Nov

Introduction

Chest pain accounts for 1% of all GP consultations, but in only 8%-18% of cases is it an indicator of underlying ischemic heart disease.¹ Given the potential diagnostic uncertainty associated with chest pain at initial presentation, specialist evaluation of patients in a Rapid Access Chest Pain Clinic (RACPC) is of value and represents an important process in the evaluation of symptoms. These clinics were established with the aim of providing rapid outpatient assessment of patients with suspected cardiac disease in order to permit earlier provision of appropriate treatment and investigations where required.

Stable chest pain typically presents as angina, a triad of dull central chest pain, brought on with exertion and relieved by rest or GTN spray. The aetiology is usually stable atherosclerotic plaque disease which is associated with low mortality and can be treated with oral anti-anginals, as demonstrated by meta-analyses and the landmark COURAGE study. ^{2, 3}

NICE Clinical Guideline 95 (NICE CG95) suggests that choice of initial investigation for stable chest pain should be guided by a patient’s pre-test probability of having CAD. Calculations of the pre-test probability take into consideration a patient’s age, gender, cardiac risk factors and symptoms. Patients are defined as high risk of cardiac disease if they have diabetes, smoke or have hyperlipidaemia (total cholesterol >6.47mmol/litre). Patients with none of the above are considered low risk. Symptoms are defined as “typical angina” if the pain is: 1) constricting discomfort in the front of the chest or in the neck, shoulders, jaw or arms; 2) is precipitated by physical exertion and 3) is relieved by rest or GTN spray within approximately five minutes. Pain is defined as “atypical angina” if only two of the above criteria are met and defined as “non-anginal” if one or none of the above criteria are met.

NICE pre-test probabilities of CAD (Table 1), are based on a version of Diamond and Forrester’s pre-test probabilities published in 1979, modified using data from Duke’s cohort study, published in 1993.^{4, 5, 6} Recent studies suggest that these NICE pre-test probabilities may overestimate the prevalence of CAD in a primary care population and may risk over investigating patients.^{7, 8} In addition to having financial implications, this may cause patients undue anxiety and unnecessarily put them at risk of complications.

Table 1: NICE Clinical Guideline 95 pre-test probabilities table.

Each cell represents the percentage risk of each group of patients having CAD, based on their typicality of symptoms, gender, age and cardiac risk factors (lo, low and hi, high)⁴

ESC guidelines utilise an updated, validated model of the Diamond-Forrester model by Genders et al. to create pre test probabilities of CAD (Table 2), based on patient’s age, gender and typicality of symptoms. ^{9, 10}

Table 2: ESC guidelines clinical pre-test probabilities in patients with stable chest pain symptoms 

Each cell represents likelihood of each group of patients having CAD, based on typicality of symptoms, age and gender.⁹

We hypothesised that strict adherence to NICE guidelines results in over-estimation of the pre-test probability of CAD and therefore over-investigation of patients presenting with stable chest pain. ESC guidelines may offer more accurate pre-test probabilities of CAD and allow a more targeted and cost-effective use of investigations.

Methodology

Clinic records of all patients who attended the RACPC at Tunbridge Wells Hospital between July 2005 and December 2012 were reviewed. This service is run by a cardiology specialist. Patient demographics, cardiac risk factors and information regarding the nature of patient symptoms were collected prospectively and completed at the time of the patient’s RACPC appointment. Results of cardiac investigations were collected from paper and computerised records, and included diagnoses of significant CAD made following invasive coronary angiogram. These results were compared with patients’ pre-test probabilities of CAD calculated using both NICE and the ESC’s calculation methods. Outcome and readmissions were obtained from electronic records from the Maidstone and Tunbridge Wells NHS Trust computer records retrospectively.

Results

Study population

A total of 1968 records were reviewed. 59% (n = 1162) of patients were male and 41% (n = 806) were female. Their mean age was 60 years. At initial assessment, 69.8% patients (n=1373) had non-anginal chest pain, 19.5% (n=383) had atypical angina and 10.8% (n=212) had typical angina, based on the NICE guideline definitions of chest pain.

97.2% (n= 1912) patients underwent further investigation; 15% (n=256) of these were subsequently diagnosed as having significant CAD, accounting for their symptoms. The 2.8% (n=56) of patients who did not undergo investigation either chose not to, were unable to, were lost to follow up, or were diagnosed as having a non-cardiac cause of their symptoms at the initial RACPC appointment.

NICE CG95 pre test probabilities compared against cohort data

Table 3: NICE guidelines 95 pre test probabilities compared against cohort data

Each cell represents the proportion (%) of cohort patients from each group who were diagnosed with CAD. We have colour-coded cells to represent the NICE estimated pre-test probability of CAD in each group. Red cells represent 61-90+% probability, pink cells represents 30-60% probability, blue cells represent 10-29% probability and white cells represents <10% probability of CAD according to NICE Guidelines. “ – “ marks a cell where pre-test probabilities of CAD could not be calculated for cohort patients.

Table 4: A comparison of NICE pre-test probabilities and cohort patient data.

The risk of CAD as predicted by NICE guidelines 95 on the left compared with the actual number of cohort patients in each category and the proportion of those patients diagnosed with significant CAD.

The average discrepancy between the pre-test probability and actual incidence of CAD in cohort patients was 28% (range 20% - 88%). In 48% of cells in the NICE CG95 pre-test probability table (Table 1) the pre-test probability of CAD was overestimated by 30% or more (Table 3). A marked discrepancy between pre-test probability and actual incidence of CAD was found between “high risk” and “very low risk” patients. On average, high risk patients had an overestimated pre-test probability of 34.3 – 40.9% per cell compared with low risk patients whose pre-test probability was only overestimated by 6.5% (Table 3).

The cells highlighted in dark red in table 3 represent high risk patients whose pre-test probability was of 61-90+%, according to NICE CG95. In our cohort, only 31.2% (n=214, 95% CI 27.6-34.5) of high risk patients in this category were diagnosed with CAD. On average, actual incidence of CAD compared with pre-test probability was overestimated by 34.4% – 40.9% in each cell.

The pink cells in table 3 represent medium risk patients with a pre-test probability of CAD of 30-60%, according to NICE CG95. In our cohort, only 4.4% (n=24, 95% CI 3.0 – 6.5) of medium risk patients had a positive angiogram (Table 4). The average overestimate of actual incidence against pre-test probability was 35.9%.

The cells highlighted in blue in table 3 represent low risk patients with a pre-test probability of CAD of 10-29%, according to NICE CG95. In our cohort, only 2.5% (n=7, 95% CI 1.2 – 5.0) of low risk patients were diagnosed with CAD (Table 4). On average, the pre-test probability of CAD exceeded the found incidence of CAD by 18.6% (Table 3).

The white cells in table 3 represent very low risk patients with pre-test probability of CAD <10% according to NICE CG95. In our cohort, only 0.28% (n= 1, 95% CI 0.1 – 1.6) of patients were diagnosed with CAD. Average overestimation in this group was 6.5% in each cell.

ESC guidelines pre test probabilities compared against cohort data

Table 5: A comparison of ESC pre-test probabilities with cohort patient data.

Each cell shows the proportion (%) of cohort patients from each group diagnosed with CAD. Each cell is colour coded to correspond with the ESC estimated pre-test probability. Dark red cells represent >85% probability, pale pink cells represent 66-85% probability, pale blue cells represent 15-65% probability and white cells represent <15% probability.

Table 6: A comparison of ESC pre-test probabilities and cohort patient data

The risk of CAD as predicted by ESC guidelines on the left compared with the actual number of cohort patients in each category and the proportion of those patients diagnosed with significant CAD.

