Hypophosphatemia attenuates improvements in vitality after intravenous iron treatment in patients with inflammatory bowel disease.

PURPOSE: Iron deficiency anemia is common in people with inflammatory bowel disease (IBD), causing deterioration in quality of life, which can be reversed by treatment that increases iron stores and hemoglobin levels. The present post hoc analyses estimate health state utility values for patients with IBD after treatment with ferric derisomaltose or ferric carboxymaltose and evaluate the health domains driving the changes. METHODS: SF-36v2 responses were recorded at baseline and day 14, 35, 49, and 70 from 97 patients enrolled in the randomized, double-blind, PHOSPHARE-IBD trial (ClinicalTrials.gov ID: NCT03466983), in which patients with IBD across five European countries were randomly allocated to either ferric derisomaltose or ferric carboxymaltose. Changes in SF-36v2 scale scores and SF-6Dv2 health utility values were analyzed by mixed models. RESULTS: In both treatment arms, SF-6Dv2 utility values and all SF-36v2 scale scores, except Bodily Pain, improved significantly (p = < 0.0001). The improvement in SF-6Dv2 utility values showed no significant treatment group difference. The improvement in utility values was completely explained by improvement in Vitality scores. Vitality scores showed significantly larger improvement with ferric derisomaltose versus ferric carboxymaltose (p = 0.026). Patients with the smallest decrease in phosphate had significantly larger improvements in Vitality scores at each time point (p = < 0.05 for all comparisons) and overall (p = 0.0006). CONCLUSIONS: Utility values improved significantly with intravenous iron treatment. Improvement in utility values was primarily driven by Vitality scores, which showed significantly greater improvement in the ferric derisomaltose arm. Smaller decreases in phosphate were associated with significantly higher Vitality scores, suggesting that quality of life improvement is attenuated by hypophosphatemia. The utility values can inform future cost-utility analysis.

A step-by-step guide to ileoanal J-pouch MRI interpretation.

BACKGROUND: Multidisciplinary management of patients with an ileoanal pouch requires dedicated imaging to identify structural problems of the pouch associated with dysfunction. The purpose of this study is to provide a framework for interpretation of magnetic resonance imaging (MRI) scan of the ileoanal pouch to enable surgeons and radiologists to work cohesively, optimise diagnosis and ultimately improve patient care. METHODS: We propose a protocol for structured MRI assessment of the ileal pouch, aiming to provide surgeons a systematic report of the anatomy, its variations and pouch complications. This guide consists of studying the characteristics of the bowel, mesentery and anal canal. RESULTS: The presented checklist is designed to systematically interpret and identify abnormalities of the ileoanal pouch on MRI. It focuses on the characteristics of the bowel (encompassing pre-pouch ileum, pouch and rectal cuff), mesentery and anal canal. The different elements of the checklist are presented in the associated supplementary video. CONCLUSIONS: A combination of clinical assessment, endoscopic evaluations and imaging is fundamental to achieving accurate diagnosis of ileoanal pouch surgery complications and pouch dysfunction.

Healthcare use attributable to COVID-19: a propensity-matched national electronic health records cohort study of 249,390 people in Wales, UK.

BACKGROUND: To determine the extent and nature of changes associated with COVID-19 infection in terms of healthcare utilisation, this study observed healthcare contact 1 to 4 and 5 to 24 weeks following a COVID-19 diagnosis compared to propensity-matched controls. METHODS: Two hundred forty nine thousand three hundred ninety Welsh individuals with a positive reverse transcription-polymerase chain reaction (RT-PCR) test were identified from data from national PCR test results. After elimination criteria, 98,600 positive individuals were matched to test negative and never tested controls using propensity matching. Cohorts were split on test location. Tests could be taken in either the hospital or community. Controls were those who had tested negative in their respective environments. Survival analysis was utilised for first clinical outcomes which are grouped into primary and secondary. Primary outcomes include post-viral-illness and fatigue as an indication of long-COVID. Secondary outcomes include clinical terminology concepts for embolism, respiratory conditions, mental health conditions, fit notes, or hospital attendance. Increased instantaneous risk for positive individuals was quantified using hazard ratios (HR) from Cox regression, while absolute risk (AR) and relative risk were quantified using life table analysis. RESULTS: Analysis was conducted using all individuals and stratified by test location. Cases are compared to controls from the same test location. Fatigue (HR: 1.77, 95% CI: 1.34-2.25, p = < 0.001) and embolism (HR: 1.50, 95% CI: 1.15-1.97, p = 0.003) were more likely to occur in all positive individuals in the first 4 weeks; however, anxiety and depression (HR: 0.83, 95% CI: 0.73-0.95, p = 0.007) were less likely. Positive individuals continued to be more at risk of fatigue (HR: 1.47, 95% CI: 1.24-1.75, p = < 0.001) and embolism (HR: 1.51, 95% CI: 1.13-2.02, p = 0.005) after 4 weeks. All positive individuals are also at greater risk of post-viral illness (HR: 4.57, 95% CI: 1.77-11.80, p = 0.002). Despite statistical association between testing positive and several conditions, life table analysis shows that only a small minority of the study population were affected. CONCLUSIONS: Community COVID-19 disease is associated with increased risks of post-viral-illness, fatigue, embolism, and respiratory conditions. Despite elevated risks, the absolute healthcare burden is low. Subsequently, either very small proportions of people experience adverse outcomes following COVID-19 or they are not presenting to healthcare.

