Interventions for female drug-using offenders.

Cochrane Database Syst Rev. 2019 Dec 13;12:CD010910

Authors: Perry AE, Martyn-St James M, Burns L, Hewitt C, Glanville JM, Aboaja A, Thakkar P, Santosh Kumar KM, Pearson C, Wright K

Abstract
BACKGROUND: This review represents one in a family of three reviews focusing on the effectiveness of interventions in reducing drug use and criminal activity for offenders.
OBJECTIVES: To assess the effectiveness of interventions for female drug-using offenders in reducing criminal activity, or drug use, or both.
SEARCH METHODS: We searched 12 electronic bibliographic databases up to February 2019.
SELECTION CRITERIA: We included randomised controlled trials (RCTs).
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.
MAIN RESULTS: We included 13 trials with 2560 participants. Interventions were delivered in prison (7/13 studies, 53%) and community (6/13 studies, 47%) settings. The rating of bias was affected by the lack of clear reporting by authors, and we rated many items as 'unclear'. In two studies (190 participants) collaborative case management in comparison to treatment as usual did not reduce drug use (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.20 to 2.12; 1 study, 77 participants; low-certainty evidence), reincarceration at nine months (RR 0.71, 95% CI 0.32 to 1.57; 1 study, 77 participants; low-certainty evidence), and number of subsequent arrests at 12 months (RR 1.11, 95% CI 0.83 to 1.49; 1 study, 113 participants; low-certainty evidence). One study (36 participants) comparing buprenorphine to placebo showed no significant reduction in self-reported drug use at end of treatment (RR 0.57, 95% CI 0.27 to 1.20) and three months (RR 0.58, 95% CI 0.25 to 1.35); very low-certainty evidence. No adverse events were reported. One study (38 participants) comparing interpersonal psychotherapy to a psychoeducational intervention did not find reduction in drug use at three months (RR 0.67, 95% CI 0.30 to 1.50; low-certainty evidence). One study (31 participants) comparing acceptance and commitment therapy (ACT) to a waiting list showed no significant reduction in self-reported drug use using the Addiction Severity Index (mean difference (MD) -0.04, 95% CI -0.37 to 0.29) and abstinence from drug use at six months (RR 2.89, 95% CI 0.73 to 11.43); low-certainty evidence. One study (314 participants) comparing cognitive behavioural skills to a therapeutic community programme and aftercare showed no significant reduction in self-reported drug use (RR 0.86, 95% CI 0.58 to 1.27), re-arrest for any type of crime (RR 0.73, 95% CI 0.52 to 1.03); criminal activity (RR 0.80, 95% CI 0.63 to 1.03), or drug-related crime (RR 0.95, 95% CI 0.68 to 1.32). A significant reduction for arrested (not for parole) violations at six months follow-up was significantly in favour of cognitive behavioural skills (RR 0.43, 95% CI 0.25 to 0.77; very low-certainty evidence). A second study with 115 participants comparing cognitive behavioural skills to an alternative substance abuse treatment showed no significant reduction in reincarceration at 12 months (RR 0.70, 95% CI 0.43 to 1.12; low certainty-evidence. One study (44 participants) comparing cognitive behavioural skills and standard therapy versus treatment as usual showed no significant reduction in Addiction Severity Index (ASI) drug score at three months (MD 0.02, 95% CI -0.05 to 0.09) and six months (MD -0.02, 95% CI -0.09 to 0.05), and incarceration at three months (RR 0.46, 95% CI 0.04 to 4.68) and six months (RR 0.51, 95% CI 0.20 to 1.27); very low-certainty evidence. One study (171 participants) comparing a single computerised intervention versus case management showed no significant reduction in the number of days not using drugs at three months (MD -0.89, 95% CI -4.83 to 3.05; low certainty-evidence). One study (116 participants) comparing dialectic behavioural therapy and case management (DBT-CM) versus a health promotion intervention showed no significant reduction at six months follow-up in positive drug testing (RR 0.67, 95% CI 0.43 to 1.03), number of people not using marijuana (RR 1.23, 95% CI 0.95 to 1.59), crack (RR 1.00, 95% CI 0.87 to 1.14), cocaine (RR 1.02, 95% CI 0.93 to 1.12), heroin (RR 1.05, 95% CI 0.98 to 1.13), methamphetamine (RR 1.02, 95% CI 0.87 to 1.20), and self-reported drug use for any drug (RR 1.20, 95% CI 0.92 to 1.56); very low-certainty evidence. One study (211 participants) comparing a therapeutic community programme versus work release showed no significant reduction in marijuana use at six months (RR 1.03, 95% CI 0.19 to 5.65), nor 18 months (RR 1.00, 95% CI 0.07 to 14.45), heroin use at six months (RR 1.59, 95% CI 0.49 to 5.14), nor 18 months (RR 1.92, 95% CI 0.24 to 15.37), crack use at six months (RR 2.07, 95% CI 0.41 to 10.41), nor 18 months (RR 1.64, 95% CI 0.19 to 14.06), cocaine use at six months (RR 1.09, 95% CI 0.79 to 1.50), nor 18 months (RR 0.93, 95% CI 0.64 to 1.35). It also showed no significant reduction in incarceration for drug offences at 18 months (RR 1.45, 95% CI 0.87 to 2.42); with overall very low- to low-certainty evidence. One study (511 participants) comparing intensive discharge planning and case management versus prison only showed no significant reduction in use of marijuana (RR 0.79, 95% CI 0.53 to 1.16), hard drugs (RR 1.12, 95% CI 0.88 to 1.43), crack cocaine (RR 1.08, 95% CI 0.75 to 1.54), nor positive hair testing for marijuana (RR 0.75, 95% CI 0.55 to 1.03); it found a significant reduction in arrests (RR 0.19, 95% CI 0.04 to 0.87), but no significant reduction in drug charges (RR 1.07, 95% CI 0.75 to 1.53) nor incarceration (RR 1.09, 95% CI 0.86 to 1.39); moderate-certainty evidence. One narrative study summary (211 participants) comparing buprenorphine pre- and post-release from prison showed no significant reduction in drug use at 12 months post-release; low certainty-evidence. No adverse effects were reported.
AUTHORS' CONCLUSIONS: The studies showed a high degree of heterogeneity for types of comparisons, outcome measures and small samples. Descriptions of treatment modalities are required. On one outcome of arrest (no parole violations), we identified a significant reduction when cognitive behavioural therapy (CBT) was compared to a therapeutic community programme. But for all other outcomes, none of the interventions were effective. Larger trials are required to increase the precision of confidence about the certainty of evidence.

