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Study Design: A sex- and age-matched case-control study and a cross-sectional study. Objective: In our previous study, patients with early-onset (Methods: In Study 1, the simple brief-type self-administered diet history questionnaire (BDHQ) was used to compare nutrient intake levels of early-onset OPLL patients (n = 13) with those of sex- and age-matched non-OPLL controls (n = 39) or with those of common OPLL (onset age ≥ 50 years, n = 62). In Study 2, serological validation was conducted for thoracic OPLL patients (n = 77) and non-OPLL controls (n = 101) in a nationwide multicenter study in Japan. Results: The BDHQ showed that the early-onset OPLL patients had significantly lower intakes of vitamins A and B6 than non-OPLL controls. These results were validated by lower serum vitamins A and B6 levels in the early-onset thoracic OPLL patients. The severity of OPLL negatively correlated with serum vitamin A levels in male early-onset OPLL patients. The multiple regression analysis revealed that the severity of thoracic OPLL had an association with onset age and serum vitamin A level. Conclusions: Vitamin A deficiency resulting from unbalanced dietary habits is associated with exacerbation of male early-onset OPLL.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the formation of antigen–antibody complexes which trigger an immune response. We investigate certain autoantibodies including nucleosome, double-stranded DNA (dsDNA), Smith, ribonucleoprotein, and Sjögren's syndrome-related antigens, and examine their associations with disease activity, damage accrual, and SLE-related clinical and serological manifestations in patients with SLE. We conducted a cross-sectional study with a total 293 patients (90.4% female, mean age 46.87±12.94 years) and used the Systemic Lupus Erythematosus Disease Activity Index 2000 and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) to evaluate disease activity and disease-related damage, respectively. Systemic Lupus Erythematosus Disease Activity Index scores were significantly higher in anti-nucleosome-positive (3.87±2.72 vs 2.52±2.76, p=0.004) and anti-dsDNA-positive (3.08±2.91 vs 2.04±2.48, p=0.010) patients compared with patients without these antibodies. SDI scores were also significantly higher in anti-nucleosome-positive patients (1.61±1.99 vs 0.89±1.06, p=0.004). The presence of antinucleosome (p=0.019) and anti-dsDNA antibodies (p=0.001) both correlated significantly with the incidence of nephritis; anti-La antibodies were associated with arthritis (p=0.022), and we also observed a relationship between the presence of antinucleosome antibodies and leukopenia (p=0.011). Patients with antinucleosome or anti-dsDNA antibodies had a higher disease activity and were likely to have nephritis. Antinucleosome was also associated with more damage accrual. A greater understanding of these autoantibodies could lead to the development of new approaches to more accurate assessments of SLE.

Despite hypertension ranks among the leading causes of chronic kidney disease (CKD), the impact of chronic hypertensive nephropathy, the so-called ‘nephrosclerosis’ (NS), on CKD progression is often unpredictable, particularly in elderly population. We have conducted a prospective, observational study to define renal function patterns and outcomes in elderly CKD individuals with or without NS. Three hundred four individuals with an already established CKD were categorized according to the etiology of CKD. NS was defined as the presence of CKD associated with long-term essential hypertension, hypertensive retinopathy, left ventricular hypertrophy and minimal proteinuria. Time trajectories in estimated glomerular filtration rate (eGFR) (CKD-Epi) were computed over a 4-year follow-up. In addition, we analyzed the occurrence of a composite outcome of doubling of serum creatinine levels, eGFR reduction ≥25% and/or the need of chronic renal replacement therapy. CKD was secondary to nephrosclerosis (CKD-NS) in 220 (72.3%). In the whole cohort, the average estimated annual GFR slope was 1.8 mL/min/1.73 m2. eGFR decline was slower in CKD-NS as compared with others (1.4 vs 3.4 mL/min/1.73 m2; p

Sonographic septation is associated with prolonged hospitalization and increased mortality in patients diagnosed with empyema. However, it is unknown whether sonographic septation is associated with complicated parapneumonic effusion (CPPE) or the need for invasive procedures among patients with pneumonia. In this retrospective study, we included 180 patients with non-purulent neutrophilic exudative pleural effusion secondary to pulmonary infections such as pneumonia and lung abscess. We performed univariate and multivariate logistic regression analyses, including baseline clinical characteristics, values from blood samples, and sonographic echogenicity, to identify variables correlated with CPPE and the need for invasive procedures. Seventy of the 180 included patients (38.89%) displayed sonographic septation. Multivariate logistic regression analysis identified that sonographic septation (adjusted OR (AOR)=3.38 (95% CI 1.64 to 6.98), p=0.001) and younger age (AOR=2.63 (95% CI 1.24 to 5.58), p=0.012) were independently associated with CPPE. With regard to treatment strategy, sonographic septation (AOR 9.06 (95% CI 3.71 to 22.11), p

This study aims to establish a new scoring system based on biomarkers for predicting in-hospital mortality of children admitted to the pediatric intensive care unit (PICU). The biomarkers were chosen using the least absolute shrinkage and selection operator (LASSO)-logistic regression in this observational case-control study. The performance of the new predictive model was evaluated by the area under the receiver operating characteristic curve (AUC). Calibration plot was established to validate the new score accompanied by the Hosmer-Lemeshow test. There were 8818 patients included in this study. Finally, six predictors were included in the LASSO-regression model. Albumin 452 U/L, lactate >3.2 mmol/L, urea >5.6 mmol/L, arterial PH 6.9 mmol/L were treated as risk factors for higher mortality. The new score ranged from 1 to 6 among all the included patients. In the training set, the AUC of the probability of in-hospital mortality for the new predictive model was 0.81 (95% CI 0.79 to 0.84), which is larger than for the Pediatric Critical Illness Score (PCIS) (0.69, 95% CI 0.66 to 0.72). Similarly, in the validating set, the AUC of the probability of in-hospital mortality was larger for the new score (0.80, 95% CI 0.77 to 0.84) than for PCIS (0.67, 95% CI 0.63 to 0.72). The calibration plot and Hosmer-Lemeshow test showed excellent calibration. The calculated ORs showed a trend that higher scores indicated higher risk of death (p value for trend

The role of thrombolysis in submassive pulmonary embolism (PE) is controversial due to the high risk of hemorrhage. This study aimed to evaluate the role of half-dose tissue-type plasminogen activator (rt-PA) in preventing death/hemodynamic decompensation in submassive (intermediate-risk) PE without increasing the risk of bleeding. In a prospective, non-randomized, open-label, single-center trial, we compared 50 mg rt-PA plus low molecular weight heparin (LMWH) with LMWH in submassive (intermediate-risk) PE. Eligible cases had confirmed pulmonary hypertension on echocardiography, and/or right ventricular cavity expansion and/or interventricular septal deviation on echocardiography, and/or right to left ventricular ratio equal to or greater than 0.9 mm on CT angiography. The primary outcome was death or hemodynamic decompensation within 7 and 30 days after treatment was given. The primary safety outcome was major extracranial bleeding or hemorrhagic stroke within 7 days. Seventy-six patients were included in the study. Total death/hemodynamic decompensation in the first 7 and 30 days was significantly less in the half-dose rt-PA group than in the LMWH group (p=0.028 and p=0.009, respectively). No significant differences were found between the two groups in terms of recurrent embolism and pulmonary hypertension at 6-month follow-up (p=1.000 and p=0.778). There was no intracranial hemorrhage in any of the patients. There were no statistically significant differences between the two groups in terms of major or minor bleeding complications. This trial showed half-dose rt-PA treatment in submassive (intermediate-risk) PE prevented death/hemodynamic decompensation in the first 7-day and 30-day period compared with LMWH treatment without increasing the risk of bleeding.

