The impact of basic dermatology education and training on primary healthcare providers in KwaZulu-Natal, South Africa.

BACKGROUND: Dermatological diseases are amongst the commonest reasons for consultation at primary care level. Yet, dermatology teaching in medical and nursing curricula is inconsistent and often insufficient to enable medical and nursing professionals to manage these conditions effectively. METHODS: We tested the knowledge of 100 doctors and 195 nurses who attended dermatology training sessions held in three health districts in the province of KwaZulu-Natal (KZN), South Africa, by using a quasi-experimental uncontrolled before-and-after study design. At the start of the session, participants were exposed to 15 slides representing common dermatological conditions; this was followed by a test. The participants then attended a series of short lectures followed by the same test. Pre- and post-intervention test scores were compared, and the results were analysed by professional status, health district and type of facility. RESULTS: The mean (standard deviation [SD]) pre-intervention test score was 40.6% (20.5%). Doctors scored significantly higher than nurses (p 0.0001). There were significant differences in performance by district (p 0.001) and type of facility (p 0.001). The mean (SD) post-intervention score improved to 68.7% (22.5%). CONCLUSION: Doctors and nurses working in the primary care sector appear to be insufficiently trained in the management of common dermatological conditions. A short period of in-service training resulted in an immediate, significant improvement in knowledge, although we did not study long-term retention beyond this. We recommend improved prequalification training in dermatology in medical and nursing schools and an expansion of continuing professional development as well as in-service training opportunities for primary care practitioners.

HIV viraemia during pregnancy in women receiving preconception antiretroviral therapy in KwaDukuza, KwaZulu-Natal.

BACKGROUND: Preconception antiretroviral therapy (PCART) followed by sustained viral suppression is effective in preventing mother-to-child transmission of HIV. The rates of persistent and transient viraemia in such patients have not been prospectively assessed in South Africa. OBJECTIVES: We determined the prevalence of transient and persistent viraemia in HIV-positive women entering antenatal care on PCART and studied variables associated with viraemia. METHODS: We performed a prospective cross-sectional observational study of HIV-positive pregnant women presenting to a primary healthcare facility in KwaZulu-Natal. All had received at least 6 months of first-line PCART. Viral load (VL) was measured, patients were interviewed, adherence estimated using a visual analogue scale and adherence counselling provided. Viral load was repeated after 4 weeks where baseline VL exceeded 50 copies/mL. RESULTS: We enrolled 82 participants. Of them, 59 (72%) pregnancies were unplanned. Fifteen participants (18.3%) were viraemic at presentation with VL > 50 copies/mL. Of these, seven (8.5%) had viral suppression (VL < 50 copies/mL), and eight remained viraemic at the second visit. Adherence correlated significantly with viraemia at baseline. Level of knowledge correlated with adherence but not with lack of viral suppression at baseline. Socio-economic indicators did not correlate with viraemia. No instances of vertical transmission were observed at birth. CONCLUSIONS: Approximately 20% of women receiving PCART may demonstrate viraemia. Half of these may be transient. Poor adherence is associated with viraemia, and efforts to encourage and monitor adherence are essential. The rate of unplanned pregnancies is high, and antiretroviral therapy programmes should focus on family planning needs of women in the reproductive age group to prevent viral non-suppression prior to pregnancy. KEYWORDS: Preconception Antiretroviral Therapy; HIV; Viraemia; Antenatal Care; Adherence.

Differentiation of breast tuberculosis and breast cancer using diffusion-weighted, T2-weighted and dynamic contrast-enhanced magnetic resonance imaging.

BACKGROUND: The use of multi-parametric magnetic resonance imaging (MRI) in the evaluation of breast tuberculosis (BTB). OBJECTIVES: To evaluate the value of diffusion-weighted imaging (DWI), T2-weighted (T2W) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in differentiating breast cancer (BCA) from BTB. METHOD: We retrospectively studied images of 17 patients with BCA who had undergone pre-operative MRI and 6 patients with pathologically proven BTB who underwent DCE-MRI during January 2014 to January 2015. RESULTS: All patients were female, with the age range of BTB patients being 23-43 years and the BCA patients being 31-74 years. Breast cancer patients had a statistically significant lower mean apparent diffusion coefficient (ADC) value (1072.10 ± 365.14), compared to the BTB group (1690.77 ± 624.05, p = 0.006). The mean T2-weighted signal intensity (T2SI) was lower for the BCA group (521.56 ± 233.73) than the BTB group (787.74 ± 196.04, p = 0.020). An ADC mean cut-off value of 1558.79 yielded 66% sensitivity and 94% specificity, whilst the T2SI cut-off value of 790.20 yielded 83% sensitivity and 83% specificity for differentiating between BTB and BCA. The homogeneous internal enhancement for focal mass was seen in BCA patients only. CONCLUSION: Multi-parametric MRI incorporating the DWI, T2W and DCE-MRI may be a useful tool to differentiate BCA from BTB.

