No secondary impact of ivermectin mass drug administration for onchocerciasis elimination on the prevalence of scabies in northwestern Ethiopia.

BACKGROUND: Mass drug administration (MDA) is among the five major strategies that are currently in use to control, eliminate or eradicate Neglected Tropical Diseases (NTDs). Optimising MDA to control multiple NTDs maximises impact. The objective of this study is to estimate the secondary impact of ivermectin MDA for onchocerciasis on the prevalence of scabies. METHODS: This quasi-experimental study was conducted in Ayu Guagusa district, northwestern Ethiopia. Scabies prevalence was estimated in surveys before the MDA, at 6 and 12 months afterwards. The sample size was 1437 people from a panel of 381 randomly selected study households. Multistage sampling was employed in randomly selecting six kebeles (the lowest administrative unit) with respective gotes (small villages) and households. All members of the selected households were invited to participate in the study and participants who were available in all three surveys formed a cohort. RESULTS: Scabies prevalence was similar prior to the MDA (13.4%, 95% CI 11.7 to 15.2%) and 6 months after (11.7%, 95% CI 10.1 to 13.2%) but was substantially greater at 12 months (22.1%, 95% CI 20.1 to 24.1%). The 6-month incidence and disappearance rates were 10.8% (95% CI 8.8 to 13.2%) and 82.6% (95% CI 75.0 to 88.6%), respectively. CONCLUSIONS: Ivermectin MDA for onchocerciasis was not observed to have a secondary impact on the prevalence of scabies over the follow-up period of 12 months.

Health service needs and perspectives of a rainforest conserving community in Papua New Guinea's Ramu lowlands: a combined clinical and rapid anthropological assessment with parallel treatment of urgent cases.

OBJECTIVES: Determine community needs and perspectives as part of planning health service incorporation into Wanang Conservation Area, in support of locally driven sustainable development. DESIGN: Clinical and rapid anthropological assessment (individual primary care assessments, key informant (KI) interviews, focus groups (FGs), ethnography) with treatment of urgent cases. SETTING: Wanang (pop. c189), a rainforest community in Madang province, Papua New Guinea. PARTICIPANTS: 129 villagers provided medical histories (54 females (f), 75 males (m); median 19 years, range 1 month to 73 years), 113 had clinical assessments (51f, 62m; median 18 years, range 1 month to 73 years). 26 ≥18 years participated in sex-stratified and age-stratified FGs (f<40 years; m<40 years; f>40 years; m>40 years). Five KIs were interviewed (1f, 4m). Daily ethnographic fieldnotes were recorded. RESULTS: Of 113 examined, 11 were 'well' (a clinical impression based on declarations of no current illness, medical histories, conversation, no observed disease signs), 62 (30f, 32m) were treated urgently, 31 referred (15f, 16m), indicating considerable unmet need. FGs top-4 ranked health issues concorded with KI views, medical histories and clinical examinations. For example, ethnoclassifications of three ((A) 'malaria', (B) 'sotwin', (C) 'grile') translated to the five biomedical conditions diagnosed most ((A) malaria, 9 villagers; (B) upper respiratory infection, 25; lower respiratory infection, 10; tuberculosis, 9; (C) tinea imbricata, 15) and were highly represented in declared medical histories ((A) 75 participants, (B) 23, (C) 35). However, 29.2% of diagnoses (49/168) were limited to one or two people. Treatment approaches included plant medicines, stored pharmaceuticals, occasionally rituals. Travel to hospital/pharmacy was sometimes undertaken for severe/refractory disease. Service barriers included: no health patrols/accessible aid post, remote hospital, unfamiliarity with institutions and medicine costs. Service introduction priorities were: aid post, vaccinations, transport, perinatal/birth care and family planning. CONCLUSIONS: This study enabled service planning and demonstrated a need sufficient to acquire funding to establish primary care. In doing so, it aided Wanang's community to develop sustainably, without sacrificing their forest home.

Scabies in the Amhara region of northern Ethiopia: a cross-sectional study of prevalence, determinants, clinical presentation and community knowledge.

