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Background Hepatitis C virus (HCV) is a genetically diverse blood-borne pathogen causing liver inflammation and damage. It is one of the global public health problems responsible for claiming thousands of lives every year. Although there are various HCV testing strategies depending on the specific circumstances and guidance of local authorities, the proportion of diagnosed HCV cases in Low- and Middle-Income Countries (LMICs) is estimated to be less than 5%. This review analyzes and documents evidence for different ways of screening HCV. Methods The updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines have been used as the basis for this scoping review. Retrieved articles were screened and extracted by three independent individuals to make sure that all pertinent literatures were included. Results A total of 8318 records were retrieved from four electronic databases (Scopus, PubMed, CINAHL and Google Scholar). Of the total retrieved records and after applying the pre-defined inclusion criteria, we included 51 studies in this review. According to the studies included in this review, three major screening approaches were noted: The universal, targeted, and risk-based HCV screening strategies. Population to screen include the baby boomer cohort, pregnant women, key populations, those experiencing homelessness, adults visiting health facilities, employees, and social event attendants. A “one-stop-shop” HCV testing initiative at different settings, such as prisons, addiction rehabilitation centers, and community dropping centers, were found to increase HCV test uptake among key populations. Integrating HCV screening with the existing HIV and Sexually Transmitted Infection (STI) clinics was highlighted to identifying and linking HCV-infected individuals to appropriate care and treatment. Although there are many ways of diagnosing HCV for treatment, identifying those who were reactive for HCV antibody first, followed by an HCV-antigen test for those antibody-positive, were found to be the most cost-efficient way of diagnosing HCV infection. Conclusion HCV screening among pregnant women, the baby boomer cohort, adults visiting health facilities, engaging in injection drug use, incarcerated individuals, and those experiencing homelessness are useful approaches in identifying HCV-antibody positive individuals. An efficient way to reach the most at-risk people is to incorporate HCV screening into community service centers and clinics.

Background Hepatitis C Virus (HCV) is a public health threat which contributes substantially to the global burden of liver disease. There is much debate about effective approaches to scaling up diagnosis of HCV among risk groups. Tayside, a region in the East of Scotland, developed low-threshold community pathways for HCV to lay the foundations of an elimination strategy. In this retrospective study, we sought to: quantify the contribution of community pathways to increasing HCV diagnosis; understand if shifting diagnosis to community settings led to a higher proportion of individuals tested for HCV being actively infected; and describe functional characteristics of the care pathways. Methods Descriptive statistics were used to for analysis of routinely-collected HCV testing data from 1999 to 2017, and a review of the development of the care pathways was undertaken. Community-based testing was offered through general practices (GP); nurse outreach clinics; prisons; drug treatment services; needle and syringe provision (NSP) sites; community pharmacies; and mosques. Results Anti-HCV screening was undertaken on 109,430 samples, of which 5176 (4.7%) were reactive. Of all samples, 77,885 (71.2%) were taken in secondary care; 25,044 (22.9%) in GPs; 2970 (2.7%) in prisons; 2415 (2.2%) in drug services; 753 (0.7%) in NSPs; 193 (0.2%) pharmacies; and 170 (0.1%) in mosques. The highest prevalence of HCV infection among those tested was in NSP sites (26%), prisons (14%), and drug treatment centres (12%). Conclusions Decentralised care pathways, particularly in harm reduction and other drug service settings, were key to increasing diagnosis of HCV in the region, but primary and secondary care remain central to elimination efforts.