The average discrepancy between pre-test probability of CAD, according to the ESC’s risk stratification table, and actual incidence of CAD in cohort patients was 20.7%. In 28% of cells, the pre-test probability of CAD exceeded the found incidence of CAD by 30% or more (Table 5).

The cells highlighted in dark red in table 5 represent very high risk patients with a pre-test probability of CAD greater than 85%, according to ESC guidelines (Table 5). 73.4% (n= 58, 95% CI 63.7 – 82.7) of cohort patients in this high-risk category were diagnosed with CAD (Table 6). On average, incidence of CAD in each cell has been overestimated by 13% in this category.

The cells highlighted in pale pink in table 5 represent high risk patients, with a pre-test probability of CAD of 66-85%, according to ESC guidelines. 58.5% (n=103, 95% CI 51.1 – 65.5) of cohort patients in this high-medium risk category were diagnosed with CAD (Table 6). On average, the pre-test probability of CAD exceeded the found incidence of CAD in each cell by 17.7% (Table 5).

The cells highlighted in pale blue in table 5 represent medium risk patients with a pre-test probability of CAD of 15-65%, according to ESC guidelines. 6.4% (n=93, CI 5.3 –7.8) of cohort patients in this risk category were diagnosed with CAD (Table 6). On average, the pre-test probability of CAD exceeded the found incidence of CAD by 24.1%in each cell (Table 5).

The cells highlighted in white in table 5 represent patients whose pre-test probability of CAD was less than 15% according to ESC guidelines. Only 0.76% (n=2, 95% CI 0.2 –2.7) of cohort patients in this risk category were diagnosed with CAD (Table 6). On average, pre-test probability of CAD exceeded found incidence of CAD in each cell by 6.2% (Table 5).

Discussion

Only 15% of a total of 1968 patients referred to RACPC were diagnosed with significant CAD. The majority (70%) of referred patients had “non-anginal” chest pain and low pre-test probabilities of CAD, reflecting the importance ascribed by General Practitioners of ruling out ischemic heart disease as the underlying cause for chest pain, even in low risk patients. This may not be surprising given the large media attention to heart disease and sustained campaigns for early warning signs of heart attack in the British media. It is therefore of great public interest for cardiac disease to be identified.

NICE CG95 pre test probabilities compared against cohort data

Comparing cohort data to the pre-test probabilities of CAD outlined in NICE CG95, NICE have overestimated the number of patients likely to have CAD in the majority of groups. Strict adherence to NICE CG95 therefore carries the risk of over-investigating patients. NICE recommend CT calcium scoring as the first line investigation for patients with a low (10-29%) pre-test probability of CAD. 284 patients fall into this category and only 7 patients were shown to have CAD. This means that 40.5 patients need to be treated in order to identify 1 positive patient (NNT= 40.5).

In patients with a medium (30-60%) pre-test probability of CAD, NICE recommends functional imaging as the first line diagnostic investigation. In our cohort 544 patients would undergo functional imaging, but only 24 of these patients would be diagnosed with CAD, NNT=22.7.

Finally, in patient groups with a high (61-90%) pre-test probability of CAD, NICE recommends invasive coronary angiography as the first line diagnostic investigation. In our cohort of 1968 patients, 691 patients had a high pre-test probability of CAD, and 214 had significant coronary artery disease on angiography, NNT= 3.2.

Although invasive coronary angiography is considered the gold standard investigation for diagnosing CAD, and permits simultaneous therapeutic intervention, the procedure is not without risk, particularly in elderly patients and those with renal impairment.¹¹ Furthermore, invasive angiography is expensive and is costed by the East Kent Hospitals University NHS Foundation Trust at £1166.02 per procedure (private correspondence).

NICE CG95 offers no guidance on managing patients who have a <10% pre-test probability of CAD. 347 of our cohort patients fell into this very low risk category and only 1 was diagnosed with CAD. Therefore, NICE CG95, if strictly adhered to, would have missed one diagnosis of CAD in our patient cohort.

ESC pre test probabilities compared against cohort data

ESC guidelines tend to offer more conservative estimates of pre-test probability of CAD compared with NICE guidelines. Using the ESC’s risk stratification table, almost all patients, except those with over 85% pre-test probability and those with less than 15% pre test probability, would be investigated for chest pain. This is due to their claim that non-invasive, image-based diagnostic methods for CAD have typical sensitivities and specificities of around 85%, so that roughly 15% of these investigations could be yielding false results. Hence, due to these inaccuracies, in patients with pre-test probabilities of CAD below 15% or above 85%, ESC state that performing no test at all could provide fewer incorrect diagnoses.⁹

In our patient cohort, 79 patients had very high (>85%) pre-test probability of CAD, but only 58 patients (73%) were diagnosed with CAD. For this patient risk group, ESC guidelines suggest that further investigation may not be necessary and that a diagnosis of CAD may be assumed. Thus, applying ESC guidelines to our cohort could result in 21 patients being incorrectly diagnosed with stable angina, and more serious causes of chest pain, for example pulmonary emboli or gastric ulceration, may be missed. However, in practice, it is likely that many patients in this very high pre-test probability category would have undergone angiography, because patients who have "severe symptoms" or who are clinically thought to have "high risk coronary anatomy" should be offered an invasive angiography with or without pressure wire studies. The vagueness of the guidelines allows interventionists to interpret this in the clinical context.

In ESC guidelines, invasive coronary angiography is not specifically recommended as a first line investigation for stable angina, regardless of the pre-test probability of CAD. In patients with a high (66-85%) pre-test probability of CAD, ESC guidelines recommend non-invasive functional imaging first line. Of the 176 patients who fell into this category, only 102 (58.0%) patients were ultimately diagnosed with CAD.

In patients with medium (15-65%) pre-test probability of CAD, ESC guidelines advise exercise ECG testing (or non-invasive imaging for ischemia if local expertise is available) as first line diagnostic investigations. Of the 1451 patients which fell into this category, only 93 were diagnosed with CAD, NNT= 15.6. Fortunately, exercise ECG testing would not expose the patient to potentially harmful radiation or medication, but their poor diagnostic power may result in the need for further investigations, despite a negative result.

In patients with low risk of CAD (<15%) ESC guidelines suggest making an assumption that the patient does not have CAD and advocates conducting no further investigations. In our cohort, 263 patients fell into this low risk category, two (0.8%) of which were diagnosed with CAD.

The ESC guidelines appear to have higher specificity than the NICE guidelines, and only two patients would have been missed had ESC guidelines been adhered to, compared to one patient missed if NICE guidance was used. Thus, although highly sensitive, ESC guidelines when applied to our cohort have lower sensitivity than NICE guidelines.

Comparison of number of investigations

Following ESC guidance for our cohort of patients would have resulted in fewer diagnostic invasive angiograms being performed than if NICE guidance had been followed. ESC guidance only recommends invasive angiography if first line, non-invasive investigations generate positive results. Overall, however, ESC guidance would result in a greater number of overall investigations being performed.

In total, NICE advises that all 691 of our high risk cohort patients should undergo invasive angiography as a first line investigation. 544 with medium risk should undergo functional testing first and 24 of these patients (assuming an angiogram would follow a positive result) would go on to have invasive angiography. 284 low risk patients should undergo CT calcium scoring first, of which 7 would go on to have functional imaging and angiography if the above logic is followed. This generates a total of 1557 investigations; 722 angiograms, 551 functional imaging investigations and 284 cardiac CT scans.

In comparison, using ESC guidance, 176 of our high risk patients would have functional imaging investigations, 103 patients with positive results would then undergo invasive angiography. 1451 patients would receive exercise ECGs, of which 93 with positive results would undergo functional imaging and invasive angiography. This generates a total of 1916 investigations; 196 angiograms, 269 functional imaging investigations and 1451 exercise ECGs.