BACKGROUND: The WHO aims to prevent, eliminate or control neglected tropical diseases, including scabies, by 2030. However, limited epidemiological data presented a challenge to control efforts, especially in high burden countries. There was a major scabies outbreak in northern Ethiopia starting in 2015 and prevalence has since increased across much of the country. OBJECTIVE: To estimate scabies prevalence, identify its predictors, and assess community perception of, and knowledge about, the infestation. DESIGN: Population-based cross-sectional study. STUDY SETTING: Ayu Guagusa district, Amhara region, northern Ethiopia. PARTICIPANTS: 1437 people who were members of 381 randomly selected households participated in the study. Five trained mid-level health workers clinically diagnosed people with scabies. OUTCOME MEASURES: Clinically diagnosed scabies infestation. DATA ANALYSIS: Multi-level logistic regression models were fitted to adjust for individual and household-level confounding variables, and identify predictors of scabies infestation. RESULTS: Scabies prevalence was 13.4% (95% CI 11.8 to 15.5). Households of more than five people (adjusted OR (aOR)=3.5, 95% CI 1.2 to 10.2) were associated with increased odds of developing scabies, however, females had lower odds (aOR=0.5 95% CI 0.3 to 0.8). Scabietic lesions most frequently involved the trunk (62.0%), and vesicles were the most common types of lesions (67.7%). Two-thirds of adult study participants had heard about scabies and most obtained scabies related information from informal sources. Only 32% of cases sought care for scabies from any source. CONCLUSION: Scabies prevalence was high, signifying the need for community-based control interventions. Host density and sex were important predictors of scabies. Despite the favourable attitude toward the effectiveness of scabies treatment, healthcare seeking was low.

A systematic literature review on the clinical efficacy of low dose naltrexone and its effect on putative pathophysiological mechanisms among patients diagnosed with fibromyalgia.

Background: Low dose naltrexone (LDN) is used off-label by many individuals with fibromyalgia to help manage their pain. There is no current systematic literature review summarising the evidence to support this use of LDN. The objectives of this study were to evaluate if patients with fibromyalgia prescribed LDN have reduced pain scores and greater quality of life compared with those allocated to placebo in randomized controlled trials. Secondly to determine if changes in inflammatory markers and brain structure and function are observed among patients with fibromyalgia taking LDN. Methods: Systematic literature searches were conducted in MEDLINE, Embase Classic + Embase, APA PsychInfo, and The Cochrane Library from inception to May 2022. Reference lists from the selected papers were cross-checked with database search results. Results: Three studies met our inclusion criteria for the assessment of efficacy, and two studies on potential LDN mechanisms. Results indicated some evidence to suggest LDN reduces pain and increases quality of life. One study reported baseline erythrocyte sedimentation rate (ESR) predicted LDN response (≥30% reduction in fibromyalgia symptoms) and a second study showed plasma concentrations of inflammatory biomarkers were lower after LDN treatment. To our knowledge, there are no brain imaging studies reporting the effect of LDN in patients with fibromyalgia. All studies were based on small sample sizes, were restricted to women and the risk of bias was assessed to be high. There is also some evidence of publication bias. Conclusion: The strength of evidence from randomized controlled trials to support the use of LDN among patients with fibromyalgia is low. Two small studies suggest ESR and cytokines may be involved in the mechanism by which LDN exerts its effects. Two trials (INNOVA and FINAL) are currently in progress, but further work is needed among men and different ethnic groups.

Positive Outcomes: Validity, reliability and responsiveness of a novel person-centred outcome measure for people with HIV.

OBJECTIVES: Despite successful treatment, people living with HIV experience persisting and burdensome multidimensional problems. We aimed to assess the validity, reliability and responsiveness of Positive Outcomes, a patient-reported outcome measure for use in clinical practice. METHODS: In all, 1392 outpatients in five European countries self-completed Positive Outcomes, PAM-13 (patient empowerment), PROQOL-HIV (quality of life) and FRAIL (frailty) at baseline and 12 months. Analysis assessed: (a) validity (structural, convergent and divergent, discriminant); (b) reliability (internal consistency, test-retest); and (c) responsiveness. RESULTS: An interpretable four-factor structure was identified: 'emotional wellbeing', 'interpersonal and sexual wellbeing', 'socioeconomic wellbeing' and 'physical wellbeing'. Moderate to strong convergent validity was found for three subscales of Positive Outcomes and PROQOL (ρ = -0.481 to -0.618, all p < 0.001). Divergent validity was found for total scores with weak ρ (-0.295, p < 0.001). Discriminant validity was confirmed with worse Positive Outcomes score associated with increasing odds of worse FRAIL group (4.81-fold, p < 0.001) and PAM-13 level (2.28-fold, p < 0.001). Internal consistency for total Positive Outcomes and its factors exceeded the conservative α threshold of 0.6. Test-retest reliability was established: those with stable PAM-13 and FRAIL scores also reported median Positive Outcomes change of 0. Improved PROQOL-HIV score baseline to 12 months was associated with improved Positive Outcomes score (r = -0.44, p < 0.001). CONCLUSIONS: Positive Outcomes face and content validity was previously established, and the remaining validity, reliability and responsiveness properties are now demonstrated. The items within the brief 22-item tool are designed to be actionable by health and social care professionals to facilitate the goal of person-centred care.

