Acute medication poisoning causing hospital admissions in childhood: a 3-year prospective observational single-center study.

Physiol Res. 2019 11 22;68(Suppl 1):S31-S38

Authors: Matalová P, Poruba M, Wawruch M, Ondra P, Urbánek K

Abstract
Although the risks of medication poisoning in children are often reported, there is a lack of studies addressing this issue. The majority of papers deal with a wide range of xenobiotics poisoning and, in particular, alcohol intoxications. All hospital admissions during three years were prospectively recorded. Patients younger than 19 years of age admitted for acute drug intoxications were further evaluated. A total of 15,069 children were admitted. Of them, 55 were hospitalized for acute medication poisoning. The condition was more common in girls (72.7 % vs. 27.3 %, p<0.01). Toddlers were the largest patient group (36.4 %). Non-steroidal anti-inflammatory drugs (NSAIDs) were the most frequently used agents, with ibuprofen being the leading drug (20 % of all cases). The route of intoxication was almost exclusively oral. Solid drug forms were involved in 40 (72.7 %) cases. There was one fatal accidental poisoning. The highest occurrence of accidental drug intoxications was in the age group from one to three years. Attempted suicides were most frequent among adolescents. We are currently actively dealing with the issue. The cohort has been expanded to include a period of ten years and is being analyzed.

PMID: 31755288 [PubMed - indexed for MEDLINE]

Reported Adverse Drug Reactions in Children and Adolescents Treated with Antipsychotics.

J Child Adolesc Psychopharmacol. 2019 03;29(2):124-132

Authors: Minjon L, van den Ban E, de Jong E, Souverein PC, Egberts TCG, Heerdink ER

Abstract
OBJECTIVES: To characterize reported adverse drug reactions (ADRs) in children and adolescents treated with antipsychotics and determine differences in relative reporting frequency between genders, age classes, and reporter types.
METHODS: Individual case safety reports of children ages 1 - 17 years in whom an antipsychotic drug was the suspected or interacting drug from the worldwide database, VigiBase, from 1968 until March 2017, were included. Reported ADRs were categorized based on the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries and clinical reasoning. Proportional reporting ratios (PRRs) and 95% confidence intervals (95% CIs) were calculated for genders, age classes, and reporter types.
RESULTS: In total, 45,201 reported ADRs were included. The most frequently reported were ADRs related to extrapyramidal syndrome (14.7%), breast disorders or blood prolactin level changes (4.7%), and cardiac arrhythmias (4.6%). Differences in relative reporting frequencies were observed between age classes and reporter types, and less prominent between genders. For example, ADRs related to hyperglycemia/new-onset diabetes mellitus were less frequently reported in children ages 1 - 5 than in children ages 12 - 17 (PRR: 0.4, 95% CI: 0.2 - 0.5). ADRs related to cardiac arrhythmias were less frequently reported by consumers compared with health care professionals (PRR: 0.5, 95% CI: 0.5 - 0.6), whereas ADRs related to a change in weight/body mass index were more frequently reported by consumers (PRR: 3.2, 95% CI: 2.9 - 3.5).
CONCLUSION: A wide spectrum of ADRs were reported in children treated with antipsychotics. The relative differences in reporting frequency between age classes and reporter types can be of help to tailor information about possible ADRs and to monitor for ADRs.

PMID: 30676073 [PubMed - indexed for MEDLINE]

Safety, tolerability, pharmacokinetics, and pharmacodynamics of macimorelin in healthy adults: Results of a single-dose, randomized controlled study.

