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Background Facilitated telemedicine is highly effective for hepatitis C virus (HCV) treatment among people with opioid use disorder (OUD). However, the long‐term impact of sustained virological response (SVR) through this model of treatment remains unexplored. We examined how people with OUD perceive SVR achieved through facilitated telemedicine. Methods We conducted two focus group discussions (FGDs) with nine participants at least 5 years post‐SVR through a randomised controlled trial of facilitated telemedicine in opioid treatment programmes (OTPs) (New York State, 2018–2020). Eligibility required active OTP enrolment at the time of FGDs. We used a semi‐structured interview guide and performed thematic analysis of FGD transcripts. Results Participants had a mean age of 52.6 years (SD = 13.7), 66.6% were male, and 88.8% identified as White. We identified three FGD themes, each corresponding to pre‐, during and post‐intervention phases (see Figure 1): (1) Attitudes towards HCV and barriers to treatment among people with OUD, (2) Embracing facilitated telemedicine for HCV care integrated into OTPs, and (3) Experiencing long‐term benefits from facilitated telemedicine across all aspects of HCV care and overall well‐being. Barriers included competing priorities, perceiving HCV treatment as a low priority, and insurance restrictions (Theme 1). Participants valued facilitated telemedicine for its convenience, empathetic clinicians, and one‐stop shop approach (Theme 2). At least 5 years post‐SVR, participants reported benefits in HCV knowledge, improved OUD recovery, and improvement in whole health (Theme 3). Conclusion At least 5 years post‐SVR, people with OUD reported improvements in OUD recovery, overall well‐being and sustained satisfaction with telemedicine‐based HCV care. These findings highlight the lasting impact of both an SVR and care delivery through facilitated telemedicine. Patient and Public Contribution In this study of patient involvement, we conducted focus groups with patient‐participants to examine the long‐term impact of receiving HCV care through facilitated telemedicine integrated into OTPs. Participants had previously taken part in a randomised controlled trial of facilitated telemedicine (New York State, 2018–2020). At least 5 years after achieving an SVR, we sought participant feedback to evaluate the long‐term impact and sustainability of facilitated telemedicine as an approach to achieve an HCV cure with the objective of informing future policy development. Participants had also contributed critical input at various stages of the original study's design and implementation. During the pilot phase, participants advocated for facilitated telemedicine in a testimonial video. Participants provided feedback on design and implementation by participating in planning and site initiation meetings. A Patient Advisory Committee ensured participant voices were integrated into the research process by representing their feedback on study conduct. Additionally, a Sustainability Committee supported public involvement by promoting educational opportunities, providing input on implementation, and addressing long‐term sustainability considerations.

Guidelines for managing abnormal cervical cancer screening results are complex and adherence is challenging for clinicians. Previous studies have identified gaps in knowledge as a possible cause; few have explored the confidence clinicians have in their management decisions. Confidence in decision-making may influence management practices, particularly when guidelines are complex and evolving. Assess whether confidence in decision-making is associated with making guideline-concordant recommendations for abnormal cervical cancer screening results. A clinician survey used vignettes to ask clinicians to make a management recommendation for different abnormal results and rate their level of confidence in their response. Physicians and advanced practice providers (APPs) at three diverse health systems in Washington, Texas, and Massachusetts. Correct response to each vignette based on either the 2012 or 2019 American Colposcopy and Cervical Pathology (ASCCP) management guidelines. In total, 501 clinicians completed the survey between October and December 2020 (response rate 53.7%). Overall, most clinicians made guideline-recommended management decisions for two vignettes (73.2 and 73.7%), but fewer were confident in their selection (48.3% and 46.6%, respectively). Clinicians who reported high levels of confidence were more often correct than those who reported lower levels of confidence (85.8% vs. 62.2% and 87.5% vs. 60.7%, both p<0.001). After adjusting for clinician and practice characteristics, confidence remained significantly associated with selecting the correct answer. Clinician confidence in management decisions for abnormal cervical cancer screening results was significantly associated with knowing guideline-concordant recommendations. Given the complexity of cervical cancer management guidelines, solutions to improve clinician confidence in decision-making are needed.