If we assume that stress echocardiograms are used as “functional imaging” we can estimate costs for our cohort when applying each set of guidelines. Costs for each investigation are supplied by East Kent Hospitals University NHS Foundation Trust and are as follows: Outpatient elective coronary angiograms are costed at £1,166.02; stress echocardiograms are costed at £132.30; exercise ECGs at £40.26 and CTs of one area at £102.47 (private correspondence). If we were to apply NICE guidelines to our cohort, £841,866.44 would be spent on angiograms, £72,897.30 would be spent on stress echocardiograms and £29,101.48 on CT scans. This is a total of £943,865.22 on investigations.

If we were to apply ESC guidelines to our cohort, £228,539.92 would be spent on coronary angiograms, £35,588.7 would be spent on stress echocardiography and £58,417.26 would be spent on exercise ECGs. A total of £322,545.88 would be spent on investigations. Overall, this is £621,319.34 cheaper than applying NICE guidelines.

Limitations of study

This study is based on data from a single site and may not be nationally representative. The final diagnosis was made clinically by an experienced interventional cardiologist, which introduces subjectivity and the risk of interpreter bias. Not all patients underwent the gold standard of invasive coronary angiography to demonstrate the presence of CAD. However, all patients were seen and fully assessed by a cardiologist and 97% underwent investigations if deemed necessary.This study has all the limitations of a registry study. In addition, costs for investigations may vary throughout the country, and indeed the world, with varying expertise available.

Conclusion

In conclusion, strict adherence to NICE CG95 over-estimates the pre-test probability of CAD in our local population group. This is consistent with previous studies conducted in South London where there is a larger Afro-Caribbean population, as well as with studies conducted in the North of England.^8,9 Adherence to ESC guidelines in place of NICE guidelines may enable a more targeted and cost-effective use of investigations. Strict application of the ESC guidelines to the study cohort would have resulted in investigations costing an estimated £322,545.88, compared to £943,865.22 if NICE guidelines were applied. However, conducting fewer investigations carries greater risk of misdiagnosis, and using ESC guidelines in isolation introduces the possibility of assuming CAD in patients without conducting investigations to confirm this.

It is advisable that local cardiology departments audit their stable chest pain guidelines to ensure that the interpretation of pre-test probabilities is in keeping with the local population. Unfortunately there is no ideal policy and local protocols should reflect the local population.

Background

Global recruitment in psychiatry has been falling for several decades because medical students and graduates have been finding it consistently unattractive ^1,2. An analysis of the career choices of newly qualified doctors in the United Kingdom (U.K.) found the same trend from 1974 to 2009; psychiatry was the first career choice for only 3-5% of medical graduates annually³. In the U.K., lack of recruitment into psychiatry had reached a crisis point by 2003 when 15% of all unfilled consultants posts in England were in psychiatry and the Royal College of Psychiatrists was finding recruitment into specialist psychiatry posts increasingly difficult^4,5. In 2012, only 78% of the Core Training year one (CT1) posts in psychiatry were filled; a serious shortfall which was overcome by overseas recruitment up until changes in immigration rules.

The factors that seem to dissuade medical students from taking up psychiatry as a future career may include: stigma, bad prognosis of psychiatric disorders, poor scientific base of psychiatry, ‘bad-mouthing’ from medical colleagues, lack of respect among peers & public, threats of violence from patients and lack of resources^1-5. However, there is evidence to suggest that many students’ attitudes towards career choice changed in a positive direction after working in psychiatry due to the perceived ‘job satisfaction’, ‘life-style’, ‘training available’ and ‘multidisciplinary approach’³.

Psychiatry has previously been ranked higher in career choice at the end of students’ clinical year⁶. To ensure a stable psychiatric workforce for the future, there is an obvious need to motivate current and future cohorts of young doctors to take up psychiatry as a career. Das & Chandrasena (1988) found that attitudes changed positively towards mental health following clinical placement in this specialty⁷. It is also known that medical students’ attitudes to psychiatry and career intentions can be improved by their experiences of teaching⁸. Students were found to develop more positive attitudes when encouraged by senior psychiatrists, had direct involvement in patient care, or saw patients respond well to treatment. Improvement in attitudes during the placement was also related to an increased intention to pursue psychiatry as a career.

Previous research into attitude to psychiatry as a specialty and career choice seems to have produced conflicting results and most of it was carried out among medical students. Since career choices in the U.K. are actually made in the first clinical year following graduation, we carried out a survey among a recent cohort of foundation year one (FY1) doctors in the South East England before and after their first clinical year.

Method

Our study sample consisted of all FY1 doctors (n=101) in one region of South East England. They participated in the study at the beginning and then at the end of their first clinical year. We used a 20–item questionnaire devised by Das & Chandrasena(1988) to ascertain their perceptions and attitudes towards psychiatry before they commenced their first clinical placement. The questionnaire was sent to them via their Medical Education Managers (MEMS). It was handed out to the FY1 doctors as part of their induction pack for completion along with a study information sheet.

At the end of their first year of working, the participants were asked to complete an amended version of the questionnaire. This included two additional questions which ascertained whether the doctor had an opportunity to work in a psychiatric post, or had any experience of psychiatry in practice (such as taster days or cases in A&E). These amended questionnaires were sent to the foundation doctors electronically via their MEMS for completion.

The data was collected and entered into a spreadsheet to prepare descriptive statistics. Comparisons for before and after exposure to psychiatry, and between the psychiatry and non-psychiatry groups were made using the chi-square test. As the data was binary, a latent class model was developed using LatentGOLD software⁹ to explore the associations between different items in the questionnaire. Responses from the questionnaires were coded as: responses which agree with a positive attitude to psychiatry or disagree with a negative attitude were coded as +1; those not sure were coded as 0; and responses which agree with a negative attitude to psychiatry or disagree with a positive attitude were coded as -1.

Results

A 100% (n=101) response rate was obtained for the first set of questionnaires completed at the beginning of the year. However, there was a significant drop in the number of questionnaires completed at the end of the year - a 53.5% response rate (n=54) generally but 61.1% (22 out of 36) for those FY1 doctors who had the opportunity or access to a post in psychiatry within their clinical year.

Initial cohort at beginning of the clinical year vs. those with no exposure to psychiatry at the end

Table 1 shows the group means for each questionnaire item, for the whole cohort at the beginning of the year compared to those with no exposure to psychiatry by the end of the year.

Table 1: All FY1 doctors before training placements started (initial cohort) versus FY1 doctors without a psychiatric post after FY1 training

Those FY1 trainees who had not worked in psychiatry during the year were significantly more positive (p = < 0.05) for psychiatry’s future, psychiatrist being better at patient communication and not over-medicating their patients. However, they remained significantly less convinced as compared to the whole cohort about psychiatry’s intellectual attraction or taking it up as a future career.

Initial cohort at beginning of the year vs. those with exposure to psychiatry at the end

Table 2 shows the group means for each questionnaire item, for the whole

cohort at the beginning of the year compared to those with exposure to psychiatry at the end of the year.

Table 2: All FY1 doctors before training placements started versus FY1 doctors with a psychiatric post during FY1 training

After a psychiatry placement, significant positive differences (p=<0.05) were observed in their responses to medical staff’s view of psychiatry, future of psychiatry and place of Electro Convulsive Therapy (ECT) in modern medicine. While there was a positive trend in most responses in favour of psychiatry, trainees remained negative about psychiatry’s status, its scientific base, curriculum & training and taking up psychiatry as a future career.

Those exposed to psychiatry vs. those not exposed to psychiatry

Table 3 compares responses between FY1 doctors exposed to psychiatry during the clinical year and those who were not.

