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Opioid prescribing remains common despite known overdose-related harms. Less is known about links to nonoverdose morbidity. We determined the association between prescribed opioid receipt with incident cardiovascular disease (CVD) using data from the Veterans Aging Cohort Study, a national prospective cohort of Veterans with/without Human Immunodeficiency Virus (HIV) receiving Veterans Health Administration care. Selected participants had no/minimal prior exposure to prescription opioids, no opioid use disorder, and no severe illness 1 year after the study start date (baseline period). We ascertained prescription opioid exposure over 3 years after the baseline period using outpatient pharmacy fill/refill data. Incident CVD ascertainment began at the end of the prescribed opioid exposure ascertainment period until the first incident CVD event, death, or September 30, 2015. We used adjusted Cox proportional hazards regression models with matching weights using propensity scores for opioid receipt to estimate CVD risk. Among 49,077 patients, 30% received opioids; the median age was 49 years, 97% were male, 49% were Black, and 47% were currently smoking. Prevalence of hypertension, diabetes, current smoking, alcohol and cocaine use disorder, and depression was higher in patients receiving opioids versus those not but were well-balanced by matching weights. Unadjusted CVD incidence rates per 1,000-person-years were higher among those receiving opioids versus those not: 17.4 (95% confidence interval [CI], 16.5-18.3) versus 14.7 (95% CI, 14.2-15.3). In adjusted analyses, those receiving opioids versus those not had an increased hazard of incident CVD (adjusted hazard ratio 1.16 [95% CI, 1.08-1.24]). Prescribed opioids were associated with increased CVD incidence, making opioids a potential modifiable CVD risk factor. PERSPECTIVE: In a propensity score weighted analysis of Veterans Administration data, prescribed opioids compared to no opioids were associated with an increased hazard of incident CVD. Higher opioid doses compared with lower doses were associated with increased hazard of incident CVD. Opioids are a potentially modifiable CVD risk factor.
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BACKGROUND: HIV disproportionally affects persons who inject drugs (PWID), but engagement with HIV pre-exposure prophylaxis (PrEP) is low. We describe the rationale and study design for a new study, "Contingency Management and Pre-Exposure Prophylaxis (PrEP) Adherence Support Services (CoMPASS)," a hybrid type 1 effectiveness-implementation trial to promote HIV risk reduction among PWID. METHODS: In four community-based programs in the northeastern United States, PrEP-eligible PWID (target n = 526) are randomized to treatment as usual or Contingency Management (CM) and, as indicated, stepped up to PrEP Adherence Support Services (CoMPASS) over 24 weeks. During CM sessions, participants receive timely tangible rewards for verifiable activities demonstrating 1) PrEP initiation and adherence, and 2) engagement with medications for opioid use disorder (MOUD) and other OUD-related care. Participants who do not have high levels of biomarker-confirmed PrEP adherence at week 12 will be stepped up to receive PrEP Adherence Support Services (PASS) consisting of strengths-based case management over 12 weeks. Interventions are delivered by trained PrEP navigators, staff embedded within the respective sites. The primary outcome is sustained PrEP adherence by dried blood spot testing at 24 weeks. To inform future implementation, we are conducting implementation-focused process evaluations throughout the clinical trial. CONCLUSIONS: Results from this protocol are anticipated to yield novel findings regarding the impact and scalability of CoMPASS to promote HIV prevention among PWID in partnership with community-based organizations. http://ClinicalTrials.gov identifier: NCT04738825.
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Fármacos Anti-HIV , Usuários de Drogas , Infecções por HIV , Profilaxia Pré-Exposição , Abuso de Substâncias por Via Intravenosa , Humanos , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Profilaxia Pré-Exposição/métodos , Abuso de Substâncias por Via Intravenosa/complicações , Comportamento de Redução do RiscoRESUMO
This cross-sectional study of US adults examines the prevalence of and characteristics associated with prescribed buprenorphine use among US adults with pain-motivated nonmedical use of prescription opioids.
