European society for trauma and emergency surgery member-identified research priorities in emergency surgery: a roadmap for future clinical research opportunities.

BACKGROUND: European Society for Trauma and Emergency Surgery (ESTES) is the European community of clinicians providing care to the injured and critically ill surgical patient. ESTES has several interlinked missions - (1) the promotion of optimal emergency surgical care through networked advocacy, (2) promulgation of relevant clinical cognitive and technical skills, and (3) the advancement of scientific inquiry that closes knowledge gaps, iteratively improves upon surgical and perioperative practice, and guides decision-making rooted in scientific evidence. Faced with multitudinous opportunities for clinical research, ESTES undertook an exercise to determine member priorities for surgical research in the short-to-medium term; these research priorities were presented to a panel of experts to inform a 'road map' narrative review which anchored these research priorities in the contemporary surgical literature. METHODS: Individual ESTES members in active emergency surgery practice were polled as a representative sample of end-users and were asked to rank potential areas of future research according to their personal perceptions of priority. Using the modified eDelphi method, an invited panel of ESTES-associated experts in academic emergency surgery then crafted a narrative review highlighting potential research priorities for the Society. RESULTS: Seventy-two responding ESTES members from 23 countries provided feedback to guide the modified eDelphi expert consensus narrative review. Experts then crafted evidence-based mini-reviews highlighting knowledge gaps and areas of interest for future clinical research in emergency surgery: timing of surgery, inter-hospital transfer, diagnostic imaging in emergency surgery, the role of minimally-invasive surgical techniques and Enhanced Recovery After Surgery (ERAS) protocols, patient-reported outcome measures, risk-stratification methods, disparities in access to care, geriatric outcomes, data registry and snapshot audit evaluations, emerging technologies interrogation, and the delivery and benchmarking of emergency surgical training. CONCLUSIONS: This manuscript presents the priorities for future clinical research in academic emergency surgery as determined by a sample of the membership of ESTES. While the precise basis for prioritization was not evident, it may be anchored in disease prevalence, controversy around aspects of current patient care, or indeed the identification of a knowledge gap. These expert-crafted evidence-based mini-reviews provide useful insights that may guide the direction of future academic emergency surgery research efforts.

Pituitary Adenomas as a Barometer for Health Care Access.

Introduction Expanding access to care has been shown to impact patient care and disease epidemiology for different disease states, but has not been studied in pituitary adenoma. We hypothesize that increasing access to care-which includes diagnostics-through the Affordable Care Act (ACA) and Medicaid expansion has increased identification of pituitary adenomas. Methods The National Cancer Institute's Surveillance, Epidemiology, and End Results database was utilized to identify patients with pituitary adenomas from 2007-to 2016 yielding 39,120 cases. Demographic, histologic, and insurance data were extracted. After stratification based on their insurance status, they were plotted to examine trends in insurance status after introduction of the ACA and Medicaid expansion. Magnetic resonance imaging (MRI) data was gathered from the Organization for Economic Co-operation and Development. A linear regression model was developed to describe the relationship between pituitary adenoma discovery and the number of MRI exams. Results Pituitary adenoma diagnoses (37.6%) and MRI examinations per 1,000 in the U.S. (32.3%) increased concurrently from 2007 to 2016. Linear regression analysis revealed a statistically significant relationship ( p = 0.0004). Those patients without insurance diagnosed with pituitary adenomas decreased 36.8% after Medicaid expansion ( p = 0.023). With respect to Medicaid utilization, significant increases of 28.5% ( p = 0.014) and 30.3% ( p = 0.00096) were noted after both the ACA enactment and Medicaid expansion, respectively. Conclusion The ACA has expanded health care access which has increased the ability to identify patients with pituitary adenomas. The present study also provides evidence that access to care is important for less prevalent diseases such as pituitary adenomas.

A scoping review to inform an auditing framework evaluating healthcare environments for inclusion of people with intellectual disability and/or autism.

People with intellectual disability and/or autism are likely to be in hospital more often, for longer, and have poorer health outcomes. Few audit tools exist to identify their barriers in mainstream healthcare environments. This study aimed to identify evidence of audit characteristics of healthcare contexts specifically for people with intellectual disability and/or autism, for conceptual development of an auditing framework. A scoping review of evaluations of healthcare environments was completed in January 2023. Findings were presented using the PAGER framework. Of the sixteen studies identified, most originated in the UK, nine focused on intellectual disability, four on autism, and three were concerned with mixed diagnosis. Six domains for auditing healthcare environments were identified: care imperatives, communication to individuals, understanding communication from individuals, providing supportive environments of care, supporting positive behaviour, and actions to make things go well. Further research is recommended to refine an audit framework.

