80-85%) are caused by venous insufficiency, followed by arterial ulcers. A comprehensive assessment of the patient, skin, vascular status, limb and ulcer is required to determine aetiology and to formulate an appropriate management plan as described above. Several researches are still going on other modalities of treatment of leg ulcers. However, all patients should be provided with both verbal and written information to help them understand their condition and treatments they receive, as this will enable them to better understand their conditions, and will support concordance between patients and staff.

Spasticity is a common symptom seen as a consequence of an injury to the brain (stroke, trauma, hypoxia, infection, cerebral palsy and post surgery), spinal cord injury or multiple sclerosis. It is a complex problem, which can cause profound disability alone or in combination with other features of upper motor neuron syndromes (figure 1). The word “spasticity” is derived from the Greek word “spasticus”, which means “To pull or To Tug”. Spasticity is defined¹ as “Disordered sensori-motor control, resulting from an upper motor neuron lesion, presenting as intermittent or sustained involuntary activation of muscles”. Simply stated, spasticity is stiffness of muscles that occurs after injury to the spinal cord or brain. Awareness of the implications and associated symptoms can minimise development of long term secondary complications (table 1). The impact of spasticity can be devastating. If not managed early and appropriately it may result in progressive disability, resulting in secondary complications such as contractures and pressure sores. This significant impact has ensured that spasticity management is a prominent feature in the national management guidelines for long term neurological conditions, promoting coordination of care between primary, secondary and social care providers. Symptoms Spasticity can range from mild muscle stiffness to severe, painful and uncontrollable muscle spasms. It is associated with both positive and negative components of upper motor neuron syndromes. Positive components include muscle overactivity, flexor and extensor spasm, hyperreflexia, athetosis, spastic dystonia, clonus, and an extensor plantar response. Common negative symptoms comprise weakness/ paralysis, early hypotonia, fatigue and loss of dexterity. Spasticity can be distinguished from rigidity by its dependence on the speed of muscle stretch and characteristic distribution in antigravity muscle groups. Spasticity does not always cause harm and can occasionally assist in the rehabilitation process by enabling a patient to stand when their limb weakness would not otherwise allow it Table 1 Clinical and functional problems associated with severe Spasticity

 Figure 1 Vicious cycle of spasticity   Assessment of spasticity Before any intervention is undertaken to modulate hypertonicity, it is important to attempt to assess the severity of spasticity. Many grading scales are used to quantify spasticity. These address the degree of muscle tone, the frequency of spontaneous spasms and the extent of hyperreflexia. Goniometry, Ashworth scale, Tardieu Scales, Goal attainment scale are only a few of these scales. One of the most widely used scales is the modified Ashworth scale². Table 2 Modified Ashworth scale

  It is also important to remember that not every “tight” muscle is spastic. The clinically detectable increase in muscle tone may be due to spasticity, rigidity or a fixed muscle contracture. Management  The key to successful spasticity management is education of the patient and carers with both verbal and written information. This allows them to understand, appreciate and be fully involved in the management plan. All patients with spasticity should be followed up by a coordinated multidisciplinary team, which allows more timely intervention and close monitor of the progress. Liaison between health and social services in both primary and secondary care is essential in long term management. This helps to deliver a more consistent approach to the individual over time (figure 2). Table 3 Aims of spasticity management.

