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1.
Foot Ankle Orthop ; 9(1): 24730114241239310, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38529013

RESUMO

Background: Total ankle arthroplasty (TAA), first developed as an alternative to ankle arthrodesis, has become an increasingly popular management option for end-stage ankle arthritis. Prior studies have shown commercial insurance payers base their coverage criteria on limited and low level of evidence research. This study aims to quantify and describe the evidence insurance companies use to support TAA coverage policies. Methods: The top 11 national commercial health insurance payers for TAA were identified. A google search was performed to identify payer coverage policies. Policy documents were examined and cited references were classified by type of reference as well as reviewed for level of evidence (LOE). Specific coverage criteria for each individual payer were then extracted. Criteria were compared to assess for similarities among commercial payers. Finally, all references cited by each payer were examined to determine whether they mentioned the specific payer criteria. Results: Six of the 11 payers had accessible coverage policies. The majority of cited references were primary journal articles (145, 60.9%) and the majority of references cited (179, 75.2%) were level III or level IV evidence. We found significant homogeneity in coverage criteria among payers. In addition, cited sources inconsistently mentioned specific payer coverage criteria. Conclusion: This study demonstrates that commercial insurance payers rely on the relatively low level of currently available scientific evidence when formulating coverage policies for TAA use and adopt criteria that have not been thoroughly analyzed in the literature. More high level of evidence research is needed to help clinicians and insurance companies further refine indications for TAA so that patients who might benefit from the procedure are adequately covered. Level of Evidence: Level IV, review.

2.
PM R ; 16(3): 239-249, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37343123

RESUMO

BACKGROUND: Women with lower extremity amputations (LEAs) tend to have poorer prosthesis-related outcomes than men, although the literature is sparse. To our knowledge, there are no prior studies examining prosthesis-related outcomes of women veterans with LEAs. OBJECTIVE: To examine gender differences (overall and by type of amputation) among veterans who underwent LEAs between 2005 and 2018, received care at the Veterans Health Administration (VHA) prior to undergoing amputation, and were prescribed a prosthesis. It was hypothesized that compared to men, women would report lower satisfaction with prosthetic services, poorer prosthesis fit, lower prosthesis satisfaction, less prosthesis use, and worse self-reported mobility. Furthermore, it was hypothesized that gender differences in outcomes would be more pronounced among individuals with transfemoral than among those with transtibial amputations. DESIGN: Cross-sectional survey. Linear regressions were used to assess overall gender differences in outcomes and gender differences based on type of amputation in a national sample of veterans. SETTING: VHA medical centers. PARTICIPANTS: The sample consisted of 449 veterans who self-identified their gender (women = 165, men = 284) with transtibial (n = 236), transfemoral (n = 135), and bilateral LEAs (n = 68) including all amputation etiologies. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Orthotics and Prosthetics User's Survey, Trinity Amputation and Prosthesis Experiences Scale, and Prosthetic Limb Users Survey of Mobility-Short Form were used to assess satisfaction with prosthetic services, prosthesis fit, prosthesis satisfaction, prosthesis use, and self-reported mobility. RESULTS: Women had poorer self-reported mobility than men (d = -0.26, 95% confidence interval -0.49 to -0.02, p < .05); this difference was small. There were no statistically significant gender differences in satisfaction with prosthetic services, prosthesis fit, prosthesis satisfaction, daily hours of prosthesis use, or by amputation type. CONCLUSIONS: Contrary to the hypothesis, prosthesis-related outcomes were similar between men and women with LEAs. Minimal differences may in part be due to receiving care from the VHA's integrated Amputation System of Care.