Growth Horm IGF Res. 2020 Apr 15;52:101321

Authors: Klaus B, Sachse R, Ammer N, Kelepouris N, Ostrow V

Abstract
OBJECTIVE: Macimorelin is an orally active ghrelin receptor agonist indicated for the diagnosis of adult growth hormone (GH) deficiency in the United States. This phase 1 study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of macimorelin (including a supratherapeutic dose to be used in a thorough QT trial) in healthy adults.
DESIGN: Participants were randomized to receive macimorelin 0.5, 1.0, or 2.0 mg/kg or placebo in 1 of 3 sequential ascending-dose cohorts. Blood samples for pharmacokinetic and pharmacodynamic assays were collected pre-dose and at specified time points over a 24-h period. Pharmacokinetic parameters assessed included area under the concentration-time curve (AUC), maximum concentration (Cmax) of macimorelin in plasma, time to Cmax (tmax), and terminal elimination half-life (t1/2). Pharmacodynamic assessments evaluated levels of GH, adrenocorticotropic hormone, thyroid-stimulating hormone, cortisol, and prolactin. Safety was assessed based on treatment-emergent adverse events (TEAEs), vital signs, 12‑lead electrocardiograms, and laboratory parameters.
RESULTS: A total of 28 healthy adults were enrolled and completed the study. Macimorelin AUC and Cmax showed less than dose-proportional increases following administration of 0.5 and 1.0 mg/kg. Mean t1/2 was 3.51 h for macimorelin 0.5 and 1.0 mg/kg and 8.29 h for macimorelin 2.0 mg/kg; median tmax occurred at 0.5 to 0.75 h. GH levels increased after dosing, with a tmax of 0.75 h to 1.0 h. Mean GH Cmax was similar with the macimorelin 0.5- and 1.0-mg/kg doses (31.9 and 37.8 ng/mL, respectively) and was ~50% lower with macimorelin 2.0 mg/kg (18.4 ng/mL). Transient increases were observed in adrenocorticotropic hormone, cortisol, and prolactin, which were not dose related. A total of 19 TEAEs were reported in 35.7% (10/28) of participants; all TEAEs were mild or moderate and resolved. A total of 12 drug-related TEAEs were reported in 8 participants. Headache was the most common drug-related TEAE. All doses of macimorelin prolonged mean QTcF by 10 to 11 ms. There were no clinically meaningful changes in vital signs or laboratory parameters.
CONCLUSIONS: Single-dose administration of macimorelin 0.5 to 2.0 mg/kg was well tolerated. Macimorelin exposure was less than dose-proportional over the dose range studied. Administration of macimorelin stimulated GH production, with the greatest increases observed in the macimorelin 0.5- and 1.0-mg/kg groups.

PMID: 32325373 [PubMed - as supplied by publisher]

Systematic review of interventions to improve safety and quality of anticoagulant prescribing for therapeutic indications for hospital inpatients.

Eur J Clin Pharmacol. 2019 Dec;75(12):1645-1657

Authors: Frazer A, Rowland J, Mudge A, Barras M, Martin J, Donovan P

Abstract
PURPOSE: Anticoagulation-associated adverse drug events are common in hospitalised patients and result in morbidity, mortality, increased length of hospital stay and higher costs of care. Many are preventable. We reviewed the literature to identify and assess interventions intended to improve safety or quality anticoagulant prescribing.
METHODS: A systematic search of EMBASE, MEDLINE, the Cochrane Library, Pretty Darn Quick-Evidence and Health Systems Evidence was undertaken to identify controlled studies assessing system-level interventions to improve prescribing of oral or parenteral therapeutic anticoagulation for any indication in hospitalised adults. Data were extracted for safety and quality outcomes, with studies grouped by intervention type for meta-analysis and narrative review.
RESULTS: Of 10,640 records screened, 19 trials evaluating 12,742 participants were included for analysis. No study specifically evaluated prescribing of low molecular weight heparins (LMWHs) or direct acting oral anticoagulants (DOACs). Our findings suggest that physician-led anticoagulation consultation services may reduce bleeding rates in high-risk patients. On meta-analysis, decision supported warfarin dosing resulted in higher proportion of time with international normalised ratio in therapeutic range (p = 0.0007). Studies of other clinical decision support systems and heparin monitoring systems did not demonstrate improved safety, and quality findings were inconsistent. Systematic education and feedback programs were not efficacious.
CONCLUSIONS: There is currently insufficient high-quality evidence to recommend any reviewed intervention, though several warrant closer evaluation. Adequately powered controlled trials assessing safety outcomes and evidence-based quality markers in high-risk patient groups and studies of interventions to improve safety of LMWH and DOAC prescribing are needed.

PMID: 31511939 [PubMed - indexed for MEDLINE]

Efficacy and safety of topical nitroglycerin in the prevention of mastectomy flap necrosis: a systematic review and meta-analysis.

Sci Rep. 2020 Apr 21;10(1):6753

Authors: Wang P, Gu L, Qin Z, Wang Q, Ma J

Abstract
Flap necrosis is a common complication after mastectomy, and nitroglycerin (NTG) ointment has been used successfully to treat it. However, it is not clear whether topical NTG can completely prevent the occurrence of flap necrosis after breast cancer surgery, and it is also unclear whether this treatment may cause side effects. Three randomized controlled trials (RCTs) and two retrospective cohort studies (RCSs) were included in our investigation. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We found that NTG significantly reduced the rates of mastectomy flap necrosis, full-thickness flap necrosis, and debridement as well as the rate of early complications other than flap necrosis. However, there was no significant difference in drug-related adverse reactions, explantation, superficial flap necrosis, infection, hematoma or seroma between the NTG and placebo groups.

PMID: 32317705 [PubMed - in process]

Post-finasteride syndrome.

