J Am Board Fam Med. 2022 May-Jun;35(3):610-628. doi: 10.3122/jabfm.2022.03.210334.

ABSTRACT

PURPOSE: To review the literature on medication safety in primary care in the electronic health record era.

METHODS: Included studies measured rates and outcomes of medication safety in patients whose prescriptions were written in primary care clinics with electronic prescribing. Four investigators independently reviewed titles and analyzed abstracts with dual-reviewer review for eligibility, characteristics, and risk of bias.

RESULTS: Of 1464 articles identified, 56 met the inclusion criteria. Forty-three studies were noninterventional and 13 included an intervention. The majority of the studies (30) used their own definition of error. The most common outcomes were potentially inappropriate prescribing/medications (PIPs), adverse drug events (ADEs), and potential prescribing omissions (PPOs). Most of the studies only included high-risk subpopulations (39), usually older adults taking > 4 medications. The rate of PIPs varied widely (0.19% to 98.2%). The rate of ADEs was lower (0.47% to 14.7%). There was poor correlation of PIP and PPO with documented ADEs leading to physical harm.

CONCLUSIONS: This literature is limited by its inconsistent and highly variable outcomes. The majority of medication safety studies in primary care were in high-risk populations and measured potential harms rather than actual harms. Applying algorithms to primary care medication lists significantly overestimates rate of actual harms.

PMID:35641040 | DOI:10.3122/jabfm.2022.03.210334

J Urol. 2022 May 31:101097JU0000000000002747. doi: 10.1097/JU.0000000000002747. Online ahead of print.

ABSTRACT

PURPOSE: The trial "OPTimized Instillation of Mitomycin for Bladder Cancer Treatment" (Optima II, clinicaltrials.gov: NCT03558503) was a Phase 2b trial evaluating a nonsurgical alternative as a primary treatment for non-muscle-invasive bladder cancer (NMIBC). Patients received six weekly instillations of UGN-102, a mitomycin-containing reverse thermal gel. This is the first study to report on patientreported side effects of UGN-102.

MATERIALS AND METHODS: Sixty-three patients enrolled in Optima II from 20 sites. Of these 63 patients, 44 were in the cohort completing a quarterly patient-reported outcome measure (PROM) assessing side effects. Changes in side effects were evaluated using the Wilcoxon signed rank test. Associations of 3month outcomes with demographic and clinical characteristics were examined with regression, controlling for baseline values. 10/44 patients (23%) were interviewed after the trial to understand tolerability for future patients making treatment decisions. Transcripts were double-coded using standard methods.

RESULTS: In the PROM cohort (n=44), 61% were men, 57% age 65+, and 89% non-Hispanic White. UGN-102 did not cause decrements in patient-reported urinary symptoms, bloating/flatulence, or malaise at the primary endpoint of 3 months. Sexual function mildly worsened. Future health worries improved. Demographics were not correlated with changes. Clinically, sexual function was correlated with new NMIBC, and bloating/flatulence were associated with TURBT within 12 months. In interviews, patients appreciated a nonsurgical alternative, would recommend the gel to other patients, and would choose the gel over surgery.

CONCLUSION: A nonsurgical, chemoablative gel (UGN-102) used as a primary treatment for NMIBC offers a more patient-centered therapeutic approach than standard treatments.

PMID:35640276 | DOI:10.1097/JU.0000000000002747

Int J Clin Oncol. 2022 May 30. doi: 10.1007/s10147-022-02179-9. Online ahead of print.

ABSTRACT

BACKGROUND: Regorafenib significantly improves overall survival in previously treated metastatic colorectal cancer patients. However, various toxicities, such as hand-foot skin reaction (HFSR), fatigue, and liver dysfunction have limited the use of regorafenib. These toxicities appear soon after treatment initiation. The ReDOS study demonstrated the effectiveness of a weekly dose-escalation therapy of regorafenib starting with a lower daily dose; however, its usefulness in Asian subjects is unknown. We conducted a phase II study to evaluate the safety and survival benefit of regorafenib dose-escalation therapy for Japanese patients.

