Concurrent Drug Research Articles

In vitro evaluation of disposable transport ventilators with combination aerosol therapy

BackgroundThe COVID-19 pandemic has highlighted the need for alternative short-term, reliable means to aid in the treatment of patients requiring ventilatory support. Concurrent aerosol drug delivery is often prescribed to...

Comparing the Prevalence of Polypharmacy and Potential Drug-Drug Interactions in Nursing Homes and in the Community Dwelling Elderly of Emilia Romagna Region.

Backround: We aimed at assessing the prevalence of polypharmacy and potential drug-drug interactions (DDIs) with clinical relevance in elderly patient on Emilia Romagna area. Both outpatients and residents in nursing homes were assessed, with only partially overlapping strategies. Methods: We defined a list of 190 pairs of potentially interacting drugs, based on literature appraisal and availability of therapeutic alternatives. January-June 2018 data on drug use in patients over 65 years-old were collected from nine Local Health Authorities of Emilia Romagna: data on community-dwelling subjects were extracted from archives of reimbursed prescriptions, while drug use in a sample of nursing homes was recorded from clinical charts in one index day within the same semester. The frequency of polypharmacy (at least five or at least 10 concurrent drugs) and of each DDI was calculated. Results: In line with different rates of polypharmacy (80% vs 16%), the risk of exposure to at least one interaction was 53.7% in nursing homes and 26.4% in outpatients. Among DDIs, in nursing homes antidepressants—anxiolytics (11.9%) ranked first, followed by antidepressants—aspirin (7.4%). In outpatients, ACE-inhibitors—non-steroidal anti-inflammatory drugs (NSAIDs) reached 7.2% followed by the calcium channel blockers—α-blockers (2.4%). Discussion: Polypharmacy and risk of DDIs appeared very different in the two settings, due to both technical and clinical reasons. In order to reduce use of benzodiazepines, NSAIDs, antidepressants and relevant DDIs, 1) defining alternative options for pain relief in elderly outpatients, and 2) implementing non-pharmacological management of insomnia and anxiety in nursing homes should be prioritized.

Prevalence of Amphetamine-Type Stimulant Use and Related Factors among Methadone Maintenance Patients in Ho Chi Minh City Vietnam: A Cross-Sectional Study

ABSTRACT The objective of this study was to determine the prevalence of amphetamine-type stimulant use and associated factors among methadone maintenance treatment (MMT) patients. In 2018, a cross-sectional study was conducted on 967 MMT patients at two methadone clinics in Ho Chi Minh City that serve Vietnamese patients. Amphetamine-type stimulant use was assessed by rapid urine test and face-to-face interview using the Alcohol, Smoking, Substance Involvement Screening Test (ASSIST) tool. The prevalence of amphetamine-type stimulant use assessed by urine test was 25.4%. According to ASSIST, the prevalence of moderate and high risk amphetamine-type stimulant use was 15.5% and 1.1%, respectively. Amphetamine-type stimulant use and hazardous use were more prevalent in younger patients, having a part-time job, drug injection, having a lower score of self-health assessment, treated with a higher dose of methadone and missing methadone dose in the past 3 months. By contrast, patients who were HIV positive were less likely to use amphetamine-type stimulants. Cannabis and heroin use were significantly associated with amphetamine-type stimulant use (OR = 1.46; 95% CI: 1.38–8.67; and OR = 1.50; CI: 1.04–2.18, respectively) and hazardous use (OR = 4.07; CI: 1.67–9.92; and OR = 2.38; CI: 1.56–3.63, respectively). Screening and interventions are needed to cope with this issue on time, particularly in young patients, having drug injection and concurrent drugs user groups.