 The first step in the management of spasticity is to identify the key aims and realistic goals of therapy. Understanding the underlying pathology and possible prognosis is helpful in planning these goals (table 3). Other key points to consider are: ·          Identification and management of any trigger or aggravating factors-Initial assessment should exclude any co morbidity that may worsen spasticity such as pressure sores, chronic pain, infection (commonly urinary tract infection), constipation or in-growing toe nails.·          Instigation of an effective and realistic physical programme including attention to posture and positioning Figure 2
Approach to spasticity assessmentComprehensive assessment of spasticityRecognition of underlying provocative factorsImpact on the individualMeasurement of spasticityPotential goals- individualised and person focussed 
Initial approachEducation to patient/ and their family /carersMultidisciplinary team assessmentIdentification of clear treatment goalsEstablish mechanism for monitoring and review  Management Manage triggering factorsBalance between positioning and movementPosture and seatingPhysical therapy and active exercise programmeSplinting and use of orthoticsPharmacotherapy A)      Physical modalities·          Stretching- this intervention has the benefit of being benign and non-invasive. Maintaining muscle length through passive or active exerciseand stretching regimens including standing or splinting canbe key to managing spasticity both in the short and the longterm.·          Cooling of muscles- this inhibits mono synaptic stretch reflex and lowers the receptor’s sensitivity, different techniques such as quick icing and evaporating spray like ethyl chloride are occasionally used.·          Heat-heat may increase the elasticity of the muscles. Techniques used include ultrasound, fluidotherapy, paraffin, superficial heat and whirlpools. These techniques should be combined with stretching and exercise.·          Orthosis/equipment/ aids – an orthosis or splint is an external device designed to apply, distribute or remove forces to or from the body in a controlled manner to control body motions and /or alter the shape of body tissues. E.g. ankle foot orthosis, insoles, ankle supports, wrist/ hand/ elbow splints, knee splints, spinal brace, hip brace, neck collar. Some equipment can also aid positioning e.g. T roles, wedges, cushions and foot straps.These are usually used in combination with other modalities like botox therapy. Attention to posture and positioning, whichmay include the provision and regular review of seating systems,is paramount in managing severe spasticity·          Massage– althoughvarious techniques are in use there is no evidence to support this·          Dynamic physiotherapy technique- many schools of physiotherapy claim that particular technique has antispastic and functional benefits, particularly for the more mobile person. E.g. Bobath technique, proprioceptive neuromuscular facilitation, Brunnstrom technique. B) Electrical therapy·          Functional Electrical stimulation –Thisis an adjunct to physiotherapythat can be of benefit to selected individuals who are predominantlyaffected by upper motor neuron pathologies resulting in a foot drop. Randomised controlled trial by Burridge et al in patients following stroke found that the use of functional electrical stimulation in combination with physiotherapy was statistically superior to physiotherapy alone³·          Transcutaneous electrical nerve stimulation – this has been found to reduce spasticitythrough its nociceptive action and reduction of pain. C) PharmacologicalMedicationshould always be used as adjunct to good general management and education. Identification of treatment goals will help optimise drug therapy not only in terms of choice of agent, but also in timing and dose. Aims of medication should be to improve function or relieve troublesome symptoms rather than to simply reduce the degree of spasticity. Table 4 Useful things to remember to optimise medication effects

 Table 5 Different methods of delivery of medication

 The oral agentsAlthough different categories of drugs are available, those most commonly used to treat spasticity are baclofen,tizanidine, benzodiazepines, dantrolene, and gabapentin^{4, 5, 6}. Different agents act through different mechanisms (table 6 and 7) for e.g. GABA-like (baclofen, benzodiazepine), central alpha 2 agonists (tizanidine, clonidine) and peripheral anti-spastics (dantrolene). Antispastic drugs act in the CNS either by suppression of excitation (glutamate), enhancement of inhibition (GABA, glycine) or a combination of the two. Table 6 Mechanism of action of commonly used oral antispasticity medication