METHODS: Patients with sufficient organ function, who had previously received more than two lines of chemotherapy were included. Regorafenib was started at 80 mg/day and escalated to 120 mg/day in Week 2 and 160 mg/day in Week 3, if no severe drug-related toxicities were observed. The primary endpoint was cancer progression-free survival (PFS). Tumor response and progression were assessed radiologically every 8 weeks. This study was registered in the University Hospital Medical Information Network (UMIN#UMIN000028933).

RESULTS: 57 patients were enrolled and all started regorafenib at 80 mg/day. 32 patients (56.1%) were subsequently escalated to 120 mg/day and 19 (33.3%) to 160 mg/day. Only 8 patients (14.0%) discontinued treatment because of adverse events. Median PFS was 1.9 months. Median overall survival was 8.9 months, the response rate was 0%, and the disease control rate was 31.6%. The most frequent adverse event greater than grade 3 was hypertension (19.3%), followed by HFSR (14.0%).

CONCLUSIONS: Regorafenib dose-escalation therapy is well tolerated with PFS-like regorafenib standard therapy.

PMID:35635652 | DOI:10.1007/s10147-022-02179-9

Int J Mol Sci. 2022 May 15;23(10):5515. doi: 10.3390/ijms23105515.

ABSTRACT

Immunotherapy is a milestone in the treatment of poor-prognosis pediatric acute lymphoblastic leukemia (ALL) and is expected to improve treatment outcomes and reduce doses of conventional chemotherapy without compromising the effectiveness of the therapy. However, both chemotherapy and immunotherapy cause side effects, including neurological ones. Acute neurological complications occur in 3.6-11% of children treated for ALL. The most neurotoxical chemotherapeutics are L-asparaginase (L-ASP), methotrexate (MTX), vincristine (VCR), and nelarabine (Ara-G). Neurotoxicity associated with methotrexate (MTX-NT) occurs in 3-7% of children treated for ALL and is characterized by seizures, stroke-like symptoms, speech disturbances, and encephalopathy. Recent studies indicate that specific polymorphisms in genes related to neurogenesis may have a predisposition to MTX toxicity. One of the most common complications associated with CAR T-cell therapy is immune effector cell-associated neurotoxicity syndrome (ICANS). Mechanisms of neurotoxicity in CAR T-cell therapy are still unknown and may be due to disruption of the blood-brain barrier and the effects of elevated cytokine levels on the central nervous system (CNS). In this review, we present an analysis of the current knowledge on the mechanisms of neurotoxicity of standard chemotherapy and the targeted therapy in children with ALL.

PMID:35628334 | PMC:PMC9146746 | DOI:10.3390/ijms23105515

Int J Mol Sci. 2022 May 10;23(10):5332. doi: 10.3390/ijms23105332.

ABSTRACT

Gastrointestinal toxicity (GIT) is a debilitating side effect of Irinotecan (CPT-11) and limits its clinical utility. Gut dysbiosis has been shown to mediate this side effect of CPT-11 by increasing gut bacterial β-glucuronidase (GUSB) activity and impairing the intestinal mucosal barrier (IMB). We have recently shown the opposing effects of omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) on the gut microbiome. We hypothesized that elevated levels of tissue n-3 PUFA with a decreased n-6/n-3 PUFA ratio would reduce CPT-11-induced GIT and associated changes in the gut microbiome. Using a unique transgenic mouse (FAT-1) model combined with dietary supplementation experiments, we demonstrate that an elevated tissue n-3 PUFA status with a decreased n-6/n-3 PUFA ratio significantly reduces CPT-11-induced weight loss, bloody diarrhea, gut pathological changes, and mortality. Gut microbiome analysis by 16S rRNA gene sequencing and QIIME2 revealed that improvements in GIT were associated with the reduction in the CPT-11-induced increase in both GUSB-producing bacteria (e.g., Enterobacteriaceae) and GUSB enzyme activity, decrease in IMB-maintaining bacteria (e.g., Bifidobacterium), IMB dysfunction and systemic endotoxemia. These results uncover a host-microbiome interaction approach to the management of drug-induced gut toxicity. The prevention of CPT-11-induced gut microbiome changes by decreasing the tissue n-6/n-3 PUFA ratio could be a novel strategy to prevent chemotherapy-induced GIT.