Prevalence of breast tuberculosis: Retrospective analysis of 65 patients attending a tertiary hospital in Durban, South Africa.

BACKGROUND: Breast tuberculosis (BTB) is uncommon, but not rare. Knowledge of the ways in which it can present can prevent unnecessary invasive procedures and delay in diagnosis. OBJECTIVES: To describe the clinical and radiological findings in patients with BTB, including evaluation of current treatment methods. METHODS: We retrospectively analysed 65 patients diagnosed with BTB at Addington and King Edward VIII hospitals, Durban, South Africa, between 2000 and 2013. Demographic, clinical and radiological findings and treatment outcomes were noted. RESULTS: A total of 11,092 patients underwent breast investigations between 2009 and 2013, with a prevalence of BTB for the period of 0.3% (30 patients). Of the 65 patients diagnosed between 2000 and 2013, 64 were female (98.5%) and one was male (1.5%). The age range was 23-69 years (mean 38.5). The most common mammographic pattern was density (39.4%) and the least common a mass (6.1%). Isolated axillary lymphadenitis was found in 12.1%. Abscess was the commonest ultrasound pattern (39.0%). Of the 47 patients with a known history of pulmonary tuberculosis (TB), 68.1% (n=32) did not have radiological evidence of previous or concurrent pulmonary TB, nor was there evidence of TB elsewhere. Of 47 patients with known HIV status, 34 were HIV-positive. Fine-needle aspiration cytology had sensitivity of only 28% compared with 94% for histology. Of those treated, 72.7% obtained full resolution following 9 months of TB treatment; 25.0% did not complete treatment, and 2.3% (n=1) died while on treatment. Follow-up data on relapse rates after treatment completion and disease resolution are scanty. CONCLUSION: Understanding and being aware of the various presentations of BTB make it possible to treat most patients successfully.

The spectrum of skin diseases in a black population in Durban, KwaZulu-Natal, South Africa.

BACKGROUND: Precise knowledge of the prevalence and spectrum of skin diseases in a population allows for effective planning for provision of dermatology services and distribution of resources. There are no published data on the epidemiology of skin disorders in Durban, KwaZulu-Natal. OBJECTIVE: We investigated the prevalence of skin diseases in black African patients attending a predominantly black private healthcare facility and profiled the patients. METHODS: Clinical charts of all black African patients seen between January 2003 and December 2010 in a private practice in Durban were reviewed. The diseases seen were described and the prevalence calculated. RESULTS: A total of 6664 patient charts were reviewed. The five most common conditions were acne, eczemas, dyschromias, infections, and hair disorders. These data agree with reports from other parts of the world. LIMITATIONS: Selection bias was presented by a single private practice, thus data may not be fully representative of our population. CONCLUSION: Acne, eczemas, dyschromias, infections, and hair disorders are, in that order, the five most common disorders encountered.

Should essays and other "open-ended"-type questions retain a place in written summative assessment in clinical medicine?

