Description: Although patient and public involvement in research is a requirement for research funding in many countries, the knowledge base for how to effectively involve people—and evidence of the effectiveness of involvement—is weak. This article describes how methods used in participatory health research were used to involve patients, clients, providers and community health workers across all stages of a realist review. Sustained involvement enabled better identification of the components of the complex intervention of community-based peer support. It also challenged assumptions of how peer support is constructed, leading the review team to question whether the process of designing and implementing interventions has more influence on effectiveness than previously recognised in empirical studies. We conclude with a discussion on when sustained involvement should be used, and the challenges of incorporating it into the traditional researcher-led approach to systematic reviews.

Description: Aims The WHO's draft HCV elimination targets propose an 80% reduction in incidence and a 65% reduction in HCV-related deaths by 2030. We estimate the treatment scale-up required and cost-effectiveness of reaching these targets among injecting drug use (IDU)-acquired infections using Australian disease estimates. Methods A mathematical model of HCV transmission, liver disease progression and treatment among current and former people who inject drugs (PWID). Treatment scale-up and the most efficient allocation to priority groups (PWID or patients with advanced liver disease) were determined; total healthcare and treatment costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) compared with inaction were calculated. Results 5662 (95% CI 5202 to 6901) courses per year (30/1000 IDU-acquired infections) were required, prioritised to patients with advanced liver disease, to reach the mortality target. 4725 (3278–8420) courses per year (59/1000 PWID) were required, prioritised to PWID, to reach the incidence target; this also achieved the mortality target, but to avoid clinically unacceptable HCV-related deaths an additional 5564 (1959–6917) treatments per year (30/1000 IDU-acquired infections) were required for 5 years for patients with advanced liver disease. Achieving both targets in this way cost $A4.6 ($A4.2–$A4.9) billion more than inaction, but gained 184 000 (119 000–417 000) QALYs, giving an ICER of $A25 121 ($A11 062–$A39 036) per QALY gained. Conclusions Achieving WHO elimination targets with treatment scale-up is likely to be cost-effective, based on Australian HCV burden and demographics. Reducing incidence should be a priority to achieve both WHO elimination goals in the long-term.

Description: We thank Dr Tseng and colleagues for their interest 1 in our recent study that identified a negative association between the presence of hepatitis B virus (HBV) basal core promoter (BCP)/precore (PC) and precore (PC) variants mutants at baseline and lower likelihood of hepatitis B surface antigen (HBsAg) loss among 157 subjects with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) treated for 4 years with tenofovir therapy. 2–4 The likelihood of HBsAg loss was 41% in subjects with wild-type (WT) sequence at the BCP/PC loci versus 3% in subjects with detectable BCP/PC variants (next generation sequencing (NGS), Illumina MiSeq—threshold for detection 〉1%). The cohort included subjects with a broad range of HBV genotypes (genotype A, n=36 (23%); genotype B, n=24 (15%); genotype C, n=51 (32%) and genotype D, n=46 (29%)). HBsAg loss was more common in subjects with genotype A/D (24%)...

Description: Massively parallel sequencing (MPS) technology has become routinely available for diagnosis, prognostication and therapeutic decision-making in haematological malignancies. However, increased throughput and wider coverage of genes can have unintended consequences. Germline variants of potential clinical significance (GVPCSs) detected during cancer testing may have implications for patients and families beyond the biological evaluation of a specific tumour. 721 reports generated from MPS panels used in the routine testing of myeloid and lymphoid malignancies were reviewed and variants within genes of potential germline relevance ( TP53 , RUNX1 , GATA2 and WT1 in all contexts and CBL , KRAS and NRAS in the setting of juvenile myelomonocytic leukaemia) were analysed. A variant allele fraction threshold of ≥33.09% for considering germline origin of variants within cancer samples was established. The detection rate of incidental, pathogenic germline variants was 0.42%. Patient education and confirmatory germline sample testing of GVPCSs in appropriate circumstances are recommended.