PMID:35628140 | PMC:PMC9140600 | DOI:10.3390/ijms23105332

J Clin Pharm Ther. 2022 May 28. doi: 10.1111/jcpt.13696. Online ahead of print.

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Erythropoiesis-stimulating agent (ESA) hyporesponsiveness is an important cause for the undertreatment of anaemia. A decrease in haemoglobin (Hb) levels was observed during the initial stage of the conversion from ESA to roxadustat. The study aims to investigate the effectiveness and safety of adding roxadustat to an ESA for the treatment of ESA-hyporesponsive anaemia in patients on peritoneal dialysis (PD).

METHODS: Patients on PD with ESA-hyporesponsive anaemia were enrolled from January 2020 to April 2020 with a 24-week follow-up period. Patients were treated with roxadustat at a starting dose of 50 or 100 mg thrice weekly without changing the ESA dose. Roxadustat and ESA dose adjustments were made as needed to maintain Hb levels within 11.0 to 13.0 g/dl. Efficacy outcomes and safety were assessed.

RESULTS AND DISCUSSION: Nine patients were recruited in the study. Both the cumulative responsive rate and maintenance rate of Hb > 11 g/dl were 100%. Six patients required ESA dose reduction from ≥15,000 UI/week to ≤7000 IU/week at week 24. No drug-related severe adverse events were observed in this study.

WHAT IS NEW AND CONCLUSION: The addition of roxadustat effectively and smoothly corrected anaemia in patients who were hyporesponsive to ESA, and permitted reduction of the ESA dose.

PMID:35633100 | DOI:10.1111/jcpt.13696

J Clin Med. 2022 May 17;11(10):2820. doi: 10.3390/jcm11102820.

ABSTRACT

BACKGROUND: Pemafibrate is a novel selective peroxisome proliferator-activated receptor-α modulator, which was demonstrated to reduce serum triglyceride level with few drug-related adverse events in phase II and III clinical trials. However, its clinical implication in real-world practice remains unknown. Triglyceride/HDL-cholesterol ratio is a surrogate of small dense LDL-cholesterol, which is a newly proposed cardiovascular risk factor independent of LDL-cholesterol levels.

METHODS: Consecutive patients who received pemafibrate between April 2020 and September 2021 and continued therapy for at least 3 months were included in this retrospective analysis. The primary outcome was the trend in triglyceride/HDL-cholesterol ratio during the 3-month treatment period. The change in cardiovascular event rate between the one-year pre-treatment period and the on-treatment period was also analyzed.

RESULTS: A total of 19 patients (median age 63 years, 74% men) were included and continued pemafibrate therapy for 3 months without any drug-related adverse events. Sixteen were add-on and three were conversions from other fibrates. Triglyceride/HDL-cholesterol ratio decreased significantly from 5.85 (4.19, 16.1) to 3.14 (2.39, 4.62) (p < 0.001). The cardiovascular event rate decreased significantly from 0.632 events/year to 0.080 events/year (p < 0.001).

CONCLUSIONS: Pemafibrate therapy might have the potential to lower triglyceride/HDL-cholesterol ratio and decrease cardiovascular events.

PMID:35628945 | DOI:10.3390/jcm11102820

Clin Nutr ESPEN. 2022 Jun;49:678. doi: 10.1016/j.clnesp.2022.02.117. Epub 2022 Mar 4.

