Diagnostics for a two-stage joint survival model.

A two-stage joint survival model is used to analyse time to event outcomes that could be associated with biomakers that are repeatedly collected over time. A Two-stage joint survival model has limited model checking tools and is usually assessed using standard diagnostic tools for survival models. The diagnostic tools can be improved and implemented. Time-varying covariates in a two-stage joint survival model might contain outlying observations or subjects. In this study we used the variance shift outlier model (VSOM) to detect and down-weight outliers in the first stage of the two-stage joint survival model. This entails fitting a VSOM at the observation level and a VSOM at the subject level, and then fitting a combined VSOM for the identified outliers. The fitted values were then extracted from the combined VSOM which were then used as time-varying covariate in the extended Cox model. We illustrate this methodology on a dataset from a multi-centre randomised clinical trial. A multi-centre trial showed that a combined VSOM fits the data better than an extended Cox model. We noted that implementing a combined VSOM, when desired, has a better fit based on the fact that outliers are down-weighted.

Blood and virus detection on barber clippers.

BACKGROUND: Bleeding from the popular clean-shave 'chiskop' haircut was recently reported as prevalent in South Africa (SA), a country with 6.9 million HIV-infected people. OBJECTIVES: To investigate the prevalence of barber hair clipper contamination with blood and HIV and hepatitis B viruses. METHODS: Fifty barbers from three townships in Cape Town, SA, were invited to participate. One clipper from each barber was collected immediately after it had been used for a clean-shave haircut. Each clipper was rinsed with phosphate-buffered saline and then submerged in viral medium. The polymerase chain reaction (PCR) was used to identify the blood-specific RNA marker haemoglobin beta (HBB), hepatitis B virus (HBV) and HIV. RESULTS: The clean-shave haircut was the most common haircut requested by clients (78%). Of the clippers collected, 42% were positive for HBB, confirming detection of blood, none were positive for HIV, and 4 (8%) were positive for HBV. Two clippers (clippers 16 and 20) were positive on qualitative HBV PCR. HBV DNA from clipper 16 clustered with genotype A sequences from SA, India, Brazil and Martinique, while clipper 20 clustered with SA genotype D sequences. The clipper 20 sequence was identical to a subtype D sequence (GenBank accession AY233291) from Gauteng, SA. CONCLUSIONS: This study confirms that there is significant contamination of barber hair clippers with blood and blood-borne viruses. Hepatitis B was detected with enough DNA copies to pose a risk of transmitting infection. Although HIV was not detected in this small study, the risk of transmission should be quantified. Further studies to investigate barber clipper sterilisation practices and whether the clean-shave hairstyle is an independent risk factor for HIV, HBV and hepatitis C virus infections are warranted. Public education on individual clipper ownership (as is the case with a toothbrush) should be advocated for clean-shave and blade-fade haircuts.

Blood and virus detection on barber clippers

Background. Bleeding from the popular clean-shave 'chiskop' haircut was recently reported as prevalent in South Africa (SA), a country with 6.9 million HIV-infected people.Objectives. To investigate the prevalence of barber hair clipper contamination with blood and HIV and hepatitis B viruses.Methods. Fifty barbers from three townships in Cape Town, SA, were invited to participate. One clipper from each barber was collected immediately after it had been used for a clean-shave haircut. Each clipper was rinsed with phosphate-buffered saline and then submerged in viral medium. The polymerase chain reaction (PCR) was used to identify the blood-specific RNA marker haemoglobin beta (HBB), hepatitis B virus (HBV) and HIV.Results. The clean-shave haircut was the most common haircut requested by clients (78%). Of the clippers collected, 42% were positive for HBB, confirming detection of blood, none were positive for HIV, and 4 (8%) were positive for HBV. Two clippers (clippers 16 and 20) were positive on qualitative HBV PCR. HBV DNA from clipper 16 clustered with genotype A sequences from SA, India, Brazil and Martinique, while clipper 20 clustered with SA genotype D sequences. The clipper 20 sequence was identical to a subtype D sequence (GenBank accession AY233291) from Gauteng, SA.Conclusions. This study confirms that there is significant contamination of barber hair clippers with blood and blood-borne viruses. Hepatitis B was detected with enough DNA copies to pose a risk of transmitting infection. Although HIV was not detected in this small study, the risk of transmission should be quantified. Further studies to investigate barber clipper sterilisation practices and whether the clean-shave hairstyle is an independent risk factor for HIV, HBV and hepatitis C virus infections are warranted. Public education on individual clipper ownership (as is the case with a toothbrush) should be advocated for clean-shave and blade-fade haircuts

Higher concentrations of dithranol appear to induce hair growth even in severe alopecia areata.

