Eur J Heart Fail. 2023 Jan 16. doi: 10.1002/ejhf.2772. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The aim of the SCIENCE trial was to investigate whether a single treatment with direct intramyocardial injections of adipose tissue derived mesenchymal stromal cells (CSCC_ASCs) was safe and improved cardiac function in patients with chronic ischemic heart failure with reduced ejection fraction (HFrEF).

METHODS: The study was a European multi-centre double-blinded placebo-controlled phase II trial using allogeneic CSCC_ASCs from healthy donors or placebo (2:1 randomization). Main inclusion criteria were NYHA II-III, left ventricular ejection fraction (LVEF) < 45%, and NT-ProBNP levels>300 pg/mL. CSCC_ASCs or placebo (isotonic saline) were injected directly into viable myocardium. Primary endpoint was change in left ventricular end-systolic volume (LVESV) at 6 months follow up measured by echocardiography.

RESULTS: A total of 133 symptomatic HFrEF patients were included. The treatment was safe without any drug-related severe adverse events or difference in cardiac related adverse events during a 3-years follow-up period. There were no significant differences between the groups during follow up in LVESV (0.3 ± 5.0 ml, P = 0.945), nor in secondary endpoints left ventricular end-diastolic volume (-2.0 ± 6.0 ml, P = 0.736) and LVEF (-1.6 ± 1.0%, P = 0.119). The NYHA classification improved slightly within the first year in both groups without any difference between groups. There were no changes in 6-Minute Walk Test, NT-ProBNP, CRP or quality-of-life the first year in any of the two groups.

CONCLUSION: The SCIENCE trial demonstrated safety of intramyocardial allogeneic CSCC_ASC therapy in patients with chronic HFrEF. However, it was not possible to improve the predefined endpoints and induce restoration of cardiac function or clinical symptoms.

PMID:36644821 | DOI:10.1002/ejhf.2772

Prim Care Companion CNS Disord. 2023 Jan 10;25(1):21r03223. doi: 10.4088/PCC.21r03223.

ABSTRACT

Objective: US demographic trends show an increasing proportion of adults aged > 65 years old, approximately 1 million of whom are living with an opioid use disorder (OUD). OUD may be particularly problematic in this age group due to age-related pain syndromes and comorbidities that increase the risk of side effects, overdose, and death. The objective of this review was to assess the safety and efficacy of medications for OUD (MOUD) in the elderly.

Data Sources: A systematic search of the literature in PubMed, CINAHL, MEDLINE, Embase, and Cochrane Library databases was conducted from January 1992 through October 2021. The following terms were used: elderly, older adults, opioid use disorder, opioid dependence, buprenorphine, methadone, and medication-assisted treatment.

Study Selection: The search yielded 633 results. After following PRISMA guidelines and careful manual exclusion, 13 studies were selected for the review. No studies examining use of buprenorphine were identified for MOUD.

Results: The application of methadone for MOUD in the elderly shows that use is limited by preexisting conditions such as cardiac conduction abnormalities, which are more prevalent in the elderly than in the general population. Buprenorphine and naltrexone have been documented to have fewer interactions and potentially lethal adverse effects compared to methadone.

Conclusion: Future studies should focus on the application of buprenorphine or naltrexone for MOUD in the elderly.

PMID:36638540 | DOI:10.4088/PCC.21r03223

Pulmonology. 2023 Jan 11:S2531-0437(22)00262-8. doi: 10.1016/j.pulmoe.2022.11.004. Online ahead of print.

ABSTRACT

BACKGROUND: The carbonic anhydrase inhibitor acetazolamide stimulates ventilation through metabolic acidosis mediated by renal bicarbonate excretion. In animal models, acetazolamide attenuates acute hypoxia-induced pulmonary hypertension (PH), but its efficacy in treating patients with PH due to pulmonary vascular disease (PVD) is unknown.

