Endocarditis, drug use and biological sex: A statewide analysis comparing sex differences in drug use-associated infective endocarditis with other drug-related harms.

OBJECTIVES: Hospitalizations for drug use-associated infective endocarditis (DUA-IE) have risen sharply across the United States over the past decade. The sex composition of DUA-IE remains less clear, and studies have indicated a possible shift to more females. We aimed to compare more recent statewide hospitalization rates for DUA-IE in females versus males and contextualize them among other drug-related harms in North Carolina (NC). METHODS: This study was a retrospective analysis using public health datasets of all NC hospital discharges for infective endocarditis from 2016 to 2020. Drug use-related hospitalizations were identified using ICD-10-CM codes. Discharge rates by year and sex for DUA-IE and non-DUA-IE were calculated and compared to fatal overdoses and acute hepatitis C (HCV). Temporal, demographic, and pregnancy trends were also assessed. RESULTS: Hospitalizations rates for DUA-IE were 9.7 per 100,000 over the five-year period, and 1.2 times higher among females than males. Females composed 57% of DUA-IE hospitalizations over the period. Conversely, fatal overdose, acute HCV, and non-DUA-IE hospitalization rates were higher among males. Age, county of residence, and pregnancy status did not explain the higher DUA-IE among females. CONCLUSION: Females now comprise the majority of DUA-IE hospitalizations in NC, unlike other drug-related harms. No clear demographic or geographic associations were found, and further research is needed to explain this phenomenon. Preventing invasive infections among females who inject drugs should be prioritized.

Inpatient Hepatitis C Treatment Coordination and Initiation for Patients Who Inject Drugs.

BACKGROUND: With hepatitis C (HCV) incidence rising due to injection drug use, people who inject drugs (PWID) are a priority population for direct-acting antivirals (DAA). However, significant barriers exist. At our institution, hospitalized PWID were screened for HCV but not effectively linked to care. AIM: To improve retention in HCV care among hospitalized PWID. SETTING: Quaternary academic center in the Southeast US from August 2021 through August 2022. PARTICIPANTS: Hospitalized PWID with HCV. PROGRAM DESCRIPTION: E-consultation-prompted care coordination and HCV treatment with outpatient telehealth. PROGRAM EVALUATION: Care cascades were constructed to assess retention and HCV treatment, with the primary outcome defined as DAA completion or sustained virologic response after week 4. Of 28 patients, 11 started DAAs inpatient, 8 initiated outpatient, and 9 were lost to follow-up or transferred care. Overall, 82% were linked to care and 52% completed treatment. For inpatient initiators, 73% achieved the outcome. Of non-inpatient initiators, 71% were linked to care, 53% started treatment, and 36% achieved the outcome. DISCUSSION: Inpatient HCV treatment coordination, including DAA initiation, and telehealth follow-up, was feasible and highly effective for hospitalized PWID. Future steps should address barriers to inpatient DAA treatment and expand this model to other similar patient populations.

Systemic therapies for preventing or treating aromatase inhibitor-induced musculoskeletal symptoms in early breast cancer.