An Bras Dermatol. 2020 Mar 25;:

Authors: Pereira AFJR, Coelho TOA

Abstract
Finasteride is a 5α-reductase enzyme inhibitor that has been approved for the treatment of male androgenic alopecia since 1997. Over time, it has been considered a safe and well-tolerated drug with rare and reversible side effects. Recently there have been reports of adverse drug-related reactions that persisted for at least three months after discontinuation of this drug, and the term post-finasteride syndrome arose. It includes persistent sexual, neuropsychiatric, and physical symptoms. Studies to date cannot refute or confirm this syndrome as a nosological entity. If it actually exists, it seems to occur in susceptible people, even if exposed to small doses and for short periods, and symptoms may persist for long periods. Based on currently available data, the use of 5α-reductase inhibitors in patients with a history of depression, sexual dysfunction, or infertility should be carefully and individually assessed.

PMID: 32317131 [PubMed - as supplied by publisher]

Pembrolizumab monotherapy in Japanese patients with advanced ovarian cancer: Subgroup analysis from the KEYNOTE-100.

Cancer Sci. 2020 Apr;111(4):1324-1332

Authors: Nishio S, Matsumoto K, Takehara K, Kawamura N, Hasegawa K, Takeshima N, Aoki D, Kamiura S, Arakawa A, Kondo E, Hirakawa T, Yamamoto K, Aoki M, Stein K, Keefe S, Fujiwara K, Ushijima K

Abstract
Interim results from the two-cohort, phase 2 KEYNOTE-100 study (NCT02674061) of 376 patients with previously treated advanced recurrent ovarian cancer (ROC) showed that pembrolizumab monotherapy was associated with an objective response rate (ORR) of 8.0% (95% CI, 5.4-11.2). We present outcomes for the Japanese patients (n = 21) enrolled in KEYNOTE-100. Patients with epithelial ROC had received either 1-3 prior chemotherapy lines and had platinum-free interval or treatment-free interval (PFI; TFI) of 3-12 months (cohort A) or 4-6 prior chemotherapy lines and had PFI/TFI of ≥3 months (cohort B). All patients received pembrolizumab 200 mg every 3 weeks as monotherapy for 2 years or until progression, death, unacceptable toxicity or consent withdrawal. Primary objectives were ORR per RECIST v1.1 for each cohort and higher programmed death ligand-1 (PD-L1) tumor expression. The relationship between PD-L1 expression (measured as combined positive score [CPS]) and ORR was assessed. Twenty-one Japanese patients (cohort A, n = 19; cohort B, n = 2) were treated. The median (range) age was 57 (37-78) years; 19 (90.5%) patients had ECOG status of 0 and 16 (76.2%) patients had stage III-IV disease. ORR was 19.0% (95% CI, 5.4-41.9) and seemed to increase with increasing PD-L1 expression. A total of 13 (61.9%) patients had treatment-related adverse events (TRAE), and 5 (23.8%) had grade 3-4 TRAE. There were no treatment-related deaths in this subpopulation. Pembrolizumab monotherapy was associated with antitumor activity in Japanese patients with ROC, with no new safety signals identified in this subpopulation. The data suggested a trend toward higher PD-L1 expression among some patients with higher ORR.

PMID: 32012411 [PubMed - indexed for MEDLINE]

Evaluation of Acute Kidney Injury Associated With Anticancer Drugs Used in Gastric Cancer in the Japanese Adverse Drug Event Report Database.

Ann Pharmacother. 2019 12;53(12):1200-1206

Authors: Uchida M, Kondo Y, Suzuki S, Hosohata K

Abstract
Background: Development of acute kidney injury (AKI) depends on the severity of renal dysfunction, clinical setting, comorbid factors, and geographical location. Gastric cancer is one of the deadliest malignancies worldwide, and its incidence is significantly high in Japan. Objective: We analyzed the rank-order of the association of anticancer agents for gastric cancer with AKI using a spontaneous reporting system database, the Japanese Adverse Drug Event Report database. Methods: We performed a retrospective pharmacovigilance disproportionality analysis using the adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency between April 2004 and March 2017. Results: Anticancer drug-related AKI was common in patients in their 60s and 70s (39.2% and 43.2%, respectively). AKI occurred most frequently within 1 month after anticancer drug administration. The signals of AKI were reported after treatment with S-1 (tegafur/gimeracil/oteracil), cisplatin (CDDP), and capecitabine, with significant adjusted reporting odds ratios (95% CI) of 1.50 (1.09-2.07), 3.43 (2.48-4.74), and 1.82 (1.15-2.90), respectively. CDDP-induced AKI was more likely to occur in patients who were male, hypertension, or diabetes mellitus. Conclusion and Relevance: This study showed that most AKI cases were related to S-1 and/or CDDP adjuvant chemotherapy for gastric cancer treatment. The data also clarified that AKIs occurred within 1 month and that their clinical outcomes were more severe than previous reports of drug-induced AKI in general medicine. Our study provides useful information to minimize the risks of administration to patients at high risk for S-1 and/or CDDP containing chemotherapy-induced AKI.