Pre-exposure prophylaxis and bacterial sexually transmitted infections (STIs) among gay and bisexual men.

OBJECTIVES: While pre-exposure prophylaxis (PrEP) prevents HIV acquisition among gay, bisexual and other men who have sex with men (GBM), PrEP-using GBM may be more likely to engage in sexual behaviours associated with bacterial STIs. We examined associations between PrEP use, condomless anal sex (CAS), number of anal sex partners, oral sex and bacterial STI diagnoses among GBM living in Canada's three largest cities. METHODS: Among HIV-negative/unknown-status GBM in the baseline of the Engage cohort study, we fit a structural equation model of the associations between any PrEP use, sexual behaviours and bacterial STI diagnosis. We estimated direct and indirect paths between PrEP use and STI via CAS, number of anal sex partners and oral sex. RESULTS: The sample included 2007 HIV-negative/unknown status GBM in Montreal, Toronto and Vancouver. There was a significant direct association between PrEP use and current STI diagnosis (ß=0.181; 95% CI: 0.112 to 0.247; p<0.001), CAS (ß=0.275; 95% CI: 0.189 to 0.361; p<0.001) and number of anal sex partners (ß=0.193; 95% CI: 0.161 to 0.225; p<0.001). In the mediated model, the direct association between PrEP use and STIs was non-significant. However, the indirect paths from PrEP to CAS to STIs (ß=0.064; 95% CI: 0.025 to 0.120; p=0.008), and from PrEP to greater number of anal sex partners to CAS to STIs were significant (ß=0.059; 95% CI: 0.024 to 0.108; p=0.007). CONCLUSIONS: Our study adds to the growing awareness that PrEP use among GBM may be associated with bacterial STIs because PrEP users have more anal sex partners and are more likely to engage in CAS. The results underscore the importance of providing effective STI counselling and regular testing to PrEP users, adapting PrEP care and related STI testing to individual needs, and the need for effective prevention strategies for bacterial STIs.

Accuracy and Precision of the Computed Tomographic Angiography Perforator Localization Technique for Virtual Surgical Planning of Composite Osteocutaneous Fibular Free Flaps in Head and Neck Reconstruction.

BACKGROUND: Virtual surgical planning (VSP), computer aided design/computer aided modeling, and 3-dimensional printing technology have been shown to improve surgical accuracy and efficiency in head and neck reconstruction. However, persisting criticism of the technology is that it does not adequately address the soft tissue-related aspects of reconstructive surgery. Prior publication on the computed tomographic angiography (CTA) perforator localization technique has demonstrated how soft tissue planning can be incorporated directly into existing VSP workflows. PURPOSE: The aim of this study is to prospectively assess the accuracy, precision, negative predictive value (NPV), and positive predictive value (PPV) of the CTA perforator localization technique for VSP of osteocutaneous fibular free flaps. MATERIALS AND METHODS: A prospective observational study in a consecutive cohort of subjects undergoing VSP of osteocutaneous fibular free flaps at Mayo Clinic between 2018 and 2020 was completed. All cutaneous perforators from the peroneal system of the selected donor leg were identified preoperatively through a previously reported CTA tracing method and registered into the VSP. Perforators were classified as primary or secondary based on whether the perforators were targeted for use in the final reconstructive plan. Perforator measurements obtained from the VSP were cross-referenced with intraoperatively obtained measurements of actual perforator locations to calculate accuracy, precision, NPV, PPV, sensitivity, and specificity of the CTA localization technique. RESULTS: Sixty consecutive subjects were enrolled in the study. A total of 141 perforators were identified preoperatively on CTA and 145 perforators were identified on operative exposure. One perforator identified on preoperative CTA was not identified on surgical exposure (false positive perforator). Six perforators were identified on operative exposure alone without recognition on preoperative CTA (false negative perforators). The accuracy of CTA perforator identification was 96.52%. Median precision of perforator localization was 0.3 cm (standard deviation 0.40) between CTA and operatively identified locations. PPV of the technique was 99.29% and NPV was 90.00%. CONCLUSION: The CTA localization technique for identifying and incorporating cutaneous perforator locations into VSP of osteocutaneous fibular free flaps is a reliable, accurate, and precise technique to employ in the modern paradigm of guided surgery for head and neck reconstruction.

A Case Study of the Glycoside Hydrolase Enzyme Mechanism Using an Automated QM-Cluster Model Building Toolkit.