NO ABSTRACT

PMID:35623876 | PMC:PMC8894684 | DOI:10.1016/j.clnesp.2022.02.117

Actas Dermosifiliogr. 2022 Apr;113(4):376-387. doi: 10.1016/j.ad.2021.09.005. Epub 2021 Dec 31.

ABSTRACT

Immune checkpoint inhibitors (ICIs) have significantly advanced the treatment of cancer. They are not, however, free of adverse effects. These effects are called immune-related adverse events (irAEs) and often involve the skin. Most of the information on cutaneous irAEs comes from clinical practice. We therefore conducted a thorough review of the characteristics of cutaneous irAEs, recommendations for treatment, and their association with prognosis. The most common events are exanthema, pruritus, vitiligo, and hair loss, although ICIs can cause a wide range of cutaneous dermatoses. The reported association observed between certain reactions and a favorable response to cancer treatment should be interpreted with caution. Dermatologists should be involved in the multidisciplinary care of patients being treated with ICIs as they have an essential role in the diagnosis and treatment of cutaneous irAEs.

PMID:35623728 | DOI:10.1016/j.ad.2021.09.005

J Patient Saf. 2022 Jun 1;18(4):318-324. doi: 10.1097/PTS.0000000000000934.

ABSTRACT

OBJECTIVES: This study aimed to compare assessment methods to determine adverse drug reactions (ADRs) at nonelective hospital admission in pediatric patients, to investigate the interrater reliability of assessment methods in pediatric care, and to analyze symptoms related to ADRs and (suicidal) drug intoxications.

METHODS: For 1 year, the medical records of nonelective patients admitted to a university pediatric department were evaluated for potential ADRs using 4 assessments methods by 1 experienced rater. Krippendorff α was calculated from a sample of 14 patients evaluated by 4 experienced raters to determine interrater reliability.

RESULTS: In 1831 nonelective hospital admissions, 63.4% (1161 of 1831) of patients had received at least one drug before admission. We found a potential causal relationship between drugs and symptoms documented at admission and thus potential ADRs according to Naranjo in 23.3% (271 of 1161) of those patients, World Health Organization - Uppsala Monitoring Centre (WHO-UMC) in 22.5% (261 of 1161), Koh in 21.7% (252 of 1161), and Begaud in 16.5% (192 of 1161). The probability rating of the potential causal relationships varied considerably between the methods (Naranjo-Begaud, P < 0.01; Naranjo-Koh, P < 0.001; Koh-Begaud, P < 0.01; Begaud-WHO-UMC, P < 0.01). Acceptable interrater reliability (α ≥ 0.667) was only obtained for WHO-UMC (α = 0.7092). The most frequently identified definite ADR was sedation in 1.5% of all nonelective patients with medication before hospital admission. In 1.2% (22 of 1831) of all nonelective admissions, we found drug intoxications with suicidal intent.

CONCLUSIONS: The assessment methods showed a high variability in the determination of a potential causal relationship between drug and documented symptom, in the classification of the probability of ADRs, and suboptimal interrater reliability. Thus, their feasibility in pediatric patients is limited.

PMID:35617590 | DOI:10.1097/PTS.0000000000000934

JAMA Netw Open. 2022 May 2;5(5):e2214153. doi: 10.1001/jamanetworkopen.2022.14153.

ABSTRACT

IMPORTANCE: Nonguideline antibiotic prescribing for the treatment of pediatric infections is common, but the consequences of inappropriate antibiotics are not well described.

OBJECTIVE: To evaluate the comparative safety and health care expenditures of inappropriate vs appropriate oral antibiotic prescriptions for common outpatient pediatric infections.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included children aged 6 months to 17 years diagnosed with a bacterial infection (suppurative otitis media [OM], pharyngitis, sinusitis) or viral infection (influenza, viral upper respiratory infection [URI], bronchiolitis, bronchitis, nonsuppurative OM) as an outpatient from April 1, 2016, to September 30, 2018, in the IBM MarketScan Commercial Database. Data were analyzed from August to November 2021.