  Baclofen remains the most commonly used anti-spastic agent. The preferential indication is spasticity caused by spinal cord disease especially in multiple sclerosis. Many studies including the pilot study by Scheinberg et al ⁷ demonstrated that oral baclofen has an effect beyond placebo in improving goal-oriented tasks (such as transfers), in children with spastic quadriplegic cerebral palsy. In open-label studies of oral baclofen, the drug improved spasticity in 70-87 per cent of patients; additionally improvement in spasms was reported in 75-96 per cent of patients. In double-blind, crossover, placebo-controlled trials, baclofen was reported to be effective, producing statistically significant improvements in spasticity⁸. The main adverse effects of oral baclofen include sedation or somnolence, excessive weakness, vertigo and psychological disturbances. The incidence of adverse effects is reported to range from 10 to 75 per cent. The majority of adverse effects are not severe; most are dose related, transient and/or reversible. The main risks of oral baclofen administration are related to withdrawal; seizures, psychic symptoms and hyperthermia. These symptoms improve after the reintroduction of baclofen, usually without sequelae. When not related to withdrawal, these symptoms mainly present in patients with brain damage and in the elderly. The limited data on baclofen toxicity in patients with renal disease suggest that administration of the drug in these persons may carry an unnecessarily high risk. Tizanidine is an efficient and well tolerated antispastic. It is predominantlyan alpha 2 agonist and thus decreases presynaptic activity of theexcitatory interneurones. There is a large body of evidence for the effective use of tizanidine monotherapy in the management of spasticity ¹⁵. Tizanidine is the antispasticity drug that has been most widely compared with oral baclofen. Studies have generally found the two drugs to have equivalent efficacy, although tizanidine has better tolerability; in particular weakness was reported to occur less frequently with tizanidine than with baclofen.Dantrolene has a peripheral mechanism of action and acts primarily on muscle through inhibitingcalcium release from the sarcoplasmic reticulum. It decreasesthe excitation–coupling reaction involved in muscle contraction and can be prescribed in the different forms of spasticity. The efficacy of benzodiazepines (diazepam, tetrazepam, clonazepam) is comparable with baclofen. Although there is no evidence to suggest any difference in effectiveness between them, diazepam and dantrolene are associated with more side effects than baclofen and tizanidine. There are other compounds with anti-spastic properties (gabapentine, cyproheptadine, piracetam). Their advantage is

Table 7

rather limited when used alone. Generally, they are administrated in combination with usual anti-spastic drugs. A few short term trials have trialed gabapentin with good results ¹⁹ .Pregabalin may be of value as a systemic agent in the treatment of spasticity, although properly controlled studies with clearly defined outcome measures are required to confirm this finding ²². The Sativex Spasticity in MS Study Group²³ concluded that oromucosal whole plant cannabis-based medicine (CBM) containing delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD) may represent a useful new agent for treatment of the symptomatic relief of spasticity in MS. 
Intrathecal pump·          Baclofen- If oral drug treatment is inadequate in controlling lower limb spasticity or is not tolerated, intrathecal delivery of baclofen should be considered. This has been found to be a cost-effective strategy when compared to conventional medical management alone by Bensmail et al ²⁰ .The benefits of continuous intrathecal baclofen infusion have been demonstrated in more than 80 percent and over 65 percent of patients report an improvement in tone and spasms respectively. The main risks of intrathecal baclofen infusion are symptoms related to overdose or withdrawal. These are mostly related to catheter disruption, failure to refill the pump reservoir or failure of the pump's power source. Abrupt disruption of intrathecal baclofen can be a serious scenario with continuous spasms, tremors, temperature elevation, seizure and death having been reported.·          Phenol- As phenol is a destructive agent which indiscriminately damagesmotor and sensory nerves, it is reserved for those individualswho do not have any functional movement in the legs, who havelost bladder and bowel function and who have impaired leg sensation. Intrathecal phenol can be an effective treatmentwhich, though it requires expert administration, does not havethe long term maintenance or cost issues that are associated with intrathecalbaclofen treatment. The effect of a single injection often lastsmany months and can be repeated if necessary ²⁴. D) Nerve blockPeripheral nerve blockade/ Regional blocks/ Neurolytic blockade²⁵ are another therapeutic possibility in the treatment of spasticity. This can be done with the help of fluoroscopy or nerve stimulation. Chemical neurolysis by phenol/ alcohol is irreversible and can be used at several sites. Blocks are applied most often to 4 peripheral sites: the pectoral nerve loop, median, obturator, and tibial nerves. The main indication is debilitating or painful spasticity. Peripheral blocks with local anaesthetics are used as tests to mimic the effects of motor blocks and determine their potential adverse effects. Peripheral neurolytic blocks are easy to perform, effective, and inexpensive³⁰. E) Botulinum toxin injectionBotulinum toxin is the most widely used treatment for focal spasticity^27,28,29. The effect of the toxin is to inhibit the release of acetylcholine at the neuromuscular junction. The clinical effect of injecting botulinum toxin is reversible due to nerve sprouting and muscle reinnervation, leading to functional recovery of the muscle in a few months. It is essential that botulinum toxin injections are given in conjunction with physiotherapy in order to obtain the maximum benefit. The toxin is injected directly into the targeted muscle and an effect can be noticed from as early as 2-3 days with a maximum effect seen by about 3 weeks, lasting at least 3 months. As it is not a permanent treatment it may have to be repeated after a few months.Many randomisedcontrolled trials show that botulinum toxin is effectivein reducing muscle tone in various conditions ^{28, 29}. Brashear and colleaguesdemonstrated a reduction in spasticity in the wrist andfingers of patients following stroke with the use of botulinum toxin, together with an improvementin their disability assessment scale²⁹.E) Surgical techniqueMost surgical procedures are irreversible. This means that realistic goal setting between the health care provider, family and patient is critical. Neurosurgical techniques have been proven useful in conditions like cerebral palsy ^{32, 33}.·          Neurosurgical techniques- Anterior and posterior rhizotomy, peripheral neurotomy ³¹, Drezotomy, percutaneous radiofrequency rhizotomy, spinal cord and deep cerebellar stimulation of the superior cerebellar peduncle ³², functional neurosurgery ³³·          Orthopaedic procedures- directly act on muscles and tendons e.g. lengthening operation, tenotomy, neurectomies, and transfer of tendons. 