Background Community pharmacists are the most publicly accessible health professionals in high-income countries. There is increasing interest in conducting randomised controlled trials (RCT)—the benchmark of original evidence in the medical field—in community pharmacies. However, little evidence exists examining the challenges and opportunities of conducting RCTs in pharmacies, particularly with respect to project management. In this work, we aim to provide a narrative of lessons learned in conducting two RCTs in community pharmacies in two high-income countries. Methods We retrospectively reviewed multiple data sources including administrative and trial activity records. We conducted face-to-face and online sessions to create a list of lessons learned from our experiences and created a stakeholder map for the trials examined. We framed our findings using the Project Managements Institute’s model of the project life cycle, and descriptive statistics were used to estimate the outcomes reported. Results Ninety-six pharmacies were recruited. Across the project phases, seven high-level tasks within Initiation; 30 within Planning, 43 within Execution/Monitoring and Controlling, and 14 in Closure, were identified. Recruitment of pharmacies, developing documentation for trial drug supply, participant recruitment, and negotiation with pharmacy contracting bodies took longest to complete. Eight key stakeholder groups were identified, including public services/agencies; community pharmacies, communications actors; funders/sponsors; universities/research institutes; healthcare providers; suppliers; and regulators. Thirty lessons were identified, most critically across engaging and managing stakeholders; selecting and supporting trial sites; streamlining trial processes to minimise burden; optimising data collection and accuracy; and considering pharmacy constraints and costs. Conclusions Conducting RCTs in community pharmacies presents unique challenges across the project life cycle. Key lessons include the importance of early planning, streamlining processes to reduce staff burden, and addressing pharmacy constraints. The complexity of the work necessitates dedicated and well-resourced trial management staff to enhance stakeholder management and offer tailored supports where required. Trial registration. Not applicable.

IntroductionHepatitis C is a blood-borne virus (HCV) that can seriously damage the liver and is spread mainly through blood-to-blood contact with an infected person. Over 85% of individuals who have HCV in Scotland became infected following injecting drug use. Since people who inject drugs (PWID) are the main source of new infections, theoretical modelling has suggested that treatment of HCV infection in PWID may effectively reduce HCV prevalence and accomplish elimination. This protocol describes a clinical trial delivering HCV treatment within injecting equipment provision sites (IEPS) in Tayside, Scotland.Methods and analysisPWID attending IEPS are tested for HCV and, if they are chronically infected with HCV and eligible, invited to receive treatment within the IEPS. They are randomised to one of three treatment regimens; daily observed treatment, treatment dispensed every 2 weeks and treatment dispensed every 2 weeks together with an adherence psychological intervention (administered before treatment begins). The primary outcome is comparison of the rate of successful treatment (SVR12) in each treatment group. Secondary analyses include assessment of adherence, reinfection rates, viral resistance to treatment and interaction of the treatment with illicit drugs.Ethics and disseminationThe ADVANCE (A Direct obserVed therApy versus fortNightly CollEction) HCV trial was given favourable opinion by East of Scotland Research Ethics Committee (LR/17/ES/0089) prior to commencement.Trial registration numbersEuropean Clinical Trials Database (EudraCT) (2017-001039-38) and ClinicalTrials.gov (NCT03236506).

ObjectiveHousehold damp exposure is an important public health issue. We aimed to assess the impact of the location of household damp on respiratory outcomes during early life.MethodsHousehold damp exposure was ascertained in children recruited to the GO-CHILD multicentre birth cohort study. The frequency of respiratory symptoms, infections, healthcare utilisation and medication prescription for wheezing were collected by postal questionnaires at 12 and 24 months. Log binomial and ordered logistic regression models were fitted to the data.ResultsFollow-up was obtained in 1344 children between August 2010 and January 2016. Visible damp was present in a quarter of households (25.3%) with 1 in 12 children’s bedrooms affected (8.3%). Damp in the bathroom, kitchen or living room was not associated with any respiratory or infection-related outcomes. Damp in the child’s bedroom was associated with an increased risk of dry cough (8.7% vs 5.7%) (adjusted relative risk 1.56, 95% CI 1.07 to 2.27; p=0.021) and odds of primary care attendance for cough and wheeze (7.6% vs 4.4%) (adjusted OR 1.37, 95% CI 1.07 to 1.76; p=0.009). There were also increased risk of inhaled corticosteroid (13.3% vs 5.9%) (adjusted RR 2.22, 95% CI 1.04 to 4.74; p=0.038) and reliever inhaler (8.3% vs 5.8%) (adjusted RR 2.01, 95% CI 1.21 to 2.79; p=0.018) prescription.ConclusionDamp in the child’s bedroom was associated with increased respiratory morbidity. In children presenting with recurrent respiratory symptoms, clinicians should enquire about both the existence and location of damp, the presence of which can help prioritise those families requiring urgent household damp assessment and remediation works.