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Analgésicos Opioides , Buprenorfina , Adulto , Humanos , Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Autorrelato , Dor/tratamento farmacológico , PrescriçõesRESUMO
Background: The association between cannabis use and HIV-1 RNA (viral load) among people with HIV (PWH) engaged in care is unclear. Methods: We used data collected from 2002 to 2018 on PWH receiving antiretroviral therapy (ART) enrolled in the Veterans Aging Cohort Study. Generalized estimating equations were used to estimate associations between self-reported past-year cannabis use and detectable viral load (≥500 copies/mL), with and without adjustment for demographics, other substance use, and adherence. Results: Among 2515 participants, 97% were male, 66% were Black, the mean age was 50 years, and 33% had detectable HIV viral load at the first study visit. In unadjusted analyses, PWH with any past-year cannabis use had 21% higher odds of a detectable viral load than those with no past-year use (OR = 1.21; 95% CI, 1.07-1.37). However, there was no significant association between cannabis use and viral load after adjustment. Conclusions: Among PWH engaged in care and receiving ART, cannabis use is associated with decreased adherence in unadjusted analyses but does not appear to directly impact viral control. Future studies are needed to understand other potential risks and benefits of cannabis use among PWH.
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Fármacos Anti-HIV , Cannabis , Infecções por HIV , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Autorrelato , Carga ViralRESUMO
OBJECTIVES: Among opioid use disorder (OUD)-treating providers, to characterize adaptations used to provide medications for OUD (MOUD) and factors associated with desire to continue virtual visits post-COVID-19 pandemic. METHODS: In a national electronic survey of OUD-treating prescribers (July-August 2020), analyses restricted to X-waivered buprenorphine prescribers providing outpatient, longitudinal care for adults with OUD, quantitative and qualitative analyses of survey items and free text responses were conducted. RESULTS: Among 797 respondents, 49% were men, 57% ≥50 years, 76% White, 68% physicians. Respondents widely used virtual visits to continue prescribing existing MOUD regimens (79%), provide behavioral healthcare (71%), and initiate new MOUD prescriptions (49%). Most prescribers preferred to continue/expand use of virtual visits after COVID-19. In multivariable models, factors associated with preference to continue/expand virtual visits to initiate MOUD postpandemic were treating a moderate number of patients prepandemic (aOR = 1.67; 95%[CI] = 1.06,2.62) and practicing in an urban setting (aOR = 2.17; 95%[CI] = 1.48,3.18). Prescribing buprenorphine prepandemic (aOR = 2.06; 95%[CI] = 1.11,3.82) and working in an academic medical center (aOR = 2.47; 95%[CI] = 1.30,4.68) were associated with preference to continue/expand use of virtual visits to continue MOUD postpandemic. Prescribing naltrexone extended-release injection prepandemic was associated with preference to continue/expand virtual visits to initiate and continue MOUD (aOR = 1.51; 95%[CI] = 1.10,2.07; aOR = 1.74; 95%[CI] = 1.19,2.54). Qualitative findings suggest that providers appreciated virtual visits due to convenience and patient accessibility, but were concerned about liability and technological barriers. CONCLUSIONS: Surveyed prescribers widely used virtual visits to provide MOUD with overall positive experiences. Future studies should evaluate the impact of virtual visits on MOUD access and retention and clinical outcomes.
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Buprenorfina , COVID-19 , Transtornos Relacionados ao Uso de Opioides , Adulto , Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Feminino , Humanos , Masculino , Naltrexona/uso terapêutico , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , PandemiasAssuntos
Buprenorfina , COVID-19 , Dor Crônica , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Dor Crônica/tratamento farmacológico , Humanos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Dor/tratamento farmacológico , Melhoria de QualidadeRESUMO
OBJECTIVE: The COVID-19 pandemic has dramatically affected health care delivery, effects that are juxtaposed with health care professional (HCP) burnout and mental distress. The Opioid Use Disorder Provider COVID-19 Survey was conducted to better understand the impact of COVID-19 on clinical practice and HCP well-being. METHODS: The cross-sectional survey was e-mailed to listservs with approximately 157,000 subscribers of diverse professions between July 14 and August 15, 2020. Two dependent variables evaluated HCP functioning and work-life balance. Independent variables assessed organizational practices and HCP experiences. Covariates included participant demographic characteristics, addiction board certification, and practice setting. Multilevel multivariate logistic regression models were used. RESULTS: Among 812 survey respondents, most were men, White, and physicians, with 46% located in urban settings. Function-impairing anxiety was reported by 17%, and 28% reported more difficulty with work-life balance. Difficulty with functioning was positively associated with having staff who were sick with COVID-19 and feeling close to patients, and was negatively associated with being male and having no staff changes. Difficulty with work-life balance was positively associated with addiction board certification; working in multiple settings; having layoffs, furloughs, or reduced hours; staff illness with COVID-19; and group well-being check-ins. It was negatively associated with male gender, older age, and no staff changes. CONCLUSIONS: Demographic, provider, and organizational-practice variables were associated with reporting negative measures of well-being during the COVID-19 pandemic. These results should inform HCPs and their organizations on factors that may lead to burnout, with particular focus on gender and age-related concerns and the role of well-being check-ins.