Assuntos
Membros Artificiais , Veteranos , Masculino , Humanos , Feminino , Estudos Transversais , Fatores Sexuais , Amputação Cirúrgica
3.
Expert Rev Clin Immunol ; 19(11): 1385-1397, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37596779

RESUMO

INTRODUCTION: Janus kinase inhibitors (JAKi) have dramatically improved the treatment of various autoimmune and myeloproliferative disorders. Recently, concern has arisen regarding their safety in patients with rheumatoid arthritis. AREAS COVERED: Here, we provide a comprehensive summary of the major current and emerging JAKi and their indications, address recent studies on comparative safety, and provide insight into their future and use. We emphasize that the application of the research findings on a case-by-case basis should consider a patient's age, comorbidities, disease for which JAKi is being considered, disease activity, the JAKi target(s), alternate treatment options available for the patient, and the planned duration of JAKi. EXPERT OPINION: Rheumatologists are used to prescribing therapies in which a risk-to-benefit assessment is required as well as to screening and monitoring the safety of medications. Thus, rheumatologists are already practiced in applying specific criteria to effectively screen and monitor patients who are candidates for JAKi therapy. Ongoing research will help to clarify any mechanisms underlying differential safety signals between JAK and other therapies, what the balance between risk and efficacy is, who the susceptible subpopulations are, and whether safety signals are shared between different JAKis and across indications.


Assuntos
Antirreumáticos , Artrite Reumatoide , Inibidores de Janus Quinases , Humanos , Rotulagem de Medicamentos , Inibidores de Janus Quinases/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/efeitos adversos
4.
Nat Rev Drug Discov ; 22(9): 699-722, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37328653

RESUMO

The development of bioactive small molecules as probes or drug candidates requires discovery platforms that enable access to chemical diversity and can quickly reveal new ligands for a target of interest. Within the past 15 years, DNA-encoded library (DEL) technology has matured into a widely used platform for small-molecule discovery, yielding a wide variety of bioactive ligands for many therapeutically relevant targets. DELs offer many advantages compared with traditional screening methods, including efficiency of screening, easily multiplexed targets and library selections, minimized resources needed to evaluate an entire DEL and large library sizes. This Review provides accounts of recently described small molecules discovered from DELs, including their initial identification, optimization and validation of biological properties including suitability for clinical applications.


Assuntos
Descoberta de Drogas , Bibliotecas de Moléculas Pequenas , Humanos , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/química , Descoberta de Drogas/métodos , DNA/química , Ligantes , Biblioteca Gênica
6.
Foot Ankle Orthop ; 8(2): 24730114231179218, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37325695

RESUMO

Background: Spin is defined as the use of specific reporting strategies to highlight the beneficial effect of a treatment despite nonsignificant results. The presence of spin in peer-reviewed literature can negatively impact clinical and research practices. The purpose of this study was to identify the quantity and types of spin present in primary studies and systematic reviews using suture tape augmentation for ankle instability as a model. Methods: This study was conducted per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Each abstract was assessed for the presence of the 15 most common types of spin. Extracted data included study title, authors, publication year, journal, level of evidence, study design, funding, reported adherence to PRISMA guidelines, and PROSPERO registration. Full texts of systematic reviews were used in the assessment of study quality per A Measurement Tool to Assess Systematic Reviews Version 2 (AMSTAR 2). Results: Nineteen studies were included in the final sample. At least 1 type of spin was identified in each study except one (18 of 19, 94.7%). The most common type of spin observed was type 3 ("selective reporting or overemphasis on efficacy outcomes or analysis favoring the beneficial effect of the experimental intervention") (6 of 19, 31.6%), The second most reported category of spin was type 4 ("the conclusion claims safety based on non-statistically significant results with a wide confidence interval") (4 of 19, 21.1%). Among systematic reviews, we identified type 5 ("the conclusion claims the beneficial effect of the experimental treatment despite a high risk of bias in primary studies") in 4 out of 6 (66.7%) of the articles that were included. No significant associations were found between study characteristics and type of spin. Conclusion: In this exploration of the introduction of a new technology, we identified spin to be highly present in the abstracts of primary studies and systematic reviews concerning suture tape augmentation for ankle instability. Steps should be taken by scientific journals to ensure that spin is minimized in the abstract to accurately reflect the quality of the intervention.