Description: The independent report into the deaths of about 600 patients at Gosport War Memorial Hospital in the 1990s is a wake-up call to every health professional.1 The families affected deserve more than for...

Description: Background This study evaluates changes in sales of non-alcoholic beverages in Jamie’s Italian, a national chain of commercial restaurants in the UK, following the introduction of a £0.10 per-beverage levy on sugar-sweetened beverages (SSBs) and supporting activity including beverage menu redesign, new products and establishment of a children’s health fund from levy proceeds. Methods We used an interrupted time series design to quantify changes in sales of non-alcoholic beverages 12 weeks and 6 months after implementation of the levy, using itemised electronic point of sale data. Main outcomes were number of SSBs and other non-alcoholic beverages sold per customer. Linear regression and multilevel random effects models, adjusting for seasonality and clustering, were used to investigate changes in SSB sales across all restaurants (n=37) and by tertiles of baseline restaurant SSB sales per customer. Results Compared with the prelevy period, the number of SSBs sold per customer declined by 11.0% (–17.3% to –4.3%) at 12 weeks and 9.3% (–15.2% to –3.2%) at 6 months. For non-levied beverages, sales per customer of children’s fruit juice declined by 34.7% (–55.3% to –4.3%) at 12 weeks and 9.9% (–16.8% to –2.4%) at 6 months. At 6 months, sales per customer of fruit juice increased by 21.8% (14.0% to 30.2%) but sales of diet cola (–7.3%; –11.7% to –2.8%) and bottled waters (–6.5%; –11.0% to –1.7%) declined. Changes in sales were only observed in restaurants in the medium and high tertiles of baseline SSB sales per customer. Conclusions Introduction of a £0.10 levy on SSBs alongside complementary activities is associated with declines in SSB sales per customer in the short and medium term, particularly in restaurants with higher baseline sales of SSBs.

Description: With rapid population growth, especially in low-income and middle-income countries, the generation of waste is increasing at an unprecedented rate. For example, annual global waste arising from waste electrical and electronic equipment alone will have increased from 33.8 to 49.8 million tonnes between 2010 and 2018. Despite incineration and other waste treatment techniques, landfill still dominates waste disposal in low-income and middle-income countries. There is usually insufficient funding for adequate waste management in these countries and uptake of more advanced waste treatment technologies is poor. Without proper management, many landfills represent serious hazards as typified by the landslide in Shenzhen, China on 20 December 2015. In addition to formal waste recycling systems, approximately 15million people around the world are involved in informal waste recycling, mainly for plastics, metals, glass and paper. This review examines emerging public health challenges, in particular within low-income and middle-income countries, associated with the informal sector. While informal recyclers contribute to waste recycling and reuse, the relatively primitive techniques they employ, combined with improper management of secondary pollutants, exacerbate environmental pollution of air, soil and water. Even worse, insufficient occupational health measures expose informal waste workers to a range of pollutants, injuries, respiratory and dermatological problems, infections and other serious health issues that contribute to low life expectancy. Integration of the informal sector with its formal counterparts could improve waste management while addressing these serious health and livelihood issues. Progress in this direction has already been made notably in several Latin American countries where integrating the informal and formal sectors has had a positive influence on both waste management and poverty alleviation.