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Esgotamento Profissional , COVID-19 , Transtornos Relacionados ao Uso de Opioides , Esgotamento Profissional/epidemiologia , COVID-19/epidemiologia , Estudos Transversais , Pessoal de Saúde , Humanos , Masculino , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/terapia , Pandemias , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
Importance: Methadone access may be uniquely vulnerable to disruption during COVID-19, and even short delays in access are associated with decreased medication initiation and increased illicit opioid use and overdose death. Relative to Canada, US methadone provision is more restricted and limited to specialized opioid treatment programs. Objective: To compare timely access to methadone initiation in the US and Canada during COVID-19. Design, Setting, and Participants: This cross-sectional study was conducted from May to June 2020. Participating clinics provided methadone for opioid use disorder in 14 US states and territories and 3 Canadian provinces with the highest opioid overdose death rates. Statistical analysis was performed from July 2020 to January 2021. Exposures: Nation and type of health insurance (US Medicaid and US self-pay vs Canadian provincial). Main Outcomes and Measures: Proportion of clinics accepting new patients and days to first appointment. Results: Among 268 of 298 US clinics contacted as a patient with Medicaid (90%), 271 of 301 US clinics contacted as a self-pay patient (90%), and 237 of 288 Canadian clinics contacted as a patient with provincial insurance (82%), new patients were accepted for methadone at 231 clinics (86%) during US Medicaid contacts, 230 clinics (85%) during US self-pay contacts, and at 210 clinics (89%) during Canadian contacts. Among clinics not accepting new patients, at least 44% of 27 clinics reported that the COVID-19 pandemic was the reason. The mean wait for first appointment was greater among US Medicaid contacts (3.5 days [95% CI, 2.9-4.2 days]) and US self-pay contacts (4.1 days [95% CI, 3.4-4.8 days]) than Canadian contacts (1.9 days [95% CI, 1.7-2.1 days]) (P < .001). Open-access model (walk-in hours for new patients without an appointment) utilization was reported by 57 Medicaid (30%), 57 self-pay (30%), and 115 Canadian (59%) contacts offering an appointment. Conclusions and Relevance: In this cross-sectional study of 2 nations, more than 1 in 10 methadone clinics were not accepting new patients. Canadian clinics offered more timely methadone access than US opioid treatment programs. These results suggest that the methadone access shortage was exacerbated by COVID-19 and that changes to the US opioid treatment program model are needed to improve the timeliness of access. Increased open-access model adoption may increase timely access.
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COVID-19 , Acessibilidade aos Serviços de Saúde , Metadona/uso terapêutico , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/terapia , Pandemias , Listas de Espera , Instituições de Assistência Ambulatorial , Analgésicos Opioides , Canadá , Estudos Transversais , Financiamento Pessoal , Serviços de Saúde , Seguro Saúde , Medicaid , Estados UnidosRESUMO
Polypharmacy is associated with frailty in the general population, but little is known about polypharmacy among persons living with HIV (PLWH) on antiretroviral (ARV) therapy. We determined the association between polypharmacy and an adapted frailty-related phenotype (aFRP) via a cross-sectional study in FY 2009 of 1762 PLWH on ARV with suppressed viral load and 2679 uninfected participants in the Veterans Aging Cohort Study. The primary predictor was number of chronic outpatient non-ARV medications using pharmacy fill/refill data. The outcome was self-report of four aFRP domains: shrinking, exhaustion, slowness, low physical activity. Frailty was defined as reporting 3-4 domains while pre-frailty was 1-2. Frailty was uncommon (2% PLWH, 3% uninfected); a larger proportion demonstrated any aFRP domain (31% PLWH, 41% uninfected). Among PLWH and uninfected, median chronic non-ARV medications was 6 and 16 respectively if having any aFRP domain, and 4 and 10 when without aFRP domains. In adjusted analyses, each additional chronic non-ARV medication conferred an 11% increased odds of having any aFRP domain in PLWH (OR [95% CI] = 1.11 [1.08, 1.14]), and a 4% increase in those uninfected (OR [95% CI] = 1.04 [1.03, 1.04]). The stronger association between polypharmacy and frailty in PLWH warrants further study and potential deprescribing of medications.