PMID: 31834635 [PubMed - in process]

Durable Efficacy of Dolutegravir Plus Lamivudine in Antiretroviral Treatment-Naive Adults With HIV-1 Infection: 96-Week Results From the GEMINI-1 and GEMINI-2 Randomized Clinical Trials.

J Acquir Immune Defic Syndr. 2019 Dec 10;:

Authors: Cahn P, Madero JS, Arribas JR, Antinori A, Ortiz R, Clarke AE, Hung CC, Rockstroh JK, Girard PM, Sievers J, Man CY, Urbaityte R, Brandon DJ, Underwood M, Tenorio AR, Pappa KA, Wynne B, Gartland M, Aboud M, van Wyk J, Smith KY

Abstract
BACKGROUND: The 2-drug regimen dolutegravir + lamivudine was non-inferior to dolutegravir + tenofovir disoproxil fumarate/emtricitabine in achieving HIV-1 RNA <50 copies/mL in treatment-naive adults in the 48-week primary analysis of the GEMINI trials. We present results from the prespecified 96-week secondary analyses.
SETTING: 187 centers in 21 countries.
METHODS: GEMINI-1 and GEMINI-2 are identical, double-blind phase III studies. Participants with screening HIV-1 RNA ≤500,000 copies/mL were randomized 1:1 to once-daily dolutegravir + lamivudine or dolutegravir + tenofovir disoproxil fumarate/emtricitabine.
RESULTS: At Week 96, dolutegravir + lamivudine (N=716) was non-inferior to dolutegravir + tenofovir disoproxil fumarate/emtricitabine (N=717) in achieving HIV-1 RNA <50 copies/mL (Snapshot algorithm; -10% non-inferiority margin) in the pooled analysis (proportion of responders, 86.0% vs 89.5%, respectively; adjusted treatment difference [95% CI], -3.4% [-6.7, 0.0007]), GEMINI-1 (-4.9% [-9.8, 0.03]), and GEMINI-2 (-1.8% [-6.4, 2.7]). Proportions of participants in the HIV-1 RNA ≥50 copies/mL Snapshot category were largely unchanged from Week 48 to 96. Eleven participants taking dolutegravir + lamivudine and 7 taking dolutegravir + tenofovir disoproxil fumarate/emtricitabine met confirmed virologic withdrawal criteria through Week 96; none had treatment-emergent resistance mutations. Dolutegravir + lamivudine had a lower rate of drug-related adverse events than dolutegravir + tenofovir disoproxil fumarate/emtricitabine (19.6% vs 25.0%; relative risk ratio, 0.78; 95% CI, 0.64-0.95). Renal and bone biomarker changes favored dolutegravir + lamivudine.
CONCLUSION: Consistent with 48-week data, dolutegravir + lamivudine demonstrated long-term, non-inferior efficacy vs dolutegravir + tenofovir disoproxil fumarate/emtricitabine without increased risk of treatment-emergent resistance, supporting its use in treatment-naive HIV-1-infected individuals.