PMID: 31347378 [PubMed - indexed for MEDLINE]

The Role of the Clinical Pharmacist in a Preventive Cardiology Practice.

Ann Pharmacother. 2019 12;53(12):1214-1219

Authors: Warden BA, Shapiro MD, Fazio S

Abstract
Background: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide. In response, a multidisciplinary team approach, which includes clinical pharmacists, is recommended to improve patient outcomes. The purpose of the study was to describe interventions associated with integration of a clinical pharmacist, with an emphasis on pharmacist-generated patient cost avoidance. Methods: This is a prospective observational study detailing pharmacist-initiated interventions within an academic preventive cardiology service. Interventions targeting pharmacotherapy optimization, side effect management, patient education, medication adherence, and cost avoidance were implemented during shared office visits with providers and/or on provider consultation for remote follow-up. Tabulation of cost avoidance was arranged into 2 formats: clinical interventions implemented by the pharmacist and direct patient out-of-pocket expense reduction. Money saved per clinical intervention was extrapolated from data previously published. Patient out-of-pocket expense prior to and after pharmacist involvement was calculated to assess aggregate yearly patient cost savings. Results: Over 12 months the pharmacist intervened on 974 patients, totaling 3725 interventions. Cost avoidance strategies resulted in yearly savings of $830 748 in aggregate-$149 566 from clinical interventions and $681 182 from patient out-of-pocket expense reduction. Monthly patient out-of-pocket expense was reduced from a median (interquartile range) of $217 ($83.5-$347) before to $5 ($0-$18) after pharmacist intervention. Conclusions: Addition of a clinical pharmacist within an academic preventive cardiology clinic generated substantial pharmacotherapy interventions, resulting in significant cost avoidance for patients. The resulting cost avoidance may result in improved medication adherence and clinical outcomes.

PMID: 31342786 [PubMed - indexed for MEDLINE]

Emergency Department Visits for Psychotropic-Related Adverse Drug Events in Older Adults With Alzheimer Disease, 2013-2014.

Ann Pharmacother. 2019 12;53(12):1173-1183

Authors: Sepassi A, Watanabe JH

Abstract
Background: More than 1.3 million emergency department visits have been associated with adverse drug events (ADEs) in older adults. Increasing Alzheimer's disease (AD) prevalence in the geriatric population poses an additive risk of ADEs because of the array of psychotropic medications prescribed for AD patients. Scant research has been conducted at a nationwide level on psychotropic-related ADEs in this population. Objective: This study aimed to determine the incidence and economic burden of psychotropic ADEs in the geriatric AD population compared with the non-AD geriatric population. Methods: A retrospective analysis was conducted of geriatric AD patients who visited the ED in 2013 with a psychotropic-related ADE to determine the incidence and resource utilization of these events. The relationship between presence of AD and an ADE was analyzed using multiple logistic regression. Results: There were 427 969 Alzheimer's ED visits compared with 20 492 554 ED visits without. Of the AD cases, 1.04% were associated with at least 1 adverse event. AD cases more frequently were admitted as inpatients (64.90% vs 34.92%, P < 0.01). Common drug classes associated with AD-related ADEs were benzodiazepines, antipsychotics, and autonomic nervous system-affecting agents (adrenergic agonists, antimuscarinic agents, anticholinergic agents). There was a significantly higher likelihood for Alzheimer's cases to experience any psychotropic-related adverse event (OR = 1.66; 95% CI = 1.20, 1.82). Conclusion and Relevance: Alzheimer's patients more frequently experienced psychotropic-related adverse events and related adverse outcomes than older adults without Alzheimer's. Application of these findings should be implemented in protocol development to reduce future psychotropic-related adverse outcomes for this population.

PMID: 31342766 [PubMed - indexed for MEDLINE]

Safety, Tolerability and Immunogenicity of an MF59-adjuvanted, Cell Culture-derived, A/H5N1, Subunit Influenza Virus Vaccine: Results From a Dose-finding Clinical Trial in Healthy Pediatric Subjects.