Statistical analysis plan for the Early Youth Engagement in first episode psychosis (EYE-2) study: a pragmatic cluster randomised controlled trial of implementation, effectiveness and cost-effectiveness of a team-based motivational engagement intervention to improve engagement.

BACKGROUND: Early Intervention in Psychosis (EIP) services improve health outcomes for young people with psychosis in the medium-long term, but 25% of young people disengage in the first 12 months with costs to their mental health, families, society and health services. This study will evaluate the effectiveness of a team-based motivational engagement intervention, the Early Youth Engagement (EYE-2) intervention. METHODS AND DESIGN: The EYE-2 trial is a cluster randomised controlled trial comparing the EYE-2 intervention plus standardised EIP service to standardised EIP service alone, with randomisation at the clinical team (cluster) level. The study aimed to enrol 950 young people (aged 14-35 years) with first episode psychosis in 10 teams per arm. RESULTS: The primary outcome is time to disengagement: days from the date of allocation to care coordinator to date of the last contact following either refusal to engage with an EIP team or lack of response to EIP contact for 3 consecutive months which will be analysed using a shared frailty model. Secondary outcomes are Health of the Nation Outcome Scale (HoNOS), Process of Recovery Questionnaire (QPR), DIALOG (a service user-reported measure of quality of life and treatment satisfaction) and service use outcomes which will be analysed using mixed effects regression models. DISCUSSION: This paper is the detailed statistical analysis plan for the EYE-2 trial. Any changes to, or deviations from, this plan will be described and justified in the final trial report. TRIAL REGISTRATION: ISRCTN 51629746 . Prospectively registered on 7 May 2019. Date assigned 10 May 2019.

EmERGE mHealth Platform: Implementation and Technical Evaluation of a Digital Supported Pathway of Care for Medically Stable HIV.

In this article, we described a new mobile-Health (mHealth) supported clinical pathway of care for people living with medically stable HIV in terms of platform acceptability, usability and technical feasibility. The EmERGE mHealth platform was codesigned with clinicians and the community, developed using Scrum agile methodology, integrated with hospital information systems and validated in a large prospective cohort study of 2251 participants. The evaluation of this new paradigm of care was conducted using a tailored Health Technology Assessment: the Model for Assessment of Telemedicine Applications. Usability and acceptability were assessed through the System Usability Score and a Patient Reported Experience Measure. The EmERGE platform was successfully deployed across diverse care settings in five European countries and used by 2251 patients and more than 20 clinicians for up to 30 months. Results from the formal evaluation demonstrated that the EmERGE platform is feasible and acceptable, with a high level of usability (median System Usability Score (SUS) 85.0%) and very positive patient-reported experiences (94.2% would recommend to a friend). The EmERGE platform is a secure and General Data Protection Regulation (GDPR)-compliant system with a complete set of functionalities that could be easily adapted to other clinical conditions, clinical sites and health systems thanks to its modular technical architecture.

Health service needs and perspectives of remote forest communities in Papua New Guinea: study protocol for combined clinical and rapid anthropological assessments with parallel treatment of urgent cases.

INTRODUCTION: Our project follows community requests for health service incorporation into conservation collaborations in the rainforests of Papua New Guinea (PNG). This protocol is for health needs assessments, our first step in coplanning medical provision in communities with no existing health data. METHODS AND ANALYSIS: The study includes clinical assessments and rapid anthropological assessment procedures (RAP) exploring the health needs and perspectives of partner communities in two areas, conducted over 6 weeks fieldwork. First, in Wanang village (population c.200), which is set in lowland rainforest. Second, in six communities (population c.3000) along an altitudinal transect up the highest mountain in PNG, Mount Wilhelm. Individual primary care assessments incorporate physical examinations and questioning (providing qualitative and quantitative data) while RAP includes focus groups, interviews and field observations (providing qualitative data). Given absence of in-community primary care, treatments are offered alongside research activity but will not form part of the study. Data are collected by a research fellow, primary care clinician and two PNG research technicians. After quantitative and qualitative analyses, we will report: ethnoclassifications of disease, causes, symptoms and perceived appropriate treatment; community rankings of disease importance and service needs; attitudes regarding health service provision; disease burdens and associations with altitudinal-related variables and cultural practices. To aid wider use study tools are in online supplemental file, and paper and ODK versions are available free from the corresponding author. ETHICS AND DISSEMINATION: Challenges include supporting informed consent in communities with low literacy and diverse cultures, moral duties to provide treatment alongside research in medically underserved areas while minimising risks of therapeutic misconception and inappropriate inducement, and PNG research capacity building. Brighton and Sussex Medical School (UK), PNG Institute of Medical Research and PNG Medical Research Advisory Committee have approved the study. Dissemination will be via journals, village meetings and plain language summaries.