PMID: 31834000 [PubMed - as supplied by publisher]

High-dose Clozapine Withdrawal: A Case Report and Timeline of a Single Potential Withdrawal Seizure.

Innov Clin Neurosci. 2019 Jul-Aug;16(7-08):22-24

Authors: Skelly MK, Demler TL, Lee C

Abstract
Clozapine, a second-generation antipsychotic (SGA), is known for its superior efficacy in the treatment of refractory schizophrenia. Clozapine's hallmark side effects are well-known, including, but not limited to, drug-induced seizures associated with daily goal doses greater than 600mg and rapid dose escalation, which can also contribute to significant risk of orthostatic hypotension, bradycardia, and syncope. However, less well-known is the potential withdrawal that can occur from its rapid discontinuation. Here, we describe a case of seizure-like activity that occurred 72 hours after an abrupt high-dose clozapine discontinuation in a patient with schizoaffective disorder, bipolar type. Seizures, although known to be a high-serum-concentration-dependent side effect of clozapine, could not be excluded as a possible withdrawal syndrome in this patient.

PMID: 31832260 [PubMed]

An Intensified Regimen Containing Linezolid Could Improve Treatment Response in Mycobacterium abscessus Lung Disease.

Biomed Res Int. 2019;2019:8631563

Authors: Li H, Tong L, Wang J, Liang Q, Zhang Y, Chu N, Chen X, Duan H

Abstract
Background: Treatment response for the Mycobacterium abscessus (M. abscessus) lung disease remains far from satisfying. An effective regimen is needed to solve the problem.
Methods: We retrospectively reviewed the medical records of all patients with M. abscessus lung disease who received antibiotics regimen at Beijing Chest Hospital Affiliated to Capital Medical University between July 1, 2010, and February 1, 2018. Patients were administered a conventional antibiotics regimen (including macrolide and moxifloxacin, along with an initial 12-week course of low-dose cefoxitin and amikacin) or intensified regimen (including a higher dosage of cefoxitin and linezolid besides conventional drugs), respectively. The time to sputum-culture conversion and proportion of sputum-culture conversion in liquid broth were investigated to evaluate the efficacy and evaluation of safety by performing the classification of adverse events according to the Division of AIDS, National Institute of Allergy and Infectious Disease. Patients were followed for 18 months from baseline.
Results: In the conventional regimen group, the sputum conversion rate at 18 months was 29.4% (10/34), and the median time until sputum conversion was 2 months (IQR, 1-2 mo). Furthermore, in the intensified regimen group, the sputum conversion rate was 81.3% (13/16), and the median time until sputum conversion was 1 month (IQR, 1-1 mo). Leukopenia and drug-induced hepatotoxicity occurred more frequently in the intensified regimen group in contrast with the conventional regimen group patients. However, only 1 adverse event in the intensified regimen group was classified as severe adverse event.
Conclusions: The intensified regimen could improve sputum conversion of M. abscessus lung disease compared with conventional regimen, but close safety surveillance is necessary to monitor adverse events.

PMID: 31828137 [PubMed - in process]

Recognising injuries related to needlestick injury in farmers: the importance of identifying high pressure injections with mineral oil.

Med J Aust. 2019 Dec 09;:

Authors: Brown JA, Buckley NA, Cairns R, Wylie CE

PMID: 31816094 [PubMed - as supplied by publisher]

Effectiveness and safety of perampanel as early add-on treatment in patients with epilepsy and focal seizures in the routine clinical practice: Spain prospective study (PERADON).

Epilepsy Behav. 2019 Dec 05;102:106655

Authors: Abril Jaramillo J, Estévez María JC, Girón Úbeda JM, Vega López Ó, Calzado Rivas ME, Pérez Díaz H, García Martín G, Vila Herrero E, Chamorro-Muñoz M, Vázquez F, De la Fuente C, Redondo L, Peláez N, Santágueda P, Rodríguez Uranga JJ