We investigated the reliability of the 4Fusion® quadripodal memory staple in a consecutive series of 59 four-corner arthrodeses in a single centre. Forty-one patients (46 wrists) had a radiological and clinical assessment at a mean follow-up of 7.4 years. Thirteen patients (13 wrists) were lost to follow-up. Bone union was achieved in all but one patient. Seven patients were reoperated, six for device removal and one for nonunion. Most patients were satisfied, had a functional range of wrist mobility, good strength and were free of pain, comparable with the best previously reported series. Level of evidence: IV

Objective Determine efficacy of the novel WiiNWalk intervention on walking-related outcomes in older adults with lower limb amputation. Design Multi-site, parallel, evaluator-masked randomized controlled trial. Setting Home-setting in three Canadian cities. Participants Community-dwelling lower limb prosthesis users over 50 years of age. Interventions The WiiNWalk group (n = 38) used modified Wii Fit activities for prosthetic rehabilitation. The attention control group (n = 33) used Big Brain Academy: Wii Degree, comprising of cognitive activities. Both groups completed a 4-week supervised phase with three 1-h sessions/week in groups of three overseen by a clinician via videoconferencing and a 4-week unstructured and unsupervised phase. Main Measures Primary outcome was walking capacity (2 min walk test); secondary outcomes were balance confidence (activities-specific balance confidence scale), dynamic balance (four-step square test), and lower limb functioning (short physical performance battery). Outcomes were compared across time points with repeated measures analysis of covariance, adjusting for baseline and age. Results Mean age was 65.0 (8.4) years, with 179.5 (223.5) months post-amputation and 80% transtibial amputation. No group difference in a 2 min walk test with an effect size: 1.53 95% CI [−3.17, 6.23] m. Activities balance confidence was greater in the WiiNWalk group by 5.53 [2.53, 8.52]%. No group difference in the four-step square test −0.16 [−1.25, 0.92] s, nor short physical performance battery 0.48 [−0.65, 1.61]. A post-hoc analysis showed the greatest difference in balance confidence immediately after an unsupervised phase. Conclusions The WiiNWalk intervention improved balance confidence, but not walking-related physical function in older adult lower limb prosthesis users. Future rehabilitation games should be specific to the amputation context. Clinical Trial Registration number, NCT 01942798.

Kettil Bruun is best known for the total consumption model introduced in 1975 in the collective work “Alcohol control policy in public health perspective”. There were three tracks in particular that led Bruun's research towards the total consumption model: research on the distribution of power, research on international drug policies, and his contributions to criminology and social policy. Kettil Bruun’s lifework shows that the innovation, intersectionality, and synergy which are now rehearsed in pompous research strategies were a non-question 40 years ago. These aspects were a natural part of the scientific pursuit of answers. Maybe in a much more modest and homemade form, but all the more import in terms of applicability at the general level of principle.

Children and adolescents with Inflammatory Bowel Disease (IBD) face significant and unique challenges related to their condition. The aim of this study was to better understand some of these challenges, and to explore how Canadian youth respond to them. We interviewed 25 pediatric patients with IBD, ranging in age from 10–17, to find out about their illness experiences. Using a thematic analysis, we discerned three themes: challenges related to diagnosis, making sense of change, and navigating sociability. Taken together, they paint a picture of young people facing great uncertainty prior to diagnosis, pronounced changes to selfhood as they make lifestyle adjustments, and facing difficulties with the implications of reduced sociability because of their disease. We conclude by providing recommendations for the development of resources aimed at helping newly diagnosed pediatric patients navigate these issues.

Objectives Poisoning from psychoactive drugs and substance use disorders (SUD) have been reported among non-medical cannabis users. However, little is known about medical cannabis users and their risk for poisoning and/or development of SUD. This study assessed the risk of emergency department (ED) visits or hospitalization for 1) poisoning by psychoactive drugs and 2) mental/behavioural disorders due to the use of psychoactive drugs and other substances, in medically authorized cannabis patients in Ontario, Canada from 2014–2017. Methods A cohort study of adult patients authorized for medical cannabis that were matched to population-based controls. ED visit/hospitalization were assessed with a main diagnostic code for: 1) poisoning by psychoactive drugs; 2) mental and behavioural disorder due to psychoactive drugs or other substance use. Conditional Cox proportional hazards regressions were conducted. Results 18,653 cannabis patients were matched to 51,243 controls. During a median follow-up of 243 days, the incidence rate for poisoning was 4.71 per 1,000 person-years (95%CI: 3.71–5.99) for cases and 1.73 per 1,000 person-years (95% CI: 1.36–2.19) for controls. The adjusted hazard ratio (aHR) was 2.45 (95%CI: 1.56–3.84). For mental/behavioural disorders, the incident rates were 8.89 (95% CI: 7.47–10.57) and 5.01 (95% CI: 4.36–5.76) in the cannabis and the controls group. The aHR was 2.27 (95%CI: 1.66–3.11). No difference was observed between males and females ( P-value for interaction > 0.05). Conclusions Our study observed a short-term increased risk of ED visit/hospitalization for poisoning or for mental/behavioural disorders (from use of psychoactive drugs and other substances)- in medically authorized cannabis patients.

Purpose The intravitreal dexamethasone implant (DEX-I) is an alternative to anti-VEGF for the first-line treatment of diabetic macular oedema (DME). However, several questions remain regarding its routine use and its place in certain situations not always specified in current recommendations. A national consensus approach was, therefore, initiated by French retinal experts. Methods An iterative Delphi consensus approach was used. A steering committee (SC) of seven experts analysed data from the literature to formulate statements divided into five key areas of treatment. These statements were submitted to the independent and anonymous electronic vote of 87 French retina experts among whom 39 expressed their opinion and therefore constituted the voting panel. Results After two rounds of voting, 22 and 7 of 38 statements received a strong consensus and a good consensus, respectively. The consensus level was higher for statements regarding first-line indications and safety of DEX-I compared to those regarding efficacy assessment, reprocessing time or pathophysiological biomarkers. The panellists recommended the preferential use of DEX-I for patients with limited availability for multiple injections, those who needed to undergo cataract surgery or who had a recent cardiovascular history, and as a therapeutic alternative to anti-VEGF in patients with a history of vitrectomy, retinal serous detachment, hyper-reflective points or dry exudates in optical coherence tomography (OCT). However, some statements proposed by SC experts were not validated. Conclusion This study provides some key recommendations to clinicians treating diabetic macular oedema, which may be useful when using intravitreal dexamethasone implants in daily practice.

Children with permanent brachial plexus birth injury have a high risk of developing posterior shoulder subluxation. In 2010, we implemented a protocol to reduce the incidence of this deformity, including early passive exercises, ultrasound screening, botulinum toxin-A injections, shoulder splinting and targeted surgeries. Two-hundred and thirty-seven consecutive children treated at our institution, with a mean follow-up of 11 years (range 1 to 17) were compared in three groups: children born from 1995 to 1999 ( n = 53), 2000–2009 ( n = 109) and 2010–2019 ( n = 75). Posterior shoulder subluxation developed in 48% of all patients but the mean age at detection of shoulder subluxation decreased from 5 years to 4.9 months. Need for shoulder relocation surgery also decreased from 28% to 7%. Mean active shoulder external rotation in adduction improved from 2° to 46°. In conclusion, our established protocol has the potential to reduce the incidence of posterior shoulder subluxation in children with brachial plexus birth injury. Level of evidence: II

This study modeled disruptions in first-year undergraduates’ trajectories of mental health associated with the COVID-19 pandemic, testing whether disruptions were worse for students who moved residences, reported low family income, or were food insecure. Participants ( n = 510) at a large Canadian university reported depression, anxiety, and stress in September, November, January, and March. In March 2020, in tandem with COVID-related campus closures, students also reported for each mental health measure whether their responses were influenced by personal experiences surrounding the pandemic. As hypothesized, students who reported feeling more COVID-related disruption reported poorer mental health in March. Contrary to hypotheses, mental health disruptions were not more pronounced for students who moved, had low income, or were food insecure. Survey administration at an early stage of COVID-19 combined with supports afforded by moving in with parents and near-universal government income assistance may have mitigated the incremental distress we hypothesized for vulnerable students.

Objectives: To evaluate the utilisation and persistence of antipsychotics for the treatment of schizophrenia in Australia. Methods: A retrospective study using the Australian Pharmaceutical Benefits Scheme database of a representative 10% sample. All adults with schizophrenia who were dispensed three or more supplies of oral (including clozapine) or long-acting injectable antipsychotics between 1 June 2015 and 31 May 2020 were included. Persistence time in treatment was evaluated using survival analysis and Cox hazard ratios. Results: In all, 26,847 adults with schizophrenia were studied. Oral second-generation antipsychotics were more frequently dispensed than the other antipsychotic groups studied. Median treatment persistence times were 18.3 months for second-generation antipsychotic long-acting injectables, 10.7 months for oral second-generation antipsychotics and were significantly lower for both formulations of first-generation antipsychotics at 5.2 months (long-acting injectables) and 3.7 months (oral). The median persistence time for clozapine was significantly longer than all other antipsychotics groups. Conclusions: Oral second-generation antipsychotics and second-generation antipsychotic long-acting injectables accounted for over 75% and 13% of all antipsychotics in Australia, respectively. Concerns over medication adherence and subsequent relapse have not translated into increased long-acting injectable usage despite their significantly longer persistence. Clozapine, the single most ‘persistent’ antipsychotic, was only used in 9% of people, although up to a third of all cases are likely to be treatment-resistant. Our data suggest clinicians should give consideration to the earlier use of second-generation antipsychotic long-acting injectables and clozapine, to ameliorate prognosis in schizophrenia.