Description: Objective Hepatitis B e antigen (HBeAg) seroconversion and hepatitis B surface antigen (HBsAg) loss are important clinical outcomes for patients with chronic hepatitis B (CHB) treated with antiviral therapy. To date, there have been few studies that have evaluated viral sequence markers predicting serological response to nucleos(t)ide analogue (NA) treatment. Design We used next-generation sequencing (NGS) and quantitative HBV serology (HBeAg and HBsAg) to identify viral sequence markers associated with serological response to long-term tenofovir disoproxil fumarate therapy among HBeAg-positive patients. In the GS-US-174-0103 study, approximately half the patients seroconverted to anti-HBe by week 192 and 11% of patients exhibited HBsAg loss, the closest outcome to functional cure. The frequency of HBV variants that have previously been associated with HBV clinical outcomes was evaluated. HBV viral diversity in baseline sequences generated by NGS was calculated using Shannon entropy. Results NGS analysis of HBV sequences from 157 patients infected with genotypes A to D showed the frequency of variants in the basal core promoter (BCP) and precore (PC) regions varied by genotype and that these mutations were associated with the absence of HBsAg loss. This was the case even when mutations were present at frequencies below the threshold of detection by population sequencing. Increased viral diversity across the HBV genome as determined by NGS was also associated with reduced likelihood of HBsAg loss. Conclusion Patients with detectable BCP and/or PC variants and higher viral diversity have a lower probability of HBsAg loss during long-term NA therapy. Strategies to achieve functional cure of HBV infection through combination therapy should consider using NGS to stratify patients according to BCP/PC sequence. Consideration should also be given to earlier initiation of therapy prior to the emergence of BCP/PC variants. Trial registration number NCT00116805; Post result.

Description: Background Over recent years genetic testing for germline mutations in BRCA1/BRCA2 has become more readily available because of technological advances and reducing costs. Objective To explore the feasibility and acceptability of offering genetic testing to all women recently diagnosed with epithelial ovarian cancer (EOC). Methods Between 1 July 2013 and 30 June 2015 women newly diagnosed with EOC were recruited through six sites in East Anglia, UK into the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study. Eligibility was irrespective of patient age and family history of cancer. The psychosocial arm of the study used self-report, psychometrically validated questionnaires (Depression Anxiety and Stress Scale (DASS-21); Impact of Event Scale (IES)) and cost analysis was performed. Results 232 women were recruited and 18 mutations were detected (12 in BRCA1 , 6 in BRCA2 ), giving a mutation yield of 8%, which increased to 12% in unselected women aged 〈70 years (17/146) but was only 1% in unselected women aged ≥70 years (1/86). IES and DASS-21 scores in response to genetic testing were significantly lower than equivalent scores in response to cancer diagnosis (p〈0.001). Correlation tests indicated that although older age is a protective factor against any traumatic impacts of genetic testing, no significant correlation exists between age and distress outcomes. Conclusions The mutation yield in unselected women diagnosed with EOC from a heterogeneous population with no founder mutations was 8% in all ages and 12% in women under 70. Unselected genetic testing in women with EOC was acceptable to patients and is potentially less resource-intensive than current standard practice.

Description: Peer-reviewed publications and conference proceedings are the mainstay of data sources for systematic reviews and network meta-analyses (NMA), but access to informative unpublished data is now becoming commonplace. To explore the usefulness of three types of ‘grey’ literature-clinical trials registries, clinical study reports and data from regulatory authorities-we conducted four case studies. The reporting of outcome data in peer-reviewed publications, the clinical trials registries and the clinical study reports for two clinical trials—one in melanoma, one in juvenile idiopathic arthritis (JIA)—was examined. In addition, we assessed the value of including unpublished data from the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) in evidence syntheses of hepatitis C virus (HCV) and chronic obstructive pulmonary disease (COPD), respectively. For the clinical trials in melanoma and JIA, we identified outcome parameters on ClinicalTrials.gov additional to those reported in the peer-reviewed publications: subgroup data and additional efficacy end points/extended follow-up, respectively. The clinical study report also provided results for several subgroups unavailable elsewhere. For HCV and COPD, additional outcome data were obtained from the EMA European Public Assessment Report (EPAR) and the FDA, respectively, including data on subgroups and mortality. We conclude that data from these grey literature sources have the potential to influence results of systematic reviews and NMAs, and may thus have implications for healthcare decisions. However, it is important to consider carefully the availability, reliability and consequent usability of these data sources in systematic reviews and NMAs.