Addington Hospital

Four athletes developed water intoxication (hyponatremia) during endurance events lasting more than 7 h. The etiology of the condition appears to be voluntary hyperhydration with hypotonic solutions combined with moderate sweat sodium chloride losses. The reason why the fluid excess in these runners was not corrected by increased urinary losses is unknown. When advised to drink less during prolonged exercise, three of the athletes have subsequently completed prolonged endurance events uneventfully.

This study examined psychologists' views and practices regarding diagnostic classification systems for mental and behavioral disorders so as to inform the development of the ICD-11 by the World Health Organization (WHO). WHO and the International Union of Psychological Science (IUPsyS) conducted a multilingual survey of 2155 psychologists from 23 countries, recruited through their national psychological associations. Sixty percent of global psychologists routinely used a formal classification system, with ICD-10 used most frequently by 51% and DSM-IV by 44%. Psychologists viewed informing treatment decisions and facilitating communication as the most important purposes of classification, and preferred flexible diagnostic guidelines to strict criteria. Clinicians favorably evaluated most diagnostic categories, but identified a number of problematic diagnoses. Substantial percentages reported problems with crosscultural applicability and cultural bias, especially among psychologists outside the USA and Europe. Findings underscore the priority of clinical utility and professional and cultural differences in international psychology. Implications for ICD-11 development and dissemination are discussed.

BACKGROUND: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. METHODS AND RESULTS: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), β-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464-1610), and structural heart disease. CONCLUSIONS: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711.

Rhabdomyolysis, secondary to exertion is known to result in myoglobinuria and is occasionally associated with acute renal failure. In this study myoglobinaemia occurred in 25 of 44 runners completing a 99 km marathon. A marked rise in the values of myoglobin, lactate and the enzymes creatine kinase (CPK), aspartate transaminase (AST) and lactic dehydrogenase (LDH) was noted. A linear correlation was demonstrated between the level of serum myoglobin and the serum concentrations of urate, CPK, AST and LDH. Both the myoglobin itself and the increased concentration of urate may contribute to the acute renal failure. The pathophysiology of rhabdomyolysis during exertion is discussed in the context of other causes of myoglobinuria. A classification of rhabdomyolysis and myoglobinuria is suggested.

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BACKGROUND: The treatment of vitiligo can be challenging. Up-to-date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking. OBJECTIVES: To develop internationally agreed-upon expert-based recommendations for the treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in different online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence for different topics included in the algorithms. A survey was then given to a core group of eight experts to resolve the remaining issues. Subsequently, the recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The recommendations provided summarize the latest evidence regarding the use of topical therapies (steroids, calcineurin inhibitors and Jak-inhibitors) and systemic therapies, including steroids and other systemic immunomodulating or antioxidant agents. The different modalities of phototherapies (NB-UVB, photochemotherapy, excimer devices and home phototherapy), which are often combined with other therapies, are also summarized. Interventional approaches as well as depigmentation strategies are presented for specific indications. Finally, the status of innovative and targeted therapies under development is discussed. CONCLUSIONS: This international consensus statement culminated in expert-based clinical practice recommendations for the treatment of vitiligo. The development of new therapies is ongoing in vitiligo, and this will likely improve the future management of vitiligo, a disease that still has many unmet needs.

BACKGROUND: The treatment of vitiligo can be challenging and depends on several factors such as the subtype, disease activity, vitiligo extent, and treatment goals. Vitiligo usually requires a long-term approach. To improve the management of vitiligo worldwide, a clear and up-to-date guide based on international consensus with uniform stepwise recommendations is needed. OBJECTIVES: To reach an international consensus on the nomenclature and to develop a management algorithm for the diagnosis, assessment, and treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence of topics included in the algorithms. A survey was utilized to resolve remaining issues among a core group of eight experts. Subsequently, the unanimous recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The algorithms highlight the importance of shared decision-making. Dermatologists are encouraged to provide patients with detailed explanations of the prognosis and expected therapeutic outcomes based on clinical examination. The treatment goal should be discussed and clearly emphasized to patients given the different approaches for disease stabilization and repigmentation. The evaluation of disease activity remains a cornerstone in the tailor-made approach to vitiligo patients. CONCLUSIONS: These new treatment algorithms are intended to guide clinical decision-making in clinical practice. Promising novel therapies for vitiligo are on the horizon, further highlighting the need for reliable outcome measurement instruments and greater emphasis on shared decision-making.

