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Each point higher on the FTCD was associated with 0.83mg/day more NRT consumption, controlling for tobacco exposure. This relationship was diminished when withdrawal was controlled for, and withdrawal was associated with NRT consumption, with each point higher on the MPSS associated with a 0.12mg/day increase. Increased consumption of NRT directly predicted subsequent smoking cessation.

Higher dependence appears to lead to greater withdrawal, which appears to drive greater use of NRT. This effect may partly offset lower abstinence rates in people with higher dependence. Advice to use sufficient NRT to suppress withdrawal may increase abstinence rates.

Higher dependence appears to lead to greater withdrawal, which appears to drive greater use of NRT. This effect may partly offset lower abstinence rates in people with higher dependence. Advice to use sufficient NRT to suppress withdrawal may increase abstinence rates.

HIV prevalence among people who inject drugs (PWID) in Kenya is estimated to be 18% compared to 4.5% in the general population. Studies from high-income countries have demonstrated that methadone use is associated with increased uptake of antiretroviral therapy (ART) and higher rates of viral suppression among PWID with HIV. However, it is unclear whether methadone use has the same effect among African PWID living with HIV.

We performed a cross-sectional study to evaluate associations between methadone program participation and ART uptake and viral suppression (HIV RNA viral load <1000 copies/ml) among PWID with HIV in Kenya. Participants were recruited from needle and syringe programs and methadone clinics, interviewed on site, and samples were obtained and assayed for HIV viral loads. Univariate and multiple logistic regression were used to determine associations.

Among 679 participants, median age was 37years, 48% were female, and 24% were in a methadone program. We observed higher proportions of ART use (96% vs. 87%, p=0.001) and HIV viral suppression (78% vs. 65%, p=0.012) among PWID on methadone compared to those not on methadone treatment. PWID who were not participating in a methadone program were 3-fold more likely to be off ART and approximately twice as likely to be viremic compared to those in methadone programs (adjusted odds ratio [aOR]=3.35, 95% confidence interval [CI] 1.35-8.35 and aOR=1.90, 95% CI 1.03-3.52, respectively).

In this study, Kenyan PWID living with HIV participating in a methadone treatment program were more likely to be on ART and to have achieved viral suppression. Scale-up of methadone programs may have a positive impact on HIV epidemic control for this key population.

In this study, Kenyan PWID living with HIV participating in a methadone treatment program were more likely to be on ART and to have achieved viral suppression. Scale-up of methadone programs may have a positive impact on HIV epidemic control for this key population.

Medically treated opioid overdoses identify a population at high risk of subsequent mortality and need for treatment. This study reports on medically treated opioid overdose trends in a state with rapid fentanyl spread.

We conducted stratified trend analysis of medically treated overdose due to heroin, synthetic opioids, methadone, or other natural opioids among New Jersey Medicaid beneficiaries aged 12-64years (2014-2019); evaluated associations with demographics and co-occurring conditions; and examined trends in fentanyl penetration in suspected heroin seizures from New Jersey State Police data.

Overdose risk more than tripled from 2014 to 2019, from 120.5 to 426.8 per 100,000 person-years, respectively. Increases primarily involved heroin and synthetic opioids and were associated with co-occurring alcohol and other non-opioid drug disorders, major depressive disorder, and hepatitis C. Concurrent changes in the drug exposure environment (2015-2019) included an increase in fentanyl penetration (proportion of suspected heroin seizures that included fentanyls) from 2% to 80%, and a decrease in the proportion of Medicaid beneficiaries who received opioid analgesic prescriptions from 23% to 13%.

Results document a rapid increase in overdose risk among individuals with opioid use disorder in an environment in which fentanyl is highly prevalent, and highlight the need for intensified services and engagement of non-treatment seekers, and integrated models to address multiple co-occurring conditions and risk factors.

Results document a rapid increase in overdose risk among individuals with opioid use disorder in an environment in which fentanyl is highly prevalent, and highlight the need for intensified services and engagement of non-treatment seekers, and integrated models to address multiple co-occurring conditions and risk factors.

Flecainide is a commonly used IC antiarrhythmic. Clinical presentations of Flecainide toxicity are not commonly described.