BACKGROUND: Written assessments fall into two classes: constructed-response or open-ended questions, such as the essay and a number of variants of the short-answer question, and selected-response or closed-ended questions; typically in the form of multiple-choice. It is widely believed that constructed response written questions test higher order cognitive processes in a manner that multiple-choice questions cannot, and consequently have higher validity. DISCUSSION: An extensive review of the literature suggests that in summative assessment neither premise is evidence-based. Well-structured open-ended and multiple-choice questions appear equivalent in their ability to assess higher cognitive functions, and performance in multiple-choice assessments may correlate more highly than the open-ended format with competence demonstrated in clinical practice following graduation. Studies of construct validity suggest that both formats measure essentially the same dimension, at least in mathematics, the physical sciences, biology and medicine. The persistence of the open-ended format in summative assessment may be due to the intuitive appeal of the belief that synthesising an answer to an open-ended question must be both more cognitively taxing and similar to actual experience than is selecting a correct response. I suggest that cognitive-constructivist learning theory would predict that a well-constructed context-rich multiple-choice item represents a complex problem-solving exercise which activates a sequence of cognitive processes which closely parallel those required in clinical practice, hence explaining the high validity of the multiple-choice format. SUMMARY: The evidence does not support the proposition that the open-ended assessment format is superior to the multiple-choice format, at least in exit-level summative assessment, in terms of either its ability to test higher-order cognitive functioning or its validity. This is explicable using a theory of mental models, which might predict that the multiple-choice format will have higher validity, a statement for which some empiric support exists. Given the superior reliability and cost-effectiveness of the multiple-choice format consideration should be given to phasing out open-ended format questions in summative assessment. Whether the same applies to non-exit-level assessment and formative assessment is a question which remains to be answered; particularly in terms of the educational effect of testing, an area which deserves intensive study.

Fifty years of porphyria at the University of Cape Town.

The porphyrias are a group of disorders resulting from defective haem biosynthesis. One form, variegate porphyria, is common in South Africa as a result of a founder effect. Over the past 50 years, the University of Cape Town Faculty of Health Sciences has built and maintained an international reputation for excellence in the field of porphyria. The porphyria group is respected for its research and for its accumulated experience in the management of these disorders. Equally important has been the comprehensive and holistic care offered to patients with porphyria, and to their families.

A review of the clinical presentation, natural history and inheritance of variegate porphyria: its implausibility as the source of the 'Royal Malady'.

It has been suggested that King George III of Great Britain suffered from the haem biosynthetic disorder, variegate porphyria. This diagnosis is pervasive throughout the scientific and popular literature, and is often referred to as the 'Royal Malady.' The authors believe it inappropriate to view the case for porphyria purely in terms of symptoms, as has generally been the case in his presumptive acute porphyria diagnosis. Accordingly, this review provides a current description of the natural history and clinical presentation of the porphyrias, against which we measure the case for porphyria in George III and his relatives. The authors have critically assessed the prevalence of porphyria in a population, the expected patterns and frequency of inheritance, its penetrance and its expected natural history in affected individuals, and conclude that neither George nor his relatives had porphyria, based on four principal reasons. First, the rarity of the disease mandates a very low prior probability, and therefore implies a vanishingly low positive predictive value for any diagnostic indicator of low specificity, such as a historical reading of the symptoms. Second, penetrance of this autosomal dominant disorder is approximately 40%, and one may expect to have identified characteristic clinical features of porphyria in a large number of descendants without difficulty. Third, the symptoms of both George III and his relatives are highly atypical for porphyria and are more appropriately explained by other much commoner conditions. Finally, the natural history of the illnesses reported in this family is as atypical for variegate porphyria as are their symptoms.

Drugs in porphyria: From observation to a modern algorithm-based system for the prediction of porphyrogenicity.

The acute porphyrias are a group of disorders which result from inherited defects in the enzymes of the heme biosynthetic pathway. Affected patients are prone to potentially fatal acute attacks. These attacks are frequently precipitated by exposure to commonly used drugs. Correctly identifying the safety or otherwise of drugs in porphyria is therefore important. In this review we describe how clinical experience and the findings of experimental systems using whole animal or cell culture models have been interpreted to determine porphyrogenicity, that is the potential of a drug to induce an acute attack in a patient carrying a gene for acute porphyria. It is now well established that induction of delta-aminolevulinic acid synthase, the rate controlling enzyme of the heme biosynthetic pathway, is fundamental to porphyrogenicity, and that drug-induced hepatic heme depletion via induction or suicidal inactivation of cytochrome P450 is central to this process. The process is now sufficiently well understood that prediction of porphyrogenicity from structural and functional information alone would appear to be justified.

C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload.