INTRODUCTION: Acute appendicitis remains a common surgical condition and the importance of specific elements in the clinical diagnosis remain controversial. A variety of neoplastic and inflammatory conditions mimic acute appendicitis. The purpose of this study was to determine the presenting pattern of acute appendicitis and to review the pathological diagnosis. PATIENTS AND METHODS: This is a retrospective analysis of 324 patients who had appendicectomy for acute appendicitis at Prince Mshiyeni Memorial Hospital (Natal, South Africa) during the period January 2002 to December 2004. Patient demographics, clinical features, white cell count, operative findings, outcome and histology results were recorded on a special patient proforma. RESULTS: A total of 371 patients underwent appendicectomy during this period and 324 (M:F, 3.6:1) were available for analysis. The majority of our patients were in the second decade (43.1%) with only 29.3% presenting within 24 h of onset of symptoms. The most common symptoms were abdominal pain (100%), vomiting (57.4%) and anorexia (49.0%). Generalised and localised abdominal tenderness were present in 62.0% and 19.4% of patients, respectively. Pyrexia was noted in 41.0%. Localised and generalised peritonitis were present in 26.4% and 14.0%, respectively. The most common incisions were lower midline laparotomy (47.2%) and gridiron (37.3%). The negative appendicectomy rate was 17.0%. Acute appendiceal inflammation and gangrenous appendicitis was present in 36.1% and 9.6%, respectively. The perforation rate was 34.0% and there was a direct correlation with delayed presentation. There were no patients with carcinoid tumour or adenocarcinoma. Parasites and other associated conditions were seen in 8.6% of cases. Postoperative complications included: wound sepsis (25.3%), prolonged ileus (6.2%), peritonitis (4.6%) and chest infection (3.4%). Four patients died (1.2%) all from the perforated group. CONCLUSIONS: Our patients present late with advanced disease and complications. All surgeons should bear in mind the possibility of parasitic infestations mimicking acute appendicitis and the presence of significant unusual histological findings in our setting justifies routine histopathological examination of appendices.

co-infection contribute to elevated immune activation as measurable by these markers. In HIV-infected individuals with active, but not latent TB, we found elevated levels of soluble markers associated with monocyte activation. Interestingly, T-cell activation was elevated individuals with both latent and active TB. These results suggest that in the highly TB- and HIV-endemic settings of southern Africa, latent TB-associated T-cell activation may contribute to HIV disease progression and exacerbate the HIV epidemic. In addition, our findings indicate that aggressive campaigns to treat LTBI in HIV-infected individuals in high-burden countries will not only impact TB rates, but may also slow HIV progression.

Abstract Rationale Improving treatment outcomes while reducing drug toxicity and shortening the treatment duration to ∼6 months remains an aspirational goal for the treatment of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). Objectives To conduct a multicenter randomized controlled trial in adults with MDR/RR-TB (i.e., without resistance to fluoroquinolones or aminoglycosides). Methods Participants were randomly assigned (1:1 ratio) to a ∼6-month all-oral regimen that included levofloxacin, bedaquiline, and linezolid, or the standard-of-care (SOC) ⩾9-month World Health Organization (WHO)-approved injectable-based regimen. The primary endpoint was a favorable WHO-defined treatment outcome (which mandates that prespecified drug substitution is counted as an unfavorable outcome) 24 months after treatment initiation. The trial was stopped prematurely when bedaquiline-based therapy became the standard of care in South Africa. Measurements and Main Results In total, 93 of 111 randomized participants (44 in the comparator arm and 49 in the interventional arm) were included in the modified intention-to-treat analysis; 51 (55%) were HIV coinfected (median CD4 count, 158 cells/ml). Participants in the intervention arm were 2.2 times more likely to experience a favorable 24-month outcome than participants in the SOC arm (51% [25 of 49] vs. 22.7% [10 of 44]; risk ratio, 2.2 [1.2–4.1]; P = 0.006). Toxicity-related drug substitution occurred more frequently in the SOC arm (65.9% [29 of 44] vs. 34.7% [17 of 49]; P = 0.001)], 82.8% (24 of 29) owing to kanamycin (mainly hearing loss; replaced by bedaquiline) in the SOC arm, and 64.7% (11 of 17) owing to linezolid (mainly anemia) in the interventional arm. Adverse event–related treatment discontinuation in the safety population was more common in the SOC arm (56.4% [31 of 55] vs. 32.1% [17 of 56]; P = 0.007). However, grade 3 adverse events were more common in the interventional arm (55.4% [31 of 56] vs. 32.7 [18 of 55]; P = 0.022). Culture conversion was significantly better in the intervention arm (hazard ratio, 2.6 [1.4–4.9]; P = 0.003) after censoring those with bedaquiline replacement in the SOC arm (and this pattern remained consistent after censoring for drug replacement in both arms; P = 0.01). Conclusions Compared with traditional injectable-containing regimens, an all-oral 6-month levofloxacin, bedaquiline, and linezolid–containing MDR/RR-TB regimen was associated with a significantly improved 24-month WHO-defined treatment outcome (predominantly owing to toxicity-related drug substitution). However, drug toxicity occurred frequently in both arms. These findings inform strategies to develop future regimens for MDR/RR-TB. Clinical trial registered with www.clinicaltrials.gov (NCT 02454205).