METHODS: 28 PVD patients (15 pulmonary arterial hypertension, 13 distal chronic thromboembolic PH), 13 women, mean±SD age 61.6±15.0 years stable on PVD medications, were randomised in a double-blind crossover protocol to 5 weeks acetazolamide (250mg b.i.d) or placebo separated by a ≥2 week washout period. Primary endpoint was the change in 6-minute walk distance (6MWD) at 5 weeks. Additional endpoints included safety, tolerability, WHO functional class, quality of life, arterial blood gases, and hemodynamics (by echocardiography).

RESULTS: Acetazolamide had no effect on 6MWD compared to placebo (treatment effect: mean change [95%CI] -18 [-40 to 4]m, p=0.102) but increased arterial blood oxygenation through hyperventilation induced by metabolic acidosis. Other measures including pulmonary hemodynamics were unchanged. No severe adverse effects occurred, side effects that occurred significantly more frequently with acetazolamide vs. placebo were change in taste (22/0%), paraesthesia (37/4%) and mild dyspnea (26/4%).

CONCLUSIONS: In patients with PVD, acetazolamide did not change 6MWD compared to placebo despite improved blood oxygenation. Some patients reported a tolerable increase in dyspnoea during acetazolamide treatment, related to hyperventilation, induced by the mild drug-induced metabolic acidosis. Our findings do not support the use of acetazolamide to improve exercise in patients with PVD at this dosing.

GOV IDENTIFIER: NCT02755298.

PMID:36639329 | DOI:10.1016/j.pulmoe.2022.11.004

Brain Inj. 2023 Jan 13:1-10. doi: 10.1080/02699052.2023.2165156. Online ahead of print.

ABSTRACT

BACKGROUND: While systematic reviews have examined medication effectiveness for post-traumatic headache (PTH), they have not assessed tolerability.

OBJECTIVE: To conduct a scoping review to characterize the adverse effects of pharmacotherapy for PTH.

METHODS: CINAHL, CMA Infobase, Cochrane Library, Embase, Epistemonikos, MEDLINE, PEDro, PsycInfo, Scopus, SportDiscus, TRIP and the University of York Center for Reviews and Dissemination were searched. Studies meeting these criteria were included 1) English language, 2) involved humans with traumatic brain injury (TBI), 3) a medication for PTH was administered and 4) reported tolerability outcomes. Author(s), publication year, country of origin, study design, sample demographics, medication type, comparator, dose, treatment duration, adverse effect type and rate, discontinuation rate, and effectiveness outcomes were extracted.

RESULTS: The search yielded 2941 records; 11 studies were included (n = 324 subjects). All subjects had mild TBI except for one with moderate TBI. The following therapies were examined 1) abortive (dihydroergotamine N = 1; metoclopramide N = 1; indomethacin N = 3), 2) prophylactic (divalproex sodium N = 1; amantadine N = 1; erenumab N = 2; amitriptyline N = 2). No serious adverse effects occurred. Observed adverse effects overlap with common symptoms of TBI.

CONCLUSION: The unique needs of people with TBI must be considered when instituting pharmacotherapy. More studies specifically evaluating medication tolerability in PTH are needed.

PMID:36637191 | DOI:10.1080/02699052.2023.2165156

J Chem Inf Model. 2023 Jan 23;63(2):474-483. doi: 10.1021/acs.jcim.2c01210. Epub 2023 Jan 12.

ABSTRACT

Predicting the novel effects of drugs based on information about approved drugs can be regarded as a recommendation system. Matrix factorization is one of the most used recommendation systems, and various algorithms have been devised for it. A literature survey and summary of existing algorithms for predicting drug effects demonstrated that most such methods, including neighborhood regularized logistic matrix factorization, which was the best performer in benchmark tests, used a binary matrix that considers only the presence or absence of interactions. However, drug effects are known to have two opposite aspects, such as side effects and therapeutic effects. In the present study, we proposed using neighborhood regularized bidirectional matrix factorization (NRBdMF) to predict drug effects by incorporating bidirectionality, which is a characteristic property of drug effects. We used this proposed method for predicting side effects using a matrix that considered the bidirectionality of drug effects, in which known side effects were assigned a positive (+1) label and known treatment effects were assigned a negative (-1) label. The NRBdMF model, which utilizes drug bidirectional information, achieved enrichment of side effects at the top and indications at the bottom of the prediction list. This first attempt to consider the bidirectional nature of drug effects using NRBdMF showed that it reduced false positives and produced a highly interpretable output.