Abstract
OBJECTIVE: Perampanel (PER) has been shown to be effective as an adjunctive therapy for controlling refractory focal-onset seizures (FOS). However, the information as early add-on for the treatment of FOS in the clinical practice is still scarce and must be further assessed.
METHODS: An observational prospective study was conducted to evaluate the effectiveness of early add-on PER, assessed as 50% responders (seizure frequency reduced by at least 50% during the last 3 months as compared with baseline) rate at 6 and 12 months, in patients with FOS in the routine clinical practice of Spain.
RESULTS: One hundred and thirteen patients (mean age: 40.3 years, 51.3% male) with FOS received PER as early add-on (1st add-on: 37.2% and 2nd: 62.8%) for a mean exposure of 11 months (mean PER dose: 6.3 mg/day at month 12). At 6 months, 50.4% and 20.4% of the patients were responders and seizure-free (respectively) relative to baseline (3 months prior to PER initiation), and at 12 months, 68.1% and 26.5% of the patients were responders and seizure-free (respectively), relative to baseline (3 months prior to PER initiation). The retention rate at 6 and 12 months was 83.2% and 80.5%, respectively. The percentage of seizure-free patients at 12 months was significantly (p = 0.033) higher when PER was added as first vs. second add-on. The number of concomitant antiepileptic drugs (AEDs) was significantly reduced from baseline to 6 and 12 months (p = 0.001). Treatment was simplified in 23.9% of patients at the end of the observation period. Drug-related adverse events (AEs), most mild or moderate, were reported in 30.1% of patients, with irritability (8%) and dizziness (7.1%) as the most frequent ones.
CONCLUSIONS: This is the first observational, prospective study to evaluate efficacy and safety of early adjunctive treatment with PER in patients with focal epilepsy at 12 months. Perampanel demonstrated a good efficacy and safety profile when used at a median dose of 6 mg/day, regardless of the combination with other AEDs. Adverse events were mild or moderate, with dizziness being the most frequent one.

PMID: 31812902 [PubMed - as supplied by publisher]

Safety and tolerability of adjunctive brivaracetam in children with focal seizures: Interim analysis of pooled data from two open-label trials.

Eur J Paediatr Neurol. 2019 Nov 21;:

Authors: Patel AD, Badalamenti V, Gasalla T, Elmoufti S, Elshoff JP

Abstract
OBJECTIVE: To evaluate long-term safety and tolerability of adjunctive brivaracetam (BRV) in children with epilepsy.
METHODS: This was an interim analysis (cut-off March 15, 2017) of pooled data from two open-label, single-arm, multicentre trials. N01263 (NCT00422422) was a 3-week trial of BRV 0.8-4 mg/kg/day in patients (1 month-<16 years) with epilepsy. Patients who completed this trial could continue into a long-term follow-up trial (N01266, NCT01364597) which also directly enrolled patients (4-<17 years) with focal seizures. After dose-escalation, patients received BRV 1-5 mg/kg/day (maximum 200 mg/day) during long-term evaluation. Data are reported for patients aged 4 to <16 years with focal seizures.
RESULTS: The safety set comprised 149 patients: 34 from the initial trial (26 entered long-term trial) and 115 directly enrolled into the long-term trial. At the cut-off, 90 patients were receiving BRV (total exposure: 299.4 patient-years). Treatment-emergent adverse events (TEAEs) were reported by 140/149 (94.0%) patients, most commonly (≥20%) nasopharyngitis (24.8%), pharyngitis (22.1%), convulsion (21.5%), and pyrexia (20.1%). TEAEs considered drug-related by the investigator were reported by 56/149 (37.6%) patients, most commonly somnolence (6.0%). Two patients died; neither death was considered related to BRV. Mean changes from baseline in child behaviour rating scales were small; most patients remained in their baseline category.
CONCLUSION: In this pooled analysis of two open-label trials including long-term data, adjunctive BRV was generally well tolerated in children aged 4 to <16 years with focal seizures. These findings supported approval of BRV as a new therapy option for children aged ≥4 years with focal seizures.

PMID: 31810577 [PubMed - as supplied by publisher]

Surgical Intervention of Periocular Infantile Hemangiomas in the Era of β-Blockers.

Ophthalmic Plast Reconstr Surg. 2019 Nov 27;:

Authors: Men CJ, Ediriwickrema LS, Paik JS, Murdock J, Yen MT, Ng JD, Liu CY, Korn BS, Kikkawa DO