Background and Purpose. Pyogenic and tuberculous spondylitis can mimic malignancy. The purpose of this study was to deter mine the efficacy of diffusion-weighted magnetic resonance imaging in differentiating spinal infection and malignancy. Methods. Fifty-one consecutive patients with suspected spinal infection or malignancy were enrolled in the study. Apparent diffusion coefficients (ADCs) of paraspinal soft tissue mass and normal and abnormal vertebral bone marrow were determined on the diffusion-weighted magnetic resonance images of the spine. The mean ADCs of normal and abnormal vertebral bodies in patients with confirmed infection or malignancy were compared using nonparametric tests. Results. ADCs of 69 tuberculous, 9 pyogenic, and 50 malignant vertebral marrow lesions were significantly higher than ADCs of normal marrow. ADCs of malignant bone marrow and 5 paraspinal soft tissue lesions were significantly lower than tuberculosis and pyogenic infection. There was no significant difference between the ADCs of 44 adult and 25 pediatric tuberculous bone lesions or between tuberculosis and pyogenic infection. Using the cutoff ADC of 1.02 × 10−3mm2/s for bone marrow, the sensitivity, specificity, and accuracy were 60.26%, 66.00%, and 62.50%, respectively, for distinguishing infection from malignancy. The sensitivity, specificity, and accuracy increased to 94.12%, 82.35%, and 90.20%, respectively, when the ADCs of associated soft tissue lesions were higher than 1.17 × 10−3mm2/s. Conclusions. Diffusion-weighted magnetic resonance imaging has limited usefulness for differentiating spinal infection and malignancy.

Intravenous fluid management of trauma patients is fraught with complex decisions that are often complicated by coagulopathy and blood loss. This review discusses the fluid management in trauma patients from the perspective of the developing world. In addition, the article describes an approach to specific circumstances in trauma fluid decision-making and provides recommendations for the resource-limited environment.

Early collagen products, when used as dural substitutes, promoted severe inflammatory responses and fell into disrepute. A more recent advance, collagen sponge, which is derived from bovine flexor tendons was used in this experimental study. Collagen sponge was surgically implanted as an onlay dural replacement graft following skull trephination and dural excision in 12 primates. Macroscopic, histological and electron-microscopical evaluations were performed at periods of 1, 3 and 9 months. This preliminary animal study indicated that collagen sponge is suitable to use as a graft since it does not induce any inflammatory response or adhesions in the absence of pia arachnoid injury. If forms an ideal scaffold for the early ingrowth of fibroblasts to effect dural repair.

Two fatal cases of poisoning by paracetamol are described. Both patients were heavy imbibers of alcohol and both had swallowed less paracetamol that that generally regarded as a lethal dose. The biochemistry of paracetamol hepatotoxicity is outlined and the increased susceptibility of alcoholic patients to the hepatotoxic effects of paracetamol is remarked upon. Recent trends in the treatment of acute paracetamol poisoning are mentioned.

BACKGROUND: Anaemia is a major global health problem affecting an estimated 42% of pregnant women worldwide. There is a paucity of South African (SA) data on anaemia in pregnancy, despite the fact that parasitic infections are endemic and the nutritional status of sections of the population is poor. OBJECTIVE: To determine the prevalence of anaemia among antenatal attendees in a regional hospital in Durban, SA. METHODS: This was a cross-sectional prospective study in a regional health facility in an urban setting serving a population of low socioeconomic status. Venous blood samples to perform a full blood count were obtained from antenatal attendees at their first clinic visit. RESULTS: Two thousand pregnant women were studied; the mean (standard deviation) age and gestational age at booking was 27.6 (7.6) years and 21.7 (7.1) weeks, respectively. Eight hundred and fifty-four (42.7%) were anaemic (haemoglobin (Hb) levels<11 g/dL). The majority (81.4%) were mildly anaemic. There were five (0.6%) cases of severe anaemia (Hb<7 g/dL). The prevalence of anaemia was significantly higher in HIV-positive compared with HIV-negative pregnant women (71.3% v. 28.7%; p<0.0001). The common morphology was normochromic normocytic (n=588, 68.9%). CONCLUSION: The prevalence of anaemia was 42.7%. In the majority (81.4%) the anaemia was mild and normocytic and normochromic (68.9%). Anaemia is a common problem among antenatal attendees in an SA urban population.