7.
Arch Phys Med Rehabil ; 104(8): 1274-1281, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36906098

RESUMO

OBJECTIVE: To evaluate whether prosthetic prescription differed by gender and the extent to which differences were mediated by measured factors. DESIGN: Retrospective longitudinal cohort study using data from Veterans Health Administration (VHA) administrative databases. SETTING: VHA patients throughout the United States. PARTICIPANTS: The sample included 20,889 men and 324 women who had an incident transtibial or transfemoral amputation between 2005 and 2018. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Time to prosthetic prescription (up to 1 year). We used parametric survival analysis (an accelerated failure time model) to assess gender differences. We estimated mediation effects of amputation level, pain comorbidity burden, medical comorbidities, depression, and marital status on time to prescription. RESULTS: In the 1 year after amputation, the proportion of women (54.3%) and men (55.7%) prescribed a prosthesis was similar. However, after we controlled for age, race, ethnicity, enrollment priority, VHA region, and service-connected disability, the time to prosthetic prescription was significantly faster among men compared with women (acceleration factor=0.73; 95% confidence interval, 0.61-0.87). The difference in time to prosthetic prescription between men and women was significantly mediated by amputation level (23%), pain comorbidity burden (-14%), and marital status (5%) but not medical comorbidities or depression. CONCLUSIONS: Although the proportion of patients with prosthetic prescription at 1-year postamputation was similar between men and women, women received prosthetic prescriptions more slowly than men, suggesting that more work is needed to understand barriers to timely prosthetic prescriptions among women, and how to intervene to reduce those barriers.


Assuntos
Membros Artificiais , Veteranos , Masculino , Humanos , Feminino , Estados Unidos/epidemiologia , Estudos Longitudinais , Estudos Retrospectivos , Amputação Cirúrgica , Estudos de Coortes , Dor/epidemiologia , Prescrições , Extremidades , Extremidade Inferior/cirurgia
8.
Nat Chem Biol ; 18(11): 1184-1195, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36163383

RESUMO

Although cyclophilins are attractive targets for probing biology and therapeutic intervention, no subtype-selective cyclophilin inhibitors have been described. We discovered novel cyclophilin inhibitors from the in vitro selection of a DNA-templated library of 256,000 drug-like macrocycles for cyclophilin D (CypD) affinity. Iterated macrocycle engineering guided by ten X-ray co-crystal structures yielded potent and selective inhibitors (half maximal inhibitory concentration (IC50) = 10 nM) that bind the active site of CypD and also make novel interactions with non-conserved residues in the S2 pocket, an adjacent exo-site. The resulting macrocycles inhibit CypD activity with 21- to >10,000-fold selectivity over other cyclophilins and inhibit mitochondrial permeability transition pore opening in isolated mitochondria. We further exploited S2 pocket interactions to develop the first cyclophilin E (CypE)-selective inhibitor, which forms a reversible covalent bond with a CypE S2 pocket lysine, and exhibits 30- to >4,000-fold selectivity over other cyclophilins. These findings reveal a strategy to generate isoform-selective small-molecule cyclophilin modulators, advancing their suitability as targets for biological investigation and therapeutic development.


Assuntos
Ciclofilinas , Poro de Transição de Permeabilidade Mitocondrial , Ciclofilinas/química , Ciclofilinas/metabolismo , Peptidil-Prolil Isomerase F , Lisina , DNA
9.
BMJ Open ; 12(3): e058363, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35304400