Evaluation of a new Perinatal Mental Health Service in a University Maternity Hospital.

OBJECTIVES: Specialist Perinatal Mental Health Services (SPMHS) are a new development in Ireland. This service evaluation examined the impact of the introduction of a SPMHS multidisciplinary team (MDT) on prescribing practices and treatment pathways in an Irish maternity hospital. METHODS: Clinical charts were reviewed to collect data on all referrals, diagnoses, pharmacological and non-pharmacological interventions delivered in a SPMHS over a 3-week period in 2019. The findings were compared to the same 3-week period in 2020 following the expansion of the SPMHS MDT. RESULTS: In 2019 (n = 32) and 2020 (n = 47), most (75 and 79%, respectively) assessments were antenatal. The proportion of patients prescribed psychotropic medication within the SPMHS was not significantly different from 2019 (31%) to 2020 (23%), though more patients were already prescribed psychotropic medications at the time of referral (22% in 2019 v. 36% in 2020). There was an increase in MDT interventions in 2020 with more input from psychology, clinical nurse specialist (CNS), and social work intervention. Adherence to prescribing standards improved from 2019 to 2020. CONCLUSION: Prescribing patterns remained unchanged between 2019 and 2020. Improvement was observed in adherence to prescribing standards and there was increased provision of MDT interventions in 2020. Broader diagnostic categories were also used in 2020, possibly suggesting that the service is now providing more individualized care.

Barriers and facilitators for physical activity in rheumatic and musculoskeletal disease: a European-based survey.

Physical activity (PA) is a key strategy for improving symptoms in people with rheumatic and musculoskeletal diseases (RMDs). The aim of this study was to investigate and rank the importance of known barriers and facilitators for engaging in PA, from the perspective of people living with RMD. Five hundred thirty-three people with RMD responded to a survey (nine questions) disseminated by the People with Arthritis and Rheumatism (PARE) network of the European Alliance of Associations for Rheumatology (EULAR). The survey required participants to rank - based on their perceived importance - known PA barriers and facilitators from the literature, and specifically RMD symptoms as well as healthcare and community factors that may affect PA participation. Of the participants, 58% reported rheumatoid arthritis as their primary diagnosis, 89% were female, and 59% were between 51 and 70 years of age. Overall, participants reported fatigue (61.4%), pain (53.6%) and painful/swollen joints (50.6%) as the highest ranked barriers for engaging in PA. Conversely, less fatigue (66.8%) and pain (63.6%), and being able to do daily activities more easy (56.3%) were identified as the most important facilitators to PA. Three literature identified PA barriers, i.e., general health (78.8%), fitness (75.3%) and mental health (68.1%), were also ranked as being the most important for PA engagement. Symptoms of RMDs, such as pain and fatigue, seem to be considered the predominant barriers to PA by people with RMD; the same barriers are also the ones that they want to improve through increasing PA, suggesting a bi-directional relationship between these factors. Key Points • Symptoms of rheumatic and musculoskeletal disease (RMD) are the predominant barriers for lack of physical activity engagement. • RMD symptoms are the factors that people with RMDs want to improve when engaging in PA. • The barriers that stop people living with RMDs to do more PA are the ones that can be significantly improved through PA engagement.

Consideration-of-concept of EvolvRehab-Body for upper limb virtual rehabilitation at home for people late after stroke.