IntroductionHepatitis C virus (HCV) infection affects 0.7% of the general population, and up to 40% of people prescribed opioid substitution therapy (OST) in Scotland. In conventional care, less than 10% of OST users are tested for HCV and less than 25% of these initiate treatment. Community pharmacists see this group frequently to provide OST supervision. This study examines whether a pharmacist-led ‘test & treat’ pathway increases cure rates for HCV.Methods and analysisThis protocol describes a cluster-randomised trial where 60 community pharmacies provide either conventional or pharmacy-led care. All pharmacies offer dried blood spot testing (DBST) for HCV. Participants have attended the pharmacy for OST for 3 months; are positive for HCV genotype 1 or 3; are not co-infected with HIV and/or hepatitis B; have no decompensated liver disease; are not pregnant. For conventional care, pharmacists refer HCV-positive participants to a local centre for assessment. In the pharmacy-led arm, pharmacists assess participants themselves in the pharmacy. Drug prescribing is by nurse prescribers (conventional arm) or pharmacist prescribers (pharmacy-led arm). Treatment in both arms is delivered as daily modified directly observed therapy in a pharmacy. Primary trial outcome is number of sustained virological responses at 12 weeks after treatment completion. Secondary trial outcomes are number of tests taken; treatment uptake; completion; adherence; re-infection. An economic evaluation will assess potential cost-effectiveness. Qualitative research interviews with clients and health professionals assess acceptability of a pharmacist-led pathway.Ethics and disseminationThis protocol has been ethically approved by the East of Scotland Research Ethics Committee 2 (15/ES/0086) and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Caldicott guardian approval was given on 16 December 2016 to allow NHS Tayside to pass information to the cluster community pharmacies about the HCV test status of patients that they are seeing to provide OST supervision. NHS R&D approvals have been obtained from each health board taking part in the study. Informed consent is obtained before study enrolment and only anonymised data are stored in a secured database, enabling an audit trail. Results will be submitted to international peer-reviewed journals and presented at international conferences.Trial registration number NCT02706223; Pre-results.

P2Y receptor agonists stimulate Cl- secretion across both normal and cystic fibrosis (CF) airway epithelia, and therefore have potential for use in the treatment of CF. Although CF pathology is manifest primarily in the distal airways, most studies of P2Y-receptor-mediated airway epithelial ion transport have used cells cultured from proximal regions. Here we report the results of studies of P2Y-receptor-mediated ion transport in distal bronchi isolated from porcine lungs, cannulated and perfused. A luminal microelectrode was used to record transepithelial potential difference (PD) and cable analysis was applied to determine resistance (Rt) and equivalent short-circuit current (I(SC)). Luminal UTP (100 micromol/l) transiently hyperpolarized PD (from -5.8+/-0.3 to -6.5+/-0.4 mV) and increased I(SC) (from 47+/-6 to 55+/-8 microA cm(-2)) before inhibiting PD to below the pre-UTP level (-5.0+/-0.4 mV). The decline was attenuated by pretreatment with amiloride, and additional treatment with bumetanide inhibited the initial hyperpolarization, suggesting that UTP stimulates Cl- secretion and inhibits Na+ absorption across distal bronchi. Luminal addition of P2Y1 [ADP, 2-methylthio-ATP (2MeSATP)] and P2Y6 (UDP) receptor agonists had no effect on ion transport. Pretreatment with thapsigargin (0.3 micromol/l) did not prevent the UTP-induced increase in PD and I(SC) but attenuated the secondary fall in PD. Pretreatment with BAPTA/AM (50 micromol/l), however, had no effect on the response to UTP. Additional studies of isolated bronchial epithelial cells using Fura-2 showed that UTP increases [Ca2+]in, and this increase is blocked by pretreatment with thapsigargin. These results suggest that in intact distal bronchi luminal UTP stimulates Cl- secretion by a Ca2+-independent mechanism and inhibits Na+ absorption by a Ca2+-dependent mechanism. Both effects are likely to favour increased hydration of the airway surface, and may therefore be beneficial in CF.