RESUMO

OBJECTIVE: To estimate associations of statin use with hospitalisation, intensive care unit (ICU) admission and mortality at 30 days among individuals with and without a positive test for SARS-CoV-2. DESIGN: Retrospective cohort study. SETTING: US Veterans Health Administration (VHA). PARTICIPANTS: All veterans receiving VHA healthcare with ≥1 positive nasal swab for SARS-CoV-2 between 1 March 2020 and 10 March 2021 (cases; n=231 154) and a comparator group of controls comprising all veterans who did not have a positive nasal swab for SARS-CoV-2 but who did have ≥1 clinical lab test performed during the same time period (n=4 570 252). MAIN OUTCOMES: Associations of: (1) any statin use, (2) use of specific statins or (3) low-intensity/moderate-intensity versus high-intensity statin use at the time of positive nasal swab for SARS-CoV-2 (cases) or result of clinical lab test (controls) assessed from pharmacy records with hospitalisation, ICU admission and death at 30 days. We also examined whether associations differed between individuals with and without a positive test for SARS-CoV-2. RESULTS: Among individuals who tested positive for SARS-CoV-2, statin use was associated with lower odds of death at 30 days (OR 0.81 (95% CI 0.77 to 0.85)) but not with hospitalisation or ICU admission. Associations were similar comparing use of each specific statin to no statin. Compared with low-/moderate intensity statin use, high-intensity statin use was not associated with lower odds of ICU admission or death. Over the same period, associations of statin use with 30-day outcomes were significantly stronger among individuals without a positive test for SARS-CoV-2: hospitalisation OR 0.79 (95% CI 0.77 to 0.80), ICU admission OR 0.86 (95% CI 0.81 to 0.90) and death 0.60 (95% CI 0.58 to 0.62; p for interaction all <0.001). CONCLUSIONS: Associations of statin use with lower adverse 30-day outcomes are weaker among individuals who tested positive for SARS-CoV-2 compared with individuals without a positive test, indicating that statins do not exert SARS-CoV-2 specific effects.


Assuntos
COVID-19 , Inibidores de Hidroximetilglutaril-CoA Redutases , Veteranos , Estudos de Coortes , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estudos Retrospectivos , SARS-CoV-2
10.
Arch Rehabil Res Clin Transl ; 4(1): 100182, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35282148

RESUMO

Objectives: To determine the positive predictive value (PPV) of algorithms to identify patients with major (at the ankle or more proximal) lower extremity amputation (LEA) using Department of Veterans Affairs electronic medical records (EMR) and to evaluate whether PPV varies by sex, age, and race. Design: We conducted a validation study comparing EMR determined LEA status to self-reported LEA (criterion standard). Setting: Veterans who receive care at the Department of Veterans Affairs. Participants: We invited a national sample of patients (N=699) with at least 1 procedure or diagnosis code for major LEA to participate. We oversampled women, Black men, and men ≤40 years of age. Interventions: Not applicable. Main Outcome Measure: We calculated PPV estimates and false negative percentages for 7 algorithms using EMR LEA procedure and diagnosis codes relative to self-reported major LEA. Results: A total of 466 veterans self-reported their LEA status (68%). PPVs for the 7 algorithms ranged from 89% to 100%. The algorithm that required a single diagnosis or procedure code had the lowest PPV (89%). The algorithm that required at least 1 procedure code had the highest PPV (100%) but also had the highest proportion of false negatives (66%). Algorithms that required at least 1 procedure code or 2 or more diagnosis codes 1 month to 1 year apart had high PPVs (98%-99%) but varied in terms of false negative percentages. PPV estimates were higher among men than women but did not differ meaningfully by age or race, after accounting for sex. Conclusion: PPVs were higher if 1 procedure or at least 2 diagnosis codes were required; the difference between algorithms was marked by sex. Investigators should consider trade-offs between PPV and false negatives to identify patients with LEA using EMRs.