BACKGROUND: Adjuvant aromatase inhibitors (AI) improve survival compared to tamoxifen in postmenopausal women with hormone receptor-positive stage I to III breast cancer. In approximately half of these women, AI are associated with aromatase inhibitor-induced musculoskeletal symptoms (AIMSS), often described as symmetrical pain and soreness in the joints, musculoskeletal pain and joint stiffness. AIMSS may have significant and prolonged impact on women's quality of life. AIMSS reduces adherence to AI therapy in up to a half of women, potentially compromising breast cancer outcomes. Differing systemic therapies have been investigated for the prevention and treatment of AIMSS, but the effectiveness of these therapies remains unclear. OBJECTIVES: To assess the effects of systemic therapies on the prevention or management of AIMSS in women with stage I to III hormone receptor-positive breast cancer. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, WHO International Clinical Trials Registry Platform (ICTRP) and Clinicaltrials.gov registries to September 2020 and the Cochrane Breast Cancer Group (CBCG) Specialised Register to March 2021.  SELECTION CRITERIA: We included all randomised controlled trials that compared systemic therapies to a comparator arm. Systemic therapy interventions included all pharmacological therapies, dietary supplements, and complementary and alternative medicines (CAM). All comparator arms were allowed including placebo or standard of care (or both) with analgesia alone. Published and non-peer-reviewed studies were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies, extracted data, and assessed risk of bias and certainty of the evidence using the GRADE approach. Outcomes assessed were pain, stiffness, grip strength, safety data, discontinuation of AI, health-related quality of life (HRQoL), breast cancer-specific quality of life (BCS-QoL), incidence of AIMSS, breast cancer-specific survival (BCSS) and overall survival (OS). For continuous outcomes, we used vote-counting by reporting how many studies reported a clinically significant benefit within the confidence intervals (CI) of the mean difference (MD) between treatment arms, as determined by the minimal clinically importance difference (MCID) for that outcome scale. For dichotomous outcomes, we reported outcomes as a risk ratio (RR) with 95% CI. MAIN RESULTS: We included 17 studies with 2034 randomised participants. Four studies assessed systemic therapies for the prevention of AIMSS and 13 studies investigated treatment of AIMSS. Due to the variation in systemic therapy studies, including pharmacological, and CAM, or unavailable data, meta-analysis was limited, and only two trials were combined for meta-analysis. The certainty of evidence for all outcomes was either low or very low certainty. Prevention studies The evidence is very uncertain about the effect of systemic therapies on pain (from baseline to the end of the intervention; 2 studies, 183 women). The two studies, investigating vitamin D and omega-3 fatty acids, showed a treatment effect with 95% CIs that did not include an MCID for pain. Systemic therapies may have little to no effect on grip strength (RR 1.08, 95% CI 0.37 to 3.17; 1 study, 137 women) or on women continuing to take their AI (RR 0.16, 95% 0.01 to 2.99; 1 study, 147 women). The evidence suggests little to no effect on HRQoL and BCS-QoL from baseline to the end of intervention (the same single study; 44 women, both quality of life outcomes showed a treatment effect with 95% CIs that did include an MCID). The evidence is very uncertain for outcomes assessing incidence of AIMSS (RR 0.82, 95% CI 0.63 to 1.06; 2 studies, 240 women) and the safety of systemic therapies (4 studies, 344 women; very low-certainty evidence). One study had a US Food and Drug Administration alert issued for the intervention (cyclo-oxygenase-2 inhibitor) during the study, but there were no serious adverse events in this or any study. There were no data on stiffness, BCSS or OS. Treatment studies The evidence is very uncertain about the effect of systemic therapies on pain from baseline to the end of intervention in the treatment of AIMSS (10 studies, 1099 women). Four studies showed an MCID in pain scores which fell within the 95% CI of the measured effect (vitamin D, bionic tiger bone, Yi Shen Jian Gu granules, calcitonin). Six studies showed a treatment effect with 95% CI that did not include an MCID (vitamin D, testosterone, omega-3 fatty acids, duloxetine, emu oil, cat's claw).  The evidence was very uncertain for the outcomes of change in stiffness (4 studies, 295 women), HRQoL (3 studies, 208 women) and BCS-QoL (2 studies, 147 women) from baseline to the end of intervention. The evidence suggests systemic therapies may have little to no effect on grip strength (1 study, 107 women). The evidence is very uncertain about the safety of systemic therapies (10 studies, 1250 women). There were no grade four/five adverse events reported in any of the studies. The study of duloxetine reported more all-grade adverse events in this treatment group than comparator group. There were no data on the incidence of AIMSS, the number of women continuing to take AI, BCCS or OS from the treatment studies. AUTHORS' CONCLUSIONS: AIMSS are chronic and complex symptoms with a significant impact on women with early breast cancer taking AI. To date, evidence for safe and effective systemic therapies for prevention or treatment of AIMSS has been minimal. Although this review identified 17 studies with 2034 randomised participants, the review was challenging due to the heterogeneous systemic therapy interventions and study methodologies, and the unavailability of certain trial data. Meta-analysis was thus limited and findings of the review were inconclusive. Further research is recommended into systemic therapy for AIMSS, including high-quality adequately powered RCT, comprehensive descriptions of the intervention/placebo, and robust definitions of the condition and the outcomes being studied.

