Effects of rituximab-based B-cell depletion therapy on skin manifestations of lupus erythematosus--report of 17 cases and review of the literature

Cutaneous manifestations occur frequently in systemic lupus erythematosus (SLE) and are pathognomonic in subacute-cutaneous lupus erythematosus (SCLE) and chronic cutaneous lupus erythematosus (CCLE). Although B-cell depletion therapy (BCDT) has demonstrated efficacy in SLE with visceral involvement, its usefulness for patients with predominant skin manifestations has not been fully established. In this single-centre, retrospective study 14 consecutive SLE, one CCLE and two SCLE patients with recalcitrant skin involvement were treated with 2 × rituximab 1 g, and 1 × cyclophosphamide 750 mg. Six months after BCDT, nine of 17 (53%) patients were in complete (CR) or partial remission (PR). Relapses occurred in 12 patients (71%) at a mean time of 10 ± 1.8 months after BCDT. A second cycle of BCDT achieved a more sustained remission in seven of nine patients (78%) lasting for a mean time of 18.4 ± 2.7 months. Minor adverse events were experienced by three patients. Mean follow-up was 30 months. Our own results and the literature review demonstrate that BCDT based on rituximab is well tolerated and may be effective for cutaneous lesions of lupus erythematosus. Randomized controlled trials are necessary to further evaluate the value of BCDT for this group of patients

Meta-analytical methods to identify who benefits most from treatments: daft, deluded, or deft approach?

Identifying which individuals benefit most from particular treatments or other interventions underpins so-called personalised or stratified medicine. However, single trials are typically underpowered for exploring whether participant characteristics, such as age or disease severity, determine an individual’s response to treatment. A meta-analysis of multiple trials, particularly one where individual participant data (IPD) are available, provides greater power to investigate interactions between participant characteristics (covariates) and treatment effects. We use a published IPD meta-analysis to illustrate three broad approaches used for testing such interactions. Based on another systematic review of recently published IPD meta-analyses, we also show that all three approaches can be applied to aggregate data as well as IPD. We also summarise which methods of analysing and presenting interactions are in current use, and describe their advantages and disadvantages. We recommend that testing for interactions using within-trials information alone (the deft approach) becomes standard practice, alongside graphical presentation that directly visualises this