Background: Whole-muscle electromyography (EMG) data of the rotator cuff support external rotation (ER) strengthening exercises during shoulder rehabilitation. However, distinct neuroanatomic regions in the supraspinatus and infraspinatus exist. Differences in regional muscle activity occur during rehabilitation exercises, but little information is available for ER exertions. Hypothesis: Regional infraspinatus and supraspinatus muscle activity during standing ER exertions will differ with posture and intensity. Study Design: Descriptive laboratory study. Level of Evidence: Level 5. Methods: Twenty healthy individuals (12 men, 8 women) participated. Fine wire electrodes were inserted into 2 supraspinatus and 3 infraspinatus muscle regions. EMG data were recorded during standing isometric ER exertions at 2 intensities (maximal, submaximal) and in 7 postures defined by the angle (0°, 30°, 90°) and plane (abduction, scaption, flexion) of arm elevation. EMG data were normalized to maximum voluntary isometric contraction (% MVIC) to examine the influences of posture, intensity and their interaction on muscle activity. Results: Superior infraspinatus activity was higher in 0° of elevation (50.9% ± 5.7% MVIC) versus 30° of flexion (37.4% ± 3.9% MVIC) at maximal intensity. Inferior infraspinatus activity was higher in 90° of scaption (max = 59.8% ± 2.8% MVIC, submax = 29.4% ± 1.9% MVIC) versus 0° of elevation (max = 42.3% ± 4.5% MVIC, submax = 22.4% ± 2.8% MVIC) ( P = 0.02, P = 0.05, respectively). Anterior supraspinatus activity was highest in 90° of adbuction (max = 61.6% ± 3.1% MVIC; submax = 39.1% ± 3.8% MVIC) and lowest in 30° of flexion (max = 29.0% ± 3.4% MVIC, submax = 15.6% ± 1.7% MVIC) and 90° of flexion (max = 34.6% ± 2.4% MVIC, submax = 14.8% ± 1.9% MVIC). Posterior suprasptinatus activity was lowest in 0° of elevation (34.2% ± 3.0% MVIC), 30° of flexion (33.0% ± 3.6% MVIC) and highest in 90° of abduction (56.2% ± 4.1% MVIC) and 90° of scaption (46.7% ± 2.8% MVIC) (all Ps < 0.04). Conclusion: Regional infraspinatus and supraspinatus muscle activity differed with posture and intensity. Superior and middle infraspinatus muscle activities were similar across postures, but inferior infraspinatus activity was highest in 90° of arm elevation. Anterior and posterior supraspinatus activities were higher in the abduction and scaption planes, especially at 90° of elevation, as compared with the flexion plane. Clinical Relevance: In shoulder rehabilitation of supraspinatus tendon injuries, ER exercises in the flexion plane challenge the whole infraspinatus muscle and require lower supraspinatus muscle activity.

Rationale Whether treatment with intravenous alteplase prior to mechanical thrombectomy (MT) in acute ischemic stroke patients with large vessel occlusion is beneficial remains unclear. Aim To determine whether patients experiencing acute ischemic stroke due to occlusion of the intracranial internal carotid artery or the M1 segment of the middle cerebral artery who are referred to an endovascular stroke center and who are candidates for intravenous alteplase will have non-inferior functional outcome at 90 days when treated with MT alone (direct MT) with stent retrievers compared to patients treated with combined intravenous thrombolysis (IVT) with alteplase plus MT (IVT + MT) with stent retrievers. Sample size To randomize 404 patients 1:1 to direct MT or combined IVT+MT. Methods and design A multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) trial utilizing an adaptive statistical design. Outcomes The primary efficacy endpoint is functional independence (modified Rankin Scale 0–2) at 90 days. Secondary clinical efficacy outcomes include change in National Institutes of Health Stroke Scale score from baseline to day 1 and health-related quality of life at 90 days. Secondary technical efficacy outcomes include successful reperfusion prior to start of MT and time from randomization to successful reperfusion. Safety outcomes include all serious adverse events, symptomatic intracranial hemorrhage, and mortality up to 90 days. Discussion SWIFT DIRECT will inform physicians whether direct MT in acute ischemic stroke patients with large vessel occlusion is equally or more efficacious than combined treatment with intravenous alteplase and MT. Trial registration ClinicalTrials.gov Identifier: NCT03192332

Objectives The aim of this study was to assess occlusion rates of saphenous veins treated with the VariClose vein sealing system. Methods A retrospective analysis including a total of 64 patients from four centres from the Czech Republic. Occlusion was defined as a non-compressible vein with absence of flow with exception to the first 3 cm from the saphenofemoral or saphenopopliteal junction on duplex ultrasound. Results In 64 patients a total of 79 veins were treated. Technical success of the procedure was achieved in 74 (94%) of cases. The mean follow-up was 5.5 months. The closure rates calculated by the Kaplan-Meier method at 1, 3, 6 and 12 months were 94%, 85%, 69% and 36%, respectively, and there were no significant differences between centers. The average difference in VCSS score before and after the procedure was 1.8. Conclusions The present study demonstrated surprisingly worse occlusion rates than the current literature.

Early detection of risks for substance use disorders is essential to lifelong health and well-being for some youth. Very early-onset use is proposed as an indicator of risk for substance use disorders, but risk and protective factors related to early-onset use have not been identified. The current study compared risk and protective factors that distinguish early- and late-onset cannabis users from abstainers using data collected from a large community sample. The study also examined onset-group differences in participants’ reports of substance use disorder symptoms a decade later. Heavy episodic drinking (early-onset: OR = 7.29 CI = [1.60, 33.19]) and engagement with peers involved in deviant behaviors (early-onset: OR = 2.50 CI = [1.50, 4.13]) are risk factors for early-onset cannabis use. Protective factors, including parent monitoring (early-onset: OR = 0.73 CI = [0.58, 0.93]), engagement with peers involved in positive behaviors (early-onset: OR = 0.54 CI = [0.39, 0.76]), school engagement (early-onset: OR = 0.83 CI = [0.72, 0.96]), and academic grades (early-onset: OR = 0.37 CI = [0.21, 0.65]) also predicted early versus later onset-group differences. Early age of onset may be distinctly related to risk and protective factors previously associated with risks for substance use in all adolescents.

Correlations among survival endpoints are important for exploring surrogate endpoints of the true endpoint. With a valid surrogate endpoint tightly correlated with the true endpoint, the efficacy of a new drug/treatment can be measurable on it. However, the existing methods for measuring correlation between two endpoints impose an invalid assumption: correlation structure is constant across different treatment arms. In this article, we reconsider the definition of Kendall's concordance measure (tau) in the context of individual patient data meta-analyses of randomized controlled trials. According to our new definition of Kendall's tau, its value depends on the treatment arms. We then suggest extending the existing copula (and frailty) models so that their Kendall's tau can vary across treatment arms. Our newly proposed model, a joint frailty-conditional copula model, is the implementation of the new definition of Kendall's tau in meta-analyses. In order to facilitate our approach, we develop an original R function condCox.reg(.) and make it available in the R package joint.Cox ( https://CRAN.R-project.org/package=joint.Cox ). We apply the proposed method to a gastric cancer dataset (3288 patients in 14 randomized trials from the GASTRIC group). This data analysis concludes that Kendall's tau has different values between the surgical treatment arm and the adjuvant chemotherapy arm ( p-value

Purpose The purpose of this study was to investigate pulmonary function and health-related quality of life after traditional growing rod (TGR) procedures. Methods Between January 2006 and December 2017, a retrospective observational study of 17 early onset scoliosis (EOS) patients with a mean follow-up of 6.2 years (2.3 to 10.4) was conducted. The forced expiratory volume in one second (FEV1), expiratory forced vital capacity (FVC) and 24-Item Early Onset Scoliosis Questionnaire (EOSQ-24) score before the index surgery and at last follow-up were investigated. Results The mean percentage of predicted FEV1 improved from 50% (20% to 86%) to 53% (15% to 80%; p = 0.08); and the mean percentage of predicted FVC improved from 51% (24% to 81%) to 55% (25% to 89%; p = 0.06). The mean EOSQ-24 score was 78.2 (58 to 90) preoperatively and 77.2 (55 to 88) at last follow-up, there was no statistical difference (p = 0.70). The subdomain scores of pulmonary function (p < 0.01) and daily living (p < 0.01) significantly improved, whereas the subdomain scores of pain (p < 0.01), emotion (p < 0.01) and satisfaction (p = 0.02) significantly declined at last follow-up. Conclusion The TGR procedure was associated with stable pulmonary function and decline in EOSQ-24 pain, emotion and satisfaction scores. Level of Evidence Level III, retrospective cohort study.