EXPOSURES: Inappropriate (ie, non-guideline-recommended) vs appropriate (ie, guideline-recommended) oral antibiotic agents dispensed from an outpatient pharmacy on the date of infection.

MAIN OUTCOMES AND MEASURES: Propensity score-weighted Cox proportional hazards models were used to estimate hazards ratios (HRs) and 95% CIs for the association between inappropriate antibiotic prescriptions and adverse drug events. Two-part models were used to calculate 30-day all-cause attributable health care expenditures by infection type. National-level annual attributable expenditures were calculated by scaling attributable expenditures in the study cohort to the national employer-sponsored insurance population.

RESULTS: The cohort included 2 804 245 eligible children (52% male; median [IQR] age, 8 [4-12] years). Overall, 31% to 36% received inappropriate antibiotics for bacterial infections and 4% to 70% for viral infections. Inappropriate antibiotics were associated with increased risk of several adverse drug events, including Clostridioides difficile infection and severe allergic reaction among children treated with a nonrecommended antibiotic agent for a bacterial infection (among patients with suppurative OM, C. difficile infection: HR, 6.23; 95% CI, 2.24-17.32; allergic reaction: HR, 4.14; 95% CI, 2.48-6.92). Thirty-day attributable health care expenditures were generally higher among children who received inappropriate antibiotics, ranging from $21 to $56 for bacterial infections and from -$96 to $97 for viral infections. National annual attributable expenditure estimates were highest for suppurative OM ($25.3 million), pharyngitis ($21.3 million), and viral URI ($19.1 million).

CONCLUSIONS AND RELEVANCE: In this cohort study of children with common infections treated in an outpatient setting, inappropriate antibiotic prescriptions were common and associated with increased risks of adverse drug events and higher attributable health care expenditures. These findings highlight the individual- and national-level consequences of inappropriate antibiotic prescribing and further support implementation of outpatient antibiotic stewardship programs.

PMID:35616940 | DOI:10.1001/jamanetworkopen.2022.14153

Pediatr Int. 2022 Jan;64(1):e15126. doi: 10.1111/ped.15126.

ABSTRACT

BACKGROUND: Distinguishing allergic reactions from non-allergic type B adverse drug reactions (ADRs) to antibiotics is challenging, particularly in children, because we lack epidemiological information that can be used in primary care situations. This study aimed to investigate the characteristics of type B ADRs to antibiotics and antibiotic allergy (AA) in previously healthy children.

METHODS: This was a retrospective cohort study of previously healthy children admitted for treating urinary tract infections over a 10 year period. The primary outcome was the frequency of type B ADRs and AAs that were assessed by pediatricians. Secondary outcomes include demographic data about patients' backgrounds, infections, treatments, ADRs, and action against ADRs. All the data were collected via patients' medical records.

RESULTS: Out of 791 participants, type B ADRs were reported in 77 children (9.7%), and AA labeling was performed in six children (0.8%). Physicians assessed 30.4% of type B ADRs as severe or life-threatening symptoms. All patients were discharged without long-term complications. Physicians detected the primary cause (individual patient host factors or environmental risks) in 39 cases of type B ADRs.

CONCLUSION: Type B ADRs to antibiotics were frequently reported even in previously healthy children. Physicians should use appropriate techniques (e.g., specialist consulting and skin testing) when they suspect that a type B ADR might be an AA. Labeling and de-labeling programs and tools for type B ADRs related to antibiotics should be implemented to prevent the mislabeling of AA.

PMID:35616171 | DOI:10.1111/ped.15126

J Nepal Health Res Counc. 2022 Mar 13;19(4):762-766. doi: 10.33314/jnhrc.v19i04.3714.

ABSTRACT

BACKGROUND: Drug is a double-edged sword. Though important, Adverse Drug Reactions under-reporting is real and is mainly due to lack of awareness. No published research has ever evaluated the perspective of third year medical students towards Adverse Drug Reactions reporting. The objective of the study was to evaluate awareness of Adverse Drug Reactions and its reporting among Third-year Medical Students of BP Koirala Institute of Health Science.