Introduction.
 
This legislation is based on rules established by case law about how to work with people who lack capacity (either on a temporary or permanent basis).
                 
The Act provides a definition of capacity, a functional test for capacity (see Box 1) and a checklist for Best Interest decision making which are under pinned by five key principles (See box 2). The Act is supported by a Code of Practice.
 
The Act, which applies to all adults aged 16 years or over (with some exceptions), provides a clear definition of incapacity, and for deciding if a person lacks capacity in respect of a particular matter.
 
“A person lacks capacity in relation to a decision or proposed intervention if, at the material time, he is unable to make a decision for himself in relation to the matter or proposed intervention because of an impairment of, or a disturbance in the functioning of the mind or brain. It does not matter whether the impairment or disturbance is permanent or temporary.” (S2 (1) and (2) MCA 2005.

It is important to note that the decision is always ‘time specific’ and ‘issue specific’. It is also a test applied both to people with temporary or fluctuating capacity (such as people experiencing mental ill-health) and those whose decision making ability is permanently impaired (such as people with a learning disability)
 
The Act starts from the presumption that those we work with do have capacity, and requires staff to involve them as much as possible in their own treatment and care including when there is evidence that they lack capacity in a particular matter.
 
The Act also introduces a statutory right to advocacy for those lacking capacity and “unbefriended” through the Independent Mental Capacity Advocacy Service (IMCA), Lasting Powers of Attorney for health and welfare and property and finance and two new criminal offences, i.e. “the wilful neglect or ill treatment of a person lacking capacity” (S 44 MCA 2005.)
 
The MCA will also apply when someone is detained under the Mental Health Act 1983. For example if the person lacks capacity to consent to treatment for a physical health issue rather than treatment related to mental disorder.
 
The Act has introduced safeguards for medical practitioners when working with advanced decisions made by people in advance for how they wish to be treated when or if they lose capacity in the future.
 
Best Interests Check List.
 
The best interests checklist represents the issues that decision makers must consider when decisions or interventions are made on behalf of someone who lacks capacity, if the decisions (and the decision maker) are to be protected by the MCA
 
The checklist items include that the decision maker:-
 
·         Must not make their judgement based merely on the person’s age, appearance, condition (or diagnosis);
 
·         Must take into account whether the person is likely to regain capacity with regard to the decision in hand, and whether the decision can wait;
 
·         Must as far as reasonably practicable, ‘permit and encourage’ the person to communicate, including by acting to improve his or her ability to communicate (for example, by using an advocate);
 
·         Must not, where the decision relates to life sustaining treatment, be motivated by a desire to bring about the relevant person’s death;
 
·         Must so far as is possible consider the person’s past wishes and any preferences (particularly when written down) stated by him or her when they had capacity;
 
·         Must take account of the beliefs and values that would have been likely to influence the person’s decision had they had capacity;
 
·         Must, if practical and appropriate, consult anyone previously named by the patient as someone who should be consulted, any carers, anyone who has a relevant lasting power of attorney – a ‘donee’ (remembering that there are two kinds of LPA – (i) personal welfare, and (ii) property and affairs), and any appointed court deputy about their views concerning what would be in the person’s best interests.
 