Acyclovir As a Potential Add-On Treatment for COVID-19; A Narrative Review

Introduction: There are successful reports of the concomitant management of herpes infection and coronavirus disease 2019 (COVID-19), using both acyclovir (ACV) and COVID-19 treatment regimens. Furthermore, ACV has been proposed to effectively treat COVID-19, through various mechanisms, such as inhibition of viral proteases, multiple viral gene expressions, and RNA-dependent RNA polymerase (RdRP). Therefore, this study aimed to review the reported cases of patients with concomitant herpes infection and COVID-19, receiving concurrent antiviral drugs for herpetic lesions. Methods: A search was done to find the relevant articles, published between December 2019 and December 2020, with no language limitations, in the PubMed database, using the Medical Subject Headings (MeSH) terms related to herpes simplex virus or herpes zoster (namely, shingles) combined with COVID-19. Accordingly, the reports of the concomitant herpes infection and COVID-19, receiving concurrent antiviral drugs for herpetic lesions were included. Results: Out of 90 articles, 11 records reporting the cases of herpes infection and concurrent laboratory-confirmed COVID-19, receiving antiherpetic therapies, were reviewed. There were 28 patients (age range of 7-82 years) with laboratory-confirmed COVID-19, concomitant with reactivation of herpes infection, receiving antiviral drugs alongside candidate COVID-19 treatment regimens, but no mortality. The mean (standard deviation [SD] range) age of these 28 patients during treatment was 56.4 (18.6 [7-82]) years, and the majority were male (n=18, 64.3%). A total number of 20 patients had also received ACV and eight cases had been administered with other two antiviral compounds, including seven cases with valacyclovir, and one case with famciclovir, with no mortality. Conclusion: The potential use of ACV, as an add-on therapy, along with candidate COVID-19 treatment regimens was proposed in this study. However, further clinical trials are recommended to test this hypothetical adjuvant therapy.

Binge Drinking, Other Substance Use, and Concurrent Use in the U.S., 2016–2018

The use of multiple substances heightens the risk of overdose. Multiple substances, including alcohol, are commonly found among people who experience overdose-related mortality. However, the associations between alcohol use and the use of a range of other substances are often not assessed. Therefore, this study examines the associations between drinking patterns (e.g., binge drinking) and other substance use in the U.S., the concurrent use of alcohol and prescription drug misuse, and how other substance use varies by binge-drinking frequency. Past 30-day alcohol and other substance use data from the 2016-2018 National Survey on Drug Use and Health were analyzed in 2020 among 169,486 U.S. respondents aged ≥12 years. The prevalence of other substance use ranged from 6.0% (nondrinkers) to 24.1% (binge drinkers). Among people who used substances, 22.2% of binge drinkers reported using substances in 2 additional substance categories. Binge drinking was associated with 4.2 (95% CI=3.9, 4.4) greater adjusted odds of other substance use than nondrinking. Binge drinkers were twice as likely to report concurrent prescription drug misuse while drinking as nonbinge drinkers. The prevalence of substance use increased with binge-drinking frequency. Binge drinking was associated with other substance use and concurrent prescription drug misuse while drinking. These findings can guide the implementation of a comprehensive approach to prevent binge drinking, substance misuse, and overdoses. This might include population-level strategies recommended by the Community Preventive Services Task Force to prevent binge drinking (e.g., increasing alcohol taxes and regulating alcohol outlet density).

Mycophenolate Mofetil (Cellcept) Induced Pneumonitis: Case Report and Review of Literature

Mycophenolate is used to treat several disease conditions. Several side effects have been reported in several reported cases; however, a few other side effects have been underreported, for example, post-transplant pneumonitis. This case demonstrates suspected mycophenolate-associated pneumonitis, which was masked by the concurrent immune-modulatory drugs that the patients were taking. The pneumonitis became evident after the withdrawal of the immune drugs. This seldomly reported pneumonitis and mycophenolate association calls for further vigilance and a high index of suspicion by physicians when pneumonitis develops in patients taking this valuable medication.

Optic Neuropathy and Scleritis as the Presenting Feature of Lepra Reaction

A major problem in the management of leprosy patients is the occurrence of "reactions". These reactions are the consequences of the dynamic nature of the immune response to <i>Mycobacterium leprae</i> (<i>M. leprae</i>) that may occur before, during, or following the completion of multi-drug therapy (MDT). They can be of two types- Type 1 lepra reaction and Type 2 lepra reaction also known as Erythema Nodosum Leprosum (ENL). We report an unusual case of a 35 year old male patient who initially presented with complaints of a central scotoma. He neither had visible skin lesion suggestive of leprosy nor a history of either completion or concurrent anti leprosy drug treatment. He was diagnosed to be a case of anterior ischemic optic neuropathy for which he was treated with intravenous injections of methylprednisolone to which he significantly responded. Two months later, he complained of diminution of vision, redness and pain in the left eye which was diagnosed as scleritis. He was managed with topical prednisolone acetate eye drops. Within a week, the patient developed skin lesions over the cheekbones, ear lobules and the back of his hands. He was referred to a rheumatologist and a dermatologist for the same. The dermatologist suspected the lesions to be a manifestation of a Lepra Reaction. The presence of lepra bacilli was confirmed after taking a biopsy from the raised lesions and he turned out to be a case of undiagnosed lepromatous leprosy. He was subsequently treated with anti-leprosy drugs according to the WHO-MDT-MB along with a cover of steroids. After three months of initiation of this treatment, his ocular and dermatological lesions completely resolved. This is a unique case in which anterior ischemic optic neuropathy and scleritis preceded the symptom of leprosy, manifested as skin lesions.