Alopecia areata (AA) is the commonest autoimmune cause of non-scarring alopecia. Topical treatments including corticosteroids and irritants maybe beneficial. Studies report variable hair regrowth with dithranol (anthralin) but all used low concentrations (0.1-1.25%) and inconsistent measurements of AA severity. We report retrospective data (2005-2014) of 102 patients who had failed ultra-potent topical steroids and were referred to a specialist hair clinic for treatment with dithranol up to 3%. The severity of alopecia areata tool was used and participants graded as mild (<25%), moderate (>25 to 75%), and severe (>75%) hair loss. Compared with baseline any and at-least 50% hair regrowth [72%, 68%, 50% and 61.5%, 48.4%, 37.5%, in mild, moderate and severe AA respectively] occurred in all groups (median treatment duration 12 months). Twenty-nine patients (28.4%) were discharged with complete regrowth; with no difference in proportions in severity groups (33.3%, 29%, and 21.9%) but in the period to discharge [7.9, 6.3, and 29.4 months (p-values <.05)] for mild, moderate, and severe AA. Treatment trials of 12 months with dithranol at higher concentrations may be an option in patients who failed potent topical or intra-lesional steroids) regardless of AA severity. Randomized trials (of less staining formulations) of dithranol are warranted.

Geometric classification of scalp hair for valid drug testing, 6 more reliable than 8 hair curl groups.

INTRODUCTION: Curly hair is reported to contain higher lipid content than straight hair, which may influence incorporation of lipid soluble drugs. The use of race to describe hair curl variation (Asian, Caucasian and African) is unscientific yet common in medical literature (including reports of drug levels in hair). This study investigated the reliability of a geometric classification of hair (based on 3 measurements: the curve diameter, curl index and number of waves). MATERIALS AND METHODS: After ethical approval and informed consent, proximal virgin (6cm) hair sampled from the vertex of scalp in 48 healthy volunteers were evaluated. Three raters each scored hairs from 48 volunteers at two occasions each for the 8 and 6-group classifications. One rater applied the 6-group classification to 80 additional volunteers in order to further confirm the reliability of this system. The Kappa statistic was used to assess intra and inter rater agreement. RESULTS: Each rater classified 480 hairs on each occasion. No rater classified any volunteer's 10 hairs into the same group; the most frequently occurring group was used for analysis. The inter-rater agreement was poor for the 8-groups (k = 0.418) but improved for the 6-groups (k = 0.671). The intra-rater agreement also improved (k = 0.444 to 0.648 versus 0.599 to 0.836) for 6-groups; that for the one evaluator for all volunteers was good (k = 0.754). CONCLUSIONS: Although small, this is the first study to test the reliability of a geometric classification. The 6-group method is more reliable. However, a digital classification system is likely to reduce operator error. A reliable objective classification of human hair curl is long overdue, particularly with the increasing use of hair as a testing substrate for treatment compliance in Medicine.

Affordable moisturisers are effective in atopic eczema: A randomised controlled trial.