Background Community pharmacists are in a unique position to prevent opioid-related deaths through the provision of naloxone. However, for those identified as candidates for take-home naloxone, the acceptance rate remains low. Value would be gained from knowing what patient demographics and pharmacist actions are associated with increased patient acceptance of naloxone. Methods Through a state-wide program, community pharmacists screened all patients receiving an opioid prescription for risk of opioid misuse and/or accidental overdose. Pharmacists prescribed and/or dispensed take-home naloxone to patients at elevated risk. Naloxone acceptance rates were stratified based on risk factors for misuse and overdose to determine which patients are most likely to accept naloxone. Patient acceptance of naloxone and risks were captured electronically. Results Pharmacist-initiated naloxone recommendations based on risk screening resulted in a 5.81% take-home naloxone acceptance rate. Individuals that were taking multiple opioid medications were most likely to accept the naloxone (20.45%). Concurrent disease states or medications (COPD, concurrent anxiety/depression medication, concurrent sleep aid) were associated with a statistically significant increase in the rate of naloxone acceptance. Acceptance of take-home naloxone increased as a patient risk for opioid misuse and/or accidental overdose increased. Conclusion Patient acceptance of naloxone at the community pharmacy level was notably higher compared to national naloxone dispensing rates when pharmacists implemented a patient screening and systematic risk-based approach to identify candidates in need of take-home naloxone.

Background Sentinel events are negative health-related events that trigger change in risky health behaviors. Despite its presumed major role in behavior change, the sentinel event effect has received little empirical attention. Through analysis of qualitative interviews, we explored how sentinel events trigger behavior change. Methods Thematic analysis and concept mapping were used to develop a preliminary model of the sentinel event effect among a sample of 24 adult heavy drinking Mexican-origin men previously admitted to a hospital due to injury. The model was checked against cases that did versus did not report change in alcohol use following an alcohol-related negative event. Results Findings suggest that sentinel events may arouse negative emotional reactions, encourage reflection on the negative consequences of drinking, and cause reevaluation of the severity and significance of drinking. These processes may increase motivation to change. Conclusions Findings support the concept of the sentinel event as a natural intervention, and identifies potential social-cognitive and motivational mechanisms through which it influences change. Findings stand to inform research on mechanisms underlying brief intervention effects, and research that seeks to identify treatment targets.

This study aimed to assess the effects of non-surgical periodontal treatment (NSPT) of chronic periodontitis on insulin sensitivity, glucose tolerance, and serum C reactive protein (CRP) level in individuals without diabetes. Twenty individuals without diabetes with chronic periodontitis underwent NSPT, which consisted of complete scaling, polishing, root planing, and irrigation of the periodontal pockets with a 10% povidone-iodine solution. Periodontal indices (plaque index, gingival bleeding index, pocket depth, and clinical attachment loss), insulin sensitivity using the Short Insulin Tolerance Test index (KITT), glucose tolerance derived from oral glucose tolerance test, and serum CRP level were measured before and 3 months after the intervention. This study was carried out at the National Obesity Center of Yaoundé Central Hospital, Cameroon. After 3 months, we observed significant improvement in periodontal parameters (all p Trial registration number NCT02830113.

Background Pregnancy and the delivery of an infant mark a unique time of engagement in healthcare for women in treatment for opioid use disorder (OUD). The American College of Obstetrics and Gynecology calls for a comprehensive approach to perinatal healthcare delivery for pregnant women with OUD in order to facilitate improved health outcomes and increase patient-provider collaboration. Yet, there is little knowledge regarding the perceptions of women with OUD regarding the current delivery of healthcare which could inform a personalized, tailored approach to perinatal healthcare delivery. Methods Four focus groups consisting of 22 women with OUD were conducted, transcribed, and analysed using qualitative thematic analysis methodology. Results Women reported an overall lack of preparation for the birth and neonatal healthcare experiences and identified opportunities for greater support by the healthcare team. Women emphasized the desire for evidence-based preparation from trusted sources about delivery, neonatal abstinence syndrome, breastfeeding, and how their medications affect their pregnancy and baby. Women reported receiving a varied amount of support from healthcare providers in their transition to motherhood, but women predominantly reported receiving emotional and informational support from their mothers and partners. Conclusions The knowledge obtained in this study points to gaps in perinatal healthcare delivery for women with OUD. Improving the delivery of perinatal healthcare may contribute to increased engagement by women with OUD, and ultimately improve outcomes for a vulnerable population.

Background Interactions with healthcare workers can provide effective entrance into treatment, ensuring retention and lifelong recovery for individuals with Substance Use Disorder (SUD). Healthcare providers approach the challenges of patient management with different skills, comfort levels, and viewpoints. Individuals in recovery also provide crucial perspectives relevant to the complex aspects of the drug epidemic. The purpose of this study was to determine if perceptions of SUD diverge among individuals in recovery, physicians, nurses and medical students. Methods A survey consisting of 29 Likert statements was deployed to physicians, nurses, medical students, and persons with SUD in recovery. Respondents were asked to rate their level of agreement on statements about SUD such as treatment, stigma, medications for opioid use disorder (MOUD), naloxone kits, safe injection sites, and methamphetamine usage. Separate Welch's analysis of variances (ANOVAs) were conducted to determine differences between the respondent groups and each statement. For any statistically significant findings, Games-Howell post-hoc analyses were employed. Results A total of 523 individuals provided survey responses: individuals in recovery ( n = 111), physicians ( n = 113), nurses ( n = 206), and medical students ( n = 93). Survey results revealed the majority of items had statistically significant differences in respondent groups. Perceptions diverged on items related to treatment, stigma, MOUD, take-home naloxone kits, safe injection sites, needle exchange programs, and methamphetamine. Conclusion As healthcare providers and policymakers develop treatment strategies to engage those with SUD in quality treatment, they will benefit from understanding how different viewpoints on SUD affect treatment for these individuals. These attitudes impact stigma, willingness to prescribe new treatments, and development of clinical relationships. The insight from this study allows for important discussions on the substance use health crisis and further inquiry on why these differences exist and how the diverging viewpoints may impact the lives of persons with SUD.

Background Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an evidence-based intervention for patients with substance use disorders, but this intervention is under-utilized. Little is known about the implementation of SBIRT in acute care facilities. The purpose of this study is to describe implementation of SBIRT by nurses in acute care hospitals. Methods A qualitative descriptive design was used for this study. Registered nurses who agreed to participate in the study completed a 1:1 interview using a semi-structured interview guide. Interviews were audio recorded and transcribed and then data were analyzed using qualitative content analysis. Results When implementing SBIRT in an acute care setting, participants identified several factors that affect implementation. Some nurses felt that it is “one more thing to do” but other nurses feel that it was a “good, simple” screening tool that does not take long to do and can “plant the seeds of change” for patients. Additionally, participants mentioned barriers and facilitators related to the patients’ responses to SBIRT and organizational factors. Conclusions This study identified several barriers and facilitators to SBIRT implementation related to the nurses, patients, and organization. By understanding the factors that influence implementation, healthcare providers can develop strategies to support effective implementation of SBIRT.