Alcohol Problems among Prisoners: Subgroup Variations, Concurrent Drug Problems, and Treatment Needs

Background/Aims: Alcohol problems in the prison population are understudied, underdetected, and undertreated. Our aims were to identify subgroups of inmates whose pre-prison drinking behavior indicated a high need for alcohol-related interventions, to assess the prevalence of concurrent alcohol and drug problems, and to compare dual-dependent inmates and those who were alcohol-dependent alone with respect to the severity of their drinking problems. Methods: Data stemmed from the nationwide Norwegian Offender Mental Health and Addiction (NorMA) study. Both male (n = 1,356) and female (n = 90) inmates took part in the study, representing about 40% of the prison population in Norway at the time of the data collection (2013–2014). Pre-prison substance use problems were assessed using the Alcohol Use Disorders Identification Test (AUDIT) and the Drug Use Disorders Identification Test (DUDIT). Results: A majority (55%) had an AUDIT positive screen (score ≥8), which is indicative of alcohol problems of some severity, and 18% were possible alcohol-dependent (score ≥20). A positive screen was associated with younger age, lower education, violent offending, driving while intoxicated (DWI), and previous criminal convictions. Two-thirds (68%) of those who screened positive on the AUDIT had also a DUDIT positive screen (score ≥6), and a similar overlap between possible alcohol dependence and possible drug dependence (score ≥25) was observed. Inmates with possible dual dependence (12% of all) had higher mean scores on the AUDIT than those with possible alcohol dependence only (7% of all). Conclusions: More than half of the prisoners in Norway had AUDIT scores that indicated they could benefit from alcohol-related interventions, and the prevalence was elevated in younger, less educated groups of previously convicted DWI, and violent offenders. Alcohol problems were most often combined with drug problems, and possible dual dependence was associated with particularly severe drinking problems.

Misuse of Prescription and Illicit Drugs in Middle Adulthood in the Context of the Opioid Epidemic

Background: The United States’ opioid epidemic continues to escalate overdose deaths. Understanding its extent is complicated by concurrent misuse of other prescription or illicit drugs, increasing risk for overdose. Current surveillance using electronic medical records and police data has limitations and frequently fails to distinguish middle-aged adults from other age groups in reporting. Objectives: The purpose of this analysis is to (1) describe characteristics of middle-aged US adults who report misusing prescription and illicit drugs and (2) evaluate if misusing prescription opioids increases risk of misusing other drugs. Methods: We analyzed data from 12,300 adults ages 32–42 from Wave V of the Add Health study collected from 2016 to 2018. Self-reported past 30-day misuse of prescription sedatives, tranquilizers, stimulants, and opioids as well as cocaine, crystal methamphetamine, heroin, and other illicit drugs were analyzed for associations with demographic characteristics in weighted bivariate analysis and multivariable logistic regression. Results: Those misusing prescription opioids were more likely to misuse prescription sedatives, tranquilizers, and stimulants compared to those not misusing prescription opioids. Those misusing prescription opioids were also more likely to misuse heroin, crystal meth, cocaine, and other illicit drugs. Higher levels of education and personal income were protective for prescription opioid misuse, any prescription drug misuse, and any illicit drug misuse. Race/ethnicity was not significantly associated with prescription opioid misuse. Conclusions/Importance: Our analysis shows those misusing prescription opioids are at high risk of misusing other prescription and illicit drugs. Practitioners and researchers should consider concurrent drug misuse when treating and studying opioid misuse disorders.