Glycoside hydrolase enzymes are important for hydrolyzing the ß-1,4 glycosidic bond in polysaccharides for deconstruction of carbohydrates. The two-step retaining reaction mechanism of Glycoside Hydrolase Family 7 (GH7) was explored with different sized QM-cluster models built by the Residue Interaction Network ResidUe Selector (RINRUS) software using both the wild-type protein and its E217Q mutant. The first step is the glycosylation, in which the acidic residue 217 donates a proton to the glycosidic oxygen leading to bond cleavage. In the subsequent deglycosylation step, one water molecule migrates into the active site and attacks the anomeric carbon. Residue interaction-based QM-cluster models lead to reliable structural and energetic results for proposed glycoside hydrolase mechanisms. The free energies of activation for glycosylation in the largest QM-cluster models were predicted to be 19.5 and 31.4 kcal mol-1 for the wild-type protein and its E217Q mutant, which agree with experimental trends that mutation of the acidic residue Glu217 to Gln will slow down the reaction; and are higher in free energy than the deglycosylation transition states (13.8 and 25.5 kcal mol-1 for the wild-type protein and its mutant, respectively). For the mutated protein, glycosylation led to a low-energy product. This thermodynamic sink may correspond to the intermediate state which was isolated in the X-ray crystal structure. Hence, the glycosylation is validated to be the rate-limiting step in both the wild-type and mutated enzyme.

Mother-Baby Friendly Philippines: Using Citizen Reporting to Improve Compliance to the International Code of Marketing of Breastmilk Substitutes.

INTRODUCTION: In 1986, the Philippines was one of the first countries to pass national legislation on the International Code of Marketing of Breastmilk Substitutes in the form of Executive Order (EO) 51 and Republic Act (RA) 10028. While violations against the legislation and corresponding sanctions are clearly defined, infractions remain unreported or go unpunished. Enforcement of the laws remains a significant challenge as government capacities suffer from inadequate resources to regularly monitor breastfeeding-related law violations. To address these gaps, The Department of Health (Philippines) and the World Vision Development Foundation developed a reporting platform to enable citizen reporting of EO 51 and RA 10028 violations as part of the Mother-Baby Friendly Philippines (MBFP) initiative. METHODS: Upon completion of the project, the Alliance for Improving Health Outcomes Inc. conducted 68 surveys and 24 key informant interviews and focus group discussions with individuals who participated in trainings on EO 51 and RA 10028, community health workers, representatives of local government units and hospitals involved in breastfeeding programs, and city health officials to document benefits, challenges, and lessons learned. RESULTS: The intention and interest of consulted stakeholders to uphold the law by reporting violations through the platform indicate that citizen reporting can be harnessed as an effective tool for reporting violations. Nevertheless, multiple challenges remain in reporting and following up on Code violations. DISCUSSION: The platform provided citizens with an opportunity to report violations, but, in reality, the status of action and feedback did not change. There is a need to strengthen implementation and enforcement at all levels of relevant national government agencies and improve feedback loops on reported violations.

Prevalence and predictive factors of strain among caregivers of people with disability: results from R-Care community survey, Kerala, India.

PURPOSE: Caregivers of people with disability experience difficulties in a variety of care domains. Understanding the predictive factors of caregiver strain is important in developing and implementing evidence-based intervention to reduce the difficulties experienced by the carers. METHODS: The current study is a cross sectional comprehensive one-phase survey conducted in randomly selected sub-districts (taluks) of the Ernakulam district in Kerala. Primary caregivers (n = 851) for persons with different kinds of disability were identified with the help of ASHAs (Accredited Social Health Activities) from the selected geographical locations and were interviewed in a house-to-house survey after obtaining written informed consent. Validated tools measuring caregiver strain, financial burden, access to services and wellbeing were used to study the population. RESULTS: Majority of the caregivers were females (77.3%) and spouses (35.2%). Of the caregivers 27% reported high levels of caregiver strain. The major factors associated with caregiver strain were female gender (B = 1.379, p = 0.000), financial issues (B = 0.105, p = 0.000), the general health of caregivers (B = 0.467, p = 0.000) and issues relating to employment (B = 0.956, p = 0.000) and the availability of government welfare services (B = 1.138, p = 0.000). CONCLUSION: High caregiver burden and strain is experienced by almost a third of people caring for a person with a disability. Comprehensive interventions to reduce caregiver strain should be developed.Implications for rehabilitationThe rehabilitation sector needs to be made aware of the high levels of caregiver strain (especially in carers who were female, unemployed, have health issues and lack formal support).To improve wellbeing for people with disability we firstly need to promote social inclusion and support schemes for caregiver.Co-designed systems are needed to assist carers to access formal and informal support resources, and increase social connectedness.

