Predictive genetic testing for Huntington's disease: Exploring participant experiences of uncertainty and ambivalence between clinic appointments.

Ambivalence and uncertainty are key themes throughout the psychology of healthcare literature. This is especially so for individuals at risk of Huntington's disease (HD) deliberating the decision to undergo genetic testing because there is currently no treatment that modifies disease progression. A better understanding of the experience of making a decision about genetic prediction will help practitioners support and guide individuals through this process. Our aim was to capture participants' experiences of uncertainty and ambivalence in between their genetic counseling appointments. We explored these issues through the experiences of nine participants who were referred for predictive HD testing at four regional genetics services in England and Wales. Data consisted of recordings of clinic consultations, diaries, and an in-depth interview conducted at the end of the testing process. Data were analyzed thematically. Four themes were identified representing four possible futures, each future dependent on the decision to undergo testing and the result of that test. Our results showed that participants, as well as attending more to a future that represents their current situation of not having undergone predictive testing, also attended more to a distant future where a positive predictive result is received and symptoms have started. Participants attended less to the two futures that were more immediate once testing was undertaken (a future where a positive result is received and symptoms have not started and a future where a negative result is received). The use of diaries gave us a unique insight into these participants' experiences of ambivalence and uncertainty, psychological distress, and the emotional burden experienced. These findings help inform discussions within the clinic appointment as well as encourage researchers to consider diary use as a method of exploring what happens for individuals outside of clinical encounters.

An outbreak of SARS-CoV-2 in a public-facing office in England.

BACKGROUND: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with an attack rate of 55% (22/40 workers) occurred at a public-facing office in England from August to September 2021. Published evidence regarding outbreaks in office workplaces remains limited. AIMS: To describe an investigation of workplace- and worker-related risk factors following an outbreak of SARS-CoV-2 in a public-facing office. METHODS: The COVID-19 (coronavirus disease 2019) Outbreak Investigation to Understand Transmission (COVID-OUT) study undertook an investigation of the outbreak. This included surface sampling, occupational environmental assessment, molecular and serological testing of workers, and detailed questionnaires. RESULTS: Despite existing COVID-19 control measures, surface sampling conducted during a self-imposed 2-week temporary office closure identified viral contamination (10/60 samples, 17% positive), particularly in a small, shared security office (6/9, 67% positive) and on a window handle in one open-plan office. Targeted enhanced cleaning was, therefore, undertaken before the office reopened. Repeat surface sampling after this identified only one positive (2%) sample. Ventilation was deemed adequate using carbon dioxide monitoring (typically ≤1000 ppm). Twelve workers (30%) responded to the COVID-OUT questionnaire, and all had been vaccinated with two doses. One-third of respondents (4/12) reported direct physical or close contact with members of the public; of these, 75% (3/4) reported a divider/screen between themselves and members of the public. CONCLUSIONS: The results highlight the potential utility of surface sampling to identify SARS-CoV-2 control deficiencies and the importance of evolving, site-specific risk assessments with layered COVID-19 mitigation strategies.

Delayed tension pneumocephalus and pneumorrhacis after routine cervical spine surgery treated successfully without burr holes.

Tension pneumocephalus (TP) after spinal surgery is very rare with only a few cases reported in the English literature. Most cases of TP occur rapidly after spinal surgery. Traditionally, TP is managed using burr holes to relieve intracranial pressure. However, our case highlights a rare delayed presentation of TP and pneumorrhacis 1 month after routine cervical spine surgery. It is to our knowledge the first case of TP after spinal surgery to be treated using dural repair and supportive care. A 75-year-old woman presented with TP after having routine cervical decompression and stabilisation for cervical myelopathy. She re-presented 1 month after her initial operation with a leaking wound and altered mental status, which deteriorated rapidly shortly after admission. This, in combination with her radiographic features, influenced the decision to explore her surgical wound emergently. She made a full recovery and was discharged after 2 weeks in hospital. We hope to emphasise the need for a high index of suspicion for cerebrospinal fluid leaks and the low threshold to return to theatre to repair a potential dural defect, as well as illustrate that TP after spinal surgery can be treated successfully without burr holes.