Protection from liability offered by Section 5 of the Mental Capacity Act
 
The MCA provides legal protection for people who need to intervene in the lives of people who lack capacity so that they are able to make a decision on that person’s behalf, or provide the care the person needs, as long as they have a reasonable belief that the person lacks capacity to make the particular decision and they are working in the person’s best interests.
 
Generally, however, protection is available as long as:-
·         Reasonable steps have been taken to gain permission from the person concerned;
·         The decision maker is reasonably sure the person lacks the capacity to make a particular decision;
·         The decision maker is working in their best interests, and before making the intervention you have considered whether there is a “less restrictive’ option than the one proposed, and only ruled it out because it is less effective than the one you are now taking;
·         Restraint if needed, is a proportionate response to the risk of harm if no action is taken;
·         The action doesn’t amount to a deprivation of liberty, or conflict with an advance decision made by the person, their LPA or a Deputy;
·         The decision maker is spending money to buy goods or pay for services that are in the person’s best interests and appropriate authority has been sought.
 
In a medical context, this could be helpful on a day-to-day basis, or to deal with an emergency situation where the Mental Health Act does not apply as illustrated in the example, taken form the Code of Practice, in box 3 below.

 
Limitations to Section 5 by Section 6 Mental Capacity Act 2005.
 
It is important to recognise that section 5 of the Act does not offer practitioners total freedom from liability in providing care or treatment.

·         Life-changing events: decisions about life-changing events, such as changes in residence and serious medical treatment will only be covered under Section 5 if the decision makers firstly consult all appropriate parties, and secondly consider whether there is a less restrictive way in which the care needed can be given. If there are no families or friends that professionals can consult in these specific circumstances, or if the decision maker deems the family member or friends “inappropriate", an Independent Mental Capacity Advocate (IMCA) must be instructed to support and represent the person whilst their best interests are being determined.
 
·         The use of force, and depriving people of their Liberty: doctors and other professionals will continue to be protected by the law where, in an urgent situation, it is necessary to restrain or restrict a person who lacks capacity in order to protect them from harm. The force used must be proportionate to the risks involved. However, this protection has a ‘time limit’. Where restraint is needed on an ongoing basis (and restraint can mean the use of medication, or making a decision or making it known to a patient that they would be prevented from leaving) professionals involved won’t necessarily be protected by the MCA – this is where the Deprivation of Liberty Safeguards become important.
 
Safeguards for patients: making decisions in advance
 
Advance decisions to refuse medical treatment
People can now make advanced decisions to refuse treatment, provided that the decisions were made when the person had the capacity to make them.
 
To make a valid advance decision, a person must:
·         Be 18 years or older
·         Have capacity to make the specific decision
·         Make a decision that is applicable (i.e. specific to the care and treatment they want to refuse and the circumstances in which it will be refused )
 
The decision doesn’t need to be in writing, unless it relates to life sustaining treatment – in which case it must be in writing, and witnessed.
 
An advanced decision becomes valid and applicable when all of the conditions described within it are present.
 
If Doctors are not informed about the existence of an advanced decision then they are expected to treat someone with that person’s bet interests in mind.
           
Lasting Powers of Attorney and Deputies from the Court of Protection
 
The MCA allows people to make arrangements for others to make decisions on their behalf when or if they lack capacity.
 

• Lasting Powers of Attorney (LPAs) – The Act allows a person to appoint an attorney to act on their behalf if they should lose capacity in the future. The Act also allows people to empower an attorney to make health and welfare decisions, as well as financial & property decisions (a LPA for finance and property can be used whilst a person still has capacity, if the donee gives specific instruction). Before it can be used a LPA must be registered with the Office of the Public Guardian (see below).

• Court appointed deputies – The Act provides for a system of court appointed deputies to replace the previous system of receivership in the “old” Court of Protection. Deputies will be able to be appointed to take decisions on welfare, healthcare and financial matters as authorised by the new Court of Protection (see below) but will not be able to refuse consent to life-sustaining treatment. They will only be appointed if the Court cannot make a one-off decision to resolve the issues.