Health care systems focus on delivering routine cancer screening to eligible individuals, yet little is known about the perceptions of primary care practitioners (PCPs) about barriers to timely follow-up of abnormal results. To describe PCP perceptions about factors associated with the follow-up of abnormal breast, cervical, colorectal, and lung cancer screening test results. Survey study of PCPs from 3 primary care practice networks in New England between February and October 2020, prior to participating in a randomized clinical trial to improve follow-up of abnormal cancer screening test results. Participants were physicians and advanced practice clinicians from participating practices. Self-reported process, attitudes, knowledge, and satisfaction about the follow-up of abnormal cancer screening test results. Overall, 275 (56.7%) PCPs completed the survey (range by site, 34.9%-71.9%) with more female PCPs (61.8% [170 of 275]) and general internists (73.1% [201 of 275]); overall, 28,7% (79 of 275) were aged 40 to 49 years. Most PCPs felt responsible for managing abnormal cancer screening test results with the specific cancer type being the best factor (range, 63.6% [175 of 275] for breast to 81.1% [223 of 275] for lung; P < .001). The PCPs reported limited support for following up on overdue abnormal cancer screening test results. Standard processes such as automated reports, reminder letters, or outreach workers were infrequently reported. Major barriers to follow-up of abnormal cancer screening test results across all cancer types included limited electronic health record tools (range, 28.5% [75 of 263]-36.5%[96 of 263]), whereas 50% of PCPs felt that there were major social barriers to receiving care for abnormal cancer screening test results for colorectal cancer. Fewer than half reported being very satisfied with the process of managing abnormal cancer screening test results, with satisfaction being greatest for breast cancer (46.9% [127 of 271]) and lowest for cervical (21.8% [59 of 271]) and lung cancer (22.4% [60 of 268]). In this survey study of PCPs, important deficiencies in systems for managing abnormal cancer screening test results were reported. These findings suggest a need for comprehensive organ-agnostic systems to promote timely follow-up of abnormal cancer screening results using a primary care-focused approach across the range of cancer screening tests.

Background Guidelines for managing abnormal cervical cancer screening results are complex and adherence is challenging for clinicians. Previous studies have identified gaps in knowledge as a possible cause; few have explored the confidence clinicians have in their management decisions. Confidence in decision-making may influence management practices, particularly when guidelines are complex and evolving. Objective Assess whether confidence in decision-making is associated with making guideline-concordant recommendations for abnormal cervical cancer screening results. Design A clinician survey used vignettes to ask clinicians to make a management recommendation for different abnormal results and rate their level of confidence in their response. Participants Physicians and advanced practice providers (APPs) at three diverse health systems in Washington, Texas, and Massachusetts. Main Measures Correct response to each vignette based on either the 2012 or 2019 American Colposcopy and Cervical Pathology (ASCCP) management guidelines. Key Results In total, 501 clinicians completed the survey between October and December 2020 (response rate 53.7%). Overall, most clinicians made guideline-recommended management decisions for two vignettes (73.2 and 73.7%), but fewer were confident in their selection (48.3% and 46.6%, respectively). Clinicians who reported high levels of confidence were more often correct than those who reported lower levels of confidence (85.8% vs. 62.2% and 87.5% vs. 60.7%, both p <0.001). After adjusting for clinician and practice characteristics, confidence remained significantly associated with selecting the correct answer. Conclusions Clinician confidence in management decisions for abnormal cervical cancer screening results was significantly associated with knowing guideline-concordant recommendations. Given the complexity of cervical cancer management guidelines, solutions to improve clinician confidence in decision-making are needed.

High-grade serous ovarian carcinoma (HGSOC), an aggressive cancer associated with pathogenic variants, causes genomic instability and sensitivity to poly (ADP-ribose) polymerase inhibitors. Identifying pathogenic variants is crucial for the treatment of HGSOC; however, genetic testing is expensive and time-consuming. This study aimed to explore pathological features, particularly the presence of tumor-infiltrating lymphocytes (TILs), as potential surrogates to streamline patient selection for genetic testing. We retrospectively analyzed 58 cases of HGSOC with known variant profiles. Tumors were categorized as TIL-positive or TIL-negative based on the presence of > 40 or ≤ 40 intraepithelial lymphocytes in a single high-power field (HPF), respectively. Key pathological features, including solid, endometrioid, and transitional (SET) architecture patterns; necrosis; and mitotic activity, were evaluated within these subgroups. Statistical analyses were used to determine the associations between these features and variant status. In TIL-negative HGSOCs, SET patterns were strongly associated with pathogenic or likely pathogenic variants ( = 0.028), emerging as the most reliable morphological marker in this group. In TIL-positive HGSOCs, low mitotic activity (≤7 mitotic figure per 10 HPFs) was significantly correlated with pathogenic variants ( = 0.0002), underscoring its diagnostic significance. Necrosis and mitotic activity in TIL-negative cases and SET patterns in TIL-positive cases were not significantly associated with pathogenic variants. Combined analysis of both TIL subgroups diluted these associations, underscoring the significance of stratifying cases by the immune context. The presence of TILs affects the diagnostic value of pathological features for variant status in HGSOC. Regarding pathogenic variants, SET patterns and low mitotic activity were identified as critical markers in TIL-negative tumors and TIL-positive tumors, respectively. These associations likely stem from interactions among genomic instability, immune response, and tumor growth. Our framework leverages these insights to prioritize high-risk cases for genetic testing, thereby optimizing resource allocation. The presence of TILs is critical for understanding the association between pathological features and pathogenic variants in HGSOC. To improve pathogenic variant prediction, optimize genetic testing, and guide tailored intervention, our framework integrates immune context and morphological markers. This approach is especially useful in resource-limited settings and can enhance diagnostic efficiency and clinical decision-making.