The relationship between parental adverse childhood experiences and the health, well-being and development outcomes of their children: a systematic review.

OBJECTIVES: A growing body of research is emerging regarding the relationship between parental adverse childhood experiences (ACEs) and negative health, well-being and developmental outcomes in their children. This systematic review seeks to understand the relationship between parental ACEs and the health, well-being and developmental outcomes of their children and whether the relationships differ according to the number and type of parental ACEs. STUDY DESIGN: Systematic review. METHOD: The review includes articles published between 2000 and 2021 from studies using quantitative longitudinal methods and multivariate analysis to investigate the relationship between parental ACEs and their offspring's outcomes. Relevant studies were identified through a systematic search of five databases and findings synthesised using a narrative synthesis. This review was registered on PROSPERO (CRD42021274068). RESULTS: Nineteen studies met the inclusion criteria and were included in the review. This resulted in a combined population sample of 124,043 parents and 128,400 children. Diversity in measurement of parental ACE exposure and in the type of ACEs measured within the studies precluded a meta-analysis. Offspring of parents exposed to ACEs had a higher risk of a range of negative health, well-being and developmental outcomes. This relationship differs according to the number and type of parental ACEs, with a positive relationship observed between the number of parental ACEs and the risk of negative health, well-being and development outcomes in their children. CONCLUSIONS: These findings indicate that screening for parental ACEs by health visitors, midwives and other health or social care staff may identify an at-risk population of infants, children and adolescents and improve child outcomes.

The nationwide impact of COVID-19 on life support courses. A retrospective evaluation by Resuscitation Council UK.

Aim: To determine the impact of the COVID-19 pandemic on Resuscitation Council UK Advanced Life Support (ALS) and Immediate Life Support (ILS) course numbers and outcomes. Methods: We conducted a before-after study using course data from the Resuscitation Council UK Learning Management System between January 2018 and December 2021, using 23 March 2020 as the cut-off between pre- and post-pandemic periods. Demographics and outcomes were analysed using chi-squared tests and regression models. Results: There were 90,265 ALS participants (51,464 pre-; 38,801 post-) and 368,140 ILS participants (225,628 pre-; 142,512 post-). There was a sharp decline in participants on ALS/ILS courses due to COVID-19. ALS participant numbers rebounded to exceed pre-pandemic levels, whereas ILS numbers recovered to a lesser degree with increased uptake of e-learning versions. Mean ALS course participants reduced from 20.0 to 14.8 post-pandemic (P < 0.001).Post-pandemic there were small but statistically significant decreases in ALS Cardiac Arrest Simulation Test pass rates (from 82.1 % to 80.1 % (OR = 0.90, 95 % CI = 0.86-0.94, P < 0.001)), ALS MCQ score (from 86.6 % to 86.0 % (mean difference = -0.35, 95 % CI -0.44 to -0.26, P < 0.001)), and overall ALS course results (from 95.2 %to 94.7 %, OR = 0.92, CI = 0.85-0.99, P = 0.023). ILS course outcomes were similar post-pandemic (from 99.4 % to 99.4 %, P = 0.037). Conclusion: COVID-19 caused a sharp decline in the number of participants on ALS/ILS courses and an accelerated uptake of e-learning versions, with the average ALS course size reducing significantly. The small reduction in performance on ALS courses requires further research to clarify the contributing factors.

Management of a large outbreak of COVID-19 at a British Army training centre: lessons for the future.