• A Court of Protection – The new Court has jurisdiction relating to the whole Act. It has its own procedures and nominated judges. It is able to make declarations, decisions and orders affecting people who lack capacity and make decisions for (or appoint deputies to make decisions on behalf of) people lacking capacity. It deals with decisions concerning both property and affairs, as well as health and welfare decisions.

• A new Public Guardian – The Public Guardian has several duties under the Act and will be supported in carrying these out by an Office of the Public Guardian (OPG). The Public Guardian and his staff will be the registering authority for LPAs and deputies. They will supervise deputies appointed by the Court and provide information to help the Court make decisions. The OPG runs threes registers for Lasting Powers of Attorney, Enduring Powers of Attorney and Deputies; this information is available to members of the public. The OPG will also work together with other agencies, such as the police and social services, to respond to any concerns raised about the way in which an attorney or deputy is operating.

• Independent Mental Capacity Advocate (IMCA) – An IMCA is someone instructed to support a person who lacks capacity but has no one to speak for him or her, such as family or friends , or if family or friends are present but considered “inappropriate” to assist in the process. IMCAs must  be involved where decisions are being made about serious medical treatment or a change in the person’s accommodation where it is provided, or arranged, by the National Health Service or a local authority, and may be involved in abuse cases. The IMCA makes representations about the person’s wishes, feelings, beliefs and values, at the same time as bringing to the attention of the decision-maker all factors that are relevant to the decision. The IMCA can challenge the decision-maker on behalf of the person lacking capacity if necessary; challenges can be made via the Court of Protection or Judicial Review process. However, it is still up to the decision maker to consider what they believe is in the person’s best interests.

 
Key Concepts for doctors:
 

• Lack of capacity in one area can’t be assumed to mean lack of capacity in another – and patients should be as involved as possible in all decisions made about their treatment.
• Where it is proposed that a person move permanently into residential or nursing care, or serious medical treatment is proposed for someone who lacks capacity, the person’s relatives must be consulted about what they believe the person’s views about this would be, and whether the move or treatment would be in their best interest. If there are no relatives, an IMCA must be consulted.
• The MCA s5 protects staff from liability as long as they have a reasonable belief that a person lacks capacity, and any force used in an urgent situation is proportionate to the risks that would fall to that person if they were not restrained. Where care needs to be provided in such a restricted way that it amounts to a ‘derivation of liberty’, this needs to be authorised. From April 09, the Deprivation of Liberty Safeguards may provide the authority needed to detain someone that is unable to consent to care or treatment being provided in a registered care home or hospital setting. (The Deprivation of Liberty Safeguards are the Government’s response to the European Court of Human Rights’ requirement that the so called “Bournewood Gap” be dealt with in British Law.)
• Where staff become aware that a patient has made an advance decision refusing a particular treatment, that refusal has the same force as if the patient where making it contemporaneously, i.e. the medical treatment could not be given unless the doctor concerned was happy either that the patient did not have capacity when the decision was made, or that they did not intend the decision to have effect in the current circumstances.

 
Conclusion.
 
Anecdotally, medical practitioners appear to have been slow to make use of the powers and safeguards provided by the MCA. Relatively small numbers of referrals have been made to the IMCA services nationally to support those people that lack capacity and are “unbefriended” in the decision making processes around serious medical treatment. Only 671 eligible referrals were received by IMCA services in England and Wales in 2007/2008. (First Annual Report of the IMCA Service, July 2008). Could it be that an assumption is being made that the IMCA service may be seen more of a hindrance than a help, rather than a safeguard for the patient, in providing care and treatment?
 
The Act requires professionals to “presume capacity” rather than incapacity, for most professionals this is a challenge that we often fail to meet. It is easier to work with a presumption of incapacity and to act in that person’s best interest rather than take the time to “evidence” their capacity in relation to a variety of decisions that may need to be made.
 
The Act’s two new criminal offences have resulted in a small number of prosecutions to date. These prosecutions have tended to be brought against staff providing care in care homes or domiciliary settings rather than in hospital or other medial settings. Does this mean that staff working in hospitals or medical settings provide better care?

Introduction