OBJECTIVE: EvolvRehab-Body is a non-immersive virtual rehabilitation system that could provide high-dose, exercise-based upper limb therapy after stroke. This consideration-of-concept study investigated: adherence rate to prescribed repetitions; viability of repeated measures in preparation for a dose-articulation study; and preliminary signal of potential benefit. METHODS: Pre-post and repeated measures with people at least six months after stroke. Twelve-week intervention: exercise-based therapy via EvolvRehab-Body. Pre-post-intervention measures: Wolf Motor Function Test (WMFT); hand grip force. Repeated-during-intervention measures: Motricity Index (MI) and Action Research Arm Test (ARAT). ANALYSIS: adherence rate (%) to set repetitions; percentage of total possible measures collected; pre-to-post-intervention change estimated in relation to published minimally detectable changes of WMFT and hand grip force; and slope of plotted data for MI and ARAT (linear regression). RESULTS: Eight of twelve participants completed the 12-week intervention phase. Adherence: 88% (1710-9377 repetitions performed). Viability repeated measures: 88 of 96 (92%) ARAT and MI scores collected. Preliminary signal of potential benefit was observed in five participants but not always for the same measures. Three participants improved WMFT-time (-7.9 to -27.2 s/item), four improved WMFT-function (0.2-1.1 points/item), and nobody changed grip force. Slope of plotted data over the 12-week intervention ranged from: - 1.42 (p = 0.26) to 1.36 (p = 0.24) points-per-week for MI and - 0.30 (p = 0.40) to 1.71 (p < 0.001) points-per-week for ARAT. CONCLUSION: Findings of good adherence rate in home settings and preliminary signal of benefit for some participants gives support to proceed to a dose-articulation study. These findings cannot inform clinical practice. CONTRIBUTION OF THE PAPER.

Congenital malformations: Prevalence and characteristics of newborns admitted into Federal Medical Center, Asaba.

Background: Congenital malformations account for a significant cause of perinatal mortality and morbidity. Understanding the burden and pattern of congenital malformation is key in monitoring the trend and improving the health care of neonates especially those in low-income countries. Objective: This was a prospective cross-sectional study to determine the prevalence and characteristics of congenital malformations among neonates admitted to the neonatal unit. Method: All newborns with congenital malformation admitted into the neonatal unit of Federal Medical Center, Asaba whose parents gave consent were recruited for the study for a 1-year period from January 2020 to December 2020. Appropriately indicated laboratory and radio-diagnostic investigations were done to confirm internal anomalies. Data were collected using a structured questionnaire and analyzed with a statistical package for social sciences version 26.0. Results: The total admission for the period was 752 with 46 of the neonates (6.1%) having congenital malformation. The predominant system affected was the cardiovascular system (57%), central nervous system (33%), and digestive system (30%). Atrioventricular septal defect (31%) and patent ductus arteriosus (31%) were the commonest types of cardiovascular malformation. A significant number of newborns with congenital anomalies died (43.5%). Conclusion: Congenital malformation was seen among one in 18 neonates affecting mostly the cardiovascular and central nervous system. A high index of suspicion, early complete physical examination, and radio-diagnostic investigations are relevant for the complete evaluation of CM in neonates. Advanced maternal age was associated with the presence of multiple organ anomalies.

Bronchiectasis is associated with delayed diagnosis and adverse outcomes in the New Zealand Common Variable Immunodeficiency Disorders cohort study.

Common variable immunodeficiency disorders (CVID) are multi-system disorders where target organ damage is mediated by infective, autoimmune and inflammatory processes. Bronchiectasis is probably the most common disabling complication of CVID. The risk factors for bronchiectasis in CVID patients are incompletely understood. The New Zealand CVID study (NZCS) is a nationwide longitudinal observational study of adults, which commenced in 2006. In this analysis, the prevalence and risk factors for bronchiectasis were examined in the NZCS. After informed consent, clinical and demographic data were obtained with an interviewer-assisted questionnaire. Linked electronic clinical records and laboratory results were also reviewed. Statistical methods were applied to determine if variables such as early-onset disease, delay in diagnosis and increased numbers of infections were associated with greater risk of bronchiectasis. One hundred and seven adult patients with a diagnosis of CVID are currently enrolled in the NZCS, comprising approximately 70% of patients known to have CVID in New Zealand. Fifty patients (46·7%) had radiologically proven bronchiectasis. This study has shown that patients with compared to those without bronchiectasis have an increased mortality at a younger age. CVID patients with bronchiectasis had a greater number of severe infections consequent to early-onset disease and delayed diagnosis. Indigenous Maori have a high prevalence of CVID and a much greater burden of bronchiectasis compared to New Zealand Europeans. Diagnostic latency has not improved during the study period. Exposure to large numbers of infections because of early-onset disease and delayed diagnosis was associated with an increased risk of bronchiectasis. Earlier diagnosis and treatment of CVID may reduce the risk of bronchiectasis and premature death in some patients.