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Fragilidade , Infecções por HIV , Estudos de Coortes , Estudos Transversais , Fragilidade/epidemiologia , Infecções por HIV/tratamento farmacológico , Humanos , PolimedicaçãoRESUMO
BACKGROUND: In the current opioid epidemic, opioid addiction and overdose deaths are a public health crisis. Researchers have uncovered other concerning findings related to opioid use, such as the association between prescribed opioids and respiratory infection, including pneumonias. Potential mechanisms include the immunosuppressive effects of certain opioids, respiratory depression, and cough suppression. We conducted a systematic review assessing whether prescribed opioid receipt is a risk factor for community-acquired pneumonia (CAP). METHODS: A systematic literature search of published studies was conducted using Ovid MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Web of Science, AMED, and CINAHL from database inception through March 11, 2020. We included any clinical trial, cohort, or case-control study that reported an association between prescribed opioid receipt and CAP in adults. Two reviewers independently performed data extraction and quality assessment using the Newcastle-Ottawa Quality Assessment Scale. The risk of CAP from prescribed opioid receipt was studied by pooling studies using random effects meta-analysis. RESULTS: We identified 3229 studies after removing duplicates. After detailed selection, 33 articles were reviewed in full and eight studies (representing 567,472 patients) met inclusion criteria. The pooled effect for the four case-control studies and three cohort studies showed a significant increase in the risk of CAP requiring hospitalization among those with prescribed opioid receipt compared with those without opioid prescribed receipt (OR 1.57 [95% CI (1.34, 1.84)]; HR 1.18 [95% CI (1.00, 1.40)]). CONCLUSION: The findings suggest prescribed opioid receipt is a risk factor for CAP. The included studies examined post-operative patients and patients with chronic medical conditions. Further research is needed to examine the impact of opioids on the incidence of CAP in an otherwise healthy population.
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Infecções Comunitárias Adquiridas , Transtornos Relacionados ao Uso de Opioides , Pneumonia , Adulto , Analgésicos Opioides/efeitos adversos , Estudos de Casos e Controles , Infecções Comunitárias Adquiridas/epidemiologia , Humanos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Pneumonia/induzido quimicamente , Pneumonia/epidemiologiaRESUMO
PURPOSE OF REVIEW: We summarize recent literature on the contribution of substance use and depression to non-AIDS-related comorbidities. Discussion of recent randomized clinical trials and implementation research to curtail risk attributed to each behavioral health issue is provided. RECENT FINDINGS: Smoking, unhealthy alcohol use, opioid use, and depression are common among PWH and individually contribute to increased risk for non-AIDS-related comorbidities. The concurrence of these conditions is notable, yet understudied, and provides opportunity for linked-screening and potential treatment of more than one behavioral health factor. Current results from randomized clinical trials are inconsistent. Investigating interventions to reduce the impact of these behavioral health conditions with a focus on implementation into clinical care is important. Non-AIDS-defining cancers, cardiovascular disease, liver disease, and diabetes are leading causes of morbidity in people with HIV. Behavioral health factors including substance use and mental health issues, often co-occurring, likely contribute to the excess risk of non-AIDS-related comorbidities.