Outbreaks of emerging coronaviruses in the past two decades and the current pandemic of a novel coronavirus (SARS-CoV-2) that emerged in China highlight the importance of this viral family as a zoonotic public health threat. To gain a better understanding of coronavirus presence and diversity in wildlife at wildlife-human interfaces in three southern provinces in Viet Nam 2013-2014, we used consensus Polymerase Chain Reactions to detect coronavirus sequences. In comparison to previous studies, we observed high proportions of positive samples among field rats (34.0%, 239/702) destined for human consumption and insectivorous bats in guano farms (74.8%, 234/313) adjacent to human dwellings. Most notably among field rats, the odds of coronavirus RNA detection significantly increased along the supply chain from field rats sold by traders (reference group; 20.7% positivity, 39/188) by a factor of 2.2 for field rats sold in large markets (32.0%, 116/363) and 10.0 for field rats sold and served in restaurants (55.6%, 84/151). Coronaviruses were also detected in rodents on the majority of wildlife farms sampled (60.7%, 17/28). These coronaviruses were found in the Malayan porcupines (6.0%, 20/331) and bamboo rats (6.3%, 6/96) that are raised on wildlife farms for human consumption as food. We identified six known coronaviruses in bats and rodents, clustered in three Coronaviridae genera, including the Alpha-, Beta-, and Gammacoronaviruses. Our analysis also suggested either mixing of animal excreta in the environment or interspecies transmission of coronaviruses, as both bat and avian coronaviruses were detected in rodent feces on wildlife farms. The mixing of multiple coronaviruses, and their apparent amplification along the wildlife supply chain into restaurants, suggests maximal risk for end consumers and likely underpins the mechanisms of zoonotic spillover to people.

The advent of novel therapeutics in recent years has urged the need for a safe, non-immunogenic drug delivery vector capable of delivering therapeutic payloads specifically to diseased cells, thereby increasing therapeutic efficacy and reducing side effects. Extracellular vesicles (EVs) have garnered attention in recent years as a potentially ideal vector for drug delivery, taking into account their intrinsic ability to transfer bioactive cargo to recipient cells and their biocompatible nature. However, natural EVs are limited in their therapeutic potential and many challenges need to be overcome before engineered EVs satisfy the levels of efficiency, stability, safety and biocompatibility required for therapeutic use. Here, we demonstrate that an enzyme-mediated surface functionalization method in combination with streptavidin-mediated conjugation results in efficient surface functionalization of EVs. Surface functionalization using the above methods permits the stable and biocompatible conjugation of peptides, single domain antibodies and monoclonal antibodies at high copy number on the EV surface. Functionalized EVs demonstrated increased accumulation in target cells expressing common cancer associated markers such as CXCR4, EGFR and EpCAM both and . The functionality of this approach was further highlighted by the ability of targeting EVs to specifically deliver therapeutic antisense oligonucleotides to a metastatic breast tumor model, resulting in increased knockdown of a targeted oncogenic microRNA and improved metastasis suppression. The method was also used to equip EVs with a bifunctional peptide that targets EVs to leukemia cells and induces apoptosis, leading to leukemia suppression. Moreover, we conducted extensive testing to verify the biocompatibility, and safety of engineered EVs for therapeutic use, suggesting that surface modified EVs can be used for repeated dose treatment with no detectable adverse effects. This modular, biocompatible method of EV engineering offers a promising avenue for the targeted delivery of a range of therapeutics while addressing some of the safety concerns associated with EV-based drug delivery.