Pediatr Infect Dis J. 2019 07;38(7):757-764

Authors: Chanthavanich P, Anderson E, Kerdpanich P, Bulitta M, Kanesa-Thasan N, Hohenboken M

Abstract
BACKGROUND: A/H5N1 influenza virus has significant pandemic potential, and vaccination is the main prophylactic measure. This phase 2, randomized, observer-blind, multicenter study evaluated the safety and immunogenicity of two MF59-adjuvanted, cell culture-derived H5N1 (aH5N1c) vaccine formulations in healthy pediatric subjects 6 months to 17 years old.
METHODS: Subjects (N = 662) received 2 aH5N1c doses 3 weeks apart, containing either 7.5 μg (full dose) or 3.75 μg (half dose) hemagglutinin antigen per dose. Local reactions and adverse events (AEs) were assessed by age. Antibody responses were measured by hemagglutination inhibition assay and assessed as geometric mean titers, geometric mean ratios (GMRs) and percentages of subjects achieving titers ≥1:40 and seroconversion (NCT01776554).
RESULTS: No vaccine-related serious AEs occurred. Incidence of solicited local reactions and systemic AEs were similar across vaccine groups. Tenderness and irritability in <6-year olds, and injection site pain, myalgia and fatigue in 6-17-year olds were the most commonly reported reactions in both full- and half-dose recipients. Frequencies of AEs were lower after the second dose than the first dose in all vaccine and age groups. Three weeks after the administration of a second dose, both full- and half-dose formulations met the Center for Biologics Evaluation Research and Review (United States) and Committee for Medicinal Products for Human Use (EU) licensure criteria for titers ≥1:40 (full dose 96% subjects; half dose 86%), seroconversion (full dose 96% subjects; half dose 86%), and GMR (full dose GMR 262; half dose 84). Antibody responses were highest in 6-35-month olds.
CONCLUSIONS: In pediatric subjects, both aH5N1c vaccine formulations were well tolerated and highly immunogenic, meeting both US and EU licensure criteria for pandemic influenza vaccines.

PMID: 31194712 [PubMed - indexed for MEDLINE]

Use of Micafungin for the Prevention and Treatment of Invasive Fungal Infections in Everyday Pediatric Care in France: Results of the MYRIADE Study.

Pediatr Infect Dis J. 2019 07;38(7):716-721

Authors: Leverger G, Timsit JF, Milpied N, Gachot B

Abstract
BACKGROUND: Invasive fungal infections are responsible for significant morbidity and mortality. Safety and effectiveness of antifungal agents is a particular concern in pediatric populations, where data are often limited. Micafungin is an echinocandin with demonstrated antifungal activity against a wide spectrum of Candida spp.; this subanalysis of data from the MYRIADE study describes the use of micafungin and its therapeutic outcomes in pediatric patients, in normal clinical practice.
METHODS: MYRIADE was an observational, multicenter, national, prospective, longitudinal study conducted from January 2010 to December 2012, in patients treated with micafungin using a prophylactic or curative strategy, across 17 sites [oncohematology (n = 8), neonatal intensive care units (ICUs) (n = 5) and pediatric ICUs (n = 4)]. The treatment regimen, the achievement of the therapeutic objective and the tolerance were reported.
RESULTS: The study population consisted of 110 pediatric patients (31 neonates, 24 children <2 years old and 55 children ≥2 to <16 years old). The therapeutic objective was achieved in 49/64 (76.6%) oncohematology patients, 28/29 (96.6%) neonatal ICU patients and 12/14 (85.7%) pediatric ICU patients. Twenty-four (21.8%) children developed an adverse event (AE); more AEs were observed in oncohematology patients compared with ICU patients [17 (26.1%) vs. 7 (15.6%)]. Only one serious AE, reported in an oncohematology patient, was considered related to micafungin.
CONCLUSIONS: In the first large observational study of micafungin treatment or prophylaxis conducted under real-world conditions in France, micafungin was effective and well tolerated for prophylaxis of invasive fungal infections in pediatric oncohematology patients and for curative purposes in pediatric and neonatal ICU patients.

PMID: 31192976 [PubMed - indexed for MEDLINE]

Reducing Hematologic Toxicity With Short Course Postexposure Prophylaxis With Zidovudine for HIV-1 Exposed Infants With Low Transmission Risk.

Pediatr Infect Dis J. 2019 07;38(7):727-730

Authors: Nguyen TTT, Kobbe R, Schulze-Sturm U, Blohm M, Hollwitz B, Hertling S, Becker C, Oommen PT, Laws HJ, Martignoni F, Ole Jensen BE, Olah K, Schmidtke S, Kreuels B, Vasconcelos MK, Neubert J

Abstract
Using retrospectively collected data from 383 infants born to HIV-1-infected mothers receiving antiretroviral therapy, we compared transmission rates and hematologic toxicity between infants receiving 2-week (short course) versus longer duration zidovudine postexposure prophylaxis. Short course resulted in lower hematologic toxicity without evidence of increased vertical transmission risk.