METHODS: It was a descriptive cross-sectional questionnaire-based survey using google form conducted between 09/01/2020 to 09/28/2020. Any consenting third-year medical student of BP Koirala Institute of Health Science was eligible. Descriptive analysis of the data was performed using Microsoft Excel. Ethical clearance was obtained from Departmental-Research-Unit which is under IRC.

RESULTS: Out of 80 eligible students, 79(98.75%) participated in the survey. 31.6(25%) had reported Adverse Drug Reactions. 36.7(29%) were aware of National Adverse Drug Reactions monitoring service. 12.7(10%) were aware of BPKIHS ADR monitoring. Again, 35(49.30%) were familiar with Adverse Drug Reactions to a particular drug whereas 29(40.85%) and 28(39.44%) were even familiar with Adverse Drug Reactions to a new product and Adverse Drug Reactions of serious (life or organ threatening) nature respectively. Regarding barriers to Adverse Drug Reactions reporting, 64(83.12%) were uncertain how to report; 39(50.65%) were unaware of existing National ADR system and 33(42.86) could not decide if it was an Adverse Drug Reactions. Regarding recommendations to improve Adverse Drug Reactions reporting, 73(94.81%) recommended education and training, 57(74.03%) stressed on collaboration among health professionals; 52(67.53%) said Adverse Drug Reactions reporting should be professional obligation whereas 51(66.23%) highlighted feedback from Monitoring Centers.

CONCLUSIONS: We evaluated the awareness of Adverse Drug Reactions and its reporting among third-year medical Students of the institute which was relatively poor compared to other study population like doctors and pharmacists.

PMID:35615834 | DOI:10.33314/jnhrc.v19i04.3714

J Patient Saf. 2022 Jun 1;18(4):325-330. doi: 10.1097/PTS.0000000000000921. Epub 2021 Dec 17.

ABSTRACT

OBJECTIVES: This study aimed to investigate how many preventable adverse events (PAEs) and near misses are identified through the methods structured record review, Web-based incident reporting (IR), and daily safety briefings, and to distinguish the type of events identified by each method.

METHODS: One year of retrospective data from 2017 were collected from one patient cohort in a 422-bed acute care hospital. Preventable adverse events and near misses were collected from the hospital's existing resources and presented descriptively as number per 1000 patient-days.

RESULTS: The structured record review identified 19.9 PAEs; the IR system, 3.4 PAEs; and daily safety briefings, 5.4 PAEs per 1000 patient-days. The most common PAEs identified by the record review method were drug-related PAEs, pressure ulcers, and hospital-acquired infections. The most common PAEs identified by the IR system and daily safety briefings were fall injury and pressure ulcers, followed by skin/superficial vessel injuries for the IR system and hospital-acquired infections for the daily safety briefings. Incident reporting and daily safety briefings identified 7.8 and 31.9 near misses per 1000 patient-days, respectively. The most common near misses were related to how care is organized.

CONCLUSIONS: The different methods identified different amounts and types of PAEs and near misses. The study supports that health care organizations should adopt multiple methods to get a comprehensive review of the number and type of events occurring in their setting. Daily safety briefings seem to be a particularly suitable method for assessing an organization's inherent security and may foster a nonpunitive culture.

PMID:35617591 | DOI:10.1097/PTS.0000000000000921

J Acquir Immune Defic Syndr. 2022 May 26. doi: 10.1097/QAI.0000000000003024. Online ahead of print.

ABSTRACT

BACKGROUND: There are limited data comparing the efficacy and safety of raltegravir and dolutegravir to that of efavirenz in HIV-1/tuberculosis (TB) co-infected patients.