PMID:36635231 | DOI:10.1021/acs.jcim.2c01210

Malar J. 2023 Jan 13;22(1):17. doi: 10.1186/s12936-023-04443-3.

ABSTRACT

BACKGROUND: Mass drug administration (MDA) with primaquine (PQ) is being considered for accelerating Plasmodium vivax elimination in remaining active foci. This study aimed to determine the acceptability of MDA with PQ in malaria endemic villages in a malarious setting in the South of Thailand undergoing MDA with PQ.

METHODS: A cross-sectional mixed-methods approach was conducted in seven malaria endemic villages where MDA with PQ was implemented. The data were collected from community villagers and health workers using structured questionnaires, in-depth interviews, and focus group discussions. Descriptive statistics and logistic regression models were used for quantitative data analysis. Thematic analysis was applied for qualitative data.

RESULTS: Among a total of 469 participants from the MDA villages, 293 participants were eligible for MDA with PQ and 79.86% (234) completed 14-days of PQ. The logistic regressions indicated that males (adjusted odds ratio: 2.52 [95% confidence interval: 1.33-4.81]) and those who are farmers (2.57 [1.12-5.90]) were most likely to participate in the MDA. Among 293 participants in the post-MDA study, 74.06% had originally agreed to participate in the MDA with PQ while 25.94% had originally reported not wanting to participate in the MDA. Of those who originally reported being willing to participate in the MDA, 71.23% followed through with participation in the first or second round. Conversely, 93.24% of those who originally reported not being willing to participate in the MDA did in fact participate in the MDA. Factors contributing to higher odds of agreeing to participate and following through with participation included being male (1.98 [1.06-3.69]) and correctly responding that malaria is preventable (2.32 [1.01-5.35]) with some differences by village. Five key themes emerged from the qualitative analyses: concern about side effects from taking PQ; disbelief that malaria could be eliminated in this setting; low overall concern about malaria infections; misunderstandings about malaria; and a general need to tailor public health efforts for this unique context.

CONCLUSION: While the reported likelihood of participating in MDA was high in this setting, actual follow-through was relatively moderate, partially because of eligibility (roughly 71% of those in the follow-up survey who originally agreed to participate actually followed through with participation). One of the largest concerns among study participants was PQ-related side effects-and these concerns likely heavily influenced participant adherence to the MDA. The results of this study can be used to tailor future MDAs, or other public health interventions, in this and potentially other similar settings.

PMID:36635642 | PMC:PMC9837991 | DOI:10.1186/s12936-023-04443-3

PLoS One. 2023 Jan 12;18(1):e0280224. doi: 10.1371/journal.pone.0280224. eCollection 2023.

ABSTRACT

OBJECTIVE: Side-effects of medications cause xerostomia. There have been cases where a medication has been discontinued owing to its severe side-effects. Therefore, the xerostomia must be treated to ensure that the primary disease is managed effectively. This study analyzed the actual status of patients with medication-induced xerostomia and investigates factors associated with its improvement.

METHODS: This study assessed 490 patients diagnosed with medication-induced xerostomia who had an unstimulated salivary flow of ≤0.1 mL/min and received treatment for xerostomia at a xerostomia clinic. Patient age, sex, medical history, medications used, disease duration of xerostomia, and psychological disorders were recorded. The anticholinergic burden was assessed using the Anticholinergic Cognitive Burden scale. The unstimulated salivary flow was measured by the spitting method. According to their symptoms and diagnoses, the patients were introduced to oral lubricants, instructed on how to perform massage, and prescribed Japanese herbal medicines, and sialogogues. Factors associated with the subjective improvement of xerostomia and objective changes in the salivary flow rate were recorded at six months.