Probiotics to prevent infantile colic

Background Infantile colic is typically defined as full‐force crying for at least three hours per day, on at least three days per week, for at least three weeks. Infantile colic affects a large number of infants and their families worldwide. Its symptoms are broad and general, and while not indicative of disease, may represent a serious underlying condition in a small percentage of infants who may need a medical assessment. Probiotics are live microorganisms that alter the microflora of the host and provide beneficial health effects. The most common probiotics used are of Lactobacillus, Bifidobacterium and Streptococcus. There is growing evidence to suggest that intestinal flora in colicky infants differ from those in healthy infants, and it is suggested that probiotics can redress this balance and provide a healthier intestinal microbiota landscape. The low cost and easy availability of probiotics makes them a potential prophylactic solution to reduce the incidence and prevalence of infantile colic. Objectives To evaluate the efficacy and safety of prophylactic probiotics in preventing or reducing severity of infantile colic. Search methods In January 2018 we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, 10 other databases and two trials registers. In addition, we handsearched the abstracts of relevant meetings, searched reference lists, ran citation searches of included studies, and contacted authors and experts in the field, including the manufacturers of probiotics, to identify unpublished trials. Selection criteria Randomised control trials (RCTs) of newborn infants less than one month of age without the diagnosis of infantile colic at recruitment. We included any probiotic, alone or in combination with a prebiotic (also known as synbiotics), versus no intervention, another intervention(s) or placebo, where the focus of the study was the effect of the intervention on infantile colic. Data collection and analysis We used standard methodological procedures of Cochrane. Main results Our search yielded 3284 records, and of these, we selected 21 reports for full‐text review. Six studies with 1886 participants met our inclusion criteria, comparing probiotics with placebo. Two studies examined Lactobacillus reuteri DSM, two examined multi‐strain probiotics, one examined Lactobacillus rhamnosus, and one examined Lactobacillus paracasei and Bifidobacterium animalis. Two studies began probiotics during pregnancy and continued administering them to the baby after birth. We considered the risk of bias for randomisation as low for all six trials; for allocation concealment as low in two studies and unclear in four others. All studies were blinded, and at low risk of attrition and reporting bias. A random‐effects meta‐analysis of three studies (1148 participants) found no difference between the groups in relation to occurrence of new cases of colic: risk ratio (RR) 0.46, 95% confidence interval (CI) 0.18 to 1.19; low‐certainty evidence; I2 = 72%. A random‐effects meta‐analysis of all six studies (1851 participants) found no difference between the groups in relation to serious adverse effects (RR 1.02, 95% CI 0.14 to 7.21; low‐certainty evidence; I2 not calculable (only four serious events for one comparison, two in each group: meconium plug obstruction, patent ductus arteriosus and neonatal hepatitis). A random‐effects meta‐analysis of three studies (707 participants) found a mean difference (MD) of –32.57 minutes per day (95% CI –55.60 to –9.54; low‐certainty evidence; I2 = 93%) in crying time at study end in favour of probiotics. A subgroup analysis of the most studied agent, Lactobacillus reuteri, showed a reduction of 44.26 minutes in daily crying with a random‐effects model (95% CI –66.6 to –21.9; I2 = 92%), in favour of probiotics. Authors' conclusions There is no clear evidence that probiotics are more effective than placebo at preventing infantile colic; however, daily crying time appeared to reduce with probiotic use compared to placebo. There were no clear differences in adverse effects. We are limited in our ability to draw conclusions by the certainty of the evidence, which we assessed as being low across all three outcomes, meaning that we are not confident that these results would not change with the addition of further researc

Parent training programmes for managing infantile colic

Background Infantile colic has an effect on both infants and their parents, who become exhausted and concerned as they attempt to comfort their child. Common approaches have focused upon physical treatments to reduce symptoms, with inconclusive evidence as to their effectiveness. An alternative approach seeks to provide training, support and psychological interventions for parents. This approach is known as parent training programmes. Programmes can include soothing techniques, advice on feeding or normalisation material in any form. The teaching format can vary including face‐to‐face courses, online learning, printed materials, home visits and remote support and counselling. Here, we aim to collate the evidence on the effectiveness of these interventions and examine their effectiveness at reducing infantile colic symptoms and parental anxiety levels, and their safety. Objectives 1. To evaluate the effectiveness and safety of parent training programmes for managing colic in infants under four months of age. 2. To identify the educational content and attributes of such published programmes. Search methods In June 2019 we searched CENTRAL, MEDLINE, Embase, 13 other databases and two trials registers. We also handsearched conference abstracts, inspected the references of included studies and contacted leaders in the field for more trials. Selection criteria Randomised controlled trials (RCTs) and quasi‐RCTs investigating the effectiveness of any form of parental training programmes, alone or in combination, versus another intervention(s) or control, on infantile colic. Data collection and analysis Two authors independently selected studies for inclusion, extracted data, and assessed the risk of bias within the included studies. We used Review Manager 5 to analyse the data. We assessed the certainty of the evidence using GRADE methodology

Patient and physiotherapist perceptions of the Getting Recovery Right After Neck Dissection (GRRAND) rehabilitation intervention: a qualitative interview study embedded within a feasibility trial