The coil-globule transition in self-avoiding active polymers.

We perform numerical simulations of an active fully flexible self-avoiding polymer as a function of the quality of the embedding solvent described in terms of an effective monomer-monomer interaction. Specifically, by extracting the Flory exponent of the active polymer under different conditions, we are able to pin down the location of the coil-globule transition for different strengths of the active forces. Remarkably, we find that a simple rescaling of the temperature is capable of qualitatively capturing the dependence of the Θ-point of the polymer on the amplitude of active fluctuations. We discuss the limits of this mapping and suggest that a negative active pressure between the monomers, not unlike the one that has already been found in suspensions of active hard spheres, may also be present in active polymers.

Increased case-finding and uptake of direct-acting antiviral treatment essential for micro-elimination of hepatitis C among people living with HIV: a national record linkage study.

OBJECTIVES: Micro-elimination of hepatitis C virus (HCV) in people living with HIV (PLHIV) and co-infected with HCV has been proposed as a key contribution to the overall goal of HCV elimination. While other studies have examined micro-elimination in HIV-treated cohorts, few have considered HCV micro-elimination among those not treated for HIV or at a national level. METHODS: Through data linkage of national and sentinel surveillance data, we examined the extent of HCV testing, diagnosis and treatment among a cohort of PLHIV in Scotland identified through the national database of HIV-diagnosed individuals, up to the end of 2017. RESULTS: Of 5018 PLHIV, an estimated 797 (15%) had never been tested for HCV and 70 (9%) of these had undiagnosed chronic HCV. The odds of never having been tested for HCV were the highest in those not on HIV treatment [adjusted odds ratio (aOR) = 7.21, 95% confidence interval (CI): 5.15-10.10). Overall HCV antibody positivity was 11%, and it was at its highest among people who inject drugs (49%). Most of those with chronic HCV (91%) had attended an HCV treatment clinic but only half had been successfully treated (54% for those on HIV treatment, 12% for those not) by the end of 2017. The odds of never having been treated for HCV were the highest in those not on HIV treatment (aOR = 3.60, 95% CI: 1.59-8.15). CONCLUSIONS: Our data demonstrate that micro-elimination of HCV in PLHIV is achievable but progress will require increased effort to engage and treat those co-infected, including those not being treated for their HIV.

Serum proteomic profiling at diagnosis predicts clinical course, and need for intensification of treatment in inflammatory bowel disease.

BACKGROUND: Success in personalized medicine in complex disease is critically dependent on biomarker discovery. We profiled serum proteins using a novel proximity extension assay [PEA] to identify diagnostic and prognostic biomarkers in inflammatory bowel disease [IBD]. METHODS: We conducted a prospective case-control study in an inception cohort of 552 patients [328 IBD, 224 non-IBD], profiling proteins recruited across six centres. Treatment escalation was characterized by the need for biological agents or surgery after initial disease remission. Nested leave-one-out cross-validation was used to examine the performance of diagnostic and prognostic proteins. RESULTS: A total of 66 serum proteins differentiated IBD from symptomatic non-IBD controls, including matrix metallopeptidase-12 [MMP-12; Holm-adjusted p = 4.1 × 10-23] and oncostatin-M [OSM; p = 3.7 × 10-16]. Nine of these proteins are associated with cis-germline variation [59 independent single nucleotide polymorphisms]. Fifteen proteins, all members of tumour necrosis factor-independent pathways including interleukin-1 (IL-1) and OSM, predicted escalation, over a median follow-up of 518 [interquartile range 224-756] days. Nested cross-validation of the entire data set allowed characterization of five-protein models [96% comprising five core proteins ITGAV, EpCAM, IL18, SLAMF7 and IL8], which define a high-risk subgroup in IBD [hazard ratio 3.90, confidence interval: 2.43-6.26], or allowed distinct two- and three-protein models for ulcerative colitis and Crohn's disease respectively. CONCLUSION: We have characterized a simple oligo-protein panel that has the potential to identify IBD from symptomatic controls and to predict future disease course. Further prospective work is required to validate our findings.

Whole Blood Profiling of T-cell-Derived microRNA Allows the Development of Prognostic models in Inflammatory Bowel Disease.