Longitudinal uptake of the human papillomavirus vaccine among gay, bisexual and other men who have sex with men in British Columbia, Canada 2012-2019.

OBJECTIVES: In 2015, a publicly funded human papillomavirus (HPV) vaccination programme was implemented for gay, bisexual and other men who have sex with men (gbMSM) up to age 26 years in British Columbia, Canada. We assessed trends and correlates of HPV vaccine uptake from 2012 to 2019 in a cohort of gbMSM in Vancouver. METHODS: We recruited sexually active gbMSM aged ≥16 years using respondent-driven sampling from February 2012 to February 2015 and followed them until July 2019. We evaluated self-reported HPV vaccine trends using mixed-effects logistic regression and identified factors associated with uptake using multivariable mixed-effects Poisson regression. RESULTS: A total of 719 participants were recruited and completed the baseline visit, of whom 549 were unvaccinated with at least one follow-up visit. The median age was 33 years and 23% were living with HIV. HPV vaccination increased from 4% in 2012 to 28% in 2019 (p<0.001) among gbMSM >26 years, and from 9% in 2012 to 20% in 2017 (p<0.001) among gbMSM ≤26 years. Vaccination uptake increased after September 2015, following vaccination policy expansion (adjusted rate ratio (aRR)=1.82, 95% CI 1.06 to 3.12). In multivariable models, increased vaccination was associated with age ≤26 years vs ≥45 years (aRR=3.90; 95% CI 1.75 to 8.70), age 27-44 vs ≥45 years (aRR=2.86; 95% CI 1.46 to 5.62), involvement in gay community sports teams (aRR=2.31; 95% CI 1.15 to 4.64) and other groups (aRR=1.71; 95% CI 1.04 to 2.79), awareness of HIV-postexposure prophylaxis (aRR=5.50; 95% CI 1.31 to 23.09), recent sexually transmitted infection testing (aRR=2.72; 95% CI 1.60 to 4.60) and recent sex-work (aRR=2.59; 95% CI 1.08 to 6.19). CONCLUSIONS: Although we observed increases in HPV vaccination uptake from 2012, by 2019 HPV vaccination still remained below 30% among gbMSM in Vancouver, BC. Additional interventions are needed to increase vaccine uptake.

The Medial Femoral Condyle Free Flap for Reconstruction of Recalcitrant Defects in the Head and Neck.

BACKGROUND: Small recalcitrant defects of the mandible and maxilla may be secondary to tumor, trauma, infection, and congenital origin. Vascularized bone grafting has been shown to effectively manage these defects; however, donor sites are limited. The vascularized medial femoral condyle (MFC) provides adequate cortical cancellous bone with the option of a skin island, consistent anatomy, and minimal donor site morbidity. This article outlines the use of the MFC flap for maxillomandibular reconstruction. METHODS: A retrospective chart review of patients who required segmental maxillomandibular reconstruction with the MFC flap was conducted. A total of 9 patients (5 men and 5 women) with an average age of 45.3 years were identified. The etiology of the defects, flap sizes, and postoperative outcomes were recorded. RESULTS: Three patients had osteoradionecrosis of the neomandible after irradiation of the free fibula reconstruction, 3 patients had defects after cancer extirpation (1 mandible, 2 maxillary), 1 patient had a maxillary defect from trauma, and 2 patients had a residual cleft palate defect. All defects failed initial treatment with nonvascularized bone grafts. The average dimensions of the MFC flaps were 1.2 × 2.5 × 4 cm. Two of 9 flaps included a skin island. Eight flaps survived completely, but 1 patient suffered from flap failure requiring debridement and resulted in an oroantral fistula. Four patients received endosseous dental implants. Average time to union was 6.7 months, and average time to implant was 6.75 months. The average follow-up time was 24.9 months. CONCLUSIONS: The MFC flap is useful in the reconstruction of small segmental maxillomandibular defects and for the salvage of a neomandible after osteoradionecrosis. The MFC flap provides a reliable platform for endosseous dental implants and serves as an alternative source of vascularized bone reconstruction in the head and neck.

Management of Nasal Trauma.

Facial trauma can have long-lasting physical and mental consequences. Trauma to the nose is commonly seen in the emergency department. Nasal lacerations account for 7% of all facial lacerations. Thorough examination and documentation including photographs is important for documentation and creating a reconstruction plan. Underlying damage to cartilage or bone must be reconstructed initially or in a delayed fashion to recreate the pretrauma anatomy and function. There are several options for soft tissue nasal reconstruction, including local flaps, skin grafts, pedicle flaps, and free flaps. At present there is no standard of care for postoperative facial trauma wound care.