Table 3: FY1 doctors who had a psychiatric post versus those who did not have one

Those exposed to psychiatry agreed more often that non-psychiatric medical staffs were critical of psychiatry compared to the group not exposed to psychiatry. They also had comparatively negative responses for psychiatrists not abusing legal powers and to have the legal power to treat someone against their will. Trainees exposed to psychiatry also felt significantly (p=<0.05) positive towards psychiatry being intellectually comprehensive and adopting it as a career. However, they were less enthusiastic about psychiatrists treating patients against their will and psychiatry being the expanding frontier of medicine.

Discussion

In this study, we have ascertained attitudes of a regional cohort of FY1 doctors towards psychiatry as a specialty and as a career choice. Our findings are similar to previous research carried out among medical students, which found that there were generally negative attitudes towards psychiatry as a specialty and career choice but fairly positive attitudes towards the role of psychiatry in medicine and in society in general^1-5,10. Like others, we also found that personal experience of psychiatry placement can improve trainees’ view of psychiatry as a specialty and as a future career ^3,11.

It was interesting to find out that after a year in clinical practice but without any experience of psychiatry, trainees’ attitudes towards psychiatry as a specialty had been positive. It is difficult to know the exact reason but we can speculate that this respect for the specialty may have developed when they experienced limitations of the other specialties in medicine and/or perhaps due to the positive professional encounters with psychiatrists at the Accident & Emergency (A&E) or with psychiatric liaison teams during ward consultations. As opposed to previous research¹¹, it was heartening to note that the group with no exposure to psychiatry agreed that non-psychiatric medical staff were not critical of psychiatry; a possible sign of reduced stigma for psychiatry within the medical profession.

Despite exposure to psychiatry, FY1 doctors’ attitudes to psychiatry’s status, scientific base, curriculum & training and career choice remained somewhat negative. Similar results were found by Lyons et al¹¹ when they assessed students’ attitudes towards psychiatry after a clerkship in the specialty. There was a significant decrease in negative & stigmatising views towards mental illness after the clerkship, but no significant improvement in students' interest in psychiatry was detected¹. Goldacre et al (2013) also acknowledged mixed outcomes of early experience of working in psychiatry as it might discourage some doctors. While highlighting positive effect of the doctors’ experience of the speciality, they also cited it as a negative factor that influenced some doctors who had previously considered psychiatry as a career³.

Our study has limitations because of having a small sample and being carried out in one small region of the country. It is also worth mentioning that the group exposed to psychiatry may not have had a psychiatry placement as it also included those who had had taster days or experience in A&E. The brevity of these latter exposures cannot give someone a real sense of the specialty. The nature of this and the overall experience needs to be differentiated and the exposure quantified in the future studies. Our study findings also need to be replicated with future cohorts and in other regions for confirmation because FY training programme in the U.K. is relatively recent and placements in psychiatry have evolved⁴ over the last few years through closer collaboration between different stakeholders in the Foundation Training Programmes.

Introduction

Striae distensae, or stretch marks, are linear scars in the dermis which arise from rapid stretching of the skin over weakened connective tissue. It is a common skin condition that rarely causes any significant medical problems but is often a significant source of distress to those affected. Striae distensae were described as a clinical entity hundreds of years ago, and the first histological descriptions appeared in the medical literature in 1889.¹ With a high incidence and unsatisfactory treatments, stretch marks remain an important target of research for an optimum consensus of treatment. These appear initially as red, and later, as white lines on the skin, representing scars of the dermis, and are characterized by linear bundles of collagen lying parallel to the surface of the skin, as well as eventual loss of collagen and elastin. The estimated prevalence of striae distensae range from 50 to 80%.^2,3 The anatomical sites affected vary, with areas commonly affected including the abdomen, breasts, thighs and buttocks.⁴ The three maturation stages of striae include the acute stage (striae rubra) characterized by raised, erythematous striae, the sub-acute stage characterized by purpuric striae, and the chronic stage (striae alba), characterized by white or hypo-pigmented, atrophied striae.⁵ Although stretch marks are only harmful in extreme cases, even mild stretch marks can cause distress to the bearer⁶ (Table 1).

Table 1: Histological comparisons between striae rubrae and striae albae

Aetiology

Striae may result from a number of causes, including, but not limited to, rapid changes in weight, adolescent growth spurts, corticosteroid use or Cushing Syndrome, and generally appear on the buttocks, thighs, knees, calves, or lumbosacral area.⁷ In addition, approximately 90% of all pregnant women develop stretch marks either on their breasts and/or abdomen by the third trimester.⁸ Genetic predisposition is also presumed, since striae distensae have been reported in monozygotic twins.^9,10 There is decreased expression of collagen and fibronectin genes in affected tissue.¹¹ The role of genetic factors is further emphasised by the fact that they are common in inherited defects of connective tissue, as in Marfan’s syndrome.^12,13 Obesity and rapid increase or decrease in weight have been shown to be associated with the development of SD.¹⁴ Young male weight lifters develop striae on their shoulders.¹⁵ Striae distensae also occurs in cachetic states, such as tuberculosis, typhoid and after intense slimming diets.¹⁶ Rare etiologies include human immunodeficiency virus positive patients receiving the protease inhibitor indinavir and chronic liver disease.^13,15 A case of idiopathic striae was also reported.¹⁷

Rosenthal¹⁸ proposed four aetiological mechanisms of striae formation: insufficient development of tegument, including elastic properties deficiency; rapid stretching of the skin; endocrinal changes; and other causes, possibly toxic.

Pathogenesis

The pathogenesis of striae is unknown but probably relates to changes in the components of extracellular matrix, including fibrillin, elastin and collagen.¹⁹ There has been emphasis on the effects of skin stretching in the pathogenesis of striae because the lesions are perpendicular to the direction of skin tension.²⁰ A possible role of glucocorticoids in the pathogenesis of striae has been suggested because of an increase in the levels of steroid hormones and other metabolites found in patients exhibiting striae.²¹ There are studies suggesting the role of fibroblasts in the pathogenesis of striae. Compared to normal fibroblasts, expression of fibronectin and both type I and type III procollagen were found to be significantly reduced in fibroblasts from striae, suggesting that there exists a fundamental aberration of fibroblast metabolism in striae distensae.²²

Pathological aspects

The earliest pathological changes are subclinical to be detected by electron microscopy only. These changes include mast cell degranulation and the presence of activated macrophages in association with mid-dermal elastolysis.²³ When the lesions become become clinically visible, collagen bundles start showing structural alterations, fibroblasts become prominent, and mast cells are absent.²³ On light microscopic examination, Inflammatory changes are conspicuous in the early stage, with dermal oedema and perivascular lymphocytic cuffing.²⁴ In later stages, there is epidermal atrophy, loss of rete ridges and other appendages including hair follicles are absent.²⁵

Evaluation of striae distensae

Approaches to evaluating SD severity visually include the Davey ²⁶ and Atwal scores,²⁷ although these have not been validated specifically for SD. An objective evaluation of SD may be carried out using skin topography, imaging devices including three-dimensional (3D) cameras, reflectance confocal microscopy and epiluminescence colorimetry.^28,29,30

Table 2: Visual scoring systems for the assessment of striae distensae

Management

Striae distensae (striae alba) is a very challenging cosmetic problem for dermatologists to treat. Various modalities of treatment have been tried. Although therapeutic strategies are numerous, there is no treatment which consistently improves the appearance of striae and is safe for all skin types.³¹ Weight loss by diet alone or a combination of diet and exercise do not change the degree of striae distensae.³²