BACKGROUND: Many patients depend on moisturisers issued by public health services in the management of atopic dermatitis (AD). METHODS: In a randomised controlled trial of patients with mild to moderate AD, aged 1-12 years, study 1 compared aqueous cream v. liquid paraffin (fragrance-free baby oil) as a soap substitute, all patients using emulsifying ointment as moisturiser, and study 2 compared four moisturisers, emulsifying ointment, cetomacrogol, white petroleum jelly and glycerine/petroleum (proportion 1:2; 'the 1:2 moisturiser'), all using fragrance-free baby oil as soap substitute. Assessments were one quality of life and three AD severity scores, at baseline and weeks 4, 8 and 12. Differences were compared using repeated measures of analysis of variance. RESULTS: In both studies (120 children randomised, 20 in each group of the two trials) disease severity scores declined with time. The only significant difference was in one AD severity score (SCORing Atopic Dermatitis) in study 1, both at baseline and over time (p=0.042 and p=0.022). The groups did not differ with regard to topical steroid use or side-effects. Itching from baby oil applied as soap was reported by four patients in the two studies, the petroleum jelly group had more dropouts than the 1:2 moisturiser group, although this was not statistically significant, and 110 patients (91.7%) completed the trial. CONCLUSIONS: The small sample limits generalisability, but the duration was longer than in most AD moisturiser studies. Fragrance-free baby oil is an effective soap substitute that may be better tolerated (if irritation occurs) as a bath additive. The home-made 1:2 moisturiser may be preferable to white petroleum jelly, but both are equivalent to cetomacrogol and emulsifying ointment. Use of accessible moisturisers could reduce the cost of managing mild to moderate AD.

Health risks of the clean-shave chiskop haircut.

The clean-shave haircut known locally as the chiskop is rare among females but popular with black South African men, who are also predisposed to folliculitis keloidalis nuchae (FKN) (keloids on the back of the head). During a previous study, participants described an unexpected symptom of haircut-associated bleeding. As this is not a widely recognised entity, we conducted the present study at an HIV clinic servicing the same population, with the objective of comparing the prevalences of haircut-associated bleeding and FKN in 390 HIV-positive subjects with published data for Langa (Western Cape, South Africa). The results for HIV-positive participants were similar to the population data, but in both groups the prevalence of haircut-associated bleeding (24.5% v. 32%; p=0.17) was much higher than that of FKN (10.2% v. 10.5%), suggesting that the hairstyle increases the risk of bleeding even in people with healthy scalps without folliculitis. This study does not (and was not intended to) prove a higher HIV prevalence in chiskop wearers or in FKN sufferers, but it confirms a history of haircut-associated bleeding in at least a quarter of our male study participants. The risk of transmission of blood-borne infection via haircuts is likely to be low, but requires formal quantification. Public education on adequate sterilisation of barber equipment between haircuts and promotion of individual hair-clipper ownership for chiskop clients should not be delayed. Depilatory creams formulated for African hair offer a non-mechanical means of achieving clean-shave hairstyles.

The adapted classification of male pattern hair loss improves reliability.

BACKGROUND: The Hamilton-Norwood classification (HNC) is used to assess the severity of pattern hair loss (PHL). Conflicting associations between PHL and cardiovascular disease (CVD) have been reported from studies that used different methods to assess alopecia severity. No classification including the HNC has been validated for population studies. We aimed to simplify the HNC, produce the adapted HNC and test its reliability for use in population studies. METHODS: Identifying vertex alopecia as distinct allowed for a simpler alignment of alopecia figures where scores 4V and 5V in the adapted HNC replace IV and V in the original HNC. The two classifications were to be used by twelve of our staff (secretaries, nurses, dermatology trainees and dermatologists) to evaluate 16 men with PHL. Observer agreement was estimated using intraclass correlation coefficient (ICC) and a percentage method duplicated from the recent basic and specific (BASP) classification. RESULTS: The ICC improved with the adapted HNC when assessed by both the nurses/secretaries (from 0.47 to 0.61) and dermatology residents/consultants (from 0.68 to 0.76). Agreement using the BASP percentage method for dermatologists was 62-69% for the original and 93-100% for the adapted HNC. CONCLUSIONS: The adapted HNC increased reliability at various staff levels, making it suitable for epidemiological studies; its use in future studies could help elucidate the association between PHL and CVD.