The Comrades Marathon is a gruelling test of man's stamina and only trained athletes participate. It is surprising that of over 2,000 contestants each year on a 90-km (56.25-mile) course, severe cardiac and renal damage does not occur more often. We are able, however, to report 10 cases over 9 years when renal damage did occur. 3 cases required haemodialysis; 1 had peritoneal dialysis; 2 patients had renal biopsies. Possible idiosyncratic factors are discussed as is the pathogenesis of acute tubular necrosis.

Myco. fortuitum was isolated from subcutaneous abscesses of two patients who had been inoculated with B.C.G. and one patient who had iron injections. The organisms were resistant to a wide range of anti-tuberculous drugs. They were highly virulent for mice in which they produced symptoms of spinning disease. It is thought that the infections originated from contamination of syringes or skin.

This study investigated the clinical and biochemical features of acute renal failure in marathon runners. Over a period of 18 years (1969-1986), 19 patients were admitted to the renal unit. The histories and biochemical data of 4 patients seen in 1986 are described. The pathophysiology of acute renal failure is multifactorial and is the combined effect of rhabdomyolysis, dehydration, hypotension, nonsteroidal anti-inflammatory drugs, and hyperuricaemia. Efforts to correct dehydration have resulted in a decrease in the incidence of acute renal failure. The use of nonsteroidal anti-inflammatory drugs is to be deprecated and efforts should be made to publicize this harmful effect.

BACKGROUND: With Universal Health Coverage and Integrated People-centred Health Care, streamlined health-systems and respectful care are necessary. South Africa has made great strides in prevention of mother-to-child transmission (PMTCT) but with the great burden of HIV, a minimum of birth and 10-week HIV-PCR testing are required for the estimated 360,000 HIV-exposed infants born annually which presents many challenges including delayed results and loss to follow-up. Point-of-care (POC) HIV testing of infants addresses these challenges well and facilitates initiation of HIV-infected infants rapidly after diagnosis for best clinical outcomes. METHODS: Objectives were to determine accuracy, feasibility and acceptability of POC testing compared to standard-of-care (SOC) central-laboratory testing. HIV-exposed infants for birth PCR testing in hospital (n = 323) and follow-up at a primary health care clinic (n = 117) in Durban, South Africa were included. A baseline situational-analysis reviewed registers and phoned mothers of HIV-exposed infants prior to the intervention. An effectiveness-implementation study of the Alere™q HIV-1/2 Detect POC test (heel-prick specimen processed in 50 min) was compared with SOC with questionnaires to mothers and staff. Stata 14 was used for analysis. RESULTS: At baseline 2% of birth HIV tests were missed; only 40% of mothers could be contacted; 17% did not receive birth test result; 19% did not have a 10-week test; 39% had not received the 10-week results. There were 5(1.5%) HIV-infected and 318(98.5%) HIV-negative infants detected in hospital with all clinic babies negative. All positive infants commenced ART before discharge. Ultimately POC and SOC had perfect concordance but for 10 SOC tests researchers actively tracked-down results or repeated tests. Turn around times for SOC tests were on average 8-days (IQR 6-10 days) and for POC testing was 0-days. The POC error-rate was 9,6% with all giving a result when repeated. The majority of mothers (92%) preferred POC testing with 7% having no preference. No staff preferred SOC testing with 79% preferring POC and 21% having no preference. CONCLUSIONS: Point-of-care HIV testing for EID is accurate, feasible and acceptable, with benefits of early ART for all positive infants at birth facilities. We recommend that it be considered best practice for EID. TRIAL REGISTRATION: ISRCTN38911104 registered 9 January 2018 - retrospectively registered.

Surgery for drug-resistant tuberculosis has been shown to be safe and effective, with similar level of mortalities associated with surgical intervention observed with that for lung cancer. While surgery has been an option to treat TB in the pre-antibiotic era, it is now increasingly used to treat complications of pulmonary TB, particularly in patients with drug-resistant TB who do not respond to medical treatment. The two most frequent indications for lung resection in drug- resistant TB, are i) failed medical treatment with persistent sputum positivity or ii) patients who have had medical treatment and are sputum negative, but with persistent localized cavitary disease or bronchiectasis. Massive hemoptysis is a potentially life-threatening complication of TB. Lung resection is potentially curative in patients with massive hemoptysis and cavitary or bronchiectatic disease. Bronchial artery embolization in these patients has a high success rate but bears also the risk of recurrence. Lung resection can be safely undertaken in selected patients with HIV co-infection and pulmonary complications of TB. Ambulatory drainage is a novel, safe, affordable and effective method of draining a chronic TB associated empyema thoracis. We review here the current surgical treatment of the complications of pulmonary TB and discuss the experience from the Durban Cardiothoracic Surgery Unit for the surgical treatment of patients with complicated pulmonary TB.