Abstract
PURPOSE: To examine the role of adjuvant surgical resection of infantile hemangiomas after systemic β-blocker therapy.
METHODS: This is a multicentered retrospective study. Standard protocol for oral propranolol was employed by the referring physicians. Ocular indications for surgery included ptosis obstructing the visual axis, high degrees of astigmatism causing amblyopia, or disfigurement from residual tumor. Patients underwent complete excision or debulking.
RESULTS: Eleven girls and 4 boys were surgically treated with mean operative age of 34.4 months. Patients were followed for a mean of 19.6 months after surgery. Four patients required surgical treatment due to an inability to tolerate medical therapy secondary to drug-related side effects (including bradycardia). The other 11 patients proceeded to surgery due to residual eyelid and orbital lesions despite medical treatment. All 15 patients underwent orbitotomy for residual hemangioma excision. Four patients also underwent simultaneous levator advancement at the time of excision. In all cases, there was resolution of ptosis with clearing of the visual axis. No complications were incurred during the surgical treatment and there were no hemangioma recurrences.
CONCLUSIONS: This is the first study to report surgical management of periocular infantile hemangiomas recalcitrant to standard therapy in the β-blocker era. In patients with infantile hemangioma who have failed medical therapy, adjuvant surgical treatment still plays an important role. For patients with persistent tumor causing ocular sequelae, surgical intervention aimed at soft tissue debulking and ptosis repair can be successful in achieving excellent functional and aesthetic outcomes with minimal side effects.

PMID: 31809485 [PubMed - as supplied by publisher]

Impact of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: protocol for a multicentre prospective study.

BMJ Open. 2019 Dec 04;9(12):e031972

Authors: Li D, Dong W, Liu Y, Wang J, Mu Y, Zhou H, Wang J, Zhou S, Chen Y

Abstract
INTRODUCTION: Metoprolol is the most frequently used β-receptor blockers; however, the prescribed dose in China is far less than the recommended doses in the guidelines. Based on the Chinese and International guidelines and the Chinese clinical practice, we are conducting this study (NCT03413410) to test the feasibility and tolerability of the metoprolol optimal dosing pathway by observing the percentage of patients achieving target dose in Chinese acute coronary syndrome (ACS) patients during hospitalisation.
METHODS AND ANALYSIS: A total of about 1000 patients aged ≥18 years, hospitalised for ACS will be enrolled from ~15 hospital sites in China between February 2018 and April 2019. The percentage of patients achieving the target metoprolol dosage at discharge is the primary endpoint. The secondary endpoints included the following: mean heart rate (HR) and blood pressure (BP) of the patients who have achieved target dose at discharge and during the follow-up period, percentage of patients experiencing bradycardia (HR <50 beats/min), hypotension (BP <90/60 mm Hg) and drug-related temporary heart failure worsening during hospitalisation and 1 month after discharge, respectively. We will also assess the proportion of patients reporting metoprolol-related adverse events and the leading causes for metoprolol discontinuation.
ETHICS AND DISSEMINATION: The study protocol has been approved by the Ethics committee of the Chinese PLA General Hospital (number: S2017-112-01). Study findings will be disseminated through presentations at national and international conferences and submitted for publications in peer-reviewed journals.
TRIAL REGISTRATION NUMBER: ClinicalTrials.gov registry (NCT03413410).

PMID: 31806613 [PubMed - in process]

Oral N-acetylcysteine improves cone function in retinitis pigmentosa patients in phase 1 trial.

J Clin Invest. 2019 Dec 05;:

Authors: Campochiaro PA, Iftikhar M, Hafiz G, Akhlaq A, Tsai G, Wehling D, Lu L, Wall GM, Singh MS, Kong X

Abstract
BACKGROUND: In retinitis pigmentosa (RP) rod photoreceptors degenerate from one of many mutations after which cones are compromised by oxidative stress. N-acetylcysteine (NAC) reduces oxidative damage and increases cone function/survival in RP models. We tested the safety, tolerability, and visual function effects of oral NAC in RP patients.
METHODS: Subjects (n = 10 per cohort) received 600 mg (cohort 1), 1200 mg (cohort 2), or 1800 mg (cohort 3) NAC BID for 12 weeks and then TID for 12 weeks. Best-corrected visual acuity (BCVA), macular sensitivity, ellipsoid zone (EZ) width, and aqueous NAC were measured. Linear mixed effects models were used to estimate the rates of changes during the treatment period.
RESULTS: There were 9 drug-related gastrointestinal adverse events which resolved spontaneously or with dose reduction (MTD 1800 mg bid). During the 24 week treatment period, mean BCVA significantly improved at 0.4 (95% CI 0.2-0.6, P < 0.001), 0.5 (95% CI 0.3-0.7, P < 0.001) and 0.2 (95% CI 0.02-0.4, P = 0.03) letters/month in cohorts 1, 2 and 3, respectively. There was no significant improvement in mean sensitivity (MS) over time in cohorts 1 and 2, but there was in cohort 3 (0.15 dB/month, 95%CI 0.04-0.26). There was no significant change in mean EZ width in any cohort.
CONCLUSION: Oral NAC is safe and well-tolerated in patients with moderately advanced RP and may improve suboptimally functioning macular cones. A randomized, placebo-controlled trial is needed to determine if oral NAC can provide long term stabilization and/or improvement in visual function in patients with RP.