Topical treatments

Topical tretinoin (0.1%) ameliorates striae and the improvement may persist for almost a year after discontinuation of therapy.³³ More recently, tretinoin has been shown to improve the clinical appearance of stretch marks during the active stage (striae rubra), although with not much effect during the mature stage (striae alba).³⁴ Some of the studies have proven the inefficacy of the vitamin A derivative in the treatment of SD, but most of the patients included in these early studies presented with old lesions that had evolved into whitish atrophic scars.³⁵ A study comparing topical 20% glycolic acid and 0.05% tretinoin versus 20% glycolic acid and 10% L-ascorbic acid, found that both regimens improved the appearance of striae alba.³⁶

Hydrant Creams: 1) Trofolastin (a cream containing Centella asiatica extract, vitamin E, and collagen-elastin hydrolysates). The exact mechanism of action was identified as the stimulation of fibroblastic activity ³⁷ and an antagonistic effect against glucocorticoids.³⁸ 2) Verum (a cream containing vitamin E, panthenol, hyaluronic acid, elastin and menthol). The results suggest that the product may show the benefit of massage alone.³⁹ 3) Alphastria (a cream composed of hyaluronic acid, allantoin, vitamin A, vitamin E, and dexpanthenol). Only one study was conducted, which concluded that the product markedly lowered the incidence of stretch mark development after pregnancy.⁴⁰

Glycolic acid (GA): The exact mechanism of action of GA in the management of striae distensae is still unknown because, although GA is reported to stimulate collagen production by fibroblasts and to increase their proliferation in vivo and in vitro, which may be useful for the treatment of stretch marks.^41,42 A study comparing topical 20% glycolic acid and 0.05% tretinoin versus 20% glycolic acid and 10% L-ascorbic acid, found that both regimens improved the appearance of striae alba.⁴³

Trichloroacetic acid (TCA; 10–35%): It has been used for many years as a treatment option for striae distensae and is repeated at monthly intervals with reported improvement in texture and color of marks.⁴⁴

Other topical products: Several oils have been used in the prevention of SD. A non-randomized, comparative study investigated the effect of almond oil in the prevention of SD in which they noted significant differences in the frequency of SD between the groups (almond oil and massage 20%, almond oil alone 38.8%, control 41.2%).⁴⁵

Overall, there is limited evidence for the efficacy of topical therapy for the treatment of SD.

Microdermabrasion

Microdermabrasion may improve many skin problems including acne scars, skin texture irregularities, mottled pigmentation and fine wrinkles. Karimipour et al reported that microdermabrasion induces epidermal signal transduction pathways associated with remodelling of the dermal matrix.⁴⁶ However, studies documenting the efficacy of rnicrodermabrasion in treatment of striae are lacking. Published in 1999, a book on microdermasion written by a French dermatologist, Francois Mahuzier, and translated to English, has a chapter "Microdermabrasion of stretch marks^”.⁴⁷ The author states that 10-20 sessions of microdermabrasion at an interval of not less than 1 month, each session resulting in bleeding points, provide satisfactory results. The author concludes that, "microdermabrasion is the only effective treatment of stretch marks today."

Lasers

Lasers have recently become a popular therapeutic alternative to ameliorate and improve the appearance of stretch marks. Most commonly used lasers used include pulsed-dye laser (PDL), short- pulse carbon dioxide and erbium-substituted yttrium aluminium garnet (YAG), neodymium- doped YAG (Nd:YAG), diode, and Fraxel.

Pulsed dye laser: The dilated blood vessels render the striae rubrae a good candidate for PDL.⁴⁸ The 585- nm pulsed dye laser has a moderate beneficial effect in the treatment of striae rubra.⁴⁹ To evaluate the effectiveness of the 585-nm flashlamp-pumped pulse dye laser in treating cutaneous striae, 39 striae were treated with four treatment protocols.⁵⁰ Subjectively, striae appeared to return toward the appearance of normal skin with all protocols. Objectively, shadow profilometry revealed that all treatment protocols reduced skin shadowing in striae. Laser treatment of SD should be avoided or used with great caution in darker skin types (IV–VI), because of the possibility of pigmentary alterations after treatment.⁵¹

Excimer laser: Studies have shown temporary repigmentation and improvement of leukoderma in SD with excimer laser, although it failed to show any improvement in skin atrophy.^52,53 To evaluate the true efficacy of the 308-nm excimer laser for darkening striae alba, 10 subjects were treated using the excimer laser on the white lines of striae, while the normal skin near to and between the lines was covered with zinc oxide cream. The results of this study showed the weakly positive effect of the 308-nm excimer laser in the repigmentation of striae alba.⁵⁴

Copper Bromide laser: copper-bromide laser (577-511 nm) has been used for stretch marks. A clinical study was conducted in 15 Italian women with stretch marks, treated with the CuBr laser (577-511 nm) and followed-up for 2 years.⁵⁵ The results of the study concluded that the copper-bromide laser was effective in decreasing the size of the SD and there were some pathogenic considerations that justified the use of this laser.

1,450-nm Diode Laser: The non-ablative 1,450-nm diode laser has been shown to improve atrophic scars and may be expected to improve striae. To evaluate the efficacy of the 1,450-nm diode laser in the treatment of striae rubra and striae alba in Asian patients with skin types 4-6, striae on one half of the body in 11 patients were treated with the 1,450-nm diode laser with cryogen cooling spray with the other half serving as a control.⁵⁶ None of the patients showed any noticeable improvement in the striae on the treated side compared to baseline and to the control areas. The study concluded that the non-ablative 1,450-nm diode laser is not useful in the treatment of striae in patients with skin types 4, 5, and 6.

1,064-nm Nd:YAG Laser: A study was aimed to verify the efficacy of this laser in the treatment of immature striae in which 20 patients with striae rubra were treated using the 1,064-nm long-pulsed Nd:YAG laser.⁵⁷ A higher number of patients (55%) considered the results excellent when compared to the same assessment made by the doctor (40%).

Intense Pulsed Light: In order to assess the efficacy of IPL in the treatment of striae distensae, a prospective study was carried out in 15 women, all of them having late stage striae distensae of the abdomen.⁵⁸ All the study subjects showed clinical and microscopical improvement after IPL. It seems to be a promising method of treatment for this common problem with minimal side-effects, a wide safety margin and no downtime.

Fractional Photothermolysis: To determine the efficacy of fractional photothermolysis in striae distensae, 22 women with striae distensae were treated with two sessions each of fractional photothermolysis at a pulse energy of 30 mJ, a density level of 6, and eight passes at intervals of 4 weeks and response to treatment was assessed by comparing pre- and post-treatment clinical photography and skin biopsy samples.⁵⁹ Six of the 22 patients (27%) showed good to excellent clinical improvement from baseline, whereas the other 16 (63%) showed various degrees of improvement. This study concluded that Fractional photothermolysis may be effective in treating striae distensae, without significant side effects.

Ablative 10,600-nm carbon dioxide fractitional laser: Ablative 10,600-nm carbon dioxide fractional laser systems (CO₂ FS) have been used successfully for the treatment of various types of scars. To assess the therapeutic efficacy of CO₂ FS for the treatment of striae distensae, 27 women with striae distensae were treated in a single session with a CO₂ FS and clinical improvement was assessed by comparing pre- and post-treatment clinical photographs and participant satisfaction rates.⁶⁰ The evaluation of clinical results 3 months after treatment showed that two of the 27 participants (7.4%) had grade clinical 4 improvement, 14 (51.9%) had grade 3 improvement, nine (33.3%) had grade 2 improvement, and two (7.4%) had grade 1 improvement. None of the participants showed worsening of their striae distensae.To assess and compare the efficacy and safety of nonablative fractional photothermolysis and ablative CO(2) fractional laser resurfacing in the treatment of striae distensae, 24 ethnic South Korean patients with varying degrees of atrophic striae alba in the abdomen were enrolled in a randomized blind split study and were treated with 1,550 nm fractional Er:Glass laser and ablative fractional CO(2) laser resurfacing.⁶¹ These results of the study support the use of nonablative fractional laser and ablative CO(2) fractional laser as effective and safe treatment modalities for striae distensae of Asian skin with neither treatment showing any greater clinical improvement than the other treatment.