11.
Diabetes Care ; 45(4): 782-788, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35085391

RESUMO

OBJECTIVE: To examine associations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection/coronavirus disease 2019 with incident diabetes. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using Veterans Health Administration data. We defined all patients without preexisting diabetes with one or more nasal swabs positive for SARS-CoV-2 (1 March 2020-10 March 2021; n = 126,710) as exposed and those with no positive swab and one or more laboratory tests (1 March 2020-31 March 2021; n = 2,651,058) as unexposed. The index date for patients exposed was the date of first positive swab and for patients unexposed a random date during the month of the qualifying laboratory test. We fit sex-stratified logistic regression models examining associations of SARS-CoV-2 with incident diabetes within 120 days and all follow-up time through 1 June 2021. A subgroup analysis was performed among hospitalized subjects only to help equalize laboratory surveillance. RESULTS: SARS-CoV-2 was associated with higher risk of incident diabetes, compared with no positive tests, among men (120 days, odds ratio [OR] 2.56 [95% CI 2.32-2.83]; all time, 1.95 [1.80-2.12]) but not women (120 days, 1.21 [0.88-1.68]; all time, 1.04 [0.82-1.31]). Among hospitalized participants, SARS-CoV-2 was associated with higher risk of diabetes at 120 days and at the end of follow-up in men (OR 1.42 [95% CI 1.22-1.65] and 1.32 [1.16-1.50], respectively) but not women (0.72 [0.34-1.52] and 0.80 [0.44-1.45]). Sex ∗ SARS-CoV-2 interaction P values were all <0.1. CONCLUSIONS: SARS-CoV-2 is associated with higher risk of incident diabetes in men but not in women even after greater surveillance related to hospitalization is accounted for.


Assuntos
COVID-19 , Diabetes Mellitus , Veteranos , COVID-19/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos , SARS-CoV-2
12.
Diabetes Care ; 44(12): 2708-2713, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34615690

RESUMO

OBJECTIVE: To identify preinfection risk factors for adverse outcomes among veterans with diabetes and coronavirus disease 2019 (COVID-19) infection. RESEARCH DESIGN AND METHODS: We identified all Veterans Health Administration patients with diabetes and one or more positive nasal swab(s) for severe acute respiratory syndrome coronavirus 2 (1 March 2020-10 March 2021) (n = 64,892). We examined associations of HbA1c and glucose-lowering medication use with hospitalization, intensive care unit (ICU) admission, and mortality at 30 days using logistic regression models and during 4.4 months of follow-up (range <1-13.1) using proportional hazards models. RESULTS: Compared with HbA1c <7.0%, HbA1c ≥9.0% was associated with higher odds of hospitalization, ICU admission, and death at 30 days (odds ratio [OR] 1.27 [95% CI 1.19-1.35], 1.28 [95% CI 1.15-1.42], 1.30 [95% CI 1.17-1.44], respectively) as well as higher risk of death over 4.4 months (hazard ratio [HR] 1.22 [95% CI 1.12-1.32]). Insulin use was associated with higher odds of hospitalization, ICU admission, and death (OR 1.12 [95% CI 1.07-1.18], 1.12 [95% CI 1.04-1.22], and 1.18 [95% CI 1.09-1.27], respectively) and higher risk of death (HR 1.12 [95% CI 1.07-1.18]). Sodium-glucose cotransporter 2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor agonist (GLP1-RA), or angiotensin receptor blocker use were associated with lower odds of hospitalization (OR 0.92 [95% CI 0.85-0.99], 0.88 [95% CI 0.81-0.96], and 0.94 [95% CI 0.89-0.99], respectively). Metformin and SGLT2i use were associated with lower odds (OR 0.84 [95% CI 0.78-0.91], 0.82 [95% CI 0.72-0.94], respectively) and risk of death (HR 0.84 [95% CI 0.79-0.89], 0.82 [95% CI 0.74-0.92], respectively). CONCLUSIONS: Among veterans with diabetes and COVID-19, higher HbA1c and insulin use were directly associated with adverse outcomes, while use of a GLP1-RA, metformin, and SGLT2i was inversely associated.