METHODS: We conducted a 10-year retrospective study in four centers in France. We included all HIV-1/tuberculosis co-infected patients starting antiretroviral therapy (ART) with a rifampicin-based regimen, with a plasma HIV RNA level (VL)>1000 copies/mL. The primary endpoint was the proportion of patients with virological success i.e. with VL<50 copies/mL at W48 using an Intention-To-Treat (ITT) analysis, using last-observation-carried-forward to impute missing data. We also assessed ART safety, analyzing treatment discontinuation for adverse events.

RESULTS: Between 2010 and 2020, 117 patients were included. Thirty-nine (33.3%) were treated with raltegravir and two nucleoside reverse transcriptase inhibitors (NRTIs), 19 (16.2%) with dolutegravir (and two NRTIs) and 59 (50.4%) with efavirenz (and two NRTIs). At W48, the primary endpoint was achieved in 24 patients (61.5%) in the raltegravir group, in 12 (63.2%) in the dolutegravir group, and in 41 (69.5%) in the efavirenz group using an ITT analysis (p=0.68). Emergence of drug resistance in patients with virological failure, defined as a VL>50 copies/mL, was observed in three patients with efavirenz and one patient with raltegravir. Rate of treatment discontinuation for drug-related adverse events was 10.3%, 10.6%, 16.9% for raltegravir, dolutegravir and efavirenz respectively (p=0.67).

CONCLUSION: In this retrospective cohort study, raltegravir and dolutegravir yielded similar efficacy and safety results to efavirenz for the treatment of HIV-1/TB co-infected patients.

PMID:35616997 | DOI:10.1097/QAI.0000000000003024

Dermatol Ther. 2022 May 25:e15599. doi: 10.1111/dth.15599. Online ahead of print.

ABSTRACT

Although secukinumab has demonstrated high efficacy and favorable safety in moderate-to-severe psoriasis and psoriatic arthritis, patients developing adverse events of special interest (AESI) were reported increasingly in real-world practice. A systematic literature search of the PubMed database was conducted to identify clinical studies or case reports on secukinumab-induced AESI. More than 1077 patients (aged 18-74 years) from 55 studies were reported to have 24 AESI 3 days to 96 weeks after secukinumab treatment. The four most common AESI was inflammatory bowel disease (n > 1000), eczematous drug eruption (n > 30), drug-associated vasculitis (n = 8), and drug-induced lupus erythematosus (n = 4). Most of these AESI were only mild to moderately severe and resolved after secukinumab discontinuation without or with symptomatic treatment. Secukinumab has the potential to develop a number of AESI by probably dysregulating the different expression of polar T-cell axes (Th1, Th2, Th17, Th22, and/or Treg) and driving various cytokines in some patients. Physicians should be aware of these AESI for timely diagnosis and proper treatment. This article is protected by copyright. All rights reserved.

PMID:35614844 | DOI:10.1111/dth.15599

BMJ Open. 2022 May 24;12(5):e054584. doi: 10.1136/bmjopen-2021-054584.

ABSTRACT

OBJECTIVES: To examine the socioeconomic and demographic drivers associated with polypharmacy (5-9 medicines), extreme polypharmacy (9-20 medicines) and increased medication count.

DESIGN, SETTING AND PARTICIPANTS: A total of 5509 participants, from two waves of the English North West Coast, Household Health Survey were analysed OUTCOME MEASURES: Logistic regression modelling was used to find associations with polypharmacy and extreme polypharmacy. A negative binomial regression identified associations with increased medication count. Descriptive statistics explored associations with medication management.

RESULTS: Age and number of health conditions account for the greatest odds of polypharmacy. ORs (95% CI) were greatest for those aged 65+ (3.87, 2.45 to 6.13) and for those with ≥5 health conditions (10.87, 5.94 to 19.88). Smaller odds were seen, for example, in those prescribed cardiovascular medications (3.08, 2.36 to 4.03), or reporting >3 emergency attendances (1.97, 1.23 to 3.17). Extreme polypharmacy was associated with living in a deprived neighbourhood (1.54, 1.06 to 2.26). The greatest risk of increased medication count was associated with age, number of health conditions and use of primary care services. Relative risks (95% CI) were greatest for those aged 65+ (2.51, 2.23 to 2.82), those with ≥5 conditions (10.26, 8.86 to 11.88) or those reporting >18 primary care visits (2.53, 2.18 to 2.93). Smaller risks were seen in, for example, respondents with higher levels of income deprivation (1.35, 1.03 to 1.77). Polypharmic respondents were more likely to report medication management difficulties associated with taking more than one medicine at a time (p<0.001). Furthermore, individuals reporting a mental health condition, were significantly more likely to consistently report difficulties managing their medication (p<0.001).