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Depressão/complicações , Infecções por HIV/patologia , Transtornos Relacionados ao Uso de Opioides/complicações , Fumar/epidemiologia , Consumo de Bebidas Alcoólicas , Doenças Cardiovasculares/complicações , Comorbidade , Diabetes Mellitus/epidemiologia , Infecções por HIV/tratamento farmacológico , Humanos , Hepatopatias/complicaçõesRESUMO
BACKGROUND: Transcatheter aortic valve replacement (TAVR) may be associated with less delirium and allow faster recovery than surgical aortic valve replacement (SAVR). OBJECTIVE: To examine the association of delirium and its severity with clinical and functional outcomes after SAVR and TAVR. DESIGN: Prospective cohort study. SETTING: An academic medical center. PARTICIPANTS: A total of 187 patients, aged 70 years and older, undergoing SAVR (N = 77) and TAVR (N = 110) in 2014 to 2016. MEASUREMENTS: Delirium was assessed daily using the Confusion Assessment Method (CAM), with severity measured by the CAM-Severity (CAM-S) score (range = 0-19). Outcomes were prolonged hospitalization (9 days or more); institutional discharge; and functional status, measured by ability to perform 22 daily activities and physical tasks over 12 months. RESULTS: SAVR patients had a higher incidence of delirium than TAVR patients (50.7% vs 25.5%; P < .001), despite younger mean age (77.9 vs 83.7 years) and higher baseline Mini-Mental State Examination score (26.9 vs 24.7). SAVR patients with delirium had a shorter duration (2.2 vs 3.4 days; P = .04) with a lower mean CAM-S score (4.5 vs 5.7; P = .01) than TAVR patients with delirium. The risk of prolonged hospitalization in no, mild, and severe delirium was 18.4%, 30.8%, and 61.5% after SAVR (P for trend = .009) and 26.8%, 38.5%, and 73.3% after TAVR (P for trend = .001), respectively. The risk of institutional discharge was 42.1%, 58.3%, and 84.6% after SAVR (P for trend = .01) and 32.5%, 69.2%, and 80.0% after TAVR (P for trend <.001), respectively. Severe delirium was associated with delayed functional recovery after SAVR and persistent functional impairment after TAVR at 12 months. CONCLUSION: Less invasive TAVR was associated with lower incidence of delirium than SAVR. Once delirium developed, TAVR patients had more severe delirium and worse functional status trajectory than SAVR patients did. REGISTRATION: NCT01845207.
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Delírio/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Feminino , Fragilidade , Humanos , Incidência , Masculino , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores de RiscoRESUMO
In Caenorhabditis elegans hermaphrodites, physiological germline apoptosis is higher in cdc-25.3 mutants than in wild-type. The elevated germline apoptosis in cdc-25.3 mutants seems to be induced by accumulation of double-stranded DNA breaks (DSBs). Both DNA damage and synapsis checkpoint genes are required to increase the germline apoptosis. Notably, the number of germ cells that lose P-granule components, PGL-1 and PGL-3, increase in cdc-25.3 mutants, and the increase in germline apoptosis requires the activity of SIR-2.1, a Sirtuin orthologue. These results suggest that elevation of germline apoptosis in cdc-25.3 mutants is induced by accumulation of DSBs, leading to a loss of PGL-1 and PGL-3 in germ cells, which promotes cytoplasmic translocation of SIR-2.1, and finally activates the core apoptotic machinery.
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Apoptose/genética , Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/citologia , Caenorhabditis elegans/genética , Deleção de Genes , Homologia de Sequência do Ácido Nucleico , Espermatozoides/citologia , Fosfatases cdc25/genética , Animais , Proteínas de Caenorhabditis elegans/metabolismo , Pareamento Cromossômico , Quebras de DNA de Cadeia Dupla , Transtornos do Desenvolvimento Sexual/genética , Masculino , Meiose , Fosfatases cdc25/metabolismoRESUMO
When treating cancer using radiation therapy, it is critical to increase patient survival rates and to reduce side effects. In this respect, proton beam radiation treatment performs better than other radiation treatments because of its high target specificity. However, complications still remain after proton beam radiation treatment. Among them, the risk to progeny after irradiation of their parents is a major concern. In this study, we analyzed the transgenerational effects of proton beam irradiation using the model organism Caenorhabditis. elegans. We found that germline apoptosis increased after proton beam irradiation and its effects were sustained transgenerationally. Moreover, we identified that a germline-specific histone methyltransferase component, SET-2, has a critical role in transmitting the transgenerational effect on germline apoptosis to the next generation after proton beam irradiation.