Background Nonmedical use of prescription opioids (NUPO) is associated with heroin use and other adverse outcomes among adolescents. To inform the timing of substance use prevention activities and which substances to target, we examined age at NUPO initiation, associations between substance use initiation and current (past 30-day) NUPO, and order of NUPO initiation relative to other substances. Methods Data from 2,834 students aged 15 or older participating in the 2017 Virginia Youth Survey, the first Youth Risk Behavior Surveillance System survey to assess age at NUPO initiation and current NUPO, were analyzed in 2019. Students reported current NUPO and ages at initiation for cigarettes, alcohol, marijuana, and NUPO (categorized as 12 or younger, 13 or 14, 15 or older, or never). Associations between age at substance use initiation and current NUPO were examined using adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs). Results Overall, 12% of students reported lifetime NUPO, with 2.4%, 4.0%, and 5.6% initiating at 12 or younger, 13 or 14, and 15 or older, respectively; 5.3% reported current NUPO. Initiating cigarettes, alcohol, and marijuana at each age category (compared with never) was associated with an increased prevalence of current NUPO after adjusting for demographics and initiation of other substances. Among students initiating NUPO, initiating NUPO at 12 or younger (compared with 15 or older) was associated with an increased prevalence of current NUPO after adjusting for demographics (aPR = 1.54, 95% CI: 1.10–2.16), but not after further adjustment for initiation of other substances (aPR = 1.38, 95% CI = 0.97–1.97). Among students initiating NUPO, 45.4% initiated NUPO before or during the same age as other substances. Conclusions More than 6% of students initiated NUPO at 14 or younger. Younger substance use initiation was associated with current NUPO, suggesting that some students may benefit from prevention activities during early adolescence that address multiple substances.

Purpose To evaluate the AOSpine Thoracolumbar Spine Injury Classification System and if it is reliable and reproducible when applied to the paediatric population globally. Methods A total of 12 paediatric orthopaedic surgeons were asked to review MRI and CT imaging of 25 paediatric patients with thoracolumbar spine traumatic injuries, in order to determine the classification of the lesions observed. The evaluators classified injuries into primary categories: A, B and C. Interobserver reliability was assessed for the initial reading by Fleiss's kappa coefficient (kF) along with 95% confidence intervals (CI). For A and B type injuries, sub-classification was conducted including A0-A4 and B1-B2 subtypes. Interobserver reliability across subclasses was assessed using Krippendorff's alpha (αk) along with bootstrapped 95% CIs. A second round of classification was performed one-month later. Intraobserver reproducibility was assessed for the primary classifications using Fleiss's kappa and sub-classification reproducibility was assessed by Krippendorff's alpha (αk) along with 95% CIs. Results In total, 25 cases were read for a total of 300 initial and 300 repeated evaluations. Adjusted interobserver reliability was almost perfect (kF = 0.74; 95% CI 0.71 to 0.78) across all observers. Sub-classification reliability was substantial (αk= 0.67; 95% CI 0.51 to 0.81), Adjusted intraobserver reproducibility was almost perfect (kF = 0.91; 95% CI 0.83 to 0.99) for both primary classifications and for sub-classifications (αk = 0.88; 95% CI 0.83 to 0.93). Conclusion The inter- and intraobserver reliability for the AOSpine Thoracolumbar Spine Injury Classification System was high amongst paediatric orthopaedic surgeons. The AOSpine Thoracolumbar Spine Injury Classification System is a promising option as a uniform fracture classification in children. Level of Evidence III

Background Previous research has reported increased risk for psychosis among individuals who use cannabis during adolescence. We conducted a systematic review and meta-analysis to investigate the interaction between adolescent cannabis use and other factors in moderating risk for psychosis later in life. Method We searched four electronic databases in June 2020 for articles that assessed adolescent cannabis use, had psychosis as an outcome and analyzed for the association between adolescent cannabis use and psychosis. Analysis was done using random-effects meta-analysis and narrative synthesis. Results A total of 63 studies were included in the narrative review and 18 studies were included in the meta-analysis. Adolescent cannabis use was found to increase risk for psychosis (RR = 1.71 (95%CI, 1.47–2.00, p Conclusion Adolescent cannabis use is associated with an increased risk for psychosis later in life. In addition, there are factors that moderate this relationship; therefore there is a need for research to assess the interaction between these factors, adolescent cannabis use and psychosis risk.

Purpose We aimed to compare our parent-based exercise programem's efficacy with the foot abduction brace (FAB) Ponseti manipulation as a retention programme. Methods We conducted this prospective multicentre cohort study between August 2009 and November 2019. The included children were allocated into one of two groups according to the retention protocol. The Pirani and Laaveg-Ponseti scores were used to assess the feet clinically and functionally. Radiological assessment was performed using standing anteroposterior and lateral radiographs of the feet. We assessed the parents’ satisfaction and adherence to the retention method. SPSS version 25 was used for the statistical analysis. Results A total of 1265 feet in 973 children were included. Group A included 637 feet managed with FAB, while group B included 628 feet managed with our retention programme. All patients were followed up to the age of four years. At the final follow-up, Pirani scores in group A participants were excellent, good and poor in 515, 90, and 32 feet, respectivel, while in group B the scores were excellent, good and poor in 471, 110 and 44 feet, respectively. The mean total score of Laaveg-Ponseti was 87.81 (sd 19.82) in group A and 90.55 (sd 20.71) in group B (p = 0.02). Group B participants showed higher satisfaction with the treatment method (p = 0.011) and more adherence to the treatment (p = 0.013). Conclusion The deformity's recurrence related to the brace's non-compliance in the Ponseti method might be reduced by substituting the brace with our home-based daily stretching exercises. Level of Evidence II

Asthma is the most common life-threatening chronic disease in children. Although guidelines exist for the diagnosis and treatment of asthma, treatment of severe, pediatric asthma remains difficult. Limited studies in the pediatric population on new asthma therapies, complex issues with adolescence and adherence, health disparities, and unequal access to guideline-based care complicate the care of children with severe, persistent asthma. The purpose of this review is to provide an overview of asthma, including asthma subtypes, comorbidities, and risk factors, to discuss diagnostic considerations and pitfalls and existing treatments, and then present existing and emerging therapeutic approaches to asthma management. An improved understanding of asthma heterogeneity, clinical characteristics, inflammatory patterns, and pathobiology can help further guide the management of severe asthma in children. More studies are needed in the pediatric population to understand emerging therapeutics application in children. Effective multimodal strategies tailored to individual characteristics and a commitment to address risk factors, modifiers, and health disparities may help reduce the burden of asthma in the USA.

Obesity has recently been mentioned as a metabolic pandemic in developed and developing countries and is an important known risk factor for type 2 diabetes and cardiovascular diseases. The main mechanism responsible for obesity is insulin resistance. Adropin is a peptide-structured regulatory hormone that is suggested to play a role in insulin resistance and metabolic regulation. We aimed to evaluate the associations of serum adropin with insulin resistance and clarify the factors affecting serum adropin concentrations. The study included 50 obese patients and 22 healthy controls. Patients with chronic disease and drug use history were excluded. Serum adropin and other metabolic parameters were obtained after overnight fasting. ELISA was used to measure serum adropin concentrations. The homeostatic model assessment-insulin resistance (HOMA-IR) index was used to calculate insulin resistance. Insulin resistance was defined as HOMA-IR >2.5. Serum adropin values were found to be low in the obese otherwise healthy patient group (p

Background Limited data describes the effectiveness of strategies to optimize naloxone rescue kit distribution. Mental health clinical pharmacy specialists (CPS) at VA St. Louis HCS aimed to increase distribution of naloxone rescue kits to patients with Opioid Use Disorder (OUD). An informational letter detailing the purpose of rescue kits and how to obtain one were sent to patients with OUD who had no active order for a naloxone rescue kit within the previous year. Roughly half of these patients were targeted for follow-up education via telephone. Methods A retrospective study was conducted comparing the effectiveness of these contact methods. Study groups included those contacted by letter alone and those contacted by both letter and phone call. The primary outcome was order placement for a rescue kit within 90 days of contact. Post-hoc analysis included a multivariate regression, case-control evaluation of variables potentially associated with kit distribution. Results In total, 335 patients were included. Of 185 patients targeted for phone follow-up, 81 were reached (43.8%), and 254 received the letter alone. The primary outcome was achieved by 13 (5.1%) and 52 (64.2%) participants in the letter alone and letter plus phone contact groups, respectively ( p Conclusions In patients with OUD, those contacted by phone in addition to receiving a letter were significantly more likely to receive a naloxone kit than those contacted via letter alone. In addition to contact by phone, nonwhite race, prior participation in rehabilitation and active opioid prescription were associated with a higher rate of kit obtainment.

