Inter-rater agreement and reliability of outcome measurement instruments and staging systems used in hidradenitis suppurativa.

BACKGROUND: Monitoring disease activity over time is a prerequisite for clinical practice and research. Valid and reliable outcome measurement instruments (OMIs) and staging systems provide researchers and clinicians with benchmark tools to assess the primary and secondary outcomes of interventional trials and to guide treatment selection properly. OBJECTIVES: To investigate inter-rater reliability and agreement in instruments currently used in hidradenitis suppurativa (HS), with dermatologists experienced in HS as the rater population of interest. METHODS: In a prospective completely balanced design, 24 patients with HS underwent a physical examination by 12 raters (288 assessments) using nine instruments. The results were analysed using generalized linear mixed models. RESULTS: For the staging systems, the study found good inter-rater reliability for Hurley staging in the axillae and gluteal region, moderate inter-rater reliability for Hurley staging in the groin and for Physician's Global Assessment, and fair inter-rater reliability for refined Hurley staging and the International HS Severity Scoring System. For all the tested OMIs, the observed intervals for limits of agreement were very wide relative to the ranges of the scales. CONCLUSIONS: The very wide intervals for limits of agreement imply that substantial changes are needed in clinical research in order to rule out measurement error. The results illustrate a difficulty, even for experienced HS experts, to agree on the type and number of lesions when evaluating disease severity. The apparent caveats call for global efforts, such as the HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC) to reach consensus on how best to measure physical signs of HS reliably in randomized trials. What's already known about this topic? Without valid and reliable instruments to measure outcomes, researchers and clinicians lack the necessary benchmarks to assess primary and secondary end points of interventional trials properly. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. Several outcome measure instruments exist for HS, but their validation is generally incomplete or of relatively low methodological quality. What does this study add? Using a prospective completely balanced design this study examined inter-rater reliability with HS-experienced dermatologists as the rater population of interest. The study did not find very good reliability for any included instrument or lesion counts. This study illustrates the difficulty in finding agreement on the type and number of HS lesions, even among experts. The results question whether physical signs are best measured by a traditional physician lesion count instrument. What are the clinical implications of this work? For staging, Hurley staging and physician global visual analogue scale proved to be acceptable instruments in terms of inter-rater reliability. For the instruments designed to measure changes in health status, our study illustrates how difficult it is, even for experts, to measure the physical signs of HS using a simple rater counting. Consequently, other assessment methods of physicals signs, such as ultrasound evaluation, require consideration.

Rapidly increasing body mass index among children, adolescents and young adults in a transitioning population, South Africa, 2008-15.

Background: There is a global epidemic of overweight and obesity; however, this rate of increase is even greater in some low- and middle-income countries (LMIC). South Africa (SA) is undergoing rapid socioeconomic and demographic changes that have triggered a rapid nutrition transition. The paper focuses on the recent rate of change of body mass index (BMI) among children, adolescents and young adults, further stratified by key sociodemographic factors. Methods: We analysed mean BMI of 28 247 individuals (including children) from 7301 households by age and year, from anthropometric data from four national cross-sectional (repeated panel) surveys using non-linear fitted curves and associated 95% confidence intervals. Results: From 2008 to 2015, there was rapid rise in mean BMI in the 6-25 age band, with the highest risk (3-4+ BMI unit increase) among children aged 8-10 years. The increase was largely among females in urban areas and of middle-high socioeconomic standing. Prominent gains were also observed in certain rural areas, with extensive geographical heterogeneity across the country. Conclusions: We have demonstrated a major deviation from the current understanding of patterns of BMI increase, with a rate of increase substantially greater in the developing world context compared with the global pattern. This population-wide effect will have major consequences for national development as the epidemic of related non-communicable disease unfolds, and will overtax the national health care budget. Our refined understanding highlights that risks are further compounded for certain groups/places, and emphasizes that urgent geographical and population-targeted interventions are necessary. These interventions could include a sugar tax, clearer food labelling, revised school feeding programmes and mandatory bans on unhealthy food marketing to children.The scenario unfolding in South Africa will likely be followed in other LMICs.