Assuntos
COVID-19 , Diabetes Mellitus , Veteranos , Glucose , Humanos , SARS-CoV-2
13.
BMJ Open ; 11(9): e051885, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556516

RESUMO

OBJECTIVES: To evaluate feasibility and acceptability of a group-based nature recreation intervention (nature hiking) and control condition (urban hiking) for military Veterans with post-traumatic stress disorder (PTSD). DESIGN AND SETTING: A pilot randomised controlled trial conducted in the US Pacific Northwest. PARTICIPANTS: Veterans with PTSD due to any cause. INTERVENTIONS: Twenty-six participants were randomised to a 12-week intervention involving either six nature hikes (n=13) or six urban hikes (n=13). PRIMARY AND SECONDARY OUTCOME MEASURES: Feasibility was assessed based on recruitment, retention and attendance. Questionnaires and postintervention qualitative interviews were conducted to explore intervention acceptability. Questionnaires assessing acceptability and outcomes planned for the future trial (eg, PTSD symptoms) were collected at baseline, 6 weeks, 12 weeks (immediately after the final hike) and 24 weeks follow-up. RESULTS: Of 415 people assessed for eligibility/interest, 97 were interested and passed preliminary eligibility screening, and 26 were randomised. Mean completion of all questionnaires was 91% among those in the nature hiking group and 68% in those in the urban hiking group. Over the course of the intervention, participants in the nature and urban groups attended an average of 56% and 58%, respectively, of scheduled hikes. Acceptability of both urban and nature hikes was high; over 70% reported a positive rating (ie, good/excellent) for the study communication, as well as hike locations, distance and pace. Median PTSD symptom scores (PTSD Checklist-5) improved more at 12 weeks and 24 weeks among those in the nature versus urban hiking group. CONCLUSIONS: This pilot study largely confirmed the feasibility and acceptability of nature hiking as a potential treatment for Veterans with PTSD. Adaptations will be needed to improve recruitment and increase hike attendance for a future randomised controlled trial to effectively test and isolate the ways in which nature contact, physical activity and social support conferred by the group impact outcomes. TRIAL REGISTRATION NUMBER: NCT03997344.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Veteranos , Estudos de Viabilidade , Humanos , Projetos Piloto , Transtornos de Estresse Pós-Traumáticos/terapia , Inquéritos e Questionários
14.
J Infect Dis ; 224(6): 967-975, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34153099

RESUMO

BACKGROUND: Early convalescent plasma transfusion may reduce mortality in patients with nonsevere coronavirus disease 2019 (COVID-19). METHODS: This study emulates a (hypothetical) target trial using observational data from a cohort of US veterans admitted to a Department of Veterans Affairs (VA) facility between 1 May and 17 November 2020 with nonsevere COVID-19. The intervention was convalescent plasma initiated within 2 days of eligibility. Thirty-day mortality was compared using cumulative incidence curves, risk differences, and hazard ratios estimated from pooled logistic models with inverse probability weighting to adjust for confounding. RESULTS: Of 11 269 eligible person-trials contributed by 4755 patients, 402 trials were assigned to the convalescent plasma group. Forty and 671 deaths occurred within the plasma and nonplasma groups, respectively. The estimated 30-day mortality risk was 6.5% (95% confidence interval [CI], 4.0%-9.7%) in the plasma group and 6.2% (95% CI, 5.6%-7.0%) in the nonplasma group. The associated risk difference was 0.30% (95% CI, -2.30% to 3.60%) and the hazard ratio was 1.04 (95% CI, .64-1.62). CONCLUSIONS: Our target trial emulation estimated no meaningful differences in 30-day mortality between nonsevere COVID-19 patients treated and untreated with convalescent plasma. Clinical Trials Registration. NCT04545047.