PMID: 31033907 [PubMed - indexed for MEDLINE]

Efficacy, safety, and tolerability of a ready-to-drink bowel preparation in overweight and obese adults: subanalysis by body mass index from a phase III, assessor-blinded study.

Therap Adv Gastroenterol. 2020;13:1756284820910050

Authors: Hookey L, Bertiger G, Johnson KL, Boules M, Ando M, Dahdal DN

Abstract
Background: We performed a post hoc secondary analysis for the effect of body mass index (BMI) on the efficacy, tolerability, and safety of ready-to-drink sodium picosulfate, magnesium oxide, and citric acid (SPMC oral solution) bowel preparation.
Methods: A phase III, randomized, assessor-blinded, multicenter, noninferiority study was conducted comparing split-dose, low-volume SPMC oral solution with a powder formulation for oral solution. A post hoc secondary analysis assessed efficacy, safety, and tolerability of SPMC oral solution stratified by BMI. BMI was classified by Centers for Disease Control and Prevention definitions (underweight and normal weight: BMI < 25 kg/m2; overweight: BMI 25-29.9 kg/m2; class I obesity: BMI 30-34.9 kg/m2; class II obesity: BMI 35-39.9 kg/m2; class III/severe obesity: BMI ⩾40 kg/m2). Prespecified primary efficacy endpoint ('responders') was the proportion of participants with 'excellent' or 'good' ratings on a modified Aronchick Scale (AS). Secondary efficacy outcomes were the quality of cleansing of the right colon as assessed by the Boston Bowel Preparation Scale (BBPS); as well as selected findings from the Mayo Clinic Bowel Prep Tolerability Questionnaire. Safety assessments included adverse events (AEs) and laboratory evaluations.
Results: Between 82.8% and 92.5% of participants in any BMI group were responders by AS, and between 91.3% and 100% were responders by BBPS in the right colon. Efficacy was consistent across BMI groups, with no clear trends. Greater than 83% of participants in any BMI group found the preparation 'easy' or 'acceptable' to ingest, and the majority (>58%) rated SPMC oral solution as 'better' than a prior bowel preparation. In all BMI groups, safety data were similar to the overall cohort. Commonly reported, drug-related, treatment-emergent AEs were, by ascending BMI group, nausea (1.1%, 5.3%, 1.0%, 5.7%, and 0%) and headache (1.1%, 4.1%, 1.0%, 5.7%, and 0%).
Conclusions: Ready-to-drink SPMC oral solution had consistent, good quality colon cleansing, and favorable tolerability among participants of all BMI groups.
ClinicalTrialsgov Registration: NCT03017235.

PMID: 32313553 [PubMed]

Impact of medication review via tele-expertise on unplanned hospitalizations at 3 months of nursing homes patients (TEM-EHPAD): study protocol for a randomized controlled trial.

BMC Geriatr. 2020 Apr 20;20(1):147

Authors: Correard F, Montaleytang M, Costa M, Astolfi M, Baumstarck K, Loubière S, Amichi K, Auquier P, Verger P, Villani P, Honore S, Daumas A

Abstract
BACKGROUND: Inappropriate drug prescribing causes preventable drug-related adverse events that result in increased morbidity and mortality, additional costs and diminished quality of life. Numerous initiatives have been launched to improve the quality of drug prescribing and safeguard the security of drug administration processes in nursing homes. Against the backdrop of implementation of telemedicine services, the focus of the present work is to evaluate the impact of a telemedication review carried out by a hospital physician and pharmacist as part of the telemedicine offer.
METHODS: The present study is a randomized controlled clinical trial. A total of 364 patients will be randomized into two groups: (1) an experimental group (182 patients) benefiting from a telemedication review using tele-expertise and (2) a control group (182 patients) receiving standard care. The primary endpoint will be rate of all-cause unplanned hospital admissions occurring within 3 months of randomization. The secondary endpoints will be rate of unplanned admissions at 6 months, patient quality of life, incidence of behavioral disturbances, number of falls, number of residents prescribed at least one inappropriate medication, nursing staff satisfaction, proposed medication reviews and their acceptability rate, characteristics of patients whose general practitioners have taken account of tele-expertise, efficacy of tele-expertise as compared to standard prescription and acceptability and satisfaction surveys of participating caregivers.
DISCUSSION: In the literature, various studies have investigated the utility of structured medication review processes, but outcome measures are heterogeneous, and results vary widely. Medication review can detect medication-related problems in many patients, but evidence of clinical impact is scant. Incremental cost-effectiveness ratios will be used to compare the cost and effectiveness of the experimental strategy and that of standard care. Our approach, involving the combination of an acceptability survey and a mixed-method (qualitative and quantitative) satisfaction survey, is particularly innovative. The results of this randomized trial are expected to confirm that medication review using tele-expertise has potential as a worthwhile care management strategy for nursing home residents.
TRIAL REGISTRATION: Clinicaltrials.gov NCT03640845; registered August 21, 2018 (Clinicaltrials.gov NCT03640845).