INTRODUCTION: The COVID-19 pandemic has posed major challenges for infection control within training centres, both civilian and military. Here we present a narrative review of an outbreak that occurred at the Royal Military Academy Sandhurst (RMAS) in January-March 2021, in the context of the circulating, highly transmissible SARS-CoV-2 variant B.1.1.7. METHODS: Testing for SARS-CoV-2 was performed using a combination of reverse transcriptase PCR and Lateral Flow Devices (LFDs). Testing and isolation procedures were conducted in line with a pre-established symptom stratification system. Genomic sequencing was performed on 10 sample isolates. RESULTS: By the end of the outbreak, 185 cases (153 Officer Cadets, 32 permanent staff) had contracted confirmed COVID-19. This represented 15% of the total RMAS population. This resulted in 0 deaths and 0 hospitalisations, but due to necessary isolation procedures did represent an estimated 12 959 person-days of lost training. 9 of 10 (90%) of sequenced isolates had a reportable lineage. All of those reported were found to be the Alpha lineage B.1.1.7. CONCLUSIONS: We discuss the key lessons learnt from the after-action review by the Incident Management Team. These include the importance of multidisciplinary working, the utility of sync matrices to monitor outbreaks in real time, issues around Officer Cadets reporting symptoms, timing of high-risk training activities, infrastructure and use of LFDs. COVID-19 represents a vital learning opportunity to minimise the impact of potential future pandemics, which may produce considerably higher morbidity and mortality in military populations.

Fallibility of tattooing colonic neoplasia ahead of laparoscopic resection: a retrospective cohort study.

INTRODUCTION: Precise geographical localisation of colonic neoplasia is a prerequisite for proper laparoscopic oncological resection. Preoperative endoscopic peri-tumoural tattoo practice is routinely recommended but seldom scrutinised. METHODS: A retrospective review of recent consecutive patients with preoperative endoscopic lesional tattoo who underwent laparoscopic colonic resection as identified from our prospectively maintained cancer database with supplementary clinical chart and radiological, histological, endoscopic and theatre database/logbook interrogation. RESULTS: Some 210 patients with 'tattooed' colonic neoplasia were identified, of whom 169 underwent laparoscopic surgery (mean age 68 years, median BMI 27.8kg/m2, male-to-female ratio 95:74). The majority of tumours were malignant (149; 88%), symptomatic (133; 79%) and proximal to the splenic flexure (92; 54%). Inaccurate colonoscopist localisation judgement occurred in 12% of cases, 60% of which were corrected by preoperative staging computed tomography scan. A useful lesional tattoo was absent in 11/169 cases (6.5%) being specifically stated as present in 104 operation notes (61%) and absent in 10 (5.9%). Tumours missing overt peritumoral tattoos intraoperatively were more likely to be smaller, earlier stage and injected longer preoperatively (p=0.006), although half had histological ink staining. Eight lesions missing tattoos were radiologically occult. Four (44%) of these patients had on-table colonoscopy, and five (55%) needed laparotomy (conversion rate 55% vs 23% overall, p<0.005) with one needing a second operation to resect the initially missed target lesion. Mean (range) operative duration and postoperative length of stay of those missing tattoos compared with those with tattoos was 200 (78-300) versus 188 (50-597) min and 15.5 (4-22) versus 12(4-70) days (p>0.05). CONCLUSIONS: Tattoo in advance of attempting laparoscopic resection is vital for precision cancer surgery especially for radiologically unseen tumours to avoid adverse clinical consequence.

Physiological, perceptual, and biomechanical differences between treadmill and overground walking in healthy adults: A systematic review and meta-analysis.

This systematic review and meta-analysis aims to compare physiological, perceptual and biomechanical outcomes between walking on a treadmill and overground surfaces. Five databases (CINAHL, EMBASE, MEDLINE, SPORTDiscus, Web of Science) were searched until September 2022. Included studies needed to be a crossover design comparing biomechanical, physiological, or perceptual measures between motorised-treadmill and overground walking in healthy adults (18-65 years) walking at the same speed (<5% difference). The quality of studies were assessed using a modified Downs and Black Quality Index. Meta-analyses were performed to determine standardised mean difference ± 95% confidence intervals for all main outcome measures. Fifty-five studies were included with 1,005 participants. Relative oxygen consumption (standardised mean difference [95% confidence interval] 0.38 [0.14,0.63]) and cadence (0.22 [0.06,0.38]) are higher during treadmill walking. Whereas stride length (-0.36 [-0.62,-0.11]) and step length (-0.52 [-0.98,-0.06]) are lower during treadmill walking. Most kinetic variables are different between surfaces. The oxygen consumption, spatiotemporal and kinetic differences on the treadmill may be an attempt to increase stability due to the lack of control, discomfort and familiarity on the treadmill. Treadmill construction including surface stiffness and motor power are likely additional constraints that need to be considered and require investigation. This research was supported by an Australian Government Research Training Program (RTP) scholarship. Protocol registration is CRD42020208002 (PROSPERO International Prospective Register of Systematic Reviews) in October 2020.