Circulating microRNA's as a diagnostic tool for hepatocellular carcinoma in a hyper endemic HIV setting, KwaZulu-Natal, South Africa: a case control study protocol focusing on viral etiology.

BACKGROUND: A wide range of studies has investigated the diagnostic proficiency of extracellular microRNAs (miRNAs) in hepatocellular cancer (HCC). HCC is expected to increase in Sub-Saharan Africa (SSA), due to endemic levels of viral infection (HBV/HIV), ageing and changing lifestyles. This unique aetiological background provides an opportunity for investigating potentially novel circulating miRNAs as biomarkers for HCC in a prospective study in South Africa. METHODS: This study will recruit HCC patients from two South African cancer hospitals, situated in Durban and Pietermaritzburg in the province of KwaZulu-Natal. These cases will include both HBV mono-infected and HBV/HIV co-infected HCC cases. The control group will consist of two (2) age and sex-matched healthy population controls per HCC case randomly selected from a Durban based laboratory. The controls will exclude patients if they have any evidence of chronic liver disease. A standardised reporting approach will be adopted to detect, quantify and normalize the level of circulating miRNAs in the blood sera of HCC cases and their controls. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) will be employed to quantity extracellular miRNAs. Differences in concentration of relevant miRNA by case/control status will be assessed using the Wilcoxon rank-sum (Mann-Whitney U) test. Adjustment for multiple testing (Bonferroni correction), receiver operating curves (ROC) and optimal breakpoint analyses will be employed to identify potential thresholds for the differentiation of miRNA levels of HCC cases and their controls. DISCUSSION: Although there is a growing base of literature regarding the role of circulating miRNAs as biomarkers, this promising field remains a 'work in progress'. The aetiology of HBV infection in HCC is well understood, as well as it's role in miRNA deregulation, however, the mediating role of HIV infection is unknown. HCC incidence in SSA, including South Africa, is expected to increase significantly in the next decade. A combination of factors, therefore, offers a unique opportunity to identify candidate circulating miRNAs as potential biomarkers for HBV/HIV infected HCC.

The future cost of cancer in South Africa: An interdisciplinary cost management strategy.

The exponential rise in cancer costs in South Africa (SA) was illustrated in a recent Sunday Times article entitled 'The cost of cancer can be a debt sentence'. Our Minister of Health talks of a 'war' against the high costs of cancer drugs, and epidemiologists project a sharply rising incidence. Eminent international medical journals, such as The Lancet, underline the fact that cancer cost is a growing international problem that confronts even the richest countries. If richer countries in the world are battling to cover the costs of cancer, what is the prognosis for SA?

Carbohydrate intake, obesity, metabolic syndrome and cancer risk? A two-part systematic review and meta-analysis protocol to estimate attributability.

INTRODUCTION: Linkages between carbohydrates, obesity and cancer continue to demonstrate conflicting results. Evidence suggests inconclusive direct linkages between carbohydrates and specific cancers. Conversely, obesity has been strongly linked to a wide range of cancers. The purpose of the study is to explore linkages between carbohydrate intake and cancer types using a two-step approach. First the study will evaluate the linkages between carbohydrate intake and obesity, potentially stratified by metabolic syndrome status. Second, the estimated attributable fraction of obesity ascribed to carbohydrate intake will be multiplied against obesity attributable fractions for cancer types to give estimated overall attributable fraction for carbohydrate versus cancer type. METHODS AND ANALYSIS: We will perform a comprehensive search to identify all possible published and unpublished studies that have assessed risk factors for obesity including dietary carbohydrate intake. Scientific databases, namely PubMed MEDLINE, EMBASE, EBSCOhost and ISI Web of Science will be searched. Following study selection, paper/data acquisition, and data extraction and synthesis, we will appraise the quality of studies and risk of bias, as well as assess heterogeneity. Meta-weighted attributable fractions of obesity due to carbohydrate intake will be estimated after adjusting for other potential confounding factors (eg, physical inactivity, other dietary intake). Furthermore, previously published systematic reviews assessing the cancer-specific risk associated with obesity will also be drawn. These estimates will be linked with the attributability of carbohydrate intake in part 1 to estimate the cancer-specific burden that can be attributed to dietary carbohydrates. This systematic review protocol has been developed according to the 'Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) 2015'. ETHICS AND DISSEMINATION: The current study will be based on published literature and data, and, as such, ethics approval is not required. The final results of this two part systematic review (plus multiplicative calculations) will be published in a relevant international peer-reviewed journal. TRIAL REGISTRATION NUMBER: PROSPERO CRD42015023257.