PMID: 31805012 [PubMed - as supplied by publisher]

23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

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22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/12/04

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Acute Immune-Mediated Thrombocytopenia due to Oxaliplatin and Irinotecan Therapy.

Case Rep Oncol Med. 2019;2019:4314797

Authors: Tam EL, Draksharam PL, Park JA, Sidhu GS

Abstract
We describe a case of a 63-year-old woman with advanced colon cancer and liver metastases who was treated with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and cetuximab chemotherapy. She tolerated 13 cycles of chemotherapy without any significant hematological side effects, but after the 14th cycle, she developed melena and was admitted for severe thrombocytopenia. After supportive care, the platelet counts rapidly improved to 76,000/μL. Upon initiation of FOLFIRI and cetuximab chemotherapy, she again developed rectal bleeding and severe thrombocytopenia with a platelet count of 6000/μL. Lab testing was positive for oxaliplatin and irinotecan drug-dependent platelet antibodies on flow cytometry assay. Drug-induced thrombocytopenia (DITP) is associated with several classes of drugs with several proposed underlying mechanisms. Prospective studies are needed to further address different mechanisms of drug-induced thrombocytopenia.

PMID: 31781443 [PubMed]

Review of Statistical Methodologies for Detecting Drug-Drug Interactions Using Spontaneous Reporting Systems.

Front Pharmacol. 2019;10:1319

Authors: Noguchi Y, Tachi T, Teramachi H

Abstract
Concomitant use of multiple drugs for therapeutic purposes is known as "polypharmacy situations," which has been recognized as an important social problem recently. In polypharmacy situations, each drug not only induces adverse events (AEs) but also increases the risk of AEs due to drug-drug interactions (DDIs). The proportion of AEs caused by DDIs is estimated to be around 30% of unexpected AEs. The randomized clinical trials in pre-marketing typically focus emphasis on the verification of single drug safety and efficacy rather than the surveys of DDI, and therefore, patients on multiple drugs are usually excluded. However, unlike pre-marketing randomized clinical trials, in clinical practice (= post marketing), many patients use multiple drugs. The spontaneous reporting system is one of the significant sources drug safety surveillance in post-marketing. Commonly, signals of potential drug-induced AEs detected from this source are validated in real-world settings. Recently, not only methodological studies on signal detection of "single" drug, but also on several methodological studies on signal detection of DDIs have been conducted. On the other hand, there are few articles that systematically summarize the statistical methodology for signal detection of DDIs. Therefore, this article reviews the studies on the latest statistical methodologies from classical methodologies for signal detection of DDIs using spontaneous reporting system. This article describes how to calculate for each detection method and the major findings from the published literatures about DDIs. Finally, this article presented several limitations related to the currently used methodologies for signal detection of DDIs and suggestions for further studies.

PMID: 31780939 [PubMed]

Anastrozole-induced liver injury after a prolonged latency: a very rare complication of a commonly prescribed medication.

BMJ Case Rep. 2019 Nov 27;12(11):

Authors: Xie C, Abdullah HMA, Abdallah M, Quist E, Niazi M

Abstract
Anastrozole is an aromatase inhibitor that has been used more frequently over the last decade especially for oestrogen receptor-positive breast cancer. It has a relatively safe side effect profile. However, occasionally it has been associated with serious adverse events. Here, we present the case of a 58-year-old woman who presented with significantly elevated liver enzymes 4 years after starting anastrozole. She was not taking any other medications and an extensive workup did not reveal any other cause for her liver injury. The patient's liver enzymes normalised after discounting the anastrozole. She scored 4 on the updated Roussel Uclaf Causality Assessment Method grading system which was possible for drug-induced liver injury. A review of the literature revealed six prior cases of anastrozole-related liver injury. Anastrozole should be considered as a possible culprit in patients who develop an unexplained acute liver injury.

PMID: 31780604 [PubMed - in process]

Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance.

Nat Rev Clin Oncol. 2019 09;16(9):563-580

Authors: Martins F, Sofiya L, Sykiotis GP, Lamine F, Maillard M, Fraga M, Shabafrouz K, Ribi C, Cairoli A, Guex-Crosier Y, Kuntzer T, Michielin O, Peters S, Coukos G, Spertini F, Thompson JA, Obeid M

Abstract
Immune-checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are arguably the most important development in cancer therapy over the past decade. The indications for these agents continue to expand across malignancies and disease settings, thus reshaping many of the previous standard-of-care approaches and bringing new hope to patients. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), which are often distinctly different from the classical chemotherapy-related toxicities. Owing to the growing use of ICIs in oncology, clinicians will increasingly be confronted with common but also rare irAEs; hence, awareness needs to be raised regarding the clinical presentation, diagnosis and management of these toxicities. In this Review, we provide an overview of the various types of irAEs that have emerged to date. We discuss the epidemiology of these events and their kinetics, risk factors, subtypes and pathophysiology, as well as new insights regarding screening and surveillance strategies. We also highlight the most important aspects of the management of irAEs.