Relative oxygen consumption is greater on a treadmill when compared with overground when walking at similar speeds and needs to be considered when prescribing exercise.Walking on a treadmill results in several biomechanical changes compared to overground that may be related to changes in gait stability.It may be favourable for rehabilitation purposes for people to initially walk on a treadmill due to lower vertical ground reaction force at push-off and lower joint moments at the knee and ankle.

Left distal ureter leiomyosarcoma: a case report.

Primary leiomyosarcoma of the ureter is an extremely rare, aggressive malignancy of the urinary tract. This report describes a case of primary leiomyosarcoma of the distal left ureter in a middle-aged male, with no tumor recurrence achieved following resection and end-to-end ureteroureterostomy.

Staff and patient experience of the implementation and delivery of a virtual health care home monitoring service for COVID-19 in Melbourne, Australia.

BACKGROUND: Provision of virtual health care (VHC) home monitoring for patients who are experiencing mild to moderate COVID-19 illness is emerging as a central strategy for reducing pressure on acute health systems. Understanding the enablers and challenges in implementation and delivery of these programs is important for future implementation and re-design. The aim of this study was to explore the perspectives of staff involved with the implementation and delivery, and the experience of patients managed by, a VHC monitoring service in Melbourne, Australia during the COVID-19 pandemic. METHODS: A descriptive qualitative approach informed by naturalist inquiry was used. Staff interviews were analysed using the Consolidated Framework for Implementation Research (CFIR). Patient experience was captured using a survey and descriptive statistics were used to describe categorical responses while content analysis was used to analyse free text responses as they related to the CFIR. Finally, data from the interviews and patient experience were triangulated to see if patient experience validated data from staff interviews. RESULTS: All 15 staff were interviewed, and 271 patients were surveyed (42%). A total of four final overarching themes emerged: service implementation enablers, service delivery benefits for patients, fragmentation of care, and workforce strengths. 19 subthemes aligned with 18 CFIR constructs from staff and patient data. CONCLUSION: Rapid implementation was enabled through shared resources, dividing implementation tasks between senior personnel, engaging furloughed healthcare staff in design and delivery, and having a flexible approach that allowed for ongoing improvements. Benefits for patients included early identification of COVID-19 deterioration, as well as provision of accurate and trustworthy information to isolate safely at home. The main challenges were the multiple agencies involved in patient monitoring, which may be addressed in the future by attributing responsibility for monitoring to a single agency.

A comprehensive phylogeny helps clarify the evolutionary history of host breadth and lure response in the Australian Dacini fruit flies (Diptera: Tephritidae).