RESULTS: Xerostomia improved in 338 patients (75.3%). The improvement rate was significantly lower in patients with psychiatric disorders (63.6%) (P = 0.009). The improvement rate decreased as more anticholinergics were used (P = 0.018). However, xerostomia improved in approximately 60% of patients receiving three or more anticholinergics. The unstimulated salivary flow increased significantly more in patients who reported an improvement of xerostomia (0.033±0.053 mL/min) than in those who reported no improvement (0.013±0.02 mL/min) (P = 0.025).

CONCLUSION: Xerostomia treatment improved oral dryness in 75.3% of patients receiving xerogenic medications in this study. If xerostomia due to side-effects of medications can be improved by treatment, it will greatly contribute to the quality of life of patients with xerogenic medications and may reduce the number of patients who discontinue medications.

PMID:36634078 | PMC:PMC9836311 | DOI:10.1371/journal.pone.0280224

Age Ageing. 2023 Jan 8;52(1):afac278. doi: 10.1093/ageing/afac278.

ABSTRACT

BACKGROUND: as a result of the high prevalence of polypharmacy in nursing homes (NHs), nursing home residents (NHRs) are exposed to numerous drug-drug interactions (DDIs) that can lead to adverse drug effects, and increased morbidity and mortality.

OBJECTIVES: to evaluate (i) the prevalence of DDIs among NHRs and its evolution over time, and (ii) factors associated with a favourable evolution.

DESIGN: posthoc analysis of the COME-ON study, a cluster-randomised controlled trial aiming at reducing potentially inappropriate prescriptions in NHs, through the implementation of a complex intervention.

SETTING AND SUBJECTS: 901 NHRs from 54 Belgian NHs.

METHODS: DDIs were identified using a validated list of 66 potentially clinically relevant DDIs in older adults. We defined a favourable evolution at 15 months as the resolution of at least one DDI present at baseline, without the introduction of any new DDI. Factors associated with a favourable evolution were analysed using multivariable logistic regression.

RESULTS: at baseline, 475 NHRs (52.7%) were exposed to at least 1 DDI and 225 NHRs (25.0%) to more than one DDI. Most common DDI was 'Concomitant use of at least three central nervous system active drugs'. At 15 months, we observed a 6.3% absolute decrease in DDI prevalence in intervention group, and a 1.0% absolute increase in control group. The intervention, older age and private NH ownership were significantly associated with a favourable DDI evolution.

CONCLUSION: a high prevalence of DDI in Belgian NHs was observed, but the COME-ON intervention was associated with a favourable evolution over time.

PMID:36633299 | DOI:10.1093/ageing/afac278

Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338221150561. doi: 10.1177/15330338221150561.