Global and country underestimation of hepatocellular carcinoma (HCC) in 2012 and its implications.

PURPOSE: The problems of screening costs, as well as poor data, potentially lead to the underestimation of the incidence of hepatocellular carcinoma (HCC). In particular, this is problematic in developing countries with limited resources and poor data. The study develops a model to inform policy makers of the true incidence and potential extra cost of HCC in a developing country context. METHODS: Using Globocan 2012 data, we employed an ecological correlation design at country level to associate HCC incidence data with relevant determinant data like HBV-HCV and other exposure factors. A Poisson regression model was used to estimate potentially missed incident cases of HCC by country and region based on the country risk factor covariate values. RESULTS: The results indicated that HBV and HCV prevalence were significantly associated with HCC incidence (p<0.001) and potentially accounted for 94%% of incident HCC in 2012. We estimated a total of 120,772 potentially missed incident HCC cases in 2012. These cases are largely predicted for South Asia (>21,000), North Asia (>15,000), Western Africa (14,500) and Eastern Africa (12,500). CONCLUSIONS: Developing countries, with poorer quality data and a high historical burden of hepatitis, were predicted to have the majority of missed HCC cases in 2012 based on our model. These countries are, therefore, less able to detect, budget for or manage HCC. The high cost of HCC treatment, as well as its economic implications, poses a challenge in resource poor settings.

Bacteriology of hidradenitis suppurativa exacerbations and deep tissue cultures obtained during carbon dioxide laser treatment.

BACKGROUND: Previous studies have shown different bacteria in hidradenitis suppurativa (HS) lesions, but the literature regarding bacteria in acute exacerbation of HS is sparse. OBJECTIVES: To determine the type of bacteria isolated from HS lesions during exacerbations of the disease. METHODS: Patients with HS with acute nodules or abscesses were examined and treated by carbon dioxide laser vaporization. Bacterial samples for aerobic and anaerobic cultures were taken from the skin surface (before surgery) and then from the deeper layers (during surgery) of the lesions. At each level two samples were taken, one with a punch biopsy and one by pressing a soft agar gel against the skin. The bacterial findings were typed and quantified. RESULTS: A total of 10 patients (eight women and two men), with a mean age of 37·2 years and a mean HS duration of 14·5 years, were included. All of them had an ongoing exacerbation (mean duration 5·6 days) of their HS, with one inflamed lesion that was treated by carbon dioxide laser vaporization. Coagulase-negative staphylococci (CNS) were found in the deep layers in all 10 patients. Nine of the patients carried Corynebacterium spp. and two alpha-haemolytic streptococci at various levels. Among the anaerobic microorganisms, Gram-positive cocci were the most common bacteria. CONCLUSIONS: As found in a previous study, CNS were the most common bacteria, but contrary to what we expected, Staphylococcus aureus was not found in any cultures from acute inflammatory nodules of HS exacerbations.