Adverse drug reactions associated with concurrent acute psychiatric treatment and Covid-19 drug therapy

Objective Psychiatric patients are at increased risk of contamination, morbidity, and mortality associated with COVID-19, together with potentially more pronounced adverse effects. We present and discuss the adverse effects observed in an acute psychiatric clinic that has admitted COVID-19 patients during the first three months of the pandemic in Turkey. Methods The COVID-19 treatment schemes were formed in accordance with the national and regional guidelines at the time of admittance, which were mainly based on the use of hydroxychloroquine and other drugs. The sample consisted exclusively of inpatients, and all patients were enrolled in the study regardless of their specific diagnosis or treatment schemes. Results 4 out of 23 patients (17.4%) had experienced adverse effects, two of which had mild hepatic enzyme elevation and one had mild sinus bradycardia. Of note is that we haven’t encountered any serious complications or life-threatening events during inpatient treatment. The most emphasised adverse effect in the literature, namely QTc prolongation and ECG changes, were not observed in our sample. The adverse effects were not found to be significantly associated with patient-related factors nor dose of antipsychotic medication. Conclusions From our point of view, non-cardiac adverse effects should not be overlooked while treating comorbid psychiatric and COVID-19 patients. KEY POINTS Acute inpatient psychiatric treatment of patients who have comorbid COVID-19 is a complex situation requiring multidisciplinary action. Adverse drug reactions, which may or not result from the interaction of psychiatric and COVID-19 treatment, should be of concern for this patient group. While there is controversy over the benefits of some of the off-label COVID-19 medications, there should also be discussion over safety and concomitant medication use. In order to be adequately prepared for future escalations of COVID-19 pandemic, psychiatric services should thoroughly evaluate their initial experience with COVID-19, including from the point of drug effectiveness and safety.

Concomitant drugs with buprenorphine user deaths

BackgroundBuprenorphine is abused in several countries notwithstanding its benefits as an analgesic and as an opioid agonist treatment medication. Benzodiazepines and alcohol have previously been associated with buprenorphine toxicity. This study elucidates the role of emerging concomitant drugs in different groups of buprenorphine user deaths. MethodsAll cases in the Finnish national post-mortem toxicology database from 2016–2019 in which buprenorphine or norbuprenorphine was a laboratory finding in any post-mortem specimen and age at death of 15–64 years were investigated for cause and manner of death, concurrent drug and alcohol findings, age, and gender. ResultsThere were 792 deaths with a buprenorphine finding, of which buprenorphine was implicated in poisoning without other opioids in 271 cases (34 %). In this group of buprenorphine poisoning deaths, concomitant benzodiazepines were found in 94 % (clonazepam 53 %), illicit drugs in 63 %, gabapentinoids in 50 % (pregabalin 41 %), alcohol in 41 %, antidepressants in 32 %, and antipsychotics in 28 % of cases; only three deaths showed no benzodiazepines, alcohol, or gabapentinoids. Polydrug use was common regardless of the cause of death. In the age group 15 to 24 years, concomitant use of benzodiazepines and illicit drugs, and buprenorphine poisoning were more prevalent than in the age group 25–64 years. ConclusionsThe unprecedentedly high concomitant use of benzodiazepines in buprenorphine user deaths obscures other possible pharmacological risk factors for buprenorphine poisoning that could be relevant for prevention. Higher mortality in the younger age group suggests particularly unsafe drug use patterns that should be addressed.

Declines in Depressive Symptoms Among People who Inject Drugs Treated With Direct-Acting Antivirals While on Opioid Agonist Therapy.

BackgroundHepatitis C virus (HCV) frequently co-occurs with symptoms of depression, which are aggravated on interferon-based regimens. However, it is unknown whether HCV treatment with direct-acting antivirals (DAAs) has effects on depressive symptoms among people who inject drugs (PWID). In this study, we examined changes in depressive symptoms during and after HCV treatment among PWID on opioid agonist therapies (OATs).MethodsParticipants were 141 PWID who achieved sustained viral response after on-site HCV treatment at 3 OAT programs.Depressive symptoms were assessed using the Beck Depression Inventory–II (BDI-II) at baseline, every 4 weeks during treatment, and 12 and 24 weeks after treatment completion. Current diagnosis of depression or other psychiatric diagnoses were obtained through chart review. Use of illicit drugs was measured by urine toxicology screening. Alcohol use was measured using the Addiction Severity Index–Lite.ResultsOf the 141 PWID infected with HCV, 24.1% had severe, 9.9% had moderate, 15.6% had mild, and 50.4% had minimal levels of depression as per BDI-II scores at baseline. HCV treatment was significantly associated with reductions in depressive symptoms that persisted long term, regardless of symptom severity (P < .001) or presence of depression (P ≤ .01) or other psychiatric diagnoses (P ≤ .01) at baseline. Concurrent drug use (P ≤ .001) or hazardous alcohol drinking (P ≤ .001) did not interfere with reductions in depressive symptoms.ConclusionsDepressive symptoms are highly prevalent among HCV-infected PWID. HCV treatment was associated with sustained reductions in depressive symptoms. HCV therapy with DAAs may have important implications for PWID that go beyond HCV cure.