IntroductionExercise therapy is the most recommended treatment for chronic low back pain (LBP), with evidence supporting modest effects, likely due to the heterogeneity of patient presentations. Evidence suggests that matching individuals to the most appropriate exercise type could improve outcomes. Systematic reviews also emphasise that effective exercise interventions should be patient centred, target paraspinal muscle health and be of sufficient duration. This study addresses these gaps using a targeted care approach to identify a homogenous sample that is more likely to respond to our interventions. The inclusion of a sample with predominant nociceptive pain profile will be performed with the integration of the Pain and Disability Drivers Management Model (PDDM) and the Lumbar Spine Instability Questionnaire (LSIQ). The primary aim of this two-arm randomised controlled trial is to compare the effectiveness of motor control plus isolated lumbar extension exercises (MC+ILEX, arm 1) to free-weight resistance training (arm 2) in reducing LBP-related disability. Secondary aims include examining whether changes in multifidus composition mediate disability improvements comparing intervention effects on muscle size and quality, strength, mobility, pain, quality of life, sleep, physical activity and satisfaction; exploring baseline LSIQ scores and sex/gender as moderators of treatment response; and investigating participants’ perceptions and experiences of exercise therapy.Methods and analysisA total of 106 participants will be recruited through primary and secondary care and randomised (1:1) to receive either MC+ILEX or free-weight resistance training. Both groups will complete 48 exercise sessions over 16 weeks. The primary outcome will be disability at 16 weeks, measured by the Oswestry Disability Index. Secondary outcomes include multifidus muscle composition and size, lumbar and gluteal muscle strength, hip range of motion, pain, physical and mental function, satisfaction and recovery, health-related quality of life, sleep quality and physical activity levels. Linear mixed-effects models will be used to assess primary and secondary outcomes. Regression analyses will explore whether baseline LSIQ scores moderate treatment effects on multifidus composition and other outcomes. A subsample of participants will undergo semistructured interviews before and after the intervention to explore their illness perceptions, illness mindsets, perceptions of exercise therapy, as well as their experiences and satisfaction with the two exercise interventions. Reflexive thematic analysis will be used to analyse qualitative data.Ethics and disseminationThis study received ethics approval from the Central Ethics Research Committee of the Quebec Minister of Health and Social Services (CCER-25-26-14). Results will be submitted to peer-reviewed journals and scientific meetings.Trial registration numberISRCTN14864451.

The study aims to evaluate the effects of diurnal temperature range (DTR) on all causes, cardiovascular and respiratory conditions in the Central Coast of Vietnam, a tropical, low-income region with high DTR exposure but limited research. Daily hospital admission data from the largest hospitals in three provinces were analyzed alongside meteorological data. A time-series analysis using a generalized linear distributed lag model was conducted to examine the non-linear DTR-hospitalization association. A random-effect meta-analysis using restricted maximum likelihood was performed to calculate the pooled effects across three provinces. Stratified analyses by gender, age, season and natural disaster occurrence were conducted to identify vulnerable subpopulations. The multi-province pooled effects indicated that a 1 °C increase in DTR raised the risk of hospitalizations for all causes and respiratory diseases by 1.5% [1.2-1.8%] and 0.5% [0.0–1.0%], at lag 0–6 days. The effects of DTR on cardiovascular diseases, as well as those stratified by subgroups, were not statistically significant. Additionally, DTR had a greater adverse effect during the dry season and in the presence of natural disaster. Females and the elderly were slightly more susceptible to respiratory admissions, while males and younger individuals had a higher risk of all-cause admissions due to greater DTR effects. DTR was an independent risk factor for the exacerbation of all and specific causes, particularly among the susceptible subgroups. The findings suggested that it is necessary to take preventive measures to protect these at-risk populations from the adverse effects of extreme DTR exposure.

Heatwaves are increasingly recognized as a severe natural hazard that pose substantial threats to human wellbeing and sustainability with physical, mental, and economic impacts. Heatwave Early Warning Systems (HEWSs) have emerged as a promising solution to mitigate these adverse impacts. This study aims to valuate a Short Message Service (SMS)-based early warning system specifically targeting heat-vulnerable populations and their determinants in central Vietnam, an area prone to heat-related illnesses. By employing the contingent valuation method, individuals’ willingness to pay (WTP) for the warning system and the determinants of the WTP were assessed. The findings showed an average WTP of VND 283,110 (~USD 11) per person per year, according to the parametric estimate. The total WTP for the affected population in central Vietnam reached VND 857,283,678,000 or USD 37,273,203 per year, assuming that 50% of the heat-vulnerable population contributes to HEWSs financially. Significant determinants of WTP were identified, including bid levels, cost of heat-related illnesses, background diseases, and exposure to heat. Policymakers and health authorities can utilize these findings to develop effective adaptation strategies for preventing and mitigating heat-related illnesses, while also promoting sustainable development in central Vietnam.