Trends in hepatitis C virus seroprevalence and associated risk factors among men who have sex with men in Montréal: results from three cross-sectional studies (2005, 2009, 2018).

OBJECTIVES: To eliminate the hepatitis C virus (HCV) by 2030, Canada must adopt a microelimination approach targeting priority populations, including gay, bisexual and other men who have sex with men (MSM). Accurately describing HCV prevalence and risk factors locally is essential to design appropriate prevention and treatment interventions. We aimed to estimate temporal trends in HCV seroprevalence between 2005 and 2018 among Montréal MSM, and to identify socioeconomic, behavioural and biological factors associated with HCV exposure among this population. METHODS: We used data from three cross-sectional surveys conducted among Montréal MSM in 2005 (n=1795), 2009 (n=1258) and 2018 (n=1086). To ensure comparability of seroprevalence estimates across time, we standardised the 2005 and 2009 time-location samples to the 2018 respondent-driven sample. Time trends overall and stratified by HIV status, history of injection drug use (IDU) and age were examined. Modified Poisson regression analyses with generalised estimating equations were used to identify factors associated with HCV seropositivity pooling all surveys. RESULTS: Standardised HCV seroprevalence among all MSM remained stable from 7% (95% CI 3% to 10%) in 2005, to 8% (95% CI 1% to 9%) in 2009 and 8% (95% CI 4% to 11%) in 2018. This apparent stability hides diverging temporal trends in seroprevalence between age groups, with a decrease among MSM <30 years old and an increase among MSM aged ≥45 years old. Lifetime IDU was the strongest predictor of HCV seropositivity, and no association was found between HCV seroprevalence and sexual risk factors studied (condomless anal sex with men of serodiscordant/unknown HIV status, number of sexual partners, group sex). CONCLUSIONS: HCV seroprevalence remained stable among Montréal MSM between 2005 and 2018. Unlike other settings where HCV infection was strongly associated with sexual risk factors among MSM, IDU was the pre-eminent risk factor for HCV seropositivity. Understanding the intersection of IDU contexts, practices and populations is essential to prevent HCV transmission among MSM.

Safety of Outpatient Procedural Sedation Administered by Oral and Maxillofacial Surgeons: The Mayo Clinic Experience in 17,634 Sedations (2004 to 2019).

PURPOSE: The safety of the team anesthesia model routinely used by the specialty of oral and maxillofacial surgery has recently been called into question. The purpose of this article is to measure the frequency of adverse anesthetic events related to ambulatory surgical procedures performed under intravenous (IV) sedation by the Division of Oral and Maxillofacial Surgery at the Mayo Clinic during a 15-year period using the team anesthesia model. MATERIALS AND METHODS: A retrospective cohort study was designed, and a sample of subjects identified undergoing IV sedation at Mayo Clinic from 2004 to 2019. The primary outcome variable of interest was the presence of anesthetic-related adverse events (AEs) consistent with the World Society of Intravenous Anesthesia International Sedation Task Force's intervention-based definitions of adverse anesthetic events. Additional covariates included patient age, gender, American Society of Anesthesiologists (ASA) score, type of surgical procedure performed, and the type/dosage of medications administered periprocedurally. Univariate logistic regression analysis was used to assess for associations between AEs and covariates. RESULTS: The study identified 17,634 sedations administered to 16,609 unique subjects. In 17,634 sedations, 16 (0.1%) AEs and no subject deaths (0%) were identified. There were no statistically significant associations between AEs and age (hazard ratio [HR], 0.4; 95% confidence interval [95% CI], 0.2 to 1.3; P = .13); gender (HR, 0.9; 95% CI, 0.3 to 2.5; P = .87); ASA 2 classification (HR, 1.6; 95% CI, 0.6 to 4.5; P = .33); ASA 3 classification (HR, 1.3; 95% CI, 0.1 to 22.0; P = .86), or types of IV sedation medications administered during the procedure: fentanyl (HR, 0.4; 95% CI, 0.02 to 6.3; P = .5); midazolam (HR, 1.0; 95% CI, 0.2 to 4.3; P = .98); propofol (HR, 1.0; 95% CI, 0.3 to 3.5; P = .99); or ketamine (HR, 1.0; 95% CI, 0.1 to 7.3; P = .97). CONCLUSIONS: The frequency of AEs (0.1%) and 0% mortality rate reported in this study demonstrate that the anesthesia team model used by oral and maxillofacial surgeons compares favorably to standardized intervention-based adverse anesthetic event outcomes reported by other nonanesthesiology specialties routinely performing outpatient procedural sedation.

Microvascular Reconstruction of Total Maxillary Avascular Necrosis as a Complication of Routine Orthognathic Surgery.