Transmission of SARS-CoV-2 is uncontrolled in many parts of the world; control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant 1 , which has now been reported in 94 countries. It is unclear whether the response of the virus to vaccines against SARS-CoV-2 on the basis of the prototypic strain will be affected by the mutations found in B.1.1.7. Here we assess the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b2 2 . We measured neutralizing antibody responses after the first and second immunizations using pseudoviruses that expressed the wild-type spike protein or a mutated spike protein that contained the eight amino acid changes found in the B.1.1.7 variant. The sera from individuals who received the vaccine exhibited a broad range of neutralizing titres against the wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant. This reduction was also evident in sera from some patients who had recovered from COVID-19. Decreased neutralization of the B.1.1.7 variant was also observed for monoclonal antibodies that target the N-terminal domain (9 out of 10) and the receptor-binding motif (5 out of 31), but not for monoclonal antibodies that recognize the receptor-binding domain that bind outside the receptor-binding motif. Introduction of the mutation that encodes the E484K substitution in the B.1.1.7 background to reflect a newly emerged variant of concern (VOC 202102/02) led to a more-substantial loss of neutralizing activity by vaccine-elicited antibodies and monoclonal antibodies (19 out of 31) compared with the loss of neutralizing activity conferred by the mutations in B.1.1.7 alone. The emergence of the E484K substitution in a B.1.1.7 background represents a threat to the efficacy of the BNT162b2 vaccine. Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Current protocols using liquid disinfectants to disinfect heat-sensitive hospital items frequently fail, as evidenced by the continued isolation of bacteria following decontamination. The contamination is, in part, due to biofilm formation. We hypothesize that mild positive pressure (PP) will disrupt this biofilm structure and improve liquid disinfectant/detergent penetration to biofilm bacteria for improved killing. Staphylococcus aureus biofilm, grown on polycarbonate coupons in the biofilm reactor under shear at 35 °C for 3 days, was treated for 10 min and 60 min with various dilutions of benzalkonium chloride without PP at 1 atmosphere (atm), and with PP at 3, 5, 7, and 10 atm. The effect on biofilm and residual bacterial viability was determined by standard plate counts, confocal laser scanning microscopy, and scanning electron microscopy. Combined use of benzalkonium chloride and PP up to 10 atm significantly increased biofilm killing up to 4.27 logs, as compared to the treatment using disinfectant alone. Microscopy results were consistent with the viability plate count results. PP improved disinfectant efficacy against bacterial biofilm. The use of mild PP is possible in many flow situations or if equipment/contaminated surfaces can be placed in a pressure chamber.

Purpose Many survivors of rectal cancer experience persistent bowel dysfunction. There are few evidence-based symptom management interventions to improve bowel control. The purpose of this study is to describe recruitment and pre-randomization baseline sociodemographic, health status, and clinical characteristics for SWOG S1820, a trial of the Altering Intake, Managing Symptoms in Rectal Cancer (AIMS-RC) intervention. Methods SWOG S1820 aimed to determine the preliminary efficacy, feasibility, and acceptability of AIMS-RC, a symptom management intervention for bowel health, comparing intervention to attention control. Survivors with a history of cancers of the rectosigmoid colon or rectum, within 6–24 months of primary treatment completion, with a post-surgical permanent ostomy or anastomosis, and over 18 years of age were enrolled. Outcomes included total bowel function, low anterior resection syndrome, quality of life, motivation for managing bowel health, self-efficacy for managing symptoms, positive and negative affect, and study feasibility and acceptability. Results The trial completed accrual over a 29-month period and enrolled 117 participants from 34 institutions across 17 states and one US Pacific territory. At baseline, most enrolled participants reported self-imposed diet adjustments after surgery, persistent dietary intolerances, and bowel discomfort post-treatment, with high levels of constipation and diarrhea (grades 1–4). Conclusions SWOG S1820 was able to recruit, in a timely manner, a study cohort that is demographically representative of US survivors of rectal cancer. Baseline characteristics illustrate the connection between diet/eating and bowel symptoms post-treatment, with many participants reporting diet adjustments and persistent inability to be comfortable with dietary intake. ClinicalTrials.gov registration date 12/19/2019. ClinicalTrials.gov Identifier NCT#04205955.