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Apoptose/efeitos da radiação , Caenorhabditis elegans/fisiologia , Caenorhabditis elegans/efeitos da radiação , Células Germinativas/efeitos da radiação , Prótons/efeitos adversos , Animais , Caenorhabditis elegans/embriologia , Proteínas de Caenorhabditis elegans/metabolismo , Feminino , Células Germinativas/citologia , Masculino , Proteínas Nucleares/metabolismo , Reprodução/efeitos da radiaçãoRESUMO
Bone defects are common disease requiring thorough treatments since the bone is a complex vascularized tissue that is composed of multiple cell types embedded within an intricate extracellular matrix (ECM). For past decades, tissue engineering using cells, proteins, and scaffolds has been suggested as one of the promising approaches for effective bone regeneration. Recently, many researchers have been interested in designing effective platform for tissue regeneration by orchestrating factors involved in microenvironment around tissues. Among factors affecting bone formation, vascularization during bone development and after minor insults via endochondral and intramembranous ossification is especially critical for the long-term support for functional bone. In order to create vascularized bone constructs, the interactions between human mesenchymal stem cells (MSCs) and endothelial cells (ECs) have been investigated using both direct and indirect co-culture studies. Recently, various culture methods including micropatterning techniques, three dimensional scaffolds, and microfluidics have been developed to create micro-engineered platforms that mimic the nature of vascularized bone formation, leading to the creation of functional bone structures. This review focuses on MSCs co-cultured with endothelial cells and microengineered platforms to determine the underlying interplay between co-cultured MSCs and vascularized bone constructs, which is ultimately necessary for adequate regeneration of bone defects.
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OBJECTIVES: This study aimed to check the status of the contact investigation in congregate settings to eradicate tuberculosis (TB) in the Republic of Korea. METHODS: The "Integrated System for Disease and Public Health Management" is used for care and follow-up for patients and contacts of TB. We downloaded data for contact investigations conducted from January to December 2013. RESULTS: A total of 1,200 contact investigations in congregate settings were carried out by 25 field investigators in 2013. We performed the status of contact investigation, TB, and LTBI rate by age, accept rate of LTBI treatment, and complete rate of LTBI treatment during 2013. A total of 1,547 index TB patients, 149,166 contacts, and 259 additional TB patients were found through the investigation. Kindergartens showed the highest LTBI rate, 19.8%, among educational facilities. The second highest was in elementary schools and the subtotal LTBI rate of educational facilities was 7.8%. Social welfare/correctional facilities and workplaces showed relatively high LTBI rates of 23.8% and 23.6%, respectively. By age, individuals >35 years showed the highest LTBI rate, followed by those aged 0-4 years, 30-34 years, and 5-9 years, with rates of 18.1%, 16.4%, and 15.4% respectively. When comparing the tuberculin skin test (TST) positive conversion ratio by facility, middle school and high school were relatively high compared to the others. The accept rate of LTBI treatment in the workplace was lowest at 63% and the complete rate in elementary schools was lowest at 76.5%. CONCLUSION: TB contact investigation is considered as a meaningful strategy for preventing TB outbreaks in congregate settings and decreasing the prevalence of TB in young people. Results of this study could be used to establish the LTBI management policy.
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OBJECTIVE: To compare electrical impedance myography (EIM) 50 kHz phase to weight, motor score, paw grip endurance (PGE), CMAP amplitude, and MUNE for the identification of disease progression and the effect of riluzole in the SOD1 G93A mouse. METHODS: Twenty-three animals received 8 mg/kg/day riluzole in the drinking water starting at 6 weeks of age; 22 animals served as controls. Weight, motor score, PGE, CMAP, MUNE, and EIM were performed weekly to evaluate disease progression. RESULTS: No difference in clinical disease onset or survival was found between treated and untreated groups. In addition, all methods failed to identify any beneficial effect of riluzole. Thus, data from all animals were combined for additional analyses. Of the 4 parameters, EIM phase showed the earliest change from baseline and the most linear decline throughout the entire measurement period. In addition, EIM phase correlated with PGE, CMAP amplitude, and MUNE (Spearman râ=â0.92, 0.90, and 0.72, respectively, p<0.01 for all). The rate of EIM phase decline also correlated with individual animal survival (Spearman râ=â-0.31, p<0.05). CONCLUSIONS: At this dose, riluzole is ineffective in slowing progression of ALS. However, EIM phase shows early linear declines, supporting its potential as a useful new biomarker for preclinical drug testing.