Interobserver variability of clinical scores in hidradenitis suppurativa is low.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic recurrent disease with scars and sinus tract formation that causes substantial impact on quality of life. For evaluation of HS and treatment results, a scoring system for disease severity (Hidradenitis Suppurativa Score, HSS) has been proposed. OBJECTIVES: To describe the interobserver reliability of the HSS and further to document its correlation with risk factors and other measures of disease severity. METHODS: Sixty-one consecutive patients with HS, referred to a clinical centre with special interest in the disease, were scored according to the HSS protocol: eight patients by four dermatologists together, 23 patients by all four observers independently and 30 patients by a single observer. Interobserver variability in HSS between the four observers was investigated in the group of 23 patients. Patients' reports of weight and height, smoking habits etc., were collected, as well as Dermatology Life Quality Index (DLQI) questionnaires. RESULTS: The interobserver concordance of HSS was 0·95. Median (interquartile range, IQR) HSS for all patients was 40 (18-73); women 39 (16-68); men 60·5 (30-95). Median (IQR) HSS for nonsmokers was 26 (12-65); former smokers 30 (10-56); smokers 44 (26-108). Median (IQR) HSS for normal weight patients was 12 (10-30); overweight 43 (25-58); obese 51 (24-95). Mean ± SD DLQI for all patients was 11·3 ± 8·6. CONCLUSIONS: HSS is simple to use and shows low interobserver variability. The score correlates with suggested risk factors, indicating that it reflects a valid estimation of disease severity.

Objective scoring of hidradenitis suppurativa reflecting the role of tobacco smoking and obesity.

BACKGROUND: Hidradenitis suppurativa (HS) is a long-standing disease with abscess and often fistula formation, predominantly in the axillae and groins. The disease is difficult to treat and has a severe impact on quality of life. A clinically relevant system for scoring disease severity is lacking in HS. OBJECTIVES: To evaluate the modified Hidradenitis Suppurativa Score (HSS) and to study the impact of body mass index (BMI) and smoking habits on disease severity. METHODS: Two hundred and fifty-one consecutive patients with HS referred to a clinic with special interest in the disease were included, of whom 115 were scored. Points were given for regions involved, types of lesion (nodules, fistulas), total area involved and whether lesions were separated by normal skin. Background characteristics included BMI and smoking habits. Two hundred and forty-six patients completed the Dermatology Life Quality Index (DLQI). RESULTS: The median (interquartile range, IQR) HSS for all patients was 38 (18-66): women 38 (18-71) and men 37 (19-51). Median (IQR) HSS for smokers was 41 (22-75.5), former smokers 27 (16-53) and nonsmokers 22 (10-57). Median (IQR) HSS for patients with BMI < 25 kg m(-2) was 32 (12-54), BMI 25-30 kg m(-2) 44 (22-56) and BMI > or = 30 kg m(-2) 50 (18-86). Mean +/- SD DLQI for the whole group of patients was 10.3 +/- 7.5, median 9, and showed no significant differences between the groups studied. There was a significant positive correlation of fair degree between HSS and DLQI. There were significant differences in HSS between nonsmokers and smokers as well as between women of normal weight compared with obese women. CONCLUSIONS: The modified HSS is simple and practical and it extracts important clinical information. A connection between disease severity and BMI as well as smoking habits in patients with HS is presented. The results suggest that the HSS may be a relevant outcome measure in future therapeutic trials in HS.

What causes hidradenitis suppurativa?

Hidradenitis suppurativa (HS)--a rather common, very chronic and debilitating inflammatory skin appendage disorder with a notoriously underestimated burden of disease--has long been a playground for the high priests of nomenclature: Ask a bunch of eminent dermatologists and skin pathologists to publicly share their thoughts on what causes HS, and they will soon get entrenched in a heated debate on whether this historical term is a despicable misnomer. Fortunately, the recently founded Hidradenitis Suppurativa Foundation (HSF; http://www.hs-foundation.org), to which EXP DERMATOL serves as home journal, has broken with this unproductive tradition and has encouraged publication of the current CONTROVERSIES feature. This is exclusively devoted to discussing the pathobiology of this chronic neutrophilic folliculitis of unknown origin. Although traces of terminological bickering remain visible, it does the HS experts in our virtual debate room credit that they engage in a constructive and comprehensive dissection of potential pathogenesis pathways that may culminate in the clinical picture we know under the competing terms HS or acne inversa. These experts sketch more often complementary than mutually exclusive pathogenesis scenarios, and the outlines of a conceivable consensus on the many open pathobiology questions begin to emerge in these CONTROVERSIES. Hopefully, this heralds a welcome new tradition: to get to the molecular heart of HS pathogenesis, which can only be achieved by a renaissance of solid basic HS research, as the key to developing more effective HS therapy.