PMID: 31092901 [PubMed - indexed for MEDLINE]

Patient-Reported Outcomes in Online Communications on Statins, Memory, and Cognition: Qualitative Analysis Using Online Communities.

J Med Internet Res. 2019 Nov 28;21(11):e14809

Authors: Timimi F, Ray S, Jones E, Aase L, Hoffman K

Abstract
BACKGROUND: In drug development clinical trials, there is a need for balance between restricting variables by setting eligibility criteria and representing the broader patient population that may use a product once it is approved. Similarly, although recent policy initiatives focusing on the inclusion of historically underrepresented groups are being implemented, barriers still remain. These limitations of clinical trials may mask potential product benefits and side effects. To bridge these gaps, online communication in health communities may serve as an additional population signal for drug side effects.
OBJECTIVE: The aim of this study was to employ a nontraditional dataset to identify drug side-effect signals. The study was designed to apply both natural language processing (NLP) technology and hands-on linguistic analysis to a set of online posts from known statin users to (1) identify any underlying crossover between the use of statins and impairment of memory or cognition and (2) obtain patient lexicon in their descriptions of experiences with statin medications and memory changes.
METHODS: Researchers utilized user-generated content on Inspire, looking at over 11 million posts across Inspire. Posts were written by patients and caregivers belonging to a variety of communities on Inspire. After identifying these posts, researchers used NLP and hands-on linguistic analysis to draw and expand upon correlations among statin use, memory, and cognition.
RESULTS: NLP analysis of posts identified statistical correlations between statin users and the discussion of memory impairment, which were not observed in control groups. NLP found that, out of all members on Inspire, 3.1% had posted about memory or cognition. In a control group of those who had posted about TNF inhibitors, 6.2% had also posted about memory and cognition. In comparison, of all those who had posted about a statin medication, 22.6% (P<.001) also posted about memory and cognition. Furthermore, linguistic analysis of a sample of posts provided themes and context to these statistical findings. By looking at posts from statin users about memory, four key themes were found and described in detail in the data: memory loss, aphasia, cognitive impairment, and emotional change.
CONCLUSIONS: Correlations from this study point to a need for further research on the impact of statins on memory and cognition. Furthermore, when using nontraditional datasets, such as online communities, NLP and linguistic methodologies broaden the population for identifying side-effect signals. For side effects such as those on memory and cognition, where self-reporting may be unreliable, these methods can provide another avenue to inform patients, providers, and the Food and Drug Administration.

PMID: 31778117 [PubMed - in process]

Effect of altering the regime of oral rifampicin therapy in the treatment of persistent central serous chorioretinopathy.

Pak J Med Sci. 2019 Nov-Dec;35(6):1687-1690

Authors: Loya H, Ghoghari H, Rizvi SF, Khan A

Abstract
Objective: To study the effect of reducing the duration of rifampicin therapy in the treatment of Chronic Central Serous Chorioretinopathy.
Methods: This is interventional study conducted in Layton Rahmatullah Benevolent Trust, Free Base Eye Hospital Korangi, Karachi from February 2017 - December 2018. This randomized controlled comparative study included two groups, Groups-A comprised of 48 eyes of 40 cases with Chronic Central Serous Chorioretinopathy who were given reduced dose of oral rifampicin i.e. 600mg for one month, and Group-B consisted of 43 eyes of 40 controls with Chronic Central Serous Chorioretinopathy who were given reduced dose of oral rifampicin i.e. 300mg once daily for three months as previously stated in literature. To access the effect of therapy in both the groups, pre-treatment visual acuity on the logMAR and Optical Coherent Tomography (OCT, Heidelberg spectralis) for CMT were performed and repeated on the 1st and 3rd month post-treatment. Patients were also followed for 6 months to access any recurrence.
Results: On comparing the two groups, Group-A had improvement in VA and CMT after one month therapy of Rifampicin, Pre-treatment mean VA in Group-A was 0.85 ± 0.19 as compared to the pre-treatment mean VA in Group-B i.e. 0.74+/- 0.208, while the pre-treatment mean CMT was 609.0 ± 178.29 µm in Group-A, and 600.0 +/- 155.09 µm in Group-B respectively. After 1 month of therapy, the visual status, and CMT in Group-A was 0.29+/- 0.21 and 311.6 +/- 89.9, while Group-B, VA was 0.598 +/- 0.23 (p value 0.001%) and CMT was 512.30 +/- 148.37 (p-value 0.001%). Rifampicin was continued in Group-B till three months, and patients were re-accessed but there was no difference in VA and CMT statically. During the 3rd and 6th months of follow up no relapses were reported.
Conclusion: This comparative study showed that the group receiving oral rifampicin 600mg for one month showed better outcome at one month and third month than the group receiving oral rifampicin at a dose of 300mg once daily for three months. This gives a better compliance and lower the risk of drug induced side effects.