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Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/fisiopatologia , Músculo Esquelético/fisiopatologia , Fármacos Neuroprotetores/farmacologia , Riluzol/farmacologia , Superóxido Dismutase/genética , Substituição de Aminoácidos , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/genética , Animais , Biomarcadores/análise , Modelos Animais de Doenças , Progressão da Doença , Impedância Elétrica , Feminino , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/patologia , Força Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Miografia , Superóxido Dismutase-1RESUMO
OBJECTIVE: Recent developments in electrical impedance myography (EIM) have led to the use of handheld electrode arrays (HEAs) for data acquisition. Although preferable for several reasons, this approach tends to be more affected by subcutaneous fat (SF) than the original approach in which the impedance-measuring electrodes are widely spaced. In this study, we seek to identify the EIM parameter least impacted by subcutaneous fat (SF) when using an HEA. METHODS: 18 normal subjects underwent 50 kHz EIM and ultrasound of the medial gastrocnemius muscles on the dominant side. Coefficients of determination (R(2) values) were calculated for each of the three major EIM variables (reactance, resistance, and phase) and SF thickness. RESULTS: For both resistance and phase, a strong relationship to SF thickness was observed (R(2) = 0.64 and R(2) = 0.70, respectively, p < 0.001 for both). In contrast, for reactance, the relationship was non-significant, with R(2) = 0.07, p = 0.30. CONCLUSIONS: Unlike resistance and phase, both of which are highly impacted by SF thickness, the reactance shows no significant relationship. SIGNIFICANCE: Future clinical studies employing HEA's to perform EIM should evaluate alterations in reactance in addition to those in resistance and phase.
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Eletromiografia/instrumentação , Eletromiografia/métodos , Gordura Subcutânea/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Impedância Elétrica , Eletrodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologia , Gordura Subcutânea/diagnóstico por imagem , Ultrassonografia , Adulto JovemRESUMO
OBJECTIVE: To test a method for performing electrical impedance myography (EIM) in the mouse hind limb for the assessment of disease status in neuromuscular disease models. METHODS: An impedance measuring device consisting of a frame with electrodes embedded within an acrylic head was developed. The head was rotatable such that data longitudinal and transverse to the major muscle fiber direction could be obtained. EIM measurements were made with this device on 16 healthy mice and 14 amyotrophic lateral sclerosis (ALS) animals. Repeatability was assessed in both groups. RESULTS: The technique was easy to perform and provided good repeatability in both healthy and ALS animals, with intra-session repeatability (mean ± SEM) of 5% ± 1% and 12% ± 2%, respectively. Significant differences between healthy and ALS animals were also identified (e.g., longitudinal mean 50 kHz phase was 18 ± 0.6° for the healthy animals and 14 ± 1.0° for the ALS animals, p=0.0025). CONCLUSIONS: With this simple device, the EIM data obtained is highly repeatable and can differentiate healthy from ALS animals. SIGNIFICANCE: EIM can now be applied to mouse models of neuromuscular disease to assess disease status and the effects of therapy.
Assuntos
Esclerose Lateral Amiotrófica/enzimologia , Esclerose Lateral Amiotrófica/fisiopatologia , Membro Posterior/fisiopatologia , Mutação/genética , Miografia/métodos , Superóxido Dismutase/genética , Animais , Anisotropia , Impedância Elétrica , Feminino , Masculino , Camundongos , Miografia/instrumentação , Reprodutibilidade dos TestesRESUMO
ALS is commonly associated with a hypermetabolic state. In this study, we assess whether inhibition of this hypermetabolism via the induction of hypothyroidism can forestall disease onset and prolong life in the SOD1-G93A mouse. We treated a cohort of 16 SOD1-G93A mice with methimazole, a potent inhibitor of thyroid hormone synthesis and followed a second group of 23 untreated littermate control animals from approximately five weeks of age onward. Total thyroxine (T4) levels, weights, and rectal temperatures were obtained on a regular basis and animals were sacrificed when they were no longer able to feed themselves. Results revealed that T4 levels were effectively suppressed within two weeks of drug initiation. However, there was no significant difference between the two groups either in terms of clinical disease onset (120.1±9.3 days for treated animals and 116.7±6.3 days for untreated animals) or in terms of survival (131.4±11.7 days for treated animals and 134.0±10.0 days for untreated animals). A correlation analysis between mean T4 levels for each animal versus survival showed that, contrary to our hypothesis, higher T4 levels correlated with longer survival. In conclusion, these studies show that drug-induced hypothyroidism does not alter the disease course in the SOD1-G93A ALS mouse.