Severe complications and morbidity after orthognathic surgery are infrequently encountered and even more infrequently reported considering the extent to which this procedure is performed by surgeons within the specialty of maxillofacial surgery. Avascular necrosis of the maxilla after Le Fort I osteotomy is perhaps the most dreaded outcome of orthognathic surgery. However, it accounts for an extremely small subset of overall surgical complications. The reported risk factors associated with avascular maxillary necrosis include segmental osteotomies, vertical posterior impactions, large transverse expansions, anterior advancements exceeding 9 to 10 mm, an improper surgical technique, excessive soft tissue degloving of the maxilla, intraoperative hemorrhage, perforation or laceration of the palatal soft tissue pedicle, previous maxillary or palatal surgery, and other medical comorbidities. Although anecdotal cases of total maxillary necrosis after orthognathic surgery have been alluded to within the specialty as a whole, to the best of our knowledge, no previous studies have reported total maxillary necrosis occurring after routine orthognathic surgery. We have presented a truly unique case of total maxillary avascular necrosis that occurred after standard 1-piece Le Fort I osteotomy in a patient without medical or surgical risk factors for the complication either known preoperatively or identified postoperatively. The resultant maxillary defect from total avascular necrosis was comprehensively treated with surgical debridement of the nonviable maxilla, osteocutaneous fibular free flap reconstruction, staged endosseous implant reconstruction of the neomaxilla, and comprehensive prosthodontic rehabilitation.

Disabled People's Organisations increase access to services and improve well-being: evidence from a cluster randomized trial in North India.

BACKGROUND: Disabled People's Organisations (DPOs) are the mainstay of disability responses worldwide. Yet there is no quantitative data assessing their effectiveness in low-and middle-income countries (LMICs). The aim of this study was to measure the effectiveness of DPOs as a low-cost intervention to improve well-being and access to services and facilities for people with disabilities. METHODS: We undertook a cluster randomised intervention control trial across 39 distinct rural villages in Uttarakhand State, North India. A total of 527 participants were included from 39 villages: 302 people from 20 villages were assigned to the intervention arm and 225 from 19 villages were assigned to the control group. Over a 2-year period, people with disabilities were facilitated to form DPOs with regular home visits. Participants were also given financial support for public events and exposure visits to other DPOs. Seven domains were used to measure access and participation. RESULTS: DPO formation had improved participation in community consultations (OR 2.57, 95% CI 1.4 to 4.72), social activities (OR 2.46, 95% CI 1.38 to 4.38), DPOs (OR 14.78, 95% CI 1.43 to 152.43), access to toilet facilities (OR 3.89, 95% CI 1.31 to 11.57), rehabilitation (OR 6.83, 95% CI 2.4 to 19.42) and Government social welfare services (OR 4.82, 95% CI 2.35 to 9.91) in intervention when compared to the control. People who were part of a DPO had an improvement in having their opinion heard (OR 1.94, 95% CI 1.16 to 3.24) and being able to make friends (OR 1.63, 95% CI 1 to 2.65) compared to those who were not part of a DPO. All other well-being variables had little evidence despite greater improvement in the DPO intervention group. CONCLUSIONS: This is the first randomised control trial to demonstrate that DPOs in LMICs are effective at improving participation, access and well-being. This study supports the ongoing role of DPOs in activities related to disability inclusion and disability services. This study also suggests that supporting the establishment, facilitation and strengthening of DPOs is a cost-effective intervention and role that non-governmental organisations (NGOs) can play. TRIAL REGISTRATION: ISRCTN36867362, 9th Oct 2019 (retrospectively registered).

Membrane trafficking in osteoclasts and implications for osteoporosis.

Osteoclasts are large multinucleated cells exquisitely adapted to resorb bone matrix. Like other eukaryotes, osteoclasts possess an elaborate ensemble of intracellular organelles through which solutes, proteins and other macromolecules are trafficked to their target destinations via membrane-bound intermediaries. During bone resorption, membrane trafficking must be tightly regulated to sustain the structural and functional polarity of the osteoclasts' membrane domains. Of these, the ruffled border (RB) is most characteristic, functioning as the osteoclasts' secretory apparatus. This highly convoluted organelle is classically considered to be formed by the targeted fusion of acidic vesicles with the bone-facing plasma membrane. Emerging findings disclose new evidence that the RB is far more complex than previously envisaged, possessing discrete subdomains that are serviced by several intersecting endocytic, secretory, transcytotic and autophagic pathways. Bone-resorbing osteoclasts therefore serve as a unique model system for studying polarized membrane trafficking. Recent advances in high-resolution microscopy together with the convergence of genetic and cell biological studies in humans and in mice have helped illuminate the major membrane trafficking pathways in osteoclasts and unmask the core molecular machinery that governs these distinct vesicle transport routes. Among these, small Rab GTPases, their binding partners and members of the endocytic sorting nexin family have emerged as critical regulators. This mini review summarizes our current understanding of membrane trafficking in osteoclasts, the key molecular participants, and discusses how these transport machinery may be exploited for the development of new therapies for metabolic disorders of bone-like osteoporosis.