Excess mortality among people with podoconiosis: secondary analysis of two Ethiopian cohorts.

BACKGROUND: While morbidity attributable to podoconiosis is relatively well studied, its pattern of mortality has not been established. METHODS: We compared the age-standardised mortality ratios (SMRs) of two datasets from northern Ethiopia: podoconiosis patients enrolled in a 1-y trial and a Health and Demographic Surveillance System cohort. RESULTS: The annual crude mortality rate per 1000 population for podoconiosis patients was 28.7 (95% confidence interval [CI] 17.3 to 44.8; n=663) while that of the general population was 2.8 (95% CI 2.3 to 3.4; n=44 095). The overall SMR for the study period was 6.0 (95% CI 3.6 to 9.4). CONCLUSIONS: Podoconiosis patients experience elevated mortality compared with the general population and further research is required to understand the reasons.

A randomised controlled trial of a telephone administered brief HIV risk reduction intervention amongst men who have sex with men prescribed post-exposure prophylaxis for HIV after sexual exposure in the UK: Project PEPSE.

BACKGROUND: In western countries, men who have sex with men (MSM) are most affected by HIV and increasingly likely to engage in risky sexual behaviour. MSM who experience a potential sexual exposure to HIV (PEPSE) and receive a preventative regimen of anti-HIV treatment are at particularly high risk of acquiring HIV and could potentially benefit from targeted risk reduction behavioural interventions such as motivational interviewing (MI). PURPOSE: The aim of this trial was to examine the impact of augmented MI (MI plus information provision and behavioural skills building), over and above routine care, on reducing risky sexual behaviour in MSM prescribed PEPSE. Secondary aims of the research were to examine whether the intervention reduced sexually transmitted infections (STI) and further requests for PEP. METHODS: A parallel-group pragmatic randomised controlled trial was conducted with 175 MSM recruited from five sexual health (SH) clinics in the south east of England. The intervention was two fixed-duration sessions of telephone administered augmented MI. A manual guided the selection of individualised persuasive communication strategies based on underlying change mechanisms specified by the Information, Motivation and Behavioural Skills (IMB) model. Primary outcomes were the number of receptive and active anal intercourse (AI) partners, the use of condoms every time during receptive and active AI and the use of condoms sometimes during receptive and active AI. RESULTS: There were no significant impacts on sexual risk behaviour or any of the psychological measures, and no discernible reduction in requests for repeat PEP or rates of STIs within a year. CONCLUSION: Our behavioural intervention of augmented MI did not affect risky sexual behaviour, rates of further PEP and STIs, and psychological factors, in MSM prescribed PEPSE. TRIAL REGISTRATION NUMBERS: UKCRN ID:11436; ISRCTN00746242.

Galvanic Skin Response (GSR)/Electrodermal/Skin Conductance Biofeedback on Epilepsy: A Systematic Review and Meta-Analysis.

Objectives: Dynamic changes in psychophysiological arousal are directly expressed in the sympathetic innervation of the skin. This activity can be measured as tonic and phasic fluctuations in electrodermal activity [Galvanic Skin Response (GSR)/skin conductance]. Biofeedback training can enable an individual to gain voluntary control over this autonomic response and its central correlates. Theoretically, control of psychophysiological arousal may be harnessed as a therapy for epilepsy, to mitigate pre-ictal states. Evidence is accumulating for the clinical efficacy of GSR biofeedback training in the management of drug resistant epilepsy. In this review, we analyse current evidence of efficacy with GSR biofeedback and evaluate the methodology of each study. Method: We searched published literature pertaining to interventional studies of GSR biofeedback for epilepsy, through MEDLINE and Cochrane databases (1950-2018). Using percentage seizure reduction as an indicator of therapeutic efficacy induced by GSR biofeedback, we used meta-analytic methods to summarize extant findings. We also compare and contrast study design with relevance to the interpretation of outcomes. Results: Out of 21 articles retrieved for GSR/EDA/Skin conductance biofeedback, four studies were identified as interventional trials, involving 99 patients with drug-resistant epilepsy in total. Three of these studies included a control group and a positive therapeutic effect of biofeedback was reported in each of these. The difference in seizure frequency percentage (Biofeedback-Control) was between -54.4 and -74.0% with an overall weighted mean difference of -64.3% (95% CI: -85.4 to -43.2%). The response rates (proportion of patients manifesting >50% reduction in seizure frequency) varied from 45 to 66% across studies. Significance: This timely evaluation highlights the potential value of GSR biofeedback therapy, and informs the optimal study design of larger scale studies that are now required to more definitively establish the utility of this non-invasive, non-pharmacological interventional approach for drug-resistant epilepsy.