UVB/UVA1 Combined Therapy: Besides lasers, light sources emitting ultraviolet B (UVB) irradiation have been shown to repigment striae distensae. A study was conducted on 9 patients with mature striae alba who received 10 treatment sessions, and biopsies were taken at the baseline and end of the study.⁶² At the end of the study, all patients reported some form of hyperpigmentation that was transient and did not affect any surrounding tissues. No changes were seen on biopsy to indicate an effective remodelling collagen effect of the device, although it needs further assessment. Another study was conducted to analyse the histologic and ultrastuctural changes seen after UVB laser- or light source-induced repigmentation of striae distensae in which analyses of biopsied skin after treatment with both the UVB laser and light source showed increased melanin content, hypertrophy of melanocytes, and an increase in the number of melanocytes in all patients.⁶³

Radiofrequency devices: RF devices are based on the principle of heat generation that occurs in response to poor electrical conductance according to Ohm’s law (heat generation is directly correlated with tissue resistance). The heat that is generated is sufficient to cause thermal damage to the surrounding connective tissue,⁶⁴ which is responsible for the partial denaturation of pre-existing elastic fibers and collagen bundles.⁶⁵ Initial collagen denaturation within thermally modified deep tissue is thought to represent the mechanism for immediate tissue contraction; subsequent neocollagenesis further tightens the dermal tissue and reduces striae.⁶⁶ The efficacy and safety of combination therapy with fractionated microneedle radiofrequency (RF) and fractional carbon dioxide (CO2) laser in the treatment of striae distensae has been evaluated revealing that this combination therapy is a safe treatment protocol with a positive therapeutic effect on striae distensae.⁶⁷ A recent study evaluating the effectiveness of a RF device in combination with PDL subjected 37 Asian patients with darker skin tone with SD to a baseline treatment with a RF device and PDL.⁶⁸ All histological evaluations demonstrated an increase in the amount of collagen fibers, and six of the nine specimens showed an increase in the number of elastic fibers.TriPollar RF device appears to be a promising alternative for the treatment of striae distensae in skin phototypes IV-V.⁶⁹

Needling therapy:

To evaluate the effectiveness and safety of a disk microneedle therapy system (DTS) in the treatment of striae distensae, 16 Korean volunteers with striae distensae alba or rubra were enrolled which received three treatments using a DTS at 4-week intervals.⁷⁰ Marked to excellent improvement was noted in seven (43.8%) patients, with minimal to moderate improvement in the remaining nine. This study revealed that Disk microneedle therapy system (DTS) can be effectively and safely used in the treatment of striae distensae without any significant side effects. Another study assessed and compared the efficacy and safety of needling therapy versus CO2 fractional laser in treatment of striae and the results supported the use of microneedle therapy over CO2 lasers for striae treatment.⁷¹

Platelet-rich plasma:

Platelet-rich plasma has these wound-healing properties, affecting endothelial cells, erythrocytes, and collagen,⁷² which potentially aids in the healing of the localized chronic inflammation believed to be a factor in the aetiology of striae distensae. Platelet-rich plasma is well tolerated by the patients and is a safe and cost effective treatment option for striae distensae.

Platelet-rich plasma alone is more effective than microdermabrasion alone in the treatment of striae distensae, but it is better to use the combination of both for more and rapid efficacy.⁷³

The plasma fractional radiofrequency and transepidermal delivery of platelet-rich plasma using ultrasound has also been found to be useful in the treatment of striae distensae.⁷⁴

Since thermal damage from intradermal RF has characteristics similar to those of many wounds, combination treatment with intradermal RF and autologous PRP would eventuate in enhanced localized collagen neogenesis and redistribution. In one of the studies, three sessions of intradermal RF were used combined with autologous PRP administered once every four weeks.⁷⁵ All of the participants showed satisfactory changes and no patient was reported to show no improvement.

Transepidermal retinoic acid:

Transepidermal retinoic acid delivery using ablative fractional radiofrequency associated with acoustic pressure ultrasound has also been used for the treatment of stretch marks.⁷⁶

Conclusion

Striae distensae are an extremely common, therapeutically challenging form of dermal scarring. Adequate scientific knowledge and the evidence behind both preventative and therapeutic agents are vital in order to understand striae and to offer patients the best therapeutic options. The treatment of this cosmetically distressing condition has been disappointing and there is no widely accepted surgical procedure for improving the appearance of stretch marks. Laser therapy has been advocated as a treatment for striae distensae.

Introduction

Claimants in medical negligence cases are increasingly making use of negligent failure to warn of risk in claims for compensation following medical mishaps when an inherent risk in a medical procedure has manifested itself resulting in injury. In order to succeed the claimant must establish firstly that the failure to warn was negligent and secondly that the negligence has caused a loss. This paper focuses on causation in failure to inform cases but briefly considers the shift in judicial attitudes to the requirement to give warnings in order to explain how the duty to inform and the available remedies have diverged.

Members of the medical profession commonly believe that to find a negligent failure to inform has caused a loss to the claimant a court must be satisfied that the patient would not have consented to the treatment had they been told of the risk. This was probably true until 2004 when the House of Lords came to a surprising decision which has since received a mixed reception.

The Changing nature of the requirement to give warnings

In the early days of medical litigation whether non-disclosure amounted to negligence was left to the standards of the medical profession. A medical professional was under a duty to at least equal the standards of a reasonably skilled and competent doctor; this would be assumed if s/he had acted in accordance with a body of professional opinion. This is referred to as the Bolam test.[i] There was disquiet amongst academic lawyers that doctors were being allowed to set their own standards and over time the courts have been wrestling back control.[ii]^,[iii] Following the Recent Supreme Court ruling in Montgomery[iv] there is now no doubt that patient autonomy is paramount and the need to inform will now be judged by reference to a reasonable person in the patient’s position.

In Montgomery the claimant, a diabetic, alleged she had been given negligent advice during her pregnancy.  In particular she was not warned of risk of shoulder dystocia, the inability of the baby’s shoulders to pass through the pelvis, assessed at 9-10% for diabetic mothers and not informed of the possibility of delivery by elective caesarean section. The Consultant responsible for her care gave evidence (at paragraph 13) that she would not routinely advise diabetic mothers of this risk because if mentioned, “most women will actually say, ‘I’d rather have a caesarean section.’” The Supreme Court in finding (at paragraph 87) for the claimant held, “The doctor is therefore under a duty to take reasonable care to ensure  that  the  patient  is  aware  of  any  material  risks  involved  in  any recommended  treatment,  and  of  any  reasonable  alternative  or  variant treatments.  The  test  of  materiality  is  whether,  in  the  circumstances  of  the particular case, a reasonable person in the patient’s position would be likely to  attach significance to the risk, or the doctor is or should reasonably be aware that the particular patient would be likely to attach significance to it.” Although expressed as, “a duty to take reasonable care,” the medical professional is expected to, “ensure,” that the patient has the requisite knowledge. The test in failure to inform cases now focuses, not on the actions of the medical professional but, on the patient’s knowledge of the risks.