PMID: 31777516 [PubMed]

CD101 Topical Compared With Oral Fluconazole for Acute Vulvovaginal Candidiasis: A Randomized Controlled Trial.

J Low Genit Tract Dis. 2019 Jul;23(3):226-229

Authors: Nyirjesy P, Alessio C, Jandourek A, Lee JD, Sandison T, Sobel JD

Abstract
OBJECTIVES: Vulvovaginal candidiasis (VVC) is an infection of the vagina's mucous membranes, caused by Candida albicans in more than 90% of acute VVC. Several topical and oral azole agents are available in a variety of formulations, and all seem to have similar effectiveness. Azoles are fungistatic, meaning that the fungi are inhibited from growth or replication but are not eradicated. Recurrent infection and developing azole resistance demonstrate a significant need for alternative treatments.
MATERIALS AND METHODS: One hundred twenty-six women were randomized to 1 of the following 3 treatment cohorts: CD101 3% gel (n = 50) applied intravaginally on days 1 and 2, CD101 6% ointment (n = 50) applied intravaginally on day 1, or oral fluconazole 150 mg (n = 26) on day 1. Primary outcomes of clinical and mycological cure, as demonstrated by changes in the vaginal scores and mycological culture, were assessed on day 7 (±2 days), day 14 (±2 days), and day 28 (±7 days). Safety assessments included treatment-emergent adverse events.
RESULTS: Ninety-nine women with positive Candida culture remained in the modified intent-to-treat population with 40 in each CD101 arm and 19 in the fluconazole arm. In the CD101 gel, CD101 ointment, and oral fluconazole groups, 35%, 30%, and 52.6% demonstrated clinical cure and 45%, 40%, and 57.9% had mycological cure at day 28, respectively.
CONCLUSIONS: CD101 3% gel and CD101 6% ointment were well tolerated and produced similar rates of clinical and mycological cure in patients with an acute, moderate-to-severe episode of VVC. However, cure rates for these 2 formulations and regimens of CD101 were lower than those in patients treated with fluconazole.

PMID: 30893271 [PubMed - indexed for MEDLINE]

Impact of pharmacy collaborating services in an outpatient clinic on improving adverse drug reactions in outpatient cancer chemotherapy.

J Oncol Pharm Pract. 2019 Oct;25(7):1558-1563

Authors: Suzuki H, Suzuki S, Kamata H, Sugama Y, Demachi K, Ikegawa K, Igarashi T, Yamaguchi M

Abstract
BACKGROUND: Collaboration between pharmacists, doctors, and nurses in outpatient treatment is beneficial; however, such services are limited in Japan due to the lack of a healthcare reimbursement fee for outpatient pharmacy services at outpatient clinic.
OBJECTIVE: We evaluated the impact of a service in which clinical pharmacists collaborated with an oncologist at an outpatient clinic in the treatment of adverse drug reactions in outpatient cancer chemotherapy.
METHODS: We performed a retrospective cohort study using patients' medical records and treatment diaries. Subjects were patients who received outpatient chemotherapy via a clinical pharmacist collaboration service provided by six outpatient pharmacists and an oncologist at an outpatient clinic between June and August 2016.
RESULTS: During the study period, the total number of outpatient services was 2508, with 2055 (81%) related to chemotherapy. The six outpatient pharmacists provided interventions to 498 of the 2055 cases (24%). Of the 498 interventions, 103 (20%), in addition to oncologist's prescription, were suggested treatments for adverse drug reactions due to cancer chemotherapy. Oncologists approved a total of 82 prescription suggestions from pharmacists (79%) to 63 patients. Fifty-seven percent (n = 47) of the adverse drug reactions were improved following the pharmacists' suggested prescriptions.
CONCLUSIONS: This is the first study to clarify the benefits of outpatient pharmacy services in which pharmacists collaborate with oncologists at an outpatient clinic for the management of adverse drug reactions in cancer patients in Japan.

PMID: 30180775 [PubMed - indexed for MEDLINE]