Sertraline Pharmacokinetics in HIV-Infected and Uninfected Children, Adolescents, and Young Adults.

Objective: Due to potential disease and drug interactions, the appropriate sertraline starting dose and titration range may require adjustment in pediatric patients living with HIV. This is the first report of sertraline pharmacokinetics in HIV-infected youth. Methods: IMPAACT P1080 was a multicenter pilot study describing psychiatric medication pharmacokinetics in HIV-infected and uninfected youth. Participants were stable on sertraline, >6 to <25 years old, and (1) HIV-uninfected (HIV(-)), (2) HIV-infected taking efavirenz (EFV), or (3) HIV-infected taking boosting ritonavir/protease inhibitor (PI/r). Sampling occurred at pre-dose, 2, 4, 6, 12, and 24-h post-dose. Analyses were performed for sertraline and N-desmethylsertraline, and CYP2D6 phenotyping was completed with dextromethorphan. Results: Thirty-one participants (16 HIV(-), 12 PI/r, and 3 EFV) had median (range) weight, age, and dose of 69.5 (31.5-118.2) kg, 21.8 (9.1-24.7) years, and 75.0 (12.5-150.0) mg once daily. Sertraline exposure was highest for HIV(-) and lowest for EFV cohorts; median dose-normalized AUC 0-24 was 1176 (HIV(-)), 791 (PI/r) and 473 (EFV) ng*hr/mL, and C24 was 32.7 (HIV(-)), 20.1 (PI/r), and 12.8 (EFV) ng/mL. The urinary dextromethorphan/dextrorphan (DXM/DXO) ratio was higher in HIV(-) vs. PI/r cohorts (p = 0.01). Four HIV(-) participants were CYP2D6 poor metabolizers (ln(DXM/DXO) of >-0.5). Conclusions: HIV(-) cohort had the highest sertraline exposure. Sertraline exposure was ~40% lower in the PI/r cohort than in HIV(-); the need to alter sertraline dose ranges for PI/r participants is not clear. The impact of efavirenz on sertraline needs further investigation due to limited numbers of EFV participants.

Using Geosocial Networking Apps to Understand the Spatial Distribution of Gay and Bisexual Men: Pilot Study.

BACKGROUND: While services tailored for gay, bisexual, and other men who have sex with men (gbMSM) may provide support for this vulnerable population, planning access to these services can be difficult due to the unknown spatial distribution of gbMSM outside of gay-centered neighborhoods. This is particularly true since the emergence of geosocial networking apps, which have become a widely used venue for meeting sexual partners. OBJECTIVE: The goal of our research was to estimate the spatial density of app users across Metro Vancouver and identify the independent and adjusted neighborhood-level factors that predict app user density. METHODS: This pilot study used a popular geosocial networking app to estimate the spatial density of app users across rural and urban Metro Vancouver. Multiple Poisson regression models were then constructed to model the relationship between app user density and areal population-weighted neighbourhood-level factors from the 2016 Canadian Census and National Household Survey. RESULTS: A total of 2021 app user profiles were counted within 1 mile of 263 sampling locations. In a multivariate model controlling for time of day, app user density was associated with several dissemination area-level characteristics, including population density (per 100; incidence rate ratio [IRR] 1.03, 95% CI 1.02-1.04), average household size (IRR 0.26, 95% CI 0.11-0.62), average age of males (IRR 0.93, 95% CI 0.88-0.98), median income of males (IRR 0.96, 95% CI 0.92-0.99), proportion of males who were not married (IRR 1.08, 95% CI 1.02-1.13), proportion of males with a postsecondary education (IRR 1.06, 95% CI 1.03-1.10), proportion of males who are immigrants (IRR 1.04, 95% CI 1.004-1.07), and proportion of males living below the low-income cutoff level (IRR 0.93, 95% CI 0.89-0.98). CONCLUSIONS: This pilot study demonstrates how the combination of geosocial networking apps and administrative datasets might help care providers, planners, and community leaders target online and offline interventions for gbMSM who use apps.

An Event-Level Analysis of Condom Use During Anal Intercourse Among Self-Reported Human Immunodeficiency Virus-Negative Gay and Bisexual Men in a Treatment as Prevention Environment.

