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Purpose: This article explored Licensed Clinical Social Workers (LCSWs) beliefs, attitudes, and knowledge of Complementary and Alternative Interventions (CAI). Method: We utilized a cross-sectional online survey among a sample of 193 LCSWs. Results: Approximately 60% of LCSWs assessed for and utilized CAI professionally, and 90% personally utilized CAI. LCSWs had moderately positive beliefs, neutral attitudes, and high baseline knowledge of CAI. Age and years of practice were the only significant correlates, and the only significant predictor for assessment and utilization of CAI was positive attitudes. Discussion: As the largest group of mental health providers, we found that it is vital for LCSWs to have a solid understanding of CAI to provide effective and safe services to the clients they serve. It is hoped that the results of this study will serve as a starting point for future research on CAI among social workers, with the goal of enhancing client-centered practice. [ABSTRACT FROM AUTHOR]

Drug-resistant tuberculosis (TB) has emerged as a substantial threat to advances in global TB control over the past several decades (1). Worldwide, an estimated 630,000 cases of multidrug-resistant (MDR) TB [...]

Eluxadoline is approved for the treatment of diarrhea‐predominant irritable bowel syndrome in the United States. The impact of renal impairment on the pharmacokinetic (PK) parameters of eluxadoline is currently unknown. This phase 1, open‐label, parallel‐group study evaluated the PK and safety profile of eluxadoline in 8 participants with renal impairment and 8 matched healthy controls. Of the participants with renal impairment, 2 had severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) and 6 had end‐stage renal disease while not yet on dialysis (eGFR <15 mL/min/1.73 m2). The primary objective was to assess plasma and urine PKs, and plasma protein binding of eluxadoline. In participants with renal impairment, mean plasma concentrations of eluxadoline were consistently higher compared with matched healthy controls: 1.4‐fold higher for mean maximum plasma concentration (Cmax) and 2.2‐fold higher for mean area under the plasma concentration‐time curve from time 0 to time t. The median time to Cmax was 2.5 hours in both groups. Although eluxadoline is a locally acting drug with low oral bioavailability, because of the increased systemic exposure in participants with renal impairment as a cautionary measure the lower approved dose of 75 mg twice daily is recommended for individuals with severe renal impairment and end‐stage renal disease while not yet on dialysis. Eluxadoline 100 mg single dose was well tolerated in participants with renal impairment and matched healthy controls. [ABSTRACT FROM AUTHOR]

Eluxadoline is a mixed μ‐opioid, κ‐opioid receptor agonist, and δ‐opioid receptor antagonist, approved in the United States for adults with diarrhea‐predominant irritable bowel syndrome. This phase 1, single‐center, open‐label, single‐sequence study was conducted on 30 healthy participants to establish whether steady‐state eluxadoline increases systemic exposure of the cytochrome P450 (CYP) 3A4 substrate midazolam. Participants received oral midazolam 4 mg on day 1 with a 7‐day washout period. On days 8‐16, oral eluxadoline 100 mg was administered twice daily. On day 15, midazolam 4 mg was coadministered with the eluxadoline 100‐mg morning dose. Primary outcome measures were pharmacokinetic parameters of midazolam and 1‐hydroxy‐midazolam. The midazolam and 1‐hydroxy‐midazolam geometric mean ratios and 90%CIs for maximum plasma drug concentration were 99.0% (91.6‐107.0) and 113.8% (104.9‐123.5), respectively, and area under the plasma concentration–time curves were 90.5% (83.9‐97.6) and 105.1% (99.8‐110.7), respectively, demonstrating the 2 treatments were bioequivalent, and there was no clinically significant drug interaction. All treatment‐emergent adverse events were treatment related, mild in intensity, with no serious adverse events. These results suggest that eluxadoline has no clinically significant effect on CYP3A4 activity and is, therefore, unlikely to affect the pharmacokinetics of other CYP3A4 substrates. [ABSTRACT FROM AUTHOR]

Introduction: Linaclotide is approved for adults with moderate-to-severe irritable bowel syndrome (IBS) with constipation (IBS-C). Linaclotide is not indicated for weight loss or for patients with inflammatory bowel disease (IBD); it is contraindicated in patients with mechanical bowel obstruction (MBO). Some patients with obesity or eating disorders (ED) may use linaclotide off-label for weight loss or as a laxative. Objectives: To describe the use of linaclotide in clinical practice, including patients with potential for off-label use or misuse. Methods: Post-authorization safety study conducted in three databases from the linaclotide launch date to 2017: the Clinical Practice Research Datalink in the United Kingdom (UK), the Information System for Research in Primary Care database in Spain and the linked Patient, Prescription and Causes of Death Registries in Sweden. Cohorts of patients were identified as having IBS using diagnostic and treatment codes; IBS subtypes were identified using symptoms and treatment codes; patients with obesity, ED, MBO, and IBD were identified using diagnostic codes or body mass index. Results: There were 1319, 1981, and 5081 linaclotide users from the United Kingdom, Spain, and Sweden with a median age of 45, 57, and 51 years, respectively; most were females. In the United Kingdom, Spain, and Sweden, respectively: 59.0%, 60.3%, and 31.3% of linaclotide users had an IBS diagnosis recorded, and among those, 68.8%, 61.3%, and 92.7% were classified as IBS-C. The proportions of linaclotide users considered at risk for potential off-label use for weight loss or as a laxative were 17.1%, 29.7%, and 1.7%, and the proportions of users considered at risk of misuse due to a history of MBO or IBD were 3.5%, 4.6%, and 5.7% in the United Kingdom, Spain, and Sweden, respectively. Conclusions: Potential linaclotide off-label use and misuse appears limited, as evidenced by the small sizes of the patient subgroups at risk for off-label use and misuse. [ABSTRACT FROM AUTHOR]

Background: Eluxadoline, a United States Food and Drug Administration (FDA)-approved treatment for irritable bowel syndrome with diarrhea (IBS-D), underwent a change to its US prescribing information on 21 April 2017, contraindicating it in patients without a gallbladder due to increased risk of pancreatitis. This study aimed to elucidate the potential role of eluxadoline's label change on the number of reported spontaneous adverse events (AEs) of pancreatitis. Methods: A pharmacovigilance database (Oracle Argus) was searched for eluxadoline use and spontaneously reported pancreatitis cases from 1 January 2016 to 30 June 2018. Pancreatitis cases were reported as a proportion of the total number of reported AE cases in the safety database. The FDA's adverse event reporting system (AERS) was also interrogated for cases of pancreatitis concomitantly reported with eluxadoline use. Results: In patients who received eluxadoline, 273 reported cases of pancreatitis were recorded (total AEs n = 2191; 12.5%). When known, 28.2% of patients reporting pancreatitis had intact gallbladders (49/174). Eluxadoline was withdrawn in 97.5% of cases, with 87.1% of patients improving or recovered at time of reporting. Importantly, the reporting proportion of pancreatitis cases decreased from 14.4% to 8.9% post label change. Findings were supported by the AERS results, which demonstrated a decrease in reporting proportion from 21.2% to 12.8%. Conclusions: While cautious interpretation is warranted, post-marketing data indicate that the contraindication of eluxadoline in patients without a gallbladder led to reduced reported cases of pancreatitis, with no additional reports of moderately severe or severe cases. Eluxadoline is a safe and well-tolerated treatment option for IBS-D when used according to the label. [ABSTRACT FROM AUTHOR]

Background: Linaclotide is approved for treating irritable bowel syndrome with constipation (IBS-C; 290 µg QD) and chronic idiopathic constipation (CIC; 145 µg or 72 µg QD). These analyses aimed to assess linaclotide safety in a large, pooled Phase 3 population. Methods: In six randomized controlled trials (RCTs), patients received linaclotide (72 µg, 145 µg, 290 µg) or placebo daily for 12-26 weeks; in two long-term safety (LTS) studies, patients received open-label linaclotide for ≤78 additional weeks. Laboratory values, vital signs, and treatment-emergent adverse events (TEAEs) were assessed. Results: Overall, 3853 patients received ≥1 dose of linaclotide. The most common TEAE was diarrhea (majority [90.5% in RCTs] mild/moderate). Linaclotide patients experienced 1.1 diarrhea TEAE per patient-year in the RCTs (0.2 in placebo), and 0.3 in the LTS studies. In RCTs, 6.9% linaclotide and 3.0% placebo patients discontinued due to any adverse event (AE); 4.0% linaclotide and 0.3% placebo patients discontinued due to diarrhea. In LTS studies, 9.4% patients discontinued due to any AE, and 3.8% due to diarrhea. Serious AEs (SAEs) were rare and similar across treatment groups; there were no SAEs of diarrhea. Conclusion: These pooled analyses of patients treated for ≤104 weeks confirm linaclotide's overall safety. [ABSTRACT FROM AUTHOR]

Background: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) have emerged in high-HIVprevalence settings, which generally lack laboratory infrastructure for diagnosing TB drug resistance. Even where available, inherent delays with current drug-susceptibility testing (DST) methods result in clinical deterioration and ongoing transmission of MDR and XDR-TB. Identifying clinical predictors of drug resistance may aid in risk stratification for earlier treatment and infection control. Methods: We performed a retrospective case-control study of patients with MDR (cases), XDR (cases) and drug-susceptible (controls) TB in a high-HIV-prevalence setting in South Africa to identify clinical and demographic risk factors for drugresistant TB. Controls were selected in a 1:1:1 ratio and were not matched. We calculated odds ratios (OR) and performed multivariate logistic regression to identify independent predictors. Results: We enrolled 116, 123 and 139 patients with drug-susceptible, MDR, and XDR-TB. More than 85% in all three patient groups were HIV-infected. In multivariate analysis, MDR and XDR-TB were each strongly associated with history of TB treatment failure (adjusted OR 51.7 [CI 6.6-403.7] and 51.5 [CI 6.4-414.0], respectively) and hospitalization more than 14 days (aOR 3.8 [CI 1.1-13.3] and 6.1 [CI 1.8-21.0], respectively). Prior default from TB treatment was not a risk factor for MDR or XDR-TB. HIV was a risk factor for XDR (aOR 8.2, CI 1.3-52.6), but not MDR-TB. Comparing XDR with MDR-TB patients, the only significant risk factor for XDR-TB was HIV infection (aOR 5.3, CI 1.0-27.6). Discussion: In this high-HIV-prevalence and drug-resistant TB setting, a history of prolonged hospitalization and previous TB treatment failure were strong risk factors for both MDR and XDR-TB. Given high mortality observed among patients with HIV and drug-resistant TB co-infection, previously treated and hospitalized patients should be considered for empiric secondline TB therapy while awaiting confirmatory DST results in settings with a high-burden of MDR/XDR-TB. [ABSTRACT FROM AUTHOR]