The tribe Dacini (Diptera: Tephritidae) contains over 930 recognised species and has been widely studied due to the economic importance of some taxa, such as the Oriental fruit fly Bactrocera dorsalis. Despite the attention this group has received, very few phylogenetic reconstructions have comprehensively sampled taxa from a single biogeographic region, thereby limiting our capacity to address more targeted evolutionary questions. To study the evolution of diet breadth and male lure response, two key traits fundamental to understanding dacine diversity and the biology of pest taxa, we analysed 273 individuals representing 144 described species from Australia (80% continental coverage), the Pacific, and select close relatives from South-east Asia to estimate a dated molecular phylogenetic reconstruction of the Dacini. We utilised seven loci with a combined total of 4,332 nucleotides, to estimate both Bayesian and Maximum Likelihood phylogenies of the tribe. Consistent with other molecular phylogenies of the tribe, there was a high level of disagreement between the placement of species in the phylogeny and their current subgeneric and species-complex level taxonomies. The Australian fauna exhibit high levels of endemism, with radiations of both exclusively Australian clades, and clades that originate elsewhere (e.g. the Bactrocera dorsalis species group). Bidirectional movement of species has occurred between Papua New Guinea and Australia, with evidence for multiple incursions over evolutionary time. The Bactrocera aglaiae species group emerged sister to all other Bactrocera species examined. Divergence time estimates were âˆ¼ 30 my younger than previously reported for this group, with the tribe diverging from its most recent common ancestor âˆ¼ 43 mya. Ancestral trait reconstruction and tests for trait phylogenetic signal revealed a strong signal for the evolution of male lure response across the tree, with cue-lure/raspberry ketone lure response the ancestral trait. Methyl eugenol response has arisen on multiple, independent occasions. The evolution of host breadth exhibited a weaker signal; yet, basal groups were more likely to be host specialists. Both the evolution of lure response and host fruit use provide predictive information for the outbreak management of understudied pest fruit flies for which direct inference of these features may be lacking. Our results, which parallel those of earlier research into the closely-related African Dacus spp., demonstrate how geographically focussed taxon coverage allows Dacini phylogenetics to more explicitly test evolutionary hypotheses, thereby progressing our understanding of the evolution of this highly diverse and recently-radiated group of flies.

Genomics and justice: mitigating the potential harms and inequities that arise from the implementation of genomics in medicine.

Advances in human genetics raise many social and ethical issues. The application of genomic technologies to healthcare has raised many questions at the level of the individual and the family, about conflicts of interest among professionals, and about the limitations of genomic testing. In this paper, we attend to broader questions of social justice, such as how the implementation of genomics within healthcare could exacerbate pre-existing inequities or the discrimination against social groups. By anticipating these potential problems, we hope to minimise their impact. We group the issues to address into six categories: (i) access to healthcare in general, not specific to genetics. This ranges from healthcare insurance to personal behaviours. (ii) data management and societal discrimination against groups on the basis of genetics. (iii) epigenetics research recognises how early life exposure to stress, including malnutrition and social deprivation, can lead to ill health in adult life and further social disadvantage. (iv) psychiatric genomics and the genetics of IQ may address important questions of therapeutics but could also be used to disadvantage specific social or ethnic groups. (v) complex diseases are influenced by many factors, including genetic polymorphisms of individually small effect. A focus on these polygenic influences distracts from environmental factors that are more open to effective interventions. (vi) population genomic screening aims to support couples making decisions about reproduction. However, this remains a highly contentious area. We need to maintain a careful balance of the competing social and ethical tensions as the technology continues to develop.

Land management explains major trends in forest structure and composition over the last millennium in California's Klamath Mountains.

SignificanceWe provide the first assessment of aboveground live tree biomass in a mixed conifer forest over the late Holocene. The biomass record, coupled with local Native oral history and fire scar records, shows that Native burning practices, along with a natural lightning-based fire regime, promoted long-term stability of the forest structure and composition for at least 1 millennium in a California forest. This record demonstrates that climate alone cannot account for observed forest conditions. Instead, forests were also shaped by a regime of frequent fire, including intentional ignitions by Native people. This work suggests a large-scale intervention could be required to achieve the historical conditions that supported forest resiliency and reflected Indigenous influence.

Isolated IgG2 deficiency is an independent risk factor for exacerbations in bronchiectasis.