Assuntos
Transfusão de Componentes Sanguíneos , COVID-19/mortalidade , COVID-19/terapia , Imunização Passiva , Plasma , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Estados Unidos/epidemiologia , Veteranos , Adulto Jovem , Soroterapia para COVID-19
15.
Artigo em Inglês | MEDLINE | ID: mdl-34083248

RESUMO

INTRODUCTION: Risk factors and mediators of associations of diabetes with COVID-19 outcomes are unclear. RESEARCH DESIGN AND METHODS: We identified all veterans receiving Department of Veterans Affairs healthcare with ≥1 positive nasal swab for SARS-CoV-2 (28 February-31 July 2020; n=35 879). We assessed associations of diabetes (with and without insulin use) with hospitalization, intensive care unit (ICU) admission, or death at 30 days, and with hazard of death until the censoring date. Among participants with diabetes (n=13 863), we examined associations of hemoglobin A1c and antihyperglycemic medication use with COVID-19 outcomes. We estimated mediation between diabetes and outcomes by comorbidities (cardiovascular disease, heart failure, and chronic kidney disease), statin or ACE inhibitor/angiotensin receptor blocker (ARB) use, and cardiac biomarkers (brain natriuretic peptide and troponin). RESULTS: Diabetes with and without insulin use was associated with greater odds of hospitalization, ICU admission, and death at 30 days, and with greater hazard of death compared with no diabetes (OR 1.73, 1.76 and 1.63, and HR 1.61; and OR 1.39, 1.49 and 1.33, and HR 1.37, respectively, all p<0.0001). Prior sulfonylurea use was associated with greater odds of hospitalization and prior insulin use with hospitalization and death among patients with diabetes; among all participants, statin use was associated with lower mortality and ARB use with lower odds of hospitalization. Cardiovascular disease-related factors mediated <20% of associations between diabetes and outcomes. CONCLUSIONS: Diabetes is independently associated with adverse outcomes from COVID-19. Associations are only partially mediated by common comorbidities.


Assuntos
COVID-19 , Diabetes Mellitus , Veteranos , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Humanos , Fatores de Risco , SARS-CoV-2
17.
Respir Res ; 22(1): 62, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608007

RESUMO

BACKGROUND: Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung reducing clinical consequences of cholinergic hyperactivity. The AIRFLOW-1 study assessed safety and TLD dose in patients with moderate-to-severe, symptomatic COPD. This analysis evaluated the long-term impact of TLD on COPD exacerbations, pulmonary function, and quality of life over 3 years of follow up. METHODS: TLD was performed in a prospective, energy-level randomized (29 W vs 32 W power), multicenter study (NCT02058459). Additional patients were enrolled in an open label confirmation phase to confirm improved gastrointestinal safety after procedural modifications. Durability of TLD was evaluated at 1, 2, and 3 years post-treatment and assessed through analysis of COPD exacerbations, pulmonary lung function, and quality of life. RESULTS: Three-year follow-up data were available for 73.9% of patients (n = 34). The annualized rate of moderate to severe COPD exacerbations remained stable over the duration of the study. Lung function (FEV1, FVC, RV, and TLC) and quality of life (SGRQ-C and CAT) remained stable over 3 years of follow-up. No new gastrointestinal adverse events and no unexpected serious adverse events were observed. CONCLUSION: TLD in COPD patients demonstrated a positive safety profile out to 3 years, with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over 3 years of follow up.


Assuntos
Denervação/métodos , Volume Expiratório Forçado/fisiologia , Pulmão/inervação , Doença Pulmonar Obstrutiva Crônica/cirurgia , Qualidade de Vida , Broncoscopia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Pulmão/diagnóstico por imagem , Masculino , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fatores de Tempo
19.
Hand (N Y) ; 16(2): 193-200, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-31155949