Background The impacts of opioid use disorder and opioid-involved overdose are known, but less is known about the contexts in which people first misuse opioids, and the motivations for continued misuse. Methods In-depth interviews with 26 individuals in Allegheny County, Pennsylvania with current or past histories of opioid misuse were conducted. Narratives were analyzed to understand the circumstances and influences contributing to initial and continued misuse of opioids. Results Participants described social and familial contexts that normalized or accepted opioid misuse—this often included their own use of other illicit substances prior to initiating opioids. Participants also described initial use of opioids as related to efforts to cope with physical pain. They also described recognizing and then seeking psychological/emotional benefits from opioids. All three of these themes often overlapped and intersected in these stories of starting opioid misuse. Conclusions Opioid misuse stemmed from complex interacting influences involving coping with physical and psychological pain, perception that opioids are needed to feel “normal”, and acceptance or normalization of opioid use. This suggests a multi-pronged approach to both prevention and treatment are needed.

Background People who use illicit drugs (PWUD) experience significant barriers to healthcare. However, little is known about levels of attachment to primary care (defined as having a regular family doctor or clinic they feel comfortable with) and its association with unmet healthcare needs in this population. In a Canadian setting that features novel publicly-funded interdisciplinary primary care clinics, we sought to examine the prevalence and correlates (including attachment to primary care) of unmet healthcare needs among PWUD. Methods Data were derived from two prospective cohort studies of PWUD in Vancouver, Canada between December 2017 and November 2018. Multivariable logistic regression was used to identify factors associated with self-reported unmet healthcare needs among participants reporting any health issues. Results In total, 743 (83.6%) of 889 eligible participants reported attachment to primary care and 220 (24.7%) reported an unmet healthcare need. In multivariable analyses, attachment to primary care at an integrated care clinic (adjusted odds ratio [AOR] = 0.14; 95% Confidence Interval [CI]: 0.06–0.34) was negatively associated with an unmet healthcare need, while being treated poorly at a healthcare facility (AOR = 5.50; 95% CI: 3.59–8.60) and self-reported chronic pain (AOR = 2.00, 95% CI: 1.30–3.01) were positively associated with an unmet healthcare need. Conclusion Despite the high level of attachment to primary care, a quarter of our sample reported an unmet healthcare need. Our findings suggest that multi-level interventions are required to address the unmet need, including pain management and integrated care, to support PWUD with complex health needs.

Background Buprenorphine combined with psychosocial support is the standard of care for treatment of opioid use disorder (OUD) in office-based primary care settings. However, uptake of this treatment has been slow due to a number of addressable barriers including providers’ lack of training, staffing concerns, stigma and the need for ongoing support and consultation. This study examined acceptability and feasibility of an online Extensions for Community Healthcare Outcomes (ECHO) model intervention developed to support rural primary care clinics to expand treatment and is part of a larger study tracking the impact of participation in this ECHO on expansion of MOUD in rural primary care. Methods We developed a comprehensive, 12-week online education and mentorship intervention using ECHO aimed at supporting the entire primary care clinic to start or expand treatment using MOUD, psychosocial treatments and recovery supports. We tracked participation and collected feedback using qualitative interviews and post-session questionnaires. Results Sixty-seven primary care staff across 27 rural clinics in New Mexico participated in the study including 32 prescribers and 35 clinic support staff. Average participation was 4/12 sessions. Post-session questionnaires showed positive feedback, including that 95% or more respondents agreed or strongly agreed that the sessions were relevant and improved their confidence. Qualitative interview themes included strong endorsement of the ECHO curriculum. Clinical duties were the most common barrier to attending sessions. Conclusions Engagement of 27 clinics, the range of staff and providers who participated, and positive feedback gathered through survey and qualitative interviews provide evidence of feasibility and acceptability of MOUD ECHO to support expansion of this treatment. However, barriers to participation present an important threat to feasibility. Understanding feasibility and acceptability is an important component of research on the impact of ECHO to expand MOUD treatment.

Background To evaluate a novel, unofficial, trainee-organized, hospital addiction medicine consultation service (AMCS), we aimed to assess whether it was (1) acceptable to hospital providers and patients, (2) feasible to organize and deliver, and (3) impacted patient care. Methods We performed a retrospective descriptive study of all AMCS consultations over the first 16 months. We determined acceptability via the number of referrals received from admitting services, and the proportion of referred patients who consented to consultation. We evaluated feasibility via continuation/growth of the service over time, and the proportion of referrals successfully completed before hospital discharge. As most referrals related to opioid use disorder, we determined impact through the proportion of eligible patients offered and initiated on opioid agonist therapy (OAT) in hospital, and the proportion of patients who filled their outpatient prescription or attended their first visit with their outpatient OAT prescriber. Results The unofficial AMCS grew to involve six hospital-based residents and five supervising community-based addiction physicians. The service received 59 referrals, primarily related to injection opioid use, for 50 unique patients from 12 different admitting services. 90% of patients were seen before discharge, and 98% agreed to addiction medicine consultation. Among 34 patients with active moderate-severe opioid use disorder who were not already on OAT, 82% initiated OAT in hospital and 89% of these patients continued after discharge. Conclusions Established in response to identified gaps in patient care and learning opportunities, a novel, unofficial, trainee-organized AMCS was acceptable, feasible, and positively impacted patient care over the first 16 months. This trainee-organized, unofficial AMCS could be used as a model for other hospitals that do not yet have an official AMCS.

Background Certain communities in the United States experience greater opioid-involved overdose mortality than others. Interventions to stem overdose benefit from contextual understandings of communities’ needs and strengths in addressing the opioid crisis. This project aims to understand multiple stakeholder perspectives on the opioid epidemic in communities disproportionately affected by opioid-involved overdose mortality. Methods We performed a rapid-cycle qualitative assessment study utilizing in-depth interviews with community stakeholders and observations of community meetings in eight communities in Allegheny County, Pennsylvania, USA, disproportionately impacted by opioid-involved overdose mortality. Stakeholder categories included: current and past illicit users of opioids; medical and social service providers; emergency medical services; law enforcement; spouse or other family members of illicit users/former users of opioids; government officials; school officials; community members. Content analysis was utilized to identify themes and answer study questions. Regular feedback to stakeholders was provided to support targeted interventions. Results We performed semi-structured, in-depth interviews with 130 community stakeholders and 29 community meeting observations in 2018–2019. Participants perceived similar economic and social determinants as origins of the opioid overdose epidemic including lack of economic resources, loss of jobs, transient populations and dilapidated housing. However, they differed in their awareness of and attention to the epidemic. Awareness was dependent on the visibility of opioid use (presence of paraphernalia litter, location of drug users, media coverage, and relationship to users). Overall, there was good knowledge of naloxone for opioid overdose reversal but less knowledge about local syringe services programs. Perceptions of harm reduction efforts were ambivalent. Conclusions Members of communities impacted by the opioid epidemic perceived that economic downturn was a major factor in the opioid overdose epidemic. However, the varied beliefs within and between communities suggest that interventions need to be tailored according to the cultural norms of place.

Background In the United States, alcohol use disorder (AUD) is common and costly but substantially undertreated. Rurality is an important determinant of health that may influence receipt of evidence-based alcohol-related care. In a large, national sample of Veterans Health Administration (VA) patients with AUD with documented and non-Hispanic Black, Hispanic, or non-Hispanic White race/ethnicity, we examine whether meeting national Healthcare Effectiveness Data and Information Set (HEDIS) quality measures for specialty addictions care and receiving evidence-based medications for AUD differs across patients living in urban, large rural, and small rural areas. Methods VA electronic health record data were used to identify all patients with AUD documented in Fiscal Year 2012. Rurality was measured using a three-category rural and urban commuting area (RUCA) classification linked to patient zip code. Logistic regression models with clustered standard errors—iteratively adjusted for hypothesized confounders—were used to estimate the likelihood and marginal probabilities of receiving care for patients living in small and large rural areas, relative to urban areas. Primary outcomes included HEDIS initiation (any visit within 14 days of initial AUD visit after a 60-day period of no treatment), HEDIS engagement (2 or more AUD visits within 30 days of HEDIS initiation visit) and having any filled prescription for AUD medications (naltrexone, disulfiram, acamprosate, or topiramate). Results For all outcomes, patients living in large and small rural areas had a lower likelihood of receiving evidence-based AUD treatment than patients living in urban areas (all p-values < 0.05); differences in marginal probabilities across groups were relatively small. Conclusions In this national sample of VA patients with AUD, those living in more rural areas were less likely to receive evidence-based treatment for AUD than those living in urban areas. Further research is needed to investigate strategies to increase receipt of specialty care and pharmacotherapy in more rural areas.