BACKGROUND: Immunoglobulin G (IgG) subclass 2 deficiency is the most frequent IgG subclass deficiency identified in patients with bronchiectasis, but its clinical significance is not known. AIM: To analyse if bronchiectasis patients with isolated IgG2 deficiency at risk of recurrent exacerbations and/or hospitalization? Do patients with IgG2 deficiency have worse disease progression? DESIGN AND METHODS: This is a retrospective study (2015-20) exploring independent risk factors for recurrent exacerbations (3 or more per year) and/or hospitalization with bronchiectasis exacerbations using multivariable models using binary logistic regression. There was no patient with IgG deficiency, IgG 1, 3 or 4 deficiency, or IgA or IgM deficiency included. In this model, the authors included: serum IgG2 level; lung function; body mass index; MRC breathlessness scale; age; sex; number of bronchiectatic lobes; bacterial colonization; comorbidities; and the use of long-term immunosuppressant drugs or antibiotics for more than 28 days. Analysing 2-year longitudinal data, one-way ANOVA and Mann-Whitney U-test were used to compare bronchiectasis severity between patients with different IgG2 levels. RESULTS: Serum IgG2 levels (<2.68 g/l, 2.68-3.53 g/l and 3.54-4.45 g/l); hospital admission in the preceding 2 years; bacterial colonization with potentially pathogenic organisms and asthma were independent predictors for three or more bronchiectasis exacerbations. Those with low IgG2 levels (<2.68 g/l and 2.68-3.53 g/l), had worsening progression of their bronchiectasis, using the Bronchiectasis Severity Index, over 1 year compared with those who were IgG2 replete (>4.45 g/l) (P = 0.003, 0.013). CONCLUSION: Reduced IgG2 levels were an independent predictor for bronchiectasis exacerbations and have increased disease progression.

A multi-centred sequential trial comparing PEGASUS, an intervention to promote shared decision making about breast reconstruction with usual care.

Decision making about breast reconstruction (BR) is complex. The Patients' Expectations and Goals: Assisting Shared Understanding of Surgery (PEGASUS) intervention aims to support shared decision making by helping women and clinicians clarify and discuss their expectations around reconstructive surgery. We conducted a multi-centred sequential trial comparing PEGASUS (n = 52) with usual care (UC) (n = 86) in women considering reconstruction, who completed outcome measures at baseline, and 3, 6 and 12 months post-surgery. The primary outcome was BR-specific quality of life (Breast-Q) 6 months post-intervention. Secondary outcomes were health-related quality of life (EQ-5D-5L), capabilities (ICECAP-A) and decisional regret, compared using t-tests and Cohen's d. Comparative analyses revealed no significant differences between groups in Breast-Q scores at any time point, except for a favourable effect for UC on psychological well-being at 3 months (t = -2.41, p = .019, d= -0.59). Intervention participants reported significantly higher, therefore improved, ICECAP-A (t = -2.13, p = .037, d = -0.45) and EQ VAS (t = -2.28, p = .026, d = -0.49) scores at 12 months compared to UC. Decisional regret was significantly lower in the PEGASUS group compared to the UC group at 6 months (t =2.06, p = .044, d= -0.51), but this was not sustained at 12 months. In conclusion, the PEGASUS intervention offers some benefits to women considering BR. At times, women experienced less decisional regret, improved health-related quality of life and capability well-being. Findings are discussed in the light of fidelity testing and embedding PEGASUS into practice.

Accurate tracking of forest activity key to multi-jurisdictional management goals: A case study in California.

An essential component of sustainable forest management is accurate monitoring of forest activities. Although monitoring efforts have generally increased for many forests throughout the world, in practice, effective monitoring is complex. Determining the magnitude and location of progress towards sustainability targets can be challenging due to diverse forest operations across multiple jurisdictions, the lack of data standardization, and discrepancies between field inspections and remotely-sensed records. In this work, we used California as a multijurisdictional case study to explore these problems and develop an approach that broadly informs forest monitoring strategies. The State of California recently entered into a shared stewardship agreement with the US Forest Service (USFS) and set a goal to jointly treat one million acres of forest and rangeland annually by 2025. Currently, however, federal and state forest management datasets are disjoint. This work addresses three barriers stymying the use of federal and state archival records to assess management goals. These barriers are: 1) current databases from different jurisdictions have not been combined due to their distinct data collection processes and internal structures; 2) datasets have not been comprehensively analyzed, despite the need to understand the extent of previous treatments as well as the rate of current activity; and 3) the spatial accuracy of archival datasets has not been evaluated against remotely-sensed data. To reduce these barriers, we first aggregated existing archival forest management records between 1984 and 2019 from the USFS' Forest Activity Tracking System (FACTS) and the California Department of Forestry and Fire Protection (CAL FIRE) using a qualitative scalar of treatment intensity. Combined FACTS and CAL FIRE completed footprint acres - defined as unique areas of land where a treatment was completed at any time since 1984 - have decreased since a peak in 2008. At most, 300,000 footprint acres are completed each year, 30% of the million-acre goal. Prescribed fires - defined as direct burning operations - have risen over time, according to the FACTS hazardous fuels dataset but prescribed fire records in CAL FIRE's dataset have rapidly increased since 2016. We also refined the spatial and temporal detail of the aggregated management record using the Continuous Change Detection and Classification algorithm on satellite remote sensing data to produce a state-wide time series map of harvest disturbances. A comparison of the algorithm's refined data to the archival record potentially suggests over-reporting in both FACTS and CAL FIRE's archival datasets. Our integrated dataset provides a better assessment of current treatments and the path towards the 1-million-acre a year goal. The refined dataset leverages the strengths of complementary, albeit imperfect, monitoring strategies from archives and remotely-sensed detection.