PMID: 32312242 [PubMed - in process]

Adverse drug reactions in tuberculosis and management.

Indian J Tuberc. 2019 Oct;66(4):520-532

Authors: Prasad R, Singh A, Gupta N

Abstract
BACKGROUND: Treatment of drug susceptible tuberculosis (DS-TB) requires regimens containing first line drugs (FLDs') whereas drug resistant tuberculosis (DR-TB) are treated with regimens comprising combination of both second line drugs (SLDs') and few FLDs'. Adverse drug reactions (ADRs') to these anti-tubercular drugs are quite common as they are being used for longer duration. ADRs' may cause associated morbidity and even mortality if not recognized early. There are major concerns regarding treatment of DR-TB patients particularly with SLDs' in that they are expensive, have low efficacy and more toxic as compared to FLDs'. There may be a severe impact on adherence and higher risk of default and treatment failure affecting outcome overall if such ADRs' are not properly managed.
METHODS: A search strategy was adopted involving principal electronic databases (Pubmed, EMBASE, Google and Google scholar) of English language articles from 1990 till now, using various terms in combination. All articles with resulting titles, abstract and full text, when available were read and kept for reference.
RESULTS: 101 articles including 4 systematic reviews have been identified. The overall prevalence of ADRs' with FLDs' and SLDs' are estimated to vary from 8.0% to 85% and 69% to 96% respectively. Most ADRs' are observed in the intensive phase as compared to continuation phase. No difference in frequency of ADRs' was reported with intermittent or daily intake of anti-tubercular drugs. The occurrence of ADRs' may be influenced by multiple factors and may range from mild gastrointestinal disturbances to serious hepatotoxicity, ototoxicity, nephrotoxicity peripheral neuropathy, cutaneous ADRs', etc. Most of ADRs' are minor and can be managed without discontinuation of treatment. Some ADRs' can be major or severe causing life-threatening experience leading to either modification or discontinuation of regimen and even mortality if not recognized and treated promptly.
CONCLUSION: Early recognition by active surveillance and appropriate management of these ADRs' might improve adherence and treatment success.

PMID: 31813444 [PubMed - indexed for MEDLINE]

Systemic medications linked to an increased risk for skin malignancy.

Cutis. 2019 Oct;104(4):E32-E36

Authors: Johnson NM, Prickett KA, Phillips MA

Abstract
Over the last several decades, many new drugs that target molecular pathways in carcinogenesis and the inflammatory immune system have been developed, resulting in substantial improvements in the treatment of many malignancies and inflammatory conditions. However, an increasingly widespread deployment of these new drugs has revealed an increased tendency for patients to develop skin malignancy in some instances and questions of possible association between their use and skin cancer. Specifically, increased skin cancer risk has been reported in association with BRAF inhibitors, sonic hedgehog-inhibiting agents, Janus kinase (JAK) inhibitors, and phosphodiesterase 5 (PDE-5) inhibitors. We review the literature on each drug class and its association with skin malignancy, as well as recommendations regarding drug use, surveillance, and treatment.

PMID: 31774904 [PubMed - indexed for MEDLINE]

Anticholinergic Drug Exposure and the Risk of Dementia: There Is Modest Evidence for an Association but Not for Causality.

J Clin Psychiatry. 2019 08 06;80(4):