Mortality in Patients Treated for Tuberculous Pericarditis in Sub-Saharan Africa

Objective: To determine the mortality rate and its predictors in patients with a presumptive diagnosis of tuberculous pericarditis in sub-Saharan Africa. Design: Between 1 March 2004 and 31 October 2004; we enrolled 185 consecutive patients with presumed tuberculous pericarditis from 15 referral hospitals in Cameroon; Nigeria; and South Africa; and observed them during the 6-month course of antituberculosis treatment for the major outcome of mortality. This was an observational study; with the diagnosis and management of each patient left at the discretion of the attending physician. Using Cox regression; we have assessed the effect of clinical and therapeutic characteristics (recorded at baseline) on mortality during follow-up. Results: We obtained the vital status of 174 (94) patients (median age 33; range 14-87 years). The overall mortality rate was 26. Mortality was higher in patients who had clinical features of HIV infection than in those who did not (40versus 17; P=0.001). Independent predictors of death during follow-up were: (1) a proven non-tuberculosis final diagnosis (hazard ratio [HR] 5.35; 95confidence interval 1.76 to 16.25); (2) the presence of clinical signs of HIV infection (HR 2.28; 1.14-4.56); (3) co-existent pulmonary tuberculosis (HR 2.33; 1.20-4.54); and (4) older age (HR 1.02; 1.01-1.05). There was also a trend towards an increase in death rate in patients with haemodynamic instability (HR 1.80; 0.90-3.58) and a decrease in those who underwent pericardiocentesis (HR 0.34; 0.10-1.19). Conclusion : A presumptive diagnosis of tuberculous pericarditis is associated with a high mortality in sub-Saharan Africans. Attention to rapid aetiological diagnosis of pericardial effusion and treatment of concomitant HIV infection may reduce the high mortality associated with the disease

Marginal traction alopecia severity score: development and test of reliability.

BACKGROUND: Traction alopecia (TA) is common in African females. Although hairstyles are thought to be causal, the contribution of individual hairstyling variables to TA severity has not been quantified. The aim of the current study was to develop a severity scoring system (M-TAS score) for marginal TA, the commonest form of this disorder, and to test its reliability. METHOD: The margins of the scalp were divided into anterior and posterior with an imaginary line joining the tips of both ears. The anterior and posterior hairlines were further divided into three using the temporalis muscles and mastoid processes at the hairline as landmarks, respectively. Each examiner assessed each of the six areas. If any were found to have TA, the severity was scored using an examiner assessed system (tested once) or a picture matched score (tested twice). Ten and eight female patients with TA of varying severity were assessed by 11 and 9 examiners (dermatologists, dermatology trainees, and nurses), respectively. RESULTS: The intraclass correlation coefficient (ICC) for interobserver agreement was larger with photograph-matched scores than with examiner estimated scores reaching substantial (0.61-0.80) and excellent (0.81-100) agreement for both anterior and posterior scores irrespective of level of skill of examiner. The ICC for intraobserver agreement with the photograph matched scores was 0.99. LIMITATIONS: The diagnosis of normal margin was excellent for the anterior yet poor for the posterior margin with photograph scores. The M-TAS score is not for diagnosis but to assess severity. CONCLUSION: The photograph-based M-TAS score requires validation with larger samples but could be a useful research tool for elucidating disease prevalence and determinants of TA as well for monitoring response to treatment.

African hair length in a school population: a clue to disease pathogenesis?

BACKGROUND: Anecdotal data suggest that combed natural African hair reaches a length steady state. Easier grooming and anticipated long hair have made relaxers popular. OBJECTIVES: These hypotheses were tested in a cross-sectional survey of 1042 school children using a piloted questionnaire and hair length measurements done on four scalp regions. RESULTS: Participants included 45% boys and 55% girls. Girls consider length important for hairstyle choice (P < 0.0001). There was no difference in mean length at 2 to 5 vs. > 5 years (P = 0.3) and at 1 to < 2 vs. 2 to 5 years (P = 0.99), suggesting that a steady state is reached within 1 year after a hair cut for combed natural hair [mean, 5.1 cm (4.3)]. Relaxed hair reached length steady state > 2 years after a haircut [mean, 10.9 cm (3.6)], was longer than natural hair (P < 0.0001), shorter than expected, and significantly shorter on the occiput than the rest of the scalp (P < 0.0001). CONCLUSIONS: Persistently short combed natural hair years after a hair cut suggests that breakage eventually equals new growth (i.e., steady state), which is likely to be variable. Relaxed hair, irrespective of last haircut, is also short; chemical damage as a limit to potential lengths needs confirmation. Relatively short occipital relaxed hair could be a clue to disease pathogenesis.

Hairdressing and the prevalence of scalp disease in African adults.