S2475 The Buck Stops Here: A Case of Deer Antler Extract-Induced Liver Injury

INTRODUCTION: Liver injury secondary to prescription or over the counter drugs and supplements is an ongoing public health concern, especially with the growing marketplace of unregulated supplements. Drug induced liver injury (DILI) has been reported as the most common reason for regulatory actions instituted by the US FDA against medications and supplements. Deer antlers are the only mammalian organs that can entirely grow back once lost and their extract contains insulin-like growth factor. Many athletes admit using deer antler extract as a performance-enhancing supplement, but its safety is unknown. The following is the first reported case of a deer antler supplement induced liver injury. CASE DESCRIPTION/METHODS: A 38 YO male presented with fatigue and elevated liver chemistry tests: AST 360, ALT 1297, ALP 78 (U/L) and bilirubin 2.9 mg/dL. He was not on any medications but did note recent use of a supplement called “Bucked Up” consisting of deer antler velvet extracts, ginseng, caffeine, taurine and Himalayan rock salt. He denied any concurrent supplement, herb, drug, or alcohol use, and noted improved symptoms following stopping using the supplement 5 days prior to presentation. The patient underwent a thorough work-up which ruled out infectious causes such as viral hepatitis, CMV, HSV, EBV, biliary obstruction, genetic diseases and autoimmune hepatitis. Liver biopsy showed moderate acute lobular cholestatic hepatitis. Patient was followed for total of 150 days after the liver injury. Figure 1 shows the peaks of Alk Phos, T bili, AST and ALT throughout the follow-up period. Alk Phos and T bili peaked around day 25 after the injury, while ALT and AST peaked at the first day and decreased to normal level at day 10. Another peak in AST and ALT was noted at around day 30. At day 50, all the labs started to return to the normal level. DILI resolved spontaneously without any treatment. DISCUSSION: The updated RUCAM Causality Assessment was used to evaluate the probability of DILI secondary to the deer antler velvet blend. The R ratio was consistent with hepatocellular type injury. It showed a probable correlation with a 7-point score, which along with the patient’s clinical course confirms the diagnosis of DILI secondary to the supplement. This report represents the first case of a deer antler-based supplement leading to hepatotoxicity, highlighting the need for public awareness regarding the hepatotoxicity of deer antler extract containing supplements.Figure 1.: Lab measurements from day 0 to day 150.Table 1.: The R ratio score

Comparison of Cardiac Events Associated With Azithromycin vs Amoxicillin

Conflicting evidence exists on the association between azithromycin use and cardiac events. To compare the odds of cardiac events among new users of azithromycin relative to new users of amoxicillin using real-world data. This retrospective cohort study used data from Truven Health Analytics MarketScan database from January 1, 2009, to June 30, 2015. Patients receiving either amoxicillin or azithromycin and enrolled in a health care plan 365 days before (baseline period) the dispensing date (index date) were included in the study. Patients were matched 1:1 on high-dimensional propensity scores. Data were analyzed from October 1, 2018, to December 31, 2019. New use of azithromycin compared with new use of amoxicillin. The primary outcome consisted of cardiac events, including syncope, palpitations, ventricular arrhythmias, cardiac arrest, or death as a primary diagnosis for hospitalization at 5, 10, and 30 days from the index date. Logistic regression models were used to estimate odds ratios (ORs) with 95% CIs. After matching, the final cohort included 2 141 285 episodes of each index therapy (N = 4 282 570) (mean [SD] age of patients, 35.7 [22.3] years; 52.6% female). Within 5 days after therapy initiation, 1474 cardiac events (0.03%) occurred (708 in the amoxicillin cohort and 766 in the azithromycin cohort). The 2 most frequent events were syncope (1032 [70.0%]) and palpitations (331 [22.5%]). The odds of cardiac events with azithromycin compared with amoxicillin were not significantly higher at 5 days (OR, 1.08; 95% CI, 0.98-1.20), 10 days (OR, 1.05; 95% CI, 0.97-1.15), and 30 days (OR, 0.98; 95% CI, 0.92-1.04). Among patients receiving any concurrent QT-prolonging drug, the odds of cardiac events with azithromycin were 1.40 (95% CI, 1.04-1.87) greater compared with amoxicillin. Among patients 65 years or older and those with a history of cardiovascular disease and other risk factors, no increased risk of cardiac events with azithromycin was noted. This study found no association of cardiac events with azithromycin compared with amoxicillin except among patients using other QT-prolonging drugs concurrently. Although azithromycin is a safe therapy, clinicians should carefully consider its use among patients concurrently using other QT-prolonging drugs.