ABSTRACT

Objectives: This study was carried out to assess the efficacy and drug toxicity of anti-angiogenic tyrosine kinase inhibitor (TKI) plus chemotherapy as second-line or above therapeutic regime in advanced or metastatic gastric cancer patients. Methods: From November 2017 to April 2020, advanced or metastatic gastric cancer patients who have failed from prior treatment and received apatinib combined with irinotecan or irinotecan treatment were analyzed. The primary observed indicator was progression-free survival (PFS). Objective: response rate (ORR), disease control rate (DCR), overall survival (OS), and drug toxicity were also evaluated. Results: 26 patients received apatinib combined with irinotecan and 29 patients received irinotecan. The ORR in the combination therapy and monotherapy population was 26.9% and 17.2%, respectively. The DCR in the apatinib combined with irinotecan group was higher than in irinotecan monotherapy population (80.8% vs 55.2%, P = .043). Median PFS was 4.2 months in the combination group and 3.3 months in the monotherapy group (P = .020). Median OS was 8.0 months in the combination group and 5.9 months in the monotherapy group (P = .048). Except for ECOG PS 2, PFS and OS were generally consistent across subgroups by sex, age, number of metastatic sites and primary tumor site. The incidence of Grade 3-4 adverse events in combination and monotherapy group was 23.1% and 20.7%, respectively. In apatinib combined with irinotecan group, adverse events that were attributed to apatinib were secondary hypertension (in seven patients, 26.9%), hand-foot syndrome (5,19.2%), and proteinuria (5, 19.2%). Univariate analysis demonstrated that secondary hypertension was considered to be a favorable factor (P = .040) for longer OS in combination therapy group. Conclusions: Compared with chemotherapy alone, anti-angiogenic TKI plus chemotherapy showed better PFS, OS and DCR in advanced or metastatic gastric cancer as second-line or above therapy, with a tolerable and manageable safety profile.

PMID:36632666 | DOI:10.1177/15330338221150561

Diabetes Metab Syndr. 2023 Jan 2;17(1):102703. doi: 10.1016/j.dsx.2022.102703. Online ahead of print.

ABSTRACT

AIM: This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of lobeglitazone as compared to the standard of care (SOC) in patients with type 2 diabetes mellitus (T2DM).

METHODS: Databases were searched for relevant randomized controlled trials. The primary outcome was the comparison of the glycated hemoglobin (HbA1C) level after 24 weeks. Pooled mean differences and odds ratios were calculated using random-effects models.

RESULTS: Of 267 studies that were screened, four were included. Treatment with adjunct lobeglitazone showed a reduction in the HbA1C level [mean difference: -0.23% (95% CI: -0.62 to 0.16); p = 0.24; i2: 87%; moderate GRADE (Grading of Recommendations Assessment, Development and. Evaluation) of evidence], fasting blood glucose level [mean difference: -7.12 mg/dl (95% CI: -20.09 to 5.85); p = 0.28; i2: 87%; moderate GRADE of evidence], and lipid profile as compared to those following treatment with the SOC; however, the changes were not statistically significant. The risk of hypoglycemia was significantly lower [odds ratio: 0.24 (95% CI: 0.08 to 0.70); p < 0.05; i2: 0%; moderate GRADE of evidence] without any significant difference in the risk of drug-related adverse events [odds ratio: 1.59 (95% CI: 0.87 to 2.93); p = 0.13; i2: 0%; moderate GRADE of evidence] following treatment with lobeglitazone as compared to those following treatment with the SOC.

CONCLUSION: Treatment with adjunct lobeglitazone showed changes in the blood glycemic status and lipid profile similar to SOC in patients with T2DM, and the results were not statistically significant. Lobeglitazone was well tolerated; its safety profile was comparable to SOC.

PMID:36634469 | DOI:10.1016/j.dsx.2022.102703

N Engl J Med. 2023 Jan 12;388(2):142-153. doi: 10.1056/NEJMsa2206117.

ABSTRACT

BACKGROUND: Adverse events during hospitalization are a major cause of patient harm, as documented in the 1991 Harvard Medical Practice Study. Patient safety has changed substantially in the decades since that study was conducted, and a more current assessment of harm during hospitalization is warranted.

METHODS: We conducted a retrospective cohort study to assess the frequency, preventability, and severity of patient harm in a random sample of admissions from 11 Massachusetts hospitals during the 2018 calendar year. The occurrence of adverse events was assessed with the use of a trigger method (identification of information in a medical record that was previously shown to be associated with adverse events) and from review of medical records. Trained nurses reviewed records and identified admissions with possible adverse events that were then adjudicated by physicians, who confirmed the presence and characteristics of the adverse events.

RESULTS: In a random sample of 2809 admissions, we identified at least one adverse event in 23.6%. Among 978