BACKGROUND: We sought to identify factors associated with condom use during anal intercourse among self-identified human immunodeficiency virus-negative gay, bisexual, and other men who have sex with men (GBM) in Vancouver, Canada following "treatment as prevention" (TasP) scale-up in 2010. METHODS: Sexually active GBM were recruited using respondent-driven sampling from 2012 to 2014. We analyzed participants' most recent sexual encounter with up to their last 5 sexual partners within the past 6 months. In addition to individual- and event-level explanatory factors, we assessed potential associations with TasP awareness, TasP-related prevention practice (viral load sorting), and TasP-related attitudes (human immunodeficiency virus treatment optimism). Accounting for clustering at the respondent-driven sampling chain-level and participant-level, factors associated with event-level condom use versus nonuse were determined using a multivariable generalized linear mixed model built using backward selection and AIC minimization. RESULTS: Of 513 participants, 436 GBM (85%) reported a total of 1196 anal sex events with 56% condom use. The proportion of condom-protected sexual events decreased monthly over the study period (odds ratio [OR], 0.95 per month, 95% confidence interval [CI], 0.92-0.98). The TasP practices and attitudes were significantly associated with lower odds of condom use at the univariate level, but were no longer significant at multivariate level. In the multivariable model, event-level partner methamphetamine use (adjusted OR [aOR], 0.18; 95% CI, 0.06-0.58), frequency of recent anal intercourse with that partner (aOR, 0.97 per act; 95% CI, 0.95-0.98) and time since first sex with that partner (aOR, 0.97 per 6 months; 95% CI, 0.95-0.99) were associated with lower odds of condom use, whereas event-level participant alcohol use (aOR, 1.41; 95% CI, 1.01-1.98) and no planned future sex with that partner (aOR, 1.56; 95% CI, 1.08-2.27) were associated with greater odds of condom use. Event-level receptive-only (aOR, 2.10; 95% CI, 1.38-3.20) or insertive-only (aOR, 2.53; 95% CI, 1.64-3.90) sexual positions were associated with greater odds of condom use compared with reporting both positions. CONCLUSIONS: The TasP-related factors were not the most salient predictors of GBM's condom use. Health promotion must consider associations between condomless anal sex and substance use and relational factors.

Does size really matter? A sensitivity analysis of number of seeds in a respondent-driven sampling study of gay, bisexual and other men who have sex with men in Vancouver, Canada.

BACKGROUND: Respondent-driven sampling (RDS) is an increasingly used peer chain-recruitment method to sample "hard-to-reach" populations for whom there are no reliable sampling frames. Implementation success of RDS varies; one potential negative factor being the number of seeds used. METHODS: We conducted a sensitivity analysis on estimates produced using data from an RDS study of gay, bisexual and other men who have sex with men (GBMSM) aged ≥16 years living in Vancouver, Canada. Participants completed a questionnaire on demographics, sexual behavior and substance use. For analysis, we used increasing seed exclusion criteria, starting with all participants and subsequently removing unproductive seeds, chains of ≤1 recruitment waves, and chains of ≤2 recruitment waves. We calculated estimates for three different outcomes (HIV serostatus, condomless anal intercourse with HIV discordant/unknown status partner, and injecting drugs) using three different RDS weighting procedures: RDS-I, RDS-II, and RDS-SS. We also assessed seed dependence with bottleneck analyses and convergence plots. Statistical differences between RDS estimators were assessed through simulation analysis. RESULTS: Overall, 719 participants were recruited, which included 119 seeds and a maximum of 16 recruitment waves (mean chain length = 1.7). The sample of >0 recruitment waves removed unproductive seeds (n = 50/119, 42.0%), resulting in 69 chains (mean length = 3.0). The sample of >1 recruitment waves removed 125 seeds or recruits (17.4% of overall sample), resulting in 37 chains (mean length = 4.8). The final sample of >2 recruitment waves removed a further 182 seeds or recruits (25.3% of overall sample), resulting in 25 chains (mean length = 6.1). Convergence plots and bottleneck analyses of condomless anal intercourse with HIV discordant/unknown status partner and injecting drugs outcomes were satisfactory. For these two outcomes, regardless of seed exclusion criteria used, the crude proportions fell within 95% confidence intervals of all RDS-weighted estimates. Significant differences between the three RDS estimators were not observed. CONCLUSIONS: Within a sample of GBMSM in Vancouver, Canada, this RDS study suggests that when equilibrium and homophily are met, although potentially costly and time consuming, analysis is not negatively affected by large numbers of unproductive or lowly productive seeds.