BACKGROUND: Anecdotal reports suggest that certain scalp disorders are common in Africans and may be associated with hairstyles. OBJECTIVES: This study of 874 African adults in Cape Town was performed to test this hypothesis. METHODS: A questionnaire was administered and scalp examinations performed, after ethics approval. RESULTS: Participants included 30.9% men and 69.1% women (median age 36.1 years, range 18-99). Most men had natural hair: 91.7% vs. 24.3% women. The majority of men had recent haircuts (< 4 weeks): 74.8% vs. 9.9% women. The overall prevalence of acne (folliculitis) keloidalis nuchae (AKN) was 3.5%: higher in men than women (10.5% vs. 0.3%). AKN prevalence was not associated with whether clippers or blades were used. However, it was associated with haircut symptoms. Haircut-associated symptoms, i.e. at least one episode of transient pimples (or crusts) and bleeding (however small) were reported in 37% and 18.9% of men, respectively. The latter may have implications for disease transmission. Most women (58.7%) had chemically treated hair (49.2% relaxed and 9.6% permed hair) vs. 2.3% men. The prevalences of traction alopecia (TA) and central centrifugal cicatricial alopecia (CCCA) were 22.6% and 1.9%: higher in women (31.7% vs. 2.2% and 2.7% vs. 0%, respectively). CCCA was highest in women > 50 years (6.7% vs. 1.2%). TA prevalence was highest if the usual hairstyle was extensions attached to relaxed hair (48%). CONCLUSION: We found associations between specific scalp diseases, hairstyles, gender, and age. These associations need further study, better to elucidate determinants and to improve disease prevention and treatment.

Hairdressing is associated with scalp disease in African schoolchildren.

BACKGROUND: Anecdotal reports suggest that certain disorders are common in African hair and may be associated with hairstyles. OBJECTIVES: A cross-sectional study of 1042 schoolchildren was performed to test this hypothesis. METHODS: A questionnaire was administered and scalp examinations performed, after ethics approval. RESULTS: Participants included 45% boys and 55% girls. The majority of boys, 72.8%, kept natural hair with frequent haircuts (within 4 weeks). The prevalence of acne (folliculitis) keloidalis nuchae (AKN) was 0.67% in the whole group and highest (4.7%) in boys in the final year of high school, all of whom had frequent haircuts. The majority of girls (78.4%) had chemically relaxed hair, which was usually combed back or tied in ponytails, vs. 8.6% of boys. Traction alopecia (TA) was significantly more common with relaxed than natural hair, with an overall prevalence of 9.4% (98 of 1042) and of 17.1% in girls, in whom it increased with age from 8.6% in the first year of school to 21.7% in the last year of high school. The proportion with TA in participants with a history of braids on natural hair was lower (22.9%), but not significantly, than among those with a history of braids on relaxed hair (32.1%). No cases of central centrifugal cicatricial alopecia were identified. CONCLUSIONS: We found associations between hairstyle and disease in our population of schoolchildren. AKN appears to be associated with frequently cut natural hair and TA with relaxed hair. These associations need further study for purposes of disease prevention.

Heterozygous disruption of SERCA2a is not associated with impairment of cardiac performance in humans: implications for SERCA2a as a therapeutic target in heart failure.

OBJECTIVE: To verify whether a deficiency in the cardiac sarcoplasmic reticulum pump SERCA2a causes cardiac dysfunction in humans. DESIGN: Cardiac performance was measured in a serendipitous human model of primary SERCA2a deficiency, Darier's disease, an autosomal dominant skin disorder caused by mutations inactivating one copy of the ATP2A2 gene, which encodes SERCA2a. METHODS: Systolic and diastolic function and contractility were assessed by echocardiography at rest and during exercise in patients with Darier's disease with known mutations. Fourteen patients with Darier's disease were compared with 14 normal controls and six patients with dilated cardiomyopathy with stable heart failure. RESULTS: Resting systolic and diastolic function was normal in patients with Darier's disease and in controls. The increase in systolic function during exercise was not different between patients with Darier's disease and normal controls; neither was there a difference in contractility. As expected, patients with dilated cardiomyopathy had impaired diastolic and systolic function with depressed contractility at rest and during exercise. CONCLUSION: Contrary to expectations, heterozygous disruption of SERCA2a is not associated with the impairment of cardiac performance in humans. Attempts to increase SERCA2a levels in heart failure, although showing promise in rodent studies, may not be addressing a critical causal pathway in humans.