Background The synergistic epidemics of substance use, violence, and HIV/AIDS, also known as the SAVA syndemic, disproportionately affects vulnerable women in the United States. Methamphetamine use is closely linked with physical and sexual violence, including intimate partner violence (IPV), which heightens women's vulnerability to HIV. This mixed methods study examined the prevalence and correlates of violence among women who use methamphetamine, ( n = 209) enrolled in an HIV intervention study in San Diego, California. Methods At baseline, 209 women completed an interviewer-administered computer-assisted survey. A sub set of women who reported lifetime IPV ( n = 18) also participated in qualitative interviews to contextualize our understanding of patterns of violence over time. Results In the overall cohort, reports of lifetime (66.0%) and past 2-month (19.6%) IPV were prevalent. Moreover, women reported lifetime physical only (27.3%), sexual only (6.2%), or both forms of violence (50.7%) by multiple perpetrators. Factors independently associated with lifetime IPV were having unprotected sex with a steady partner (odds ratio [OR]: 2.50, 95% confidence interval [CI]: 1.04, 6.00) and being high on methamphetamine during unprotected sex with a steady partner (OR: 2.56, 95% CI: 1.30, 5.09) within the past 2 months. Our qualitative narratives illuminated how IPV in women's steady relationships often reflects a culmination of violent victimization throughout their lifetime which is further exacerbated by methamphetamine use and sexual risk through gendered power dynamics. Conclusions HIV prevention interventions should address the SAVA syndemic in a holistic manner, including the role of methamphetamine use in the context of women's abusive steady relationships.

Introduction: B cell depletion with rituximab (RTX) is associated with high treatment efficacy in relapsing-remitting multiple sclerosis (RRMS), with low risk of rebound phenomena with treatment interruptions, but also increased risk of mainly bacterial infections. In order to reduce infection risks, further prompted by COVID19, RTX standard dosing intervals were extended up to 24 months in a single centre setting. Aims: To determine risk of disease flares in RRMS patients with extended RTX dosing intervals. Methods: We retrospectively analysed all RRMS patients (n=719) treated with RTX included in two ongoing observational drug trials, COMBAT-MS (EudraCT 2016-003587-39) and MultipleMS (2017-002634-24). Data were extracted from the Swedish MS registry for demographics, diagnosis, treatment history, clinical relapses and magnetic resonance imaging (MRI). Relapses and/or new MRI T2 lesions/contrast enhancing lesions, were recorded at first sign of clinical or MRI disease activity, or the lack thereof, at most recent visit/MRI for patients without signs of disease activity. The maximum interval (MI) between RTX doses before a registered outcome was used as a proxy for the efficacy of different treatment protocols. Results: Out of 697 patients with valid clinical data, 35 (5%) suffered a relapse, 19 of which occurred after the first RTX dose. Of the remainder, 13 patients had a relapse with a MI of 6±3 months (n=181, 7.2%), 3 with MI extended to 12±3 (n=313, 1%), and no relapse was found with MI of 18±3 or & gt;21 months (n=140 and n=63, respectively). MRI activity was detected in 54/572 subjects (including 6 after first dose), of which 24/152 (15,8%) with MI 6±3 month, 16/244 (6.5%) with MI of 12±3 months, 9/116 (7.8%) with MI of 18±3 months and 5/60 (8.3%) with MI of & gt;21 months. No major differences were found among the four groups concerning demographics, type of prior treatment and disability, except for a lower number of RTX doses in the 6±3 month MI group (mean number of RTX doses 3.3, 5.8, 6.8 and 6.1, respectively;ANOVA p

Background Pharmacological and psychosocial interventions have only modest efficacy for Alcohol Use Disorder (AUD), and continued alcohol use has brain effects on neurocognition, which place heavy drinkers at increased risk of early onset dementia. The most common neurocognitive deficits are in the domains of executive function and memory, and these deficits may impact AUD treatment outcomes. AUD related Mild Cognitive Impairment (AUD-MCI) is a diagnosis in DSM-V and ICD-10. Donepezil, a cholinesterase inhibitor, is currently FDA approved for treatment of dementia, and recent preclinical research suggests anticholinesterase agents may treat alcoholism. Another approach to cognitive recovery is Cognitive Remediation Therapy (CRT). Recent research supports CRT efficacy in schizophrenia and related disorders, and some research suggests that CRT could improve neurocognition in substance abuse disorders (SUDs). This is the first report of an open-label clinical trial that combined donepezil with CRT to improve neurocognitive and clinical outcomes in the early phase of AUD recovery. Methods Eleven older male US Veterans with AUD-MCI as determined by Level II neurocognitive criteria and who had recently relapsed participated in an open-label trial of 13 weeks of donepezil combined with CRT. They were compared with matched historical control samples on neurocognitive and clinical outcomes. Results Participants had excellent adherence to donepezil and CRT. Neurocognitive improvements were highly significant on a composite score of learning and memory and executive function measures ( p < .0001) and was significantly better than historical matched controls ( p < .001). On a Clinical Global Impression scale, 90.9% of participants had a good clinical recovery compared with 59.5% of historical matched controls ( p Conclusions AUD-MCI has not received much research attention but is of considerable public health importance. Findings in this open-label trial of donepezil + CRT should encourage further investigation into the clinical benefit of this combined treatment for AUD-MCI.

Background Efforts to reduce the risk of opioid misuse are often focused on reducing unnecessary prescriptions for opioid medications or reducing the dose prescribed; however, not all misuse occurs in individuals with a personal prescription. This study examined trends in the proportion of adolescents and young adults (AYAs) who had an opioid-related problem (ORP) and who also had a personal opioid prescription drug claim or had a family member with an opioid prescription drug claim prior to the ORP diagnosis. Methods A retrospective cohort design was used to analyze longitudinal claims data. We identified individuals aged 12 to 25 years who had a newly diagnosed ORP in the years 2006 to 2014. Trends over time in personal or family opioid prescription drug claims within 1 year prior to ORP diagnosis were examined. Results We identified 53,560 AYAs with an ORP diagnosis. Over the entire study period, 40% of AYAs with an ORP diagnosis had a personal opioid prescription in the year prior to diagnosis, and 48% had a family member with an opioid prescription in the prior year. While the proportion of AYAs with a family prescription remained constant, the proportion with a personal prescription fell from 77.1% in 2006 to 27.3% in 2014. Conclusions The number of AYAs with an ORP increased over time, yet the proportion with a personal opioid prescription claim prior to their diagnosis decreased over time. This suggests that providers are paying greater attention to prescribing opioids to AYAs directly, although prescriptions to family members may still remain a point of access.

Purpose: Cataract and glaucoma are among the leading causes of blindness worldwide in older people, and they are often concomitant. To assess topical intraocular (IOP)-lowering agents delivery changes after cataract extraction. Material and methods: Longitudinal matched exposed–unexposed study from the French national healthcare database from January 1, 2005 to January 1, 2017. We compared individuals using topical IOP-lowering agents who underwent bilateral cataract extraction with individuals matched on IOP-lowering agents load, age, and sex who did not undergo cataract extraction. IOP-lowering agents number of drops was assessed 12 months before the first cataract extraction and compared with number of drops 12 months after the second cataract extraction. Results: About 1194 individuals treated with IOP-lowering agents were included, 597 exposed to bilateral cataract extraction and 597 unexposed to any surgery (total mean age 74.8 ± 8.3 years; 69.0% women). Mean IOP-lowering agents delivery at baseline was 1.4 daily drops in both groups. The mean number of drops decreased greater in the exposed than unexposed group (−25.5% vs −3.5%; p < 0.0001). Overall, 159 (26.6%) and 48 (8.0%) individuals in the exposed and unexposed groups interrupted medication ( p < 0.0001). Conclusions: A decrease of around one quarter of IOP-lowering agents delivery was observed after cataract extraction in the present real-life study with a longstanding interruption observed in one quarter of patients. Phacoemulsification as a standalone procedure reduces IOP-lowering agents delivery in ocular hypertension and glaucoma.