Epidemiology of fatal snakebites in the United States 1989-2018.

There are 5000-10,000 snake envenomations annually in the United States. Fortunately, few are fatal. In this study we review the epidemiology of fatal snakebites. Native snakebite cases from the American Association of Poison Control Centers (AAPCC) National Poison Data System from 1989 to 2018 were reviewed. Additional cases that were not reported to the AAPCC were identified by reviewing Wikipedia and by searching PubMed and online news outlets using various combinations of relevant keywords. We identified 101 fatal bites from native snakes. Rattlesnakes accounted for 74 (90.2%) of the 82 deaths for which the species was known or which occurred where rattlesnakes are the only native crotalids. There were five fatalities attributed to copperheads, two due to cottonmouths, and one caused by an eastern coral snake. Males were disproportionately affected. The median age for victims was 40years old. In cases for which data were available, many of the snake interactions were intentional, e.g. religious services, animal husbandry, and attempting to kill the snake. Death following envenomation from a native U.S. snake is unlikely, particularly if medical attention is sought promptly. Rattlesnake envenomations are more likely to be fatal than bites from other species. Intentionally engaging with a venomous snake raises the risk of incurring a fatal bite, as does concurrent alcohol or drug use. Age less than 12years old does not appear to be a risk factor for a fatal outcome, while elderly patients may have a slightly increased risk of death.

ACE and ARB does not increase the risk of dying from COVID‐19

Observational studies have shown that the presence of diabetes and hypertension are associated with an increased risk of mortality from COVID-19, but whether the increased risk of death occurred independent of concurrent drugs that patients are taking is unclear. Relevant to this is the speculation that ACE and ARB – drugs widely used in people with diabetes and hypertension - maybe deleterious to COVID-19 outcome due to the propensity of the virus to bind to cellular ACE-2 receptors. In the absence of clear evidence, guideline from national and international hypertension societies have recommended that patients should not discontinue these drugs in the event of COVID-19 infection. A recent study from the USA, published in the New England Journal of Medicine, have provided some reassurance of the safety of these classes of drugs during COVID-19 infection. The study investigated clinical outcomes of 8910 patients admitted to hospital with COVID-19. After adjusting for confounders, they identified that age above 65 years old, having cardiovascular disease, COPD and being a current smoker was associated with a significant doubling of mortality rate. However, reassuringly, the use of ACE and ARB was not associated with an increased risk of mortality. NEJM (doi:10.1056/NEJMoa2007621).

The multivariate analysis of results of bedaquiline use in the therapy of MDR/XDR pulmonary tuberculosis

The objective of the study:to perform the multivariate analysis of treatment outcomes in patients with multiple/extensive drug resistant tuberculosis (MDR/XDR TB), including those with HIV infection, whose chemotherapy regimens included bedaquiline.Subjects and methods:70 patients with MDR/XDR TB were enrolled in the retrospective two-center study, the multivariate analysis of treatment outcomes with bedaquiline-containing regimen was carried out.Results:the performed multivariate analysis demonstrated high efficacy and good tolerability of bedaquiline-containing regimens for MDR/XDR TB treatment even despite the continuous ineffective treatment of patients in the past. The prolonged intake of bedaquiline for more than 24 weeks was not associated with a high level of adverse reactions. It was found that the use of cycloserine/terizidone made a significant contribution to the favorable outcome of chemotherapy. The factors associated with the most unfavorable treatment outcomes were the following: age above 60 years, concurrent chronic obstructive pulmonary disease, alcohol and/or drug addiction, and smoking.

Concurrent Use of Opioids with Other Central Nervous System-Active Medications Among Older Adults.