Universal screening for substance use by Peer Support Specialists in the Emergency Department is a pathway to buprenorphine treatment.

INTRODUCTION: Evidence suggests emergency department (ED)-initiated buprenorphine as efficacious in connecting ED patients to Medications for Opioid Use Disorder (MOUD) utilizing peer support specialists (PSS). However, there are no reports of implementation of ED-initiated buprenorphine in practice. Such information is crucial to support the adoption of ED-initiated buprenorphine. METHODS: In this quality improvement pilot study, a PSS screened ED patients over age 18 with the Tobacco, Alcohol, Prescription medication, and other Substance use - 1 (TAPS-1). The PSS considered the patient a positive screen if the patient met the following criteria: risky weekly alcohol use, illicit drugs, or prescription drugs. For patients who screened positive, the PSS delivered a brief intervention and assessed interest in treatment. An ED clinician assessed patients who screened positive for heroin/opioid use and were interested in treatment for buprenorphine induction. RESULTS: From January through June 2019, 1037 patients were screened for risky substance use, and, of these, 238 (23%) screened positive. The distribution of primary substance used was: 51% alcohol, 26% cannabis, 7.5% cocaine, 7.5% heroin, and 3.3% prescription opioids. Of the 23 patients who screened positive for heroin/opioid use and requested treatment, seven were admitted to the hospital. Of the remaining 16 patients, 14 patients wanted buprenorphine treatment, seven were provided buprenorphine in the ED, and four of these attended their intake appointments for community-based MOUD treatment. CONCLUSION: ED-initiated buprenorphine facilitated by a PSS is feasible and requires coordination and planning. Approaches to ED-initiated buprenorphine that screen only for opioid use will miss many patients interested in substance use treatment.

Computed tomography texture analysis of response to second-line nivolumab in metastatic non-small cell lung cancer.

OBJECTIVES: Assess computed tomography texture analysis of patients likely to benefit from nivolumab. MATERIALS & METHODS: Texture analysis was used to quantify heterogeneity within the largest tumor before immunotherapy. Histogram analysis was classified as hyperdense (positive skewness) or hypodense (negative skewness) and subclassified on median standard deviation value or entropy measurement. RESULTS: 47 patients were included. At a median follow-up of 18 months, statistical significant differences in progression-free survival were observed when stratified by positive skewness with low entropy, hazard ratio: 0.43 (0.19-0.95); p = 0.036, and positive skewness with low standard deviation, hazard ratio: 0.42 (0.18-0.96); p = 0.04. CONCLUSION: Patients who derive a clinical benefit to Nivolumab show a computed tomography texture of a hyperdense yet homogenous tumor.

Exercise therapies for preventing or treating aromatase inhibitor-induced musculoskeletal symptoms in early breast cancer.