North America’s overdose crisis is an urgent public health issue that has resulted in thousands of deaths. As the crisis began to take hold across Canada in 2016, bereaved parents, mainly mothers, emerged as vocal advocates for drug policy reform and harm reduction, using their stories to challenge the stigma of drug-related death. In 2017, we launched a qualitative research partnership with leading family organizations in Canada, conducting interviews with 43 mothers whose children had died from substance use, to understand their experiences of drug policy advocacy. Our findings showed that participants’ motivations for engaging in advocacy were rooted in their experiences of grief, and that advocacy led to feelings of empowerment and connection to others. Our research suggests that advocacy can be cathartic and associated with healing from grief, but that “going public” in sharing a family story of substance use death can also have a considerable personal cost.

Background: Patients with complete rotator cuff tears who fail a course of nonoperative therapy can benefit from surgical repair. Purpose: This randomized trial compared mini-open (MO) versus all-arthroscopic (AA) rotator cuff repair. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Patients with rotator cuff tears were randomized to undergo MO or AA repair at 9 centers by 23 surgeons. The primary outcome (Western Ontario Rotator Cuff Index [WORC]) and secondary outcomes (American Shoulder and Elbow Surgeons [ASES] score, Shoulder Pain and Disability Index [SPADI] pain subscale, 12-Item Short Form Health Survey [SF-12], reported medication use, adverse events), as well as measurements of range of motion and strength, were collected at 1 month before surgery; at 2 and 6 weeks postoperatively; and at 3, 6, 12, 18, and 24 months postoperatively. A blinded radiologist evaluated rotator cuff integrity on magnetic resonance imaging (MRI) at baseline and 1 year. Intention-to-treat analysis of covariance with the preoperative WORC score, age, and tear size as covariates assessed continuous outcomes. Sex differences were assessed. A meta-analysis synthesized the primary outcome between MO and AA repair with previous trials. Results: From 954 patients screened, 411 were ineligible (276 because of recovery with physical therapy), 449 were screened at surgery (175 ineligible), and 274 completed follow-up (138 MO and 136 AA). The AA and MO groups were similar before surgery. WORC scores improved from 40 preoperatively to 89 (AA) and 93 (MO) at 2 years, for an adjusted mean difference of 3.4 (95% CI, –0.4 to 7.2). There were no statistically significant differences between the AA and MO groups at any time point. All secondary patient-reported outcomes were not significantly different between the MO and AA groups, except the 2-year SPADI pain score (8 vs 12, respectively; P = .02). A similar recovery in range of motion and strength occurred in both groups over time. MRI indicated minimal improvement in muscle relative to fat (AA: n = 3; MO: n = 2), with most worsening (AA: n = 25; MO: n = 24) or remaining unchanged (AA: n = 70; MO: n = 70). Opioid use was significantly reduced after surgery (from 21% to 5%). The meta-analysis indicated no significant standardized mean difference between groups in the primary outcome across all pooled studies (standardized mean difference, –0.06 [95% CI, –0.34 to 0.22]). Conclusion: Both AA and MO rotator cuff repair provide large clinical benefits, with few adverse events. There is strong evidence of equivalent clinical improvements. Trial Registration: NCT00128076.

In this commentary, we describe initial learnings from a community-based research project that explored how the relational space between residents and formal institutions in six marginalised communities in Toronto, Ontario, Canada impacted grassroots responses to the health and psycho-social stresses that were created and amplified by the coronavirus disease 2019 (COVID-19) pandemic. Our research found that grassroots community leaders stepped up to fill the gaps left by Toronto’s formal public health and emergency management systems and were essential for mitigating the psycho-social and socioeconomic impacts of the pandemic that exacerbated pre-existing inequities and systemic failures. We suggest that building community resilience in marginalised communities in Toronto can embody health promotion in action where community members, organisational, institutional and government players create the social infrastructure necessary to build on local assets and work together to promote health by strengthening community action, advocating for healthy public policy and creating supportive environments.

Objective: The aim of this study was to determine the independent value of N-terminal pro b-type natriuretic peptide, high-sensitivity cardiac troponin T, and C-reactive protein to predict onset of cardiopulmonary disease in a large, multi-center systemic sclerosis cohort followed prospectively. Methods: Subjects from the Canadian Scleroderma Research Group registry with data on N-terminal pro b-type natriuretic peptide, high-sensitivity cardiac troponin T, and C-reactive protein were identified. Outcomes of interest were death, systolic dysfunction (left ventricular ejection fraction Results: A total of 675 subjects were included with a mean follow-up of 3.0 ± 1.8 years. Subjects were predominantly women (88.4%) with mean age of 58.2 ± 11.3 years and mean disease duration of 13.7 ± 9.1 years. One hundred and one (101, 15%) subjects died during follow-up, 37 (6.4 %) developed systolic dysfunction, 18 (2.9%) arrhythmias, 34 (5.1%) pulmonary arterial hypertension, 43 (7.3%) pulmonary hypertension, and 48 (12.3%) interstitial lung disease. In multivariate analyses, elevated levels of N-terminal pro b-type natriuretic peptide, high-sensitivity cardiac troponin T, and C-reactive protein were associated with increased risk of death, while elevated levels of N-terminal pro b-type natriuretic peptide and C-reactive protein were associated with increased risk of developing pulmonary hypertension. Conclusion: In systemic sclerosis, N-terminal pro b-type natriuretic peptide, high-sensitivity cardiac troponin T, and C-reactive protein have independent predictive value for death and pulmonary hypertension. A larger study would be required to determine the predictive value of these biomarkers for less common systemic sclerosis outcomes.

Funding Information: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by the Egyptian Ministry of Higher Education and Scientific Research (MoHE) project funding (290243/2014–2015) and supported by University of Helsinki project funding (WBS300203, WBS490302), Helsinki University Hospital State funding for university-level health research (Y1014SUL05, TYH2016130), University of Helsinki thesis completion grant, Suomalais-Norjalainen Lääketieteen Säätiö (202000064), the Finnish Dental Society Apollonia, and Alfred Kordelin foundation (200155/28102020). The open access publication charges for this article were covered by HY- FinELib consortium. Publisher Copyright: © International Association for Dental Research and American Association for Dental, Oral, and Craniofacial Research 2021. The clinical translation of bone tissue engineering for reconstructing large bone defects has not advanced without hurdles. The in vivo bioreactor (IVB) concept may therefore bridge between bone tissue engineering and reconstructive surgery by employing the patient body for prefabricating new prevascularized tissues. Ideally, IVB should minimize the need for exogenous growth factors/cells. Periosteal tissues are promising for IVB approaches to prefabricate tissue-engineered bone (TEB) flaps. However, the significance of preserving the periosteal vascular supply has not been adequately investigated. This study assessed muscle IVB with and without periosteal/pericranial grafts and flaps for prefabricating TEB flaps to reconstruct mandibular defects in sheep. The sheep (n = 14) were allocated into 4 groups: muscle IVB (M group; nM = 3), muscle + periosteal graft (MP group; nMP = 4), muscle + periosteal flap (MVP group; nMVP = 4), and control group (nControl = 3). In the first surgery, alloplastic bone blocks were implanted in the brachiocephalic muscle (M) with a periosteal graft (MP) or with a vascularized periosteal flap (MVP). After 9 wk, the prefabricated TEB flaps were transplanted to reconstruct a mandibular angle defect. In the control group, the defects were reconstructed by non-prevascularized bone blocks. Computed tomography (CT) scans were performed after 13 wk and after 23 wk at termination, followed by micro-CT (µCT) and histological analyses. Both CT and µCT analysis revealed enhanced new bone formation and decreased residual biomaterial volume in the MVP group compared with control and MP groups, while the M group showed less new bone formation and more residual biomaterial. The histological analysis showed that most of the newly formed bone emerged from defect edges, but larger areas of new bone islands were found in MP and MVP groups. The MVP group showed enhanced vascularization and higher biomaterial remodeling rates. The periosteal flaps boosted the reconstructive potential of the prefabricated TEB flaps. The regenerative potential of the periosteum was manifested after the transplantation into the mechanically stimulated bony defect microenvironment.