This is the final version. Available from BMJ Publishing Group via the DOI in this record. All data relevant to the study are included in the article or uploaded as supplementary information.OBJECTIVE: The Getting Recovery Right After Neck Dissection (GRRAND) intervention is a physiotherapy programme for patients with head and neck cancer who have undergone neck dissection. The aim of this qualitative study was to understand if the intervention was useful, acceptable and whether it was feasible to conduct a randomised controlled trial (RCT). DESIGN: This qualitative study was embedded within the GRRAND-Feasibility (GRRAND-F) Study. SETTING: Participants were recruited from four acute National Health Service hospitals in England between 2020 and 2021. PARTICIPANTS: We interviewed four usual care and four intervention patient-participants from a single study site (Oxford). Six were male, two were female. All were white British ethnicity. We interviewed two physiotherapists from Oxford who delivered the GRRAND-F intervention, and physiotherapists from Birmingham, Poole and Norwich who were trained to deliver the intervention but were not able to deliver it within the study time frame. RESULTS: The analysis identified five themes: (1) Acceptability, (2) Adherence, (3) Outcomes, (4) Feasibility and (5) Stand-alone themes (prehabilitation, video consultations, healthcare use).Patient-participants and physiotherapist-participants agreed that usual care was not meeting patients' rehabilitation needs. The GRRAND intervention provided biopsychosocial support. In comparison to the usual care group, patient-participants who received the intervention were more confident that they could perform rehabilitation exercises and were more motivated to engage in long-term adaptive behaviour change. Physiotherapists felt they needed more administrative support to participate in an RCT. CONCLUSION: Participants felt that usual care was insufficient. GRRAND provided much needed, biopsychosocial support to patients. Participants were supportive that it would be feasible to test GRRAND in an RCT. TRIAL REGISTRATION NUMBER: ISRCTN11979997.National Institute of Health Research (NIHR

Parameter Estimation and Quantitative Parametric Linkage Analysis with GENEHUNTER-QMOD

Objective: We present a parametric method for linkage analysis of quantitative phenotypes. The method provides a test for linkage as well as an estimate of different phenotype parameters. We have implemented our new method in the program GENEHUNTER-QMOD and evaluated its properties by performing simulations. Methods: The phenotype is modeled as a normally distributed variable, with a separate distribution for each genotype. Parameter estimates are obtained by maximizing the LOD score over the normal distribution parameters with a gradient-based optimization called PGRAD method. Results: The PGRAD method has lower power to detect linkage than the variance components analysis (VCA) in case of a normal distribution and small pedigrees. However, it outperforms the VCA and Haseman-Elston regression for extended pedigrees, nonrandomly ascertained data and non-normally distributed phenotypes. Here, the higher power even goes along with conservativeness, while the VCA has an inflated type I error. Parameter estimation tends to underestimate residual variances but performs better for expectation values of the phenotype distributions. Conclusion: With GENEHUNTER-QMOD, a powerful new tool is provided to explicitly model quantitative phenotypes in the context of linkage analysis. It is freely available at http://www.helmholtz-muenchen.de/genepi/downloads. Copyright (C) 2012 S. Karger AG, Base

Decision-making, attitudes, and understanding among patients and relatives invited to undergo genome sequencing in the 100,000 Genomes Project: A multisite survey study

PURPOSE: The purpose of this study was to assess decisions, attitudes, and understanding of participants (patients, parents, relatives) having genome sequencing for rare disease diagnosis. METHODS: This study involved a cross-sectional observational survey with participants in the 100,000 Genomes Project. RESULTS: Survey response rate was 51% (504/978). Most participants self-reported that they had decided to undergo genome sequencing (94%) and that this was an informed decision (84%) with low decisional conflict (95%). Most self-reported that they had chosen to receive additional findings (88%) and that this was an informed decision (89%) with low decisional conflict (95%). Participants were motivated more by the desire to help others via research than by the belief it would help them obtain a diagnosis (Z = 14.23, P = 5.75 × 10-46), although both motivations were high. Concerns were relatively few but, where expressed, were more about the potential psychological impact of results than data sharing/access (Z = 9.61, P = 7.65 × 10-22). Concerns were higher among male, Asian or Asian British, and more religious participants. General and context-specific understanding of genome sequencing were both moderately high (means 5.2/9.0 and 22.5/28.0, respectively). CONCLUSION: These findings are useful to inform consent guidelines and clinical implementation of genome sequencing

Alcohol Production as an Adaptive Livelihood Strategy for Women Farmers in Tanzania and Its Potential for Unintended Consequences on Women's Reproductive Health.