RESUMO

Background: Volar radiocarpal instability is often seen after loss of fixation of volar lunate facet fragments. The pathogenesis of post-traumatic volar radiocarpal instability is poorly understood. The purpose of this study was to determine if injury to the dorsal wrist extrinsic carpal ligaments contributes to volar radiocarpal instability. Methods: Six matched pairs of cadaveric upper extremities were tested using a dynamic hand testing system. In group 1, the intact wrist, the wrist with a volar lunate facet fracture, and the fractured wrist after 500 cycles of grip were tested. In group 2, in addition to the intact and fractured wrist, the fractured wrist with the dorsal extrinsic carpal ligaments cut and the fractured wrist with the dorsal extrinsic carpal ligaments cut after 500 cycles of grip were also tested. Volar-dorsal displacement of the lunate was measured from 45° wrist flexion to 45° wrist extension in 22.5° increments with the wrist flexors/extensors loaded for each condition. Results: Volar lunate translation did not significantly increase after the volar lunate facet fracture alone, and was not evident to a significant extent until the dorsal wrist extrinsic carpal ligaments were cut. Further instability of the lunate occurred after grip cycling only with the dorsal extrinsic capsular ligaments cut. Conclusions: Injury to the dorsal wrist extrinsic carpal ligaments exacerbates volar radiocarpal instability. Unrecognized dorsal sided injury may be a contributing factor to why stable fixation of volar lunate facet fragments remains problematic after volar plating of intra-articular distal radius fractures with displaced volar lunate facet fragments.


Assuntos
Osso Semilunar , Fraturas do Rádio , Humanos , Ligamentos Articulares , Fraturas do Rádio/cirurgia , Punho , Articulação do Punho
20.
Foot Ankle Orthop ; 6(1): 2473011421993103, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35097431

RESUMO

BACKGROUND: Hallux rigidus (HR) is a common source of forefoot pain and disability. For those who fail nonoperative treatment, minimally invasive dorsal cheilectomy (MIDC) is an increasingly popular alternative to the open approach with early positive results. Early failures may be due to lose bone debris from the MIDC as well as other intra-articular pathology that cannot be addressed with MIDC alone. Metatarsophalangeal (MTP) arthroscopy can be used in addition to MIDC to assess the joint after MIDC and address any intra-articular pathology while still maintaining the benefits of minimally invasive surgery. We report our clinical outcomes following MIDC combined with MTP arthroscopy. METHODS: From November 2017 to July 2020, a retrospective analysis of all MIDC cheilectomies with MTP arthroscopy performed by the 2 senior authors was done. Wound complications, infections, revision rates, need for future surgery, conversion to fusion rates, pre- and postoperative range of motion, visual analog scale (VAS) scores, time to return to normal shoe, intraoperative arthroscopic findings, and operative time were collected. Follow-up average was 16.5 months (range 3-33 months). RESULTS: A total of 20 patients were included with an average follow-up of 16.5 months. The average VAS score improved from 7.05 preoperatively to 0.75 postoperatively (P < .05). Average range of motion in dorsiflexion increased from 32 to 48 degrees (P < .05) and plantarflexion increased from 15 to 19 degrees plantarflexion (P < .05). All patients were weightbearing as tolerated immediately after surgery in a postoperative shoe and transitioned to a regular shoe at average of 2.1 weeks. We had no wound infections, wound complications, revision surgeries, tendon injuries or nerve damage. One patient required conversion to a fusion 3 years after the index procedure. Average tourniquet time was 30.39 minutes (range 17-60 minutes) and total average operating room time was 59.7 minutes (range 40-87 minutes). On arthroscopic evaluation of the MTP joint after MIDC, 100% of patients had bone debris, 100% had synovitis, 10% had loose bodies, and 30% had large cartilage flaps within the joint. CONCLUSION: MIDC and first MTP joint arthroscopy for treatment of hallux rigidus provide improved pain relief with minimal complications while still maintaining the benefits touted for minimally invasive operative procedures. Additionally, we have shown a high rate of intra-articular debris along with intra-articular pathology such as synovitis, loose chondral flaps, and loose bodies that exist after MIDC. This combined procedure has the potential for improving patient outcomes and may minimize risk of future revision surgeries compared with MIDC alone. LEVEL OF EVIDENCE: Level IV, case series study.

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