BACKGROUND: Survival for stage I to III, hormone receptor-positive, breast cancer has substantially improved over time due to advances in screening, surgery and adjuvant therapy. However many adjuvant therapies have significant treatment-related toxicities, which worsen quality of life for breast cancer survivors. Postmenopausal women with hormone receptor-positive breast cancer are now prescribed aromatase inhibitors (AI) as standard, with longer durations of therapy, up to 10 years, being considered for certain women. AI treatment is associated with a high incidence of AI-induced musculoskeletal symptoms (AIMSS), often described as symmetrical pain and soreness in the joints, musculoskeletal pain and joint stiffness. AIMSS reduces compliance with AI therapy in up to one half of women undergoing adjuvant AI therapy, potentially compromising breast cancer outcomes. Exercise has been investigated for the prevention and treatment of AIMSS but the effect of this intervention remains unclear. OBJECTIVES: To assess the effects of exercise therapies on the prevention or management of aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) in women with stage I to III hormone receptor-positive breast cancer. SEARCH METHODS: We searched Cochrane Breast Cancer's Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases up to 13 December 2018. We also searched two conference proceedings portals and two clinical trials registries for ongoing studies or unpublished trials, or both, in August 2019. We also reviewed reference lists of the included studies. SELECTION CRITERIA: We included randomised controlled trials that compared exercise versus a comparator arm. We did not impose any restriction on the comparator arm, which could include an alternative type of exercise, no exercise or a waiting list control. Both published and non-peer-reviewed studies were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, assessed risk of bias and certainty of the evidence using the GRADE approach. The outcomes investigated were pain, joint stiffness, grip strength, health-related quality of life, cancer-specific quality of life, adherence to AI therapy, adverse events, incidence of AIMSS, breast cancer-specific survival and overall survival. For continuous outcomes that were assessed with the same instrument, we used the mean difference (MD); for those outcomes that used different instruments, we used the standardised mean difference (SMD) for the analysis. For dichotomous outcomes, we reported outcomes as an odds ratio (OR). MAIN RESULTS: We included seven studies with 400 randomised participants; one study assessed exercise for preventing AIMSS and six studies assessed treating AIMSS. For preventing AIMSS, the single study reported no difference in pain scores, grip strength or compliance to taking AI medication between groups. Data values were not provided in the study and no other outcomes were reported. For managing AIMSS, we found that the evidence for the effect of exercise therapies on overall change in worst pain scores was very uncertain (SMD -0.23, 95% confidence interval (CI) -0.78 to 0.32; 4 studies, 284 women; very low-certainty evidence). The evidence suggested that exercise therapies result in little to no difference in overall change in stiffness scores (Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) stiffness score MD -0.76, 95% CI -1.67 to 0.15 and Visual Analogues Scale (VAS) stiffness score MD -0.42, 95% CI -2.10 to 1.26; 1 study, 53 women; low-certainty evidence). The evidence was very uncertain for the outcomes of overall change in grip strength (MD 0.30, 95% CI -0.55 to 1.15; 1 study, 83 women; very low-certainty evidence); overall change in health-related quality of life (subscales of SF-36 tool ranged from least benefit of MD 1.88, 95% CI -2.69 to 6.45 to most benefit of MD 9.70, 95% CI 1.67 to 17.73; 2 studies, 123 women, very low-certainty evidence); overall change in cancer-specific quality of life (MD 4.58, 95% CI -0.61 to 9.78; 2 studies, 136 women; very low-certainty evidence); and adherence to aromatase inhibitors (OR 2.43, 95% CI 0.41 to 14.63; 2 studies, 224 women; very low-certainty evidence). There were no adverse events identified across four studies in either arm (0 events reported; 4 studies; 331 participants; low-certainty evidence). There were no data reported on incidence of AIMSS, breast cancer-specific survival or overall survival. AUTHORS' CONCLUSIONS: Given the wide-ranging benefits of exercise for people affected by cancer, it was surprising that this review provided no clear evidence of benefit for exercise therapies in women with early breast cancer with AIMSS. This review only yielded seven eligible studies with 400 participants, which is likely to have underpowered the findings. The meta-analysis was challenging due to the considerable heterogeneity amongst the trials, with a wide range of exercise regimens and follow-up periods. Despite these inconclusive findings, exercise needs to be part of routine care for women with breast cancer due to its wide-ranging benefits. Future research in this area would be enhanced with further understanding of the mechanism of AIMSS, a single clear definition of the condition, and phase III randomised controlled trials that are adequately powered to test targeted exercise interventions on the key clinical outcomes in this condition.