Authors: Andrade C

Abstract
Many observational studies published during the past 15 years have found an association between anticholinergic drug exposure and the risk of incident dementia. Animal data suggest plausible causal mechanisms for this finding. The results of a recent, large, and well-conducted study on the subject were widely disseminated by the lay and scientific media. This study addressed protopathic bias by examining anticholinergic drug exposure in time windows 1-11, 3-13, and 5-20 years before the identification of dementia. In brief, the study found that, pooling anticholinergic drug exposure across 11 drug categories, exposure in smallest to largest cumulative dosing groups was significantly associated with incident dementia risk, with an apparently dose-dependent relationship in unadjusted as well as adjusted analyses in all time windows prior to dementia identification. Whereas these findings appear compelling, there are at least 4 elephants in the room. First, only 3 of 11 anticholinergic drug categories were consistently associated with an increased risk of dementia; this suggests that anticholinergic activity may be an irrelevant common denominator. Second, for 2 of these 3 categories (antidepressant and antipsychotic drugs), confounding by indication seemed a distinct possibility. Third, in many analyses it seemed that exposure for as little as the equivalent of 1-90 days sufficed to increase the risk of dementia at a time interval of up to 20 years later; a causal mechanism here would need to have strong neurotoxic effects to result in the widespread brain changes that characterize dementia. Finally, the associations were almost uniformly stronger for vascular dementia than for Alzheimer's disease, making the identification of a causal mechanism even more challenging. Deprescribing anticholinergics to reduce state-dependent cognitive impairment, or to reduce the risk of delirium in vulnerable demographic and medical populations, is reasonable. Deprescribing anticholinergics to reduce the risk of future dementia is presently unwarranted.

PMID: 31390497 [PubMed - indexed for MEDLINE]

Association Between Drug Exposure and Occurrence of Parkinsonism in Korea: A Population-Based Case-Control Study.

Ann Pharmacother. 2019 11;53(11):1102-1110

Authors: Kim S, Cheon SM, Suh HS

Abstract
Background: Although drug-induced parkinsonism is reversible in most cases, some patients can suffer from persistent/recurrent symptoms. Therefore, prevention is the most efficient way to manage drug-induced parkinsonism. However, there is a paucity of studies exploring the relationship between parkinsonism and drug exposure. Objective: To examine the association between drug exposure and the risk of parkinsonism using Korean population-based data. Methods: We conducted a matched case-control study using the National Health Insurance Service-National Sample Cohort database. Cases and controls were defined as individuals with and without parkinsonism, respectively, between 2007 and 2013. Cases and controls were matched for sex, age group, income, type of insurance, and Charlson comorbidity index. Drug exposures, including propulsives, antipsychotics, and flunarizine, were identified at 1 year before the first date of parkinsonism and stratified by recency and cumulative dose. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% CIs. Results: We identified 5496 cases and 5496 controls. ORs for current use group of propulsives, antipsychotics, and flunarizine compared with those of the never use group were 2.812 (95% CI = 2.466-3.206), 3.009 (95% CI = 1.667-5.431), and 4.950 (95% CI = 2.711-9.037), respectively. ORs were greater in those more recently exposed and those exposed to higher cumulative doses. Conclusion and Relevance: At the population level, use of propulsives, antipsychotics, and flunarizine had a significant association with the increased risk of parkinsonism, depending on recency and cumulative dose. Drugs associated with parkinsonism should be used with careful monitoring to prevent drug-induced parkinsonism.

PMID: 31216861 [PubMed - indexed for MEDLINE]

Incidence of adverse reactions caused by first-line anti-tuberculosis drugs and treatment outcome of pulmonary tuberculosis patients in Morocco.

Infection. 2020 Feb;48(1):43-50

Authors: El Hamdouni M, Ahid S, Bourkadi JE, Benamor J, Hassar M, Cherrah Y

Abstract
PURPOSE: The treatment of tuberculosis is associated with a high incidence of adverse reactions with different degrees of severity. The aim of this study was to determine the incidence of adverse reactions caused by first-line anti-tuberculosis drugs and to evaluate the treatment outcome of TB patients in a large region of Morocco.
METHODS: It is a multi-centric observational cohort study conducted from January 01, 2014 to January 01, 2016. A questionnaire was established for data collection from clinical charts of TB patients. The study was carried out in all the 18 centers located in the Rabat-Salé-Kénitra region of Morocco where tuberculosis is treated. Adverse reactions are evaluated from the start of TB treatment until its end by a specialist clinician. The treatment outcomes are evaluated, and the definitions and classifications of these outcomes are defined according to World Health Organization guidelines.
RESULTS: Among a total number of 2532 patients treated for TB, the average age is 37.3 ± 16.4 years, 10.0% of patients produced adverse reactions. 7.4% of adverse reactions are gastrointestinal, 3.7% are cutaneous, 2.0% are hepatic, 1.14% are articular, 1.07% are immunoallergic, 0.7% are neuropsychiatric, and 0.1% are ocular. The treatment outcome of TB patients is 79.1% rate for successful treatment and 15.6% for unsuccessful treatment.
CONCLUSION: Adverse reactions caused by anti-TB drugs are frequent among patients with TB. These ADRs must be followed up by a closer monitoring during anti-TB treatment period. Treatment success outcome in our study is slightly lower than the success rate target of WHO of at least 85%.

PMID: 31165445 [PubMed - indexed for MEDLINE]