Scabies outbreaks in ten care homes for elderly people: a prospective study of clinical features, epidemiology, and treatment outcomes.

BACKGROUND: Scabies outbreaks in residential and nursing care homes for elderly people are common, subject to diagnostic delay, and hard to control. We studied clinical features, epidemiology, and outcomes of outbreaks in the UK between 2014 and 2015. METHODS: We did a prospective observational study in residential care homes for elderly people in southeast England that reported scabies outbreaks to Public Health England health protection teams. An outbreak was defined as two or more cases of scabies (in either residents or staff) at a single care home. All patients who provided informed consent were included; patients with dementia were included if a personal or nominated consultee (ie, a family member or nominated staff member) endorsed participation. Dermatology-trained physicians examined residents at initial clinical visits, which were followed by two mass treatments with topical scabicide as per local health protection team guidance. Follow-up clinical visits were held 6 weeks after initial visits. Scabies was diagnosed through pre-defined case definitions as definite, probable, or possible with dermatoscopy and microscopy as appropriate. FINDINGS: 230 residents were examined in ten outbreaks between Jan 23, 2014, and April 13, 2015. Median age was 86·9 years (IQR 81·5-92·3), 174 (76%) were female, and 157 (68%) had dementia. 61 (27%) residents were diagnosed with definite, probable, or possible scabies, of whom three had crusted scabies. Physical signs differed substantially from classic presentations. 31 (51%) of the 61 people diagnosed with scabies were asymptomatic, and only 25 (41%) had burrows. Mites were visualised with dermatoscopy in seven (11%) patients, and further confirmed by microscopy in three (5%). 35 (57%) cases had signs of scabies only on areas of the body that would normally be covered. Dementia was the only risk factor for a scabies diagnosis that we identified (odds ratio 2·37 [95% CI 1·38-4·07]). At clinical follow-up, 50 people who were initially diagnosed with scabies were examined. No new cases of scabies were detected, but infestation persisted in ten people. INTERPRETATION: Clinical presentation of scabies in elderly residents of care homes differs from classic descriptions familiar to clinicians. This difference probably contributes to delayed recognition and suboptimal management in this vulnerable group. Dermatoscopy and microscopy were of little value. Health-care workers should be aware of the different presentation of scabies in elderly people, and should do thorough examinations, particularly in people with dementia. FUNDING: Public Health England and British Skin Foundation.

The 5' → 3' exoribonuclease XRN1/Pacman and its functions in cellular processes and development.

XRN1 is a 5' → 3' processive exoribonuclease that degrades mRNAs after they have been decapped. It is highly conserved in all eukaryotes, including homologs in Drosophila melanogaster (Pacman), Caenorhabditis elegans (XRN1), and Saccharomyces cerevisiae (Xrn1p). As well as being a key enzyme in RNA turnover, XRN1 is involved in nonsense-mediated mRNA decay and degradation of mRNAs after they have been targeted by small interfering RNAs or microRNAs. The crystal structure of XRN1 can explain its processivity and also the selectivity of the enzyme for 5' monophosphorylated RNA. In eukaryotic cells, XRN1 is often found in particles known as processing bodies (P bodies) together with other proteins involved in the 5' → 3' degradation pathway, such as DCP2 and the helicase DHH1 (Me31B). Although XRN1 shows little specificity to particular 5' monophosphorylated RNAs in vitro, mutations in XRN1 in vivo have specific phenotypes suggesting that it specifically degrades a subset of RNAs. In Drosophila, mutations in the gene encoding the XRN1 homolog pacman result in defects in wound healing, epithelial closure and stem cell renewal in testes. We propose a model where specific mRNAs are targeted to XRN1 via specific binding of miRNAs and/or RNA-binding proteins to instability elements within the RNA. These guide the RNA to the 5' core degradation apparatus for controlled degradation.