CONCLUSION: Age and number of health conditions are most associated with polypharmacy. Thus, delaying or preventing the onset of long-term conditions may help to reduce polypharmacy. Interventions to reduce income inequalities and health inequalities generally could support a reduction in polypharmacy, however, more research is needed in this area. Furthermore, increased prevention and support, particularly with medication management, for those with mental health conditions may reduce adverse medication effects.

PMID:35613765 | DOI:10.1136/bmjopen-2021-054584

Stud Health Technol Inform. 2022 May 25;294:721-722. doi: 10.3233/SHTI220570.

ABSTRACT

In this article, we present a methodology and a tool for extracting and analyzing information, reported by a social media monitor, of people who have taken drugs to treat Covid-19 and the adverse effects encountered.

PMID:35612191 | DOI:10.3233/SHTI220570

Stud Health Technol Inform. 2022 May 25;294:450-454. doi: 10.3233/SHTI220499.

ABSTRACT

Adverse drug reactions (ADRs) for all drugs in Europe are described in the legally approved Summary of Product Characteristics (SmPC). An overview of all ADRs of the patients' drug list can support healthcare staff to link patient symptoms to possible ADRs. We review the possibilities and challenges to extract ADR information from SmPCs and present the development of our semi-automated procedure for extraction of ADRs from the tabulated section of the SmPCs to create a database, named Bikt, which is regularly updated and used at point of care in Sweden. The existence of five major table formats for ADRs used in the SmPCs required the development of different parsing scripts. Manual checks for correctness for all content has to be performed. The quality of extraction was investigated for all SmPCs by measuring precision, recall and F1 scores (i.e. the weighted harmonic mean of precision and recall) and compared with other methods published. We conclude that it is possible to semi-automatically extract ADR information from SmPCs. However, clear technical and content guidelines and standards for ADR tables and terms from drug registration authorities would lead to improved extraction and usability of ADR information at point of care.

PMID:35612120 | DOI:10.3233/SHTI220499

Stud Health Technol Inform. 2022 May 25;294:83-87. doi: 10.3233/SHTI220401.

ABSTRACT

Adverse drug reaction is a major public health issue. The increasing availability of medico-administrative databases offers major opportunities to detect real-life pharmacovigilance signals. We have recently adapted a pharmacoepidemiological method to the large dimension, the WCE (Weigthed Cumulative Exposure) statistical model, which makes it possible to model the temporal relationship between the prescription of a drug and the appearance of a side effect without any a priori hypothesis. Unfortunately, this method faces a computational time problem. The objective of this paper is to describe the implementation of the WCE statistical model using Graphics Processing Unit (GPU) programming as a tool to obtain the spectrum of adverse drug reactions from medico-administrative databases. The process is divided into three steps: pre-processing of care pathways using the Python library Panda, calculation of temporal co-variables using the Python library "KeOps", estimation of the model parameters using the Python library "PyTorch" - standard in deep learning. Programming the WCE method by distributing the heaviest portions (notably spline calculation) on the GPU makes it possible to accelerate the time required for this method by 1000 times using a computer graphics card and up to 10,000 times with a GPU server. This implementation makes it possible to use WCE on all the drugs on the market to study their spectrum of adverse effects, to highlight new vigilance signals and thus to have a global vigilance tool on medico-administrative database. This is a proof of concept for the use of this technology in epidemiology.

PMID:35612021 | DOI:10.3233/SHTI220401