A 62 year old man on dialysis presented for evaluation of outpatient bradycardia and hypotension. In the ED, patient had wide-complex rhythm with heart rates ranging from 76 to 127. The previous day, Flecainide and Metoprolol were discontinued and patient was dialyzed and discharged. The patient was treated empirically for possible hyperkalemia. No significant change in ECG was noted with administration of calcium. Sodium bicarbonate produced questionable benefit. Potassium level was 4.6 mmol/L. Cardiac rhythm fluctuated between sinus rhythm and wide complex tachycardia in the ED & ICU. Flecainide level was 2.1 μg/ml (normal <1 μg/ml). Toxicity developed despite previous discontinuation and dialysis prior to presentation because of Flecainide's large volume of distribution and lipopholicity. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? Although Flecainide toxicity is unccians' suspicion that WCT is not due to hyperkalemia, emphasizing the importance of reviewing patients' home medications. Sodium bicarbonate should be administered early to treat widened QRS. Amiodarone, intralipid emulsion therapy and ECMO may be considered in severe cases.The Pre-exposure Prophylaxis, Data to Care, Implementation, and Evaluation (PrIDE) multi-site demonstration project utilized a cluster evaluation approach and identified six funding recipients that evaluated similar media evaluation questions (Baltimore, Los Angeles County, Lousiana, Michigan, New York City, and Virginia). All of the evaluated social marketing campaigns were developed in collaboration with health department staff, external marketing firms, and community advisory boards (CAB) aiming to produce changes in PrEP outcomes by reaching racial/ethnic and sexual and gender minorities. Jurisdictions demonstrated changes in PrEP awareness, knowledge, willingness to take PrEP, and/or PrEP literacy following initiation of the campaigns. In data from four sites, PrEP awareness significantly increased from 72 % at baseline to 86 % at mid-project, and to 90 % post-campaigns. The campaigns illustrate the importance of partnerships and stakeholder engagement, audience segmentation, and intentional evaluation planning. As PrEP services mature, evaluating PrEP demand and PrEP use resulting from campaigns, will be necessary. Also, future campaigns for racial/ethnic and sexual and gender minorities should identify the best channels to reach each group based on their input, disaggregate data by priority group, and determine campaign effectiveness.

Our pilot clinical study of EphA2 inhibitor (dasatinib) plus paclitaxel and carboplatin showed interesting clinical activity in endometrial cancer with manageable toxicity. However, the underlying mechanisms of dasatinib resistance in uterine cancer are unknown. Here, we investigated potential mechanisms underlying resistance to EphA2 inhibitors in uterine cancer and examined the anti-tumor activity of EphA2 inhibitors alone and in combination with a MEK inhibitor.

We evaluated the antitumor activity of EphA2 inhibitors plus a MEK inhibitor using in vitro and in vivo orthotopic models of uterine cancer.

EphA2 inhibitor induced MAPK in dasatinib-resistant uterine cancer cells (HEC-1A and Ishikawa) and BRAF/CRAF heterodimerization in HEC-1A cells. EphA2 inhibitor and trametinib significantly increased apoptosis in cancer cells resistant to EphA2 inhibitors compared with controls (p < 0.01). An in vivo study with the orthotopic HEC-1A model showed significantly greater antitumor response to combination EphA2 and MEK, combined with chemotherapy, should be considered for future clinical development.

Lamotrigine, an anticonvulsant drug with inhibition properties of multi-ion channels, has been shown to be able to attenuates secondary neuronal damage by influencing different pathways. The aim of this study was to look into whether lamotrigine treatment could protect the spinal cord from experimental spinal cord ischemia-reperfusion injury.

Thirty-two rats, eight rats per group, were randomly assigned to the sham group in which only laparotomy was performed, and to the ischemia, methylprednisolone and lamotrigine groups, where the infrarenal aorta was clamped for thirty minutes to induce spinal cord ischemia-reperfusion injury. Tissue samples belonging to spinal cords were harvested from sacrificed animals twenty-four hours after reperfusion. Tumor necrosis factor-alpha levels, interleukin-1 beta levels, nitric oxide levels, superoxide dismutase activity, catalase activity, glutathione peroxidase activity, malondialdehyde levels and caspase-3 activity were studied. Light and electron microscopic evaluateuronal damage developing after spinal cord ischemia-reperfusion injury.Cardiorespiratory fitness (CRF) is intricately related to health status. The optimal approach for CRF quantification is through assessment of peak oxygen uptake (VO2), but such measurements have been largely confined to small referral populations. Here we describe protocols and methodological considerations for peak VO2 assessment and determination of volitional effort in a large community-based sample. Maximum incremental ramp cycle ergometry cardiopulmonary exercise testing (CPET) was performed by Framingham Heart Study participants at a routine study visit (2016 to 2019). Of 3,486 individuals presenting for a multicomponent study visit, 3,116 (89%) completed CPET. The sample was middle-aged (54 ± 9 years), with 53% women, body mass index 28.3 ± 5.6 kg/m2, 48% with hypertension, 6% smokers, and 8% with diabetes. Exercise duration was 12.0 ± 2.1 minutes (limits 3.7to20.5). No major cardiovascular events occurred. A total of 98%, 96%, 90%, 76%, and 57% of the sample reached peak respiratory exchange ratio (RER) values of ≥1.0, ≥1.05, ≥1.10, ≥1.15, and ≥1.20, respectively (mean peak RER = 1.21 ± 0.10). With rising peak RER values up to ≈1.10, steep changes were observed for percent predicted peak VO2, VO2 at the ventilatory threshold/peak VO2, heart rate response, and Borg (subjective dyspnea) scores. click here More shallow changes for effort dependent CPET variables were observed with higher achieved RER values. In conclusion, measurement of peak VO2 is feasible and safe in a large sample of middle-aged, community-dwelling individuals with heterogeneous cardiovascular risk profiles. Peak RER ≥1.10 was achievable by the majority of middle-aged adults and RER values beyond this threshold did not necessarily correspond to higher peak VO2 values.

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