Tolerability of four-drug antiretroviral combination therapy in primary HIV-1 infection.

OBJECTIVES: Rapid initiation of antiretroviral therapy (ART) is important for individuals with high baseline viral loads, such as in primary HIV-1 infection (PHI). Four-drug regimens are sometimes considered; however, data are lacking on tolerability. We aimed to evaluate the tolerability of four-drug regimens used in the Research in Viral Eradication of HIV-1 Reservoirs (RIVER) study. METHODS: At enrolment, ART-naïve adult participants or those newly commenced on ART were initiated or intensified to four-drug regimens within 4 weeks of PHI. Rapid start was defined as pre-confirmation or ≤ 7 days of confirmed diagnosis. Primary and secondary outcomes were patient-reported adherence measured by 7-day recall and regimen switches between enrolment and randomization, respectively. RESULTS: Overall, 54 men were included: 72.2% were of white ethnicity, with a median age of 32 years old, 42.6% had a viral load of ≥ 100 000 HIV-1 RNA copies/mL, and in 92.6% sex with men was the mode of acquisition of HIV-1. Twenty (37%) started a four-drug regimen and 34 (63%) were intensified. Rapid ART initiation occurred in 28%, 100% started in ≤ 4 weeks. By weeks 4, 12, and 24, 37.0%, 69.0%, and 94.0% were undetectable (viral load < 50 copies/mL), respectively. Adherence rates of 100% at weeks 4, 12, 22 and 24 were reported in 88.9%, 87.0%, 82.4% and 94.1% of participants, respectively. Five individuals switched to three drugs, four changed their regimen constituents, and two switched post-randomization. CONCLUSIONS: Overall, four-drug regimens were well tolerated and had high levels of adherence. Whilst their benefit over three-drug regimens is lacking, our findings should provide reassurance if a temporarily intensified regimen is clinically indicated to help facilitate treatment.

Determinants of non-adherence to anti-TB treatment in high income, low TB incidence settings: a scoping review.

BACKGROUND: Improving adherence to anti-TB treatment is a public health priority in high-income, low incidence (HILI) regions. We conducted a scoping review to identify reported determinants of non-adherence in HILI settings.METHODS: Key terms related to TB, treatment and adherence were used to search MEDLINE, EMBASE, Web of Science, PsycINFO and CINAHL in June 2019. Quantitative studies examining determinants (demographic, clinical, health systems or psychosocial) of non-adherence to anti-TB treatment in HILI settings were included.RESULTS: From 10,801 results, we identified 24 relevant studies from 10 countries. Definitions and methods of assessing adherence were highly variable, as were documented levels of non-adherence (0.9-89%). Demographic factors were assessed in all studies and clinical factors were frequently assessed (23/24). Determinants commonly associated with non-adherence were homelessness, incarceration, and alcohol or drug misuse. Health system (8/24) and psychosocial factors (6/24) were less commonly evaluated.CONCLUSION: Our review identified some key factors associated with non-adherence to anti-TB treatment in HILI settings. Modifiable determinants such as psychosocial factors are under-evidenced and should be further explored, as these may be better targeted by adherence support. There is an urgent need to standardise definitions and measurement of adherence to more accurately identify the strongest determinants.