BACKGROUND: MicroRNAs [miRNAs] are cell-specific small non-coding RNAs that can regulate gene expression and have been implicated in inflammatory bowel disease [IBD] pathogenesis. Here we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD. METHODS: In a two-stage prospective multi-centre case control study, next generation sequencing was performed on a discovery cohort of immunomagnetically separated leukocytes from 32 patients (nine Crohn's disease [CD], 14 ulcerative colitis [UC], eight healthy controls) and differentially expressed signals were validated in whole blood in 294 patients [97 UC, 98 CD, 98 non-IBD, 1 IBDU] using quantitative PCR. Correlations were analysed with phenotype, including need for early treatment escalation as a marker of progressive disease using Cox proportional hazards. RESULTS: In stage 1, each leukocyte subset [CD4+ and CD8+ T-cells and CD14+ monocytes] was analysed in IBD and controls. Three specific miRNAs differentiated IBD from controls in CD4+ T-cells, including miR-1307-3p [p = 0.01], miR-3615 [p = 0.02] and miR-4792 [p = 0.01]. In the extension cohort, in stage 2, miR-1307-3p was able to predict disease progression in IBD (hazard ratio [HR] 1.98, interquartile range [IQR]: 1.20-3.27; logrank p = 1.80 × 10-3), in particular CD [HR 2.81; IQR: 1.11-3.53, p = 6.50 × 10-4]. Using blood-based multimarker miRNA models, the estimated chance of escalation in CD was 83% if two or more criteria were met and 90% for UC if three or more criteria are met. INTERPRETATION: We have identified and validated unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These miRNAs may be able to predict treatment escalation and have the potential for clinical translation; further prospective evaluation is now indicated.

Systematic review of statistical methods for safety data in malaria chemoprevention in pregnancy trials.

BACKGROUND: Drug safety assessments in clinical trials present unique analytical challenges. Some of these include adjusting for individual follow-up time, repeated measurements of multiple outcomes and missing data among others. Furthermore, pre-specifying appropriate analysis becomes difficult as some safety endpoints are unexpected. Although existing guidelines such as CONSORT encourage thorough reporting of adverse events (AEs) in clinical trials, they provide limited details for safety data analysis. The limited guidelines may influence suboptimal analysis by failing to account for some analysis challenges above. A typical example where such challenges exist are trials of anti-malarial drugs for malaria prevention during pregnancy. Lack of proper standardized evaluation of the safety of antimalarial drugs has limited the ability to draw conclusions about safety. Therefore, a systematic review was conducted to establish the current practice in statistical analysis for preventive antimalarial drug safety in pregnancy. METHODS: The search included five databases (PubMed, Embase, Scopus, Malaria in Pregnancy Library and Cochrane Central Register of Controlled Trials) to identify original English articles reporting Phase III randomized controlled trials (RCTs) on anti-malarial drugs for malaria prevention in pregnancy published from January 2010 to July 2019. RESULTS: Eighteen trials were included in this review that collected multiple longitudinal safety outcomes including AEs. Statistical analysis and reporting of the safety outcomes in all the trials used descriptive statistics; proportions/counts (n = 18, 100%) and mean/median (n = 2, 11.1%). Results presentation included tabular (n = 16, 88.9%) and text description (n = 2, 11.1%). Univariate inferential methods were reported in most trials (n = 16, 88.9%); including Chi square/Fisher's exact test (n = 12, 66.7%), t test (n = 2, 11.1%) and Mann-Whitney/Wilcoxon test (n = 1, 5.6%). Multivariable methods, including Poisson and negative binomial were reported in few trials (n = 3, 16.7%). Assessment of a potential link between missing efficacy data and safety outcomes was not reported in any of the trials that reported efficacy missing data (n = 7, 38.9%). CONCLUSION: The review demonstrated that statistical analysis of safety data in anti-malarial drugs for malarial chemoprevention in pregnancy RCTs is inadequate. The analyses insufficiently account for multiple safety outcomes potential dependence, follow-up time and informative missing data which can compromise anti-malarial drug safety evidence development, based on the available data.

The effects of exercise on cardiovascular disease risk factors and cardiovascular physiology in rheumatoid arthritis.

Cardiovascular disease (CVD) morbidity and mortality is highly prevalent in patients with rheumatoid arthritis (RA) with debilitating effects for the individual as well as significant healthcare impact. Current evidence demonstrates that engaging in aerobic and resistance exercise (i.e. structured physical activity) can significantly improve patient-reported and clinical index-assessed outcomes in RA. In addition to this, engagement in exercise programmes improves, in a dose-dependent manner, the risk of developing CVD as well as CVD symptoms and outcomes. The present narrative review uses evidence from systematic reviews and meta-analyses as well as controlled trials, to synthesize the current state-of-the-art on the potential effects of aerobic and resistance exercise on CVD risk factors as well as on cardiac and vascular function and structure in people with RA. Where there is a lack of evidence in RA to explain potential mechanisms, relevant studies from the general population are also discussed and linked to RA.