All reported mutations in ALAS2, which encodes the rate-regulating enzyme of erythroid heme biosynthesis, cause X-linked sideroblastic anemia. We describe eight families with ALAS2 deletions, either c.1706-1709 delAGTG (p.E569GfsX24) or c.1699-1700 delAT (p.M567EfsX2), resulting in frameshifts that lead to replacement or deletion of the 19-20 C-terminal residues of the enzyme. Prokaryotic expression studies show that both mutations markedly increase ALAS2 activity. These gain-of-function mutations cause a previously unrecognized form of porphyria, X-linked dominant protoporphyria, characterized biochemically by a high proportion of zinc-protoporphyrin in erythrocytes, in which a mismatch between protoporphyrin production and the heme requirement of differentiating erythroid cells leads to overproduction of protoporphyrin in amounts sufficient to cause photosensitivity and liver disease.

An analysis of 112 acute porphyric attacks in Cape Town, South Africa: Evidence that acute intermittent porphyria and variegate porphyria differ in susceptibility and severity.

Four forms of porphyria may present clinically with the acute attack, an episodic, severe, and potentially life-threatening manifestation characterized by abdominal and neurologic symptoms. We describe our experience with 112 consecutive attacks observed and treated in 25 patients with the 2 most common forms of acute porphyria in Cape Town, South Africa; 25 attacks in 10 patients with variegate porphyria and 87 attacks in 14 patients with acute intermittent porphyria. The remaining patient experienced more than 100 sequential, severe, and poorly remitting attacks, which are not included in our analysis. In our population, the relative risk of an acute attack in acute intermittent porphyria compared with that in variegate porphyria was 14.3 (confidence intervals, 6.3-32.7). Patients with variegate porphyria were significantly older (median age at first attack, 30 yr) than those with acute intermittent porphyria (median age at first attack, 23.5 yr; p < 0.0001), and demonstrated an equal sex ratio, whereas the male:female ratio in acute intermittent porphyria was 2:12 (p < 0.0001). There was a significant difference in the incidence of factors precipitating the acute attack. Drug exposure was a frequent precipitant of the acute attack in variegate porphyria, whereas hormonal factors were more important in acute intermittent porphyria (p < 0.00001). Patients with acute intermittent porphyria also showed a trend to earlier and more frequent recurrent acute attacks following the initial admission. Mean urine precursor levels, blood pressure, pulse rate, and heme arginate requirement were all significantly higher in patients with acute intermittent porphyria. No significant difference in the frequency of serious complications or in outcome could be shown. We describe our experience with treatment with heme arginate, and provide evidence that heme arginate results in a prompt and statistically significant improvement in symptoms. The incidence of serious complications and mortality in this series was low, confirming a trend to an increasingly good prognosis for patients with acute porphyria who receive expert treatment.

Plasma fluorescence scanning and fecal porphyrin analysis for the diagnosis of variegate porphyria: precise determination of sensitivity and specificity with detection of protoporphyrinogen oxidase mutations as a reference standard.

BACKGROUND: Variegate porphyria (VP) is the autosomal dominant disorder associated with deficiency of the enzyme protoporphyrinogen oxidase (PPOX). Plasma fluorescence scanning has been reported to be a more sensitive test for VP than traditional fecal chromatography. Previous comparisons of these techniques predated identification of the PPOX gene. We assessed these techniques in a large group of patients characterized for VP at the DNA level. METHODS: We evaluated all patients for whom the genotype and a plasma scan or fecal porphyrin result were available. Mutations were detected by restriction digest analysis. Plasma fluorescence scanning was conducted according to published methods. Fecal porphyrins were identified and quantified by thin-layer chromatography. RESULTS: Plasma fluorescence scanning was assessed in 679 patients (205 with VP who were carriers of a PPOX mutation, either with disease symptoms or asymptomatic) and fecal analysis in 473 (190 with VP). Sensitivity and specificity of both tests were higher in adults than in children and higher for adults with disease symptoms than for asymptomatic carriers. In a direct comparison in 168 adults (73 with VP), plasma scanning was significantly more sensitive than fecal porphyrin analysis [sensitivity, 0.96 (95% confidence interval, 0.89-0.99) vs 0.77 (0.66-0.85)]. Fecal coproporphyrin [area under the curve, 0.87 (0.83-0.90)] was a better predictor of VP than protoporphyrin [0.80 (0.76-0.84)]. CONCLUSIONS: Plasma scanning is a more sensitive and specific test for VP than fecal porphyrin analysis. Neither test is sensitive in children, and both are less sensitive in asymptomatic carriers than in symptomatic cases. DNA analysis therefore remains the preferred method for the identification of carriers, particularly in children.