Although women occupy a central position in agriculture in many developing countries, they face numerous constraints to achieving their full potential including unequal access to assets and limited decision-making authority. We explore the intersection of agricultural livelihoods, food and economic security, and women's sexual and reproductive health in Iringa Region, Tanzania. Our goal was to understand whether the benefits of supporting women in the agricultural sector might also extend to more distal outcomes, including sexual and reproductive health. Using the Sustainable Livelihoods Framework to guide data collection, we conducted 13 focus group discussions (FGD) with female (n = 11) and male farmers (n = 2) and 20 in-depth interviews with agricultural extension officers (n = 10) and village agro-dealers (n = 10). Despite providing the majority of agricultural labor, women have limited control over land and earned income and have little bargaining power. In response to these constraints, women adopt adaptive livelihood strategies, such as alcohol production, that allow them to retain control over income and support their households. However, women's central role in alcohol production, in concert with the ubiquitous nature of alcohol consumption, places them at risk by enhancing their vulnerability to unsafe or transactional sex. This represents a dangerous confluence of risk for female farmers, in which alcohol plays an important role in income generation and also facilitates high-risk sexual behavior. Alcohol production and consumption has the potential to both directly and indirectly place women at risk for undesirable sexual and reproductive health outcomes. Group formation, better access to finance, and engaging with agricultural extension officers were identified as potential interventions for supporting women farmers and challenging harmful gender norms. In addition, joint, multi-sectoral approaches from health and agriculture and alternative income-generating strategies for women might better address the complexities of achieving safe and sustainable livelihoods for women in this context

Exposure and impact of a mass media campaign targeting sexual health amongst Scottish men who have sex with men: an outcome evaluation

Background: This paper explores the exposure and impact of a Scottish mass media campaign: Make Your Position Clear. It ran from October 2009 to July 2010, targeted gay men and other men who have sex with men (MSM), and had two key aims: to promote regular sexual health and HIV testing every 6 months, and to promote the use of appropriate condoms and water-based lubricant with each episode of anal intercourse. Methods: A cross-sectional survey (anonymous and self-report) was conducted 10 months after the campaign was launched (July 2010). Men were recruited from commercial venues. Outcome measures included use of lubricant, testing for sexually transmitted infections and HIV, and intentions to seek HIV testing within the following six months. Linear-by-linear chi-square analysis and binary logistic regressions were conducted to explore the associations between the outcome measures and campaign exposure. Results: The total sample was 822 men (62.6% response rate). Men self-identifying as HIV positive were excluded from the analysis (n = 38). Binary logistic analysis indicated that those with mid or high campaign exposure were more likely to have been tested for HIV in the previous six months when adjusted for age, area of residence and use of the “gay scene” (AOR = 1.96, 95% CI = 1.26 to 3.06, p = .003), but were not more likely to be tested for STIs (AOR = 1.37, 95% CI = 0.88 to 2.16, p = .167). When adjusted for previous HIV testing, those with mid or high campaign exposure were not more likely to indicate intention to be tested for HIV in the following six months (AOR = 1.30, 95% CI = 0.73 to 2.32, p = .367). Those with no campaign exposure were less likely than those with low exposure to have used appropriate lubricant with anal sex partners in the previous year (AOR = 0.42, 95% CI = 0.23 to 0.77, p = .005). Conclusions: The campaign had demonstrable reach. The analysis showed partial support for the role of mass media campaigns in improving sexual health outcomes. This suggests that a role for mass media campaigns remains within combination HIV prevention