Of microbes and mange: consistent changes in the skin microbiome of three canid species infected with Sarcoptes scabiei mites.

BACKGROUND: Sarcoptic mange is a highly contagious skin disease caused by the ectoparasitic mite Sarcoptes scabiei. Although it afflicts over 100 mammal species worldwide, sarcoptic mange remains a disease obscured by variability at the individual, population and species levels. Amid this variability, it is critical to identify consistent drivers of morbidity, particularly at the skin barrier. METHODS: Using culture-independent next generation sequencing, we characterized the skin microbiome of three species of North American canids: coyotes (Canis latrans), red foxes (Vulpes vulpes) and gray foxes (Urocyon cinereoargenteus). We compared alpha and beta diversity between mange-infected and uninfected canids using the Kruskal-Wallis test and multivariate analysis of variance with permutation. We used analysis of composition of microbes and gneiss balances to perform differential abundance testing between infection groups. RESULTS: We found remarkably consistent signatures of microbial dysbiosis associated with mange infection. Across genera, mange-infected canids exhibited reduced microbial diversity, altered community composition and increased abundance of opportunistic pathogens. The primary bacteria comprising secondary infections were Staphylococcus pseudintermedius, previously associated with canid ear and skin infections, and Corynebacterium spp., previously found among the gut flora of S. scabiei mites and hematophagous arthropods. CONCLUSIONS: This evidence suggests that sarcoptic mange infection consistently alters the canid skin microbiome and facilitates secondary bacterial infection, as seen in humans and other mammals infected with S. scabiei mites. These results provide valuable insights into the pathogenesis of mange at the skin barrier of North American canids and can inspire novel treatment strategies. By adopting a "One Health" framework that considers mites, microbes and the potential for interspecies transmission, we can better elucidate the patterns and processes underlying this ubiquitous and enigmatic disease.

Systematic review of analytical methods applied to longitudinal studies of malaria.

BACKGROUND: Modelling risk of malaria in longitudinal studies is common, because individuals are at risk for repeated infections over time. Malaria infections result in acquired immunity to clinical malaria disease. Prospective cohorts are an ideal design to relate the historical exposure to infection and development of clinical malaria over time, and analysis methods should consider the longitudinal nature of the data. Models must take into account the acquisition of immunity to disease that increases with each infection and the heterogeneous exposure to bites from infected Anopheles mosquitoes. Methods that fail to capture these important factors in malaria risk will not accurately model risk of malaria infection or disease. METHODS: Statistical methods applied to prospective cohort studies of clinical malaria or Plasmodium falciparum infection and disease were reviewed to assess trends in usage of the appropriate statistical methods. The study was designed to test the hypothesis that studies often fail to use appropriate statistical methods but that this would improve with the recent increase in accessibility to and expertise in longitudinal data analysis. RESULTS: Of 197 articles reviewed, the most commonly reported methods included contingency tables which comprised Pearson Chi-square, Fisher exact and McNemar's tests (n = 102, 51.8%), Student's t-tests (n = 82, 41.6%), followed by Cox models (n = 62, 31.5%) and Kaplan-Meier estimators (n = 59, 30.0%). The longitudinal analysis methods generalized estimating equations and mixed-effects models were reported in 41 (20.8%) and 24 (12.2%) articles, respectively, and increased in use over time. A positive trend in choice of more appropriate analytical methods was identified over time. CONCLUSIONS: Despite similar study designs across the reports, the statistical methods varied substantially and often represented overly simplistic models of risk. The results underscore the need for more effort to be channelled towards adopting standardized longitudinal methods to analyse prospective cohort studies of malaria infection and disease.

A case of rifampicin-induced haemolysis.

We present a case of pulmonary tuberculosis treated with a rifampicin (RMP) containing regimen, which led to marked haemolysis and acute kidney injury. The patient was shown to have RMP-induced haemolysis on detailed immunological testing. RMP is described as a rare cause of drug-induced haemolysis in the literature. However, it is a widely used drug and this complication may be severe. RMP-induced haemolysis precludes further treatment with the drug. Clinicians should consider this possibility and seek advice if patients on RMP develop haemolysis.