Chester v Afshar[v]

On 21^st November 1994 Mr Afshar carried out a microdiscectomy at three disc levels on Miss Chester. There was no complication during the operation and the surgeon was satisfied that his objectives had been met. When Miss Chester regained consciousness she reported motor and sensory impairment below the level of L2. A laminectomy shortly after midnight the next day found no cause and the surgeon’s only explanation was cauda equine contusion during the retraction of the L3 root and cauda equine dura during the L2/L3 disc removal. During the legal proceedings Miss Chester brought against Mr Afshar it was found that the operation carried an unavoidable 1-2% risk of cauda equine syndrome (CES) and that the surgeon had not warned the patient about this risk. It was further found that, had the warning been given, Miss Chester would have sought a second (and possibly third) opinion meaning that the operation would not have taken place on 21^st November.

The surgeon and the patient did not agree what was said about the risks of the operation before consent was obtained but the issue was decided in favour of the patient: the surgeon had failed to give a proper warning about the risk of CES. In order to succeed in her claim Miss Chester needed to establish that this failure had caused her loss but her lawyers did not argue that she would have refused consent if she had been informed. They took a different approach; the 1-2% risk of CES is not patient specific and is realised at random. If warned of the risk Miss Chester would have sought a second opinion meaning that the operation would have happened at a later date and possibly with a different surgeon. This subsequent operation would have carried the same 1-2% risk of CES. The High Court of Australia had previously accepted (in a different case) that the claimant can satisfy the burden by showing that, if informed, s/he would have chosen a different surgeon with a lower risk of adverse outcome but there was no evidence in this case that by choosing another surgeon Miss Chester could have reduced the risk.[vi]

At the time Mr Afshar failed to advise Miss Chester of the risks two paths should have been open to her. She could choose to have the operation with the defendant on 21^st November which resulted in CES or to seek a second opinion and undergo the operation at a later date giving her a 98-99% (a better than balance of probabilities) chance of avoiding CES. Thus the failure to inform did not increase the 2% risk of CES but the court found, as a matter of fact, that it did cause the CES. Although the physical harm that Miss Chester had suffered (because of the inevitable risk) did not fall within the scope of the doctor’s duty to inform (to allow the patient to minimise risk) a majority of the House of Lords felt that the surgeon should be held liable because otherwise the patient would be left without a remedy for the violation of her right to make autonomous decisions about treatment.

There are two leaps in Chester the first is the notion that negligence causes a loss if it induces the claimant to follow a path with an associated risk that is realised when they could have followed another path with exactly the same risk. The second is that violating a patient’s right to make autonomous decisions should, as a matter of policy, make the surgeon liable for personal injury which happens after the patient is deprived of their right to make a decision about treatment. The next two paragraphs will consider these leaps in turn.

Equally risky paths: The first leap

In Wright[vii] the patient had developed a streptococcus pyogenes infection that had seeded into her proximal femur resulting in osteomyelitis. Her admission to hospital was delayed for two days by the defendant clinic’s negligent handling of her first presentation. On admission to hospital the patient had the additional misfortune to receive woefully inadequate treatment resulting in septic arthritis and permanently restricted mobility. The patient took the questionable decision to sue the clinic but not the hospital. One of the patient’s arguments against the clinic was that had she been admitted to hospital without the two day delay she would have been treated by different staff who would, almost certainly, not have been negligent. The claimant argued that, as in Chester, although the clinic’s negligence did not increase the random risk of receiving negligent hospital care it had, as a matter of fact, caused the negligent care. Lord Justice Elias rejected this suggestion precisely because the delay had not increased the risk that the hospital would provide the patient with inadequate treatment. However, the other members of the Court of Appeal found for the patient but for another reason; given two extra days the hospital would probably have realised their mistakes and been able to correct them before any permanent harm resulted.

Violated autonomy and personal injury: The second leap

There have been attempts to expand the scope of the majority reasoning in Chester. In Meiklejohn[viii] the patient was treated for suspected non-severe acquired apastic anaemia with Anti Lymphocyte Globulin and Prednisolone the latter causing an avascular necrosis. At an initial consultation a blood sample was taken from the patient for “research purposes” but possibly to exclude dyskeratosis congenital, the condition from which he was actually suffering. The patient argued he had not given informed written consent to the taking of a blood sample for research purposes and that had he been told about the uncertainty in the diagnosis he would have delayed treatment pending the result of the blood test or asked to have been treated with Oxymetholone instead. He further argued these violations of his autonomy required that he be given a remedy for the injury which had actually occurred through a reasonable misdiagnosis of his rare condition. Lady Justice Rafferty sitting in the Court of Appeal dismissed this argument stating at paragraph 34 that, “Reference to [Chester] does not advance the case for the Claimant since I cannot identify within it any decision of principle.”

Conclusion

Courts deciding failure to warn cases have shifted the emphasis from the reasonable practices of the medical profession to the autonomy of the patient; from the duty of the medical professional to the rights of the patient. Medical professionals are now required to give enough information to allow a reasonably prudent patient to make an informed decision about their own treatment. While this change has been taking place there has been no corresponding revision of the remedies available when a patient’s autonomy is infringed. If autonomous decision making is to be properly protected a remedy should be vested in every patient who has had their autonomy infringed whether or not that patient has suffered physical injury; autonomy infringements should be actionable per se (without proof of loss) and result in the award of a modest solatium (a small payment representing the loss of the right to make an informed decision about treatment.) Under the present arrangements the wrong that the patient complains of (infringement of autonomy) is not what they are seeking damages for (personal injury.)

In a small way, the court in Chester has sought to close this gap between the patient’s right and the remedy available by extending the existing law and widened the circumstances in which damages can be recovered by a patient following an infringement of autonomy. Medical professionals who fail to warn patients of small risks may be held liable if disclosing the risk might cause the patient to delay treatment while further deliberations take place. Paradoxically it could conceivably be argued that medical professionals who fail to disclose significant risks (greater than 50%) should escape liability because the loss was more likely than not to happen anyway!

Both Chester extensions to the law have been tested independently in Wright and Meiklejohn and rejected but this does not mean that it has been overruled. The two subsequent cases were heard by the Court of Appeal which cannot overrule the House of Lords (now the Supreme Court.) Both cases were distinguished meaning that the court was satisfied that they were not factually the same as Chester. Clearly Wright is not concerned with rights to autonomy and Meiklejohn is a failure to warn of uncertainties in diagnosis or failure to obtain written informed consent to research rather than risks inherent in treatment. If the facts of Chester were to come before the Courts again the decision would have to be the same; a surgeon could not necessarily escape liability by proving that, informed of the risk, the patient would have consented to the operation.

Summary points

• Patients have a right to be informed of material risks inherent in medical treatment
• An injured patient does not necessarily need to prove they would not have consented to the operation if the risks had been disclosed
• A legal claim against a health care professional may be successful if the patient would have delayed the operation to a later date
• This extension of the law has critics but the situation is unlikely to change in the near future

Introduction:

The clinical features of early HAT are well defined, yet the features of delayed HAT are less clear. Delayed HAT is a rare complication of OLT that may present with biliary sepsis or remain asymptomatic. Sonography is extremely sensitive for the detection of HAT in symptomatic patients during the immediate postoperative period. However, the sensitivity of ultrasonography diminishes as the interval between transplantation and diagnosis of HAT increases due to collateral arterial flow. MRA is a useful adjunct in patients with indeterminate ultrasound exams and in those who have renal insufficiency or an allergy to iodinated contrast.

In the absence of hepatic failure, conservative treatment appears to be effective for patients with HAT but retransplantation may be necessary as a definitive treatment.

Case Presentation:

A 52 year old male with a history of whole graft OLT for primary sclerosing cholangitis presented with two days of fever, nausea, and mild abdominal discomfort.

One week prior to presentation, he was seen in the liver clinic for regular follow-up. At that time, he was totally asymptomatic and his laboratory workup including liver function tests were within normal range.

He has undergone OLT three years prior. At the time of transplant he required transfusion of 120 units of packed red blood cells, 60 units of fresh frozen plasma and 100 units of platelets due to extensive intraoperative bleeding secondary to chronic changes of pancreatitis and severe portal hypertension, but had an otherwise uneventful postoperative recovery.

On physical examination the temperature was 39C, heart rate was 125 beats per minute, respiratory rate was 22 bpm. Initial laboratory workup revealed a white blood cell count of 25,000/mm³, AST of 6230 U/L, ALT of 2450 U/L, total bilirubin of 11 mg/dL , BUN 55 mg/dL and Creatinine of 4.5 mg/dL. Lactate level was 5 mmol/L. Doppler ultrasonography revealed an extensive intrahepatic gas (Image 1A). Computed tomography of the abdomen and pelvis revealed extensive area of hepatic necrosis with abscess formation measuring 19x14 cm with extension of gas into the peripheral portal vein branches (Image 1B,C). Upon admission to the hospital, the patient required endotracheal intubation, mechanical ventilator support and aggressively fluid resuscitation. He was started on broad-spectrum antibiotics and a percutaneous drain was placed that drained dark, foul smelling fluid.  Cultures from the blood and the drain grew Clostridium perfringens.

Magnetic resonance imaging (MRI), MRA revealed occlusion of the hepatic artery 2 cm from its origin and also evidence of collaterals (Image 2A,B).

Image 1: (Pannel A) Doppler ultrasonography reveal extensive intrahepatic gas. (Pannel B&C) Computed tomography of the abdomen and pelvis reveal an extensive area of hepatic necrosis with abscess formation measuring 19x14 cm with extension of gas into the peripheral portal vein branches.

Image 2: MRI & MRA reveal occlusion of the hepatic artery 2 cm from its origin and also evidence of collaterals.

Following drain placement, the patient’s clinical condition markedly improved with significant reduction of liver function test values. Retransplantation was considered but delayed in the setting of infection and significant clinical and laboratory testing improvement.

The patient was transferred to the medical floor in stable condition, and the drain was then removed.

A week later the patient developed low grade fevers and tachycardia. One day later he began to experience mild abdominal discomfort and high grade fevers. Repeat CT of the abdomen revealed worsening hepatic necrosis and formation of new abscesses. His clinical condition decompensated quickly thereafter requiring endotracheal intubation, mechanical ventilation and aggressive resuscitation. Percutaneous drain was placed and again, drained pus-like, foul-smelling material. His overall condition deteriorated, and he eventually expired a few days later.

Discussion:

Delayed (more than 4 weeks after transplantation) HAT is a rare complication of OLT with an estimated incidence of at around 2.8%¹.

Risk factors associated with development of HAT include Roux-en-Y biliary reconstruction, cold ischaemia and operative time, the use of greater than 6 units of blood, the use of greater than 15 units of plasma, and the use of aortic conduits on arterial reconstruction during transplant surgery².

Collateralization is more likely to develop after Live Donor Liver Transplantation (LDLT) than after whole-graft cadaveric OLT³. Therefore, the latter is also associated with increased risk of late HAT.

Although the clinical features of early HAT are well described, the features of delayed HAT are less clearly defined¹: the patient may present with manifestations of biliary sepsis or may remain asymptomatic for years. Right upper quadrant pain has been reported to occur in both immediate and delayed HAT. The clinical presentations may include recurrent episodes of cholangitis, cholangitis with a stricture, cholangitis and intrahepatic abscesses, and bile leaks¹. Doppler ultrasonography has been extremely sensitive for the detection of HAT in symptomatic patients during the immediate postoperative period but becomes less sensitive as the interval between transplantation and diagnosis of HAT increases because of collateral arterial flow⁴.

3D gadolinium-enhanced MRA provides excellent visualization of arterial and venous anatomy with a fairly high technical success rate. MRA is a useful adjunct in patients with indeterminate ultrasonography examination in patients who have renal insufficiency or who have allergy to iodinated contrast ⁵.

Antiplatelet prophylaxis can effectively reduce the incidence of late HAT after liver transplantation, particularly in those patients at risk for this complication⁶. Vivarelli et al reported an overall incidence of late HAT of 1.67%, with a median time of presentation of 500 days; late HAT was reported in 0.4% of patients who were maintained on antiplatelet  prophylaxis compared to 2.2% in those who did not receive prophylaxis⁶. The option of performing thrombolysis remains controversial. Whether thrombolysis is a definitive therapy or mainly a necessary step in the proper diagnosis of the exact etiology of HAT depends mostly on the particular liver center and needs further analysis⁷. Definitive endoluminal success cannot be achieved without resolving associated and possible instigating underlying arterial anatomical defects. Reestablishing flow to the graft can unmask underlying lesions as well as assess surrounding vasculature thus providing anatomical information for a more elective, better plan and definitive surgical revision⁷. Whether surgical revascularization compared to retransplantation is a viable option or only a bridging measure to delay the second transplantation has been a longstanding controversy in the treatment of HAT.

Biliary or vascular reconstruction do not increase graft survival and ongoing severe sepsis at the time of re-graft results in poor survival⁷. However, although uncommon, delayed HAT is a major indication for re-transplantation⁷. In the absence of hepatic failure, conservative treatment appears to be effective for patients with hepatic artery thrombosis.

C. perfringensis an anaerobic, gram-positive rod frequently isolated from the biliary tree and gastrointestinal tract. Inoculation of Clostridium spores into necrotic tissue is associated with formation of hepatic abscess⁸.

Necrotizing infections of the transplanted liver are rare. There have been around 20 cases of gas gangrene or necrotizing infections of the liver reported in the literature. Around 60% of these  infections were caused by clostridial species with C. perfringens accounting for most of them. Around 80% of patients infected with Clostridium died, frequently within hours of becoming ill^9,10. Those who survived underwent prompt retransplantation and the infection had not resulted in shock or other systemic changes that significantly decreased the likelihood of successful retransplantation⁸.

Because the liver has contact with the gastrointestinal tract via the portal venous system, intestinal tract bacteria may enter the liver via translocation across the intestinal mucosa into the portal venous system. Clostridial species can also be found in the bile of healthy individuals undergoing cholecystectomy^9,10.

The donor liver can also be the source of bacteria. Donors may have conditions that favor the growth of bacteria in bile or the translocation of bacteria into the portal venous blood. These conditions include trauma to the gastrointestinal tract, prolonged intensive care unit admissions, periods of hypotension, use of inotropic agents, and other conditions that increase the risk of potential infection ^8,9,10. C. perfringens sepsis in OLT recipients has been uniformly fatal without emergent retransplantation. Survival from C. perfringens sepsis managed without exploratory laparotomy or emergency treatment has been extremely rarely reported⁸. In those patients who survived, and in whom the infection has not resulted in shock or multiple organ failure, retransplantation may be successful⁸.

Although our patient survived his intensive care course, his recovery was tenuous as he quickly developed additional hepatic abscesses that led to his eventual demise. Post-mortem examination in our patient revealed intra-hepatic presence of Clostridium perfringens.

He was managed conservatively since he markedly improved both clinically and by liver function tests. Because of this, retransplantation was delayed. He was also already on antiplatelet prophylaxis.

Conclusion:

We report an interesting case of Clostridium perfringens hepatic abscess due to late HAT following OLT. Although the patient initially improved with non-surgical treatment, he eventually died. In similar cases, besides aggressive work-up and medical management retransplantation may be necessary for a better long term outcome.