The primary objective was to determine the prevalence and characteristics of older adults concurrently using opioids and other central nervous system (CNS)-active medications, and the specialties of providers who ordered the medications. A secondary objective was to document medication-related adverse effects associated with such concurrent drug use. Study populations were identified as older adults aged ≥65 years with 1 year continuous medical and drug plan enrollment during 2017 and opioid use of ≥2 prescriptions for ≥15 days' supply. CNS-active medications included benzodiazepines, non-benzodiazepine hypnotics, muscle relaxants, antipsychotics, and gabapentinoids. Provider specialties were identified from the National Provider Identification database. Characteristics associated with opioids only, opioids plus 1, and opioids plus ≥2 additional CNS-active medications were determined using multinomial logistic regression. Outcome measures during 2017 included injurious falls/fractures and ≥3 emergency room (ER) visits. Among eligible insureds (N = 209,947), 57% used opioids only, 28% used opioids plus 1 additional CNS medication, and 15% used ≥2 additional medications. About 60% of opioids and other concurrent CNS medications were prescribed by the same provider, generally a primary care provider. Benzodiazepines and gabapentinoids were most often used concurrently with opioids. Health status, insomnia, anxiety, depression, and low back pain had the strongest associations with concurrent medication use. Overall, concurrent use with ≥2 CNS medications increased the likelihood of injurious falls/fractures or ≥3 ER visits in this population by about 18% and 21%, respectively. Both patients and providers may benefit from an awareness of adverse outcomes associated with concurrent opioid and other CNS-active medication use.

Effectiveness of direct-acting antivirals for hepatitis C virus infection in hepatitis C/HIV coinfected individuals: A multicenter study.

In a hepatitis C virus (HCV)/HIV-positive Brazilian cohort, evaluate the safety and efficacy of HCV DAAs, the frequency of resistance substitutions in the HCV NS5A and NS5B genes and identify predictors of treatment failure.Retrospective multicenter study of HCV/HIV patients treated with sofosbuvir (SOF)-based regimens at 10 reference centers in Brazil.Clinical and virological data were collected. Genetic diversity in the NS5A and NS5B genes was assessed by direct nucleotide sequencing. The primary outcome was sustained virological response (SVR) 12 weeks after DAA completion.Of 643 HCV/HIV patients analyzed, 74.7% were male, median CD4+ T cell count was 617 cells/mm3, 90% had an undetectable HIV viral load. HCV genotype 1 was detected in 80.2%, and 60% were taking at least 1 medication other than antiretroviral drugs during their DAA therapy. Cirrhosis was present in 42%. An SOF/daclatasvir (DCV) regimen was used in most patients (98%). The frequency of NS5A polymorphisms associated with clinically relevant resistance to DCV was 2%; no relevant NS5B variants were identified. The SVR12 rate was 92.8% in an intention to treat (ITT) analysis and 96% in a modified ITT (m-ITT) analysis. AE occurred in 1.6% of patients. By multivariate analysis, therapeutic failure was associated, in the m-ITT analysis, with concomitant use of anticonvulsant drugs (P = .001), age (P = .04), and female gender (P = .04).SOF/DCV regimens were associated with a high SVR rate in an HCV/HIV population. The use of concurrent anticonvulsant drugs and DAAs decreases the chances of achieving an SVR.

Incidence and determinants of QT interval prolongation in COVID-19 patients treated with hydroxychloroquine and azithromycin.

Combined use of hydroxychloroquine and azithromycin was globally adopted, in part due to paucity and high cost of alternative therapies. However the utility of these medications has been questioned; and thus safety becomes a major concern given clinical equipoise regarding efficacy. Both hydroxychloroquine and azithromycin continue to be administered in US clinical trials examining their potential role in prevention of infection, treatment of mild infection in ambulatory patients, and in combination with other medical regimens in treatment of patients with severe disease. These drugs also continue to be clinically utilized in hospitalized patients around the globe, often without continuous telemetry due to lack of resources. Concern regarding use of hydroxychloroquine without adequate rhythm monitoring in clinical trials has been recently expressed.1 A review of clinicaltrials.gov at the time of submission of this correspondence reveals actively recruiting trials of combined hydroxychloroquine/azithromycin with or without additional COVID-19 therapies, for both ambulatory and hospitalized patients within and outside the US. The potential for hydroxychloroquine and azithromycin to cause QT prolongation is counterbalanced by very low risk of pro-arrhythmia in the general population, and emerging evidence of relatively low risk of Torsades de Pointes (TdP) in COVID-19 patients.2,3,4,5 Thus delineation of the determinants of significant QTc prolongation and pro-arrhythmic risk for hydroxychloroquine/azithromycin is very important, especially given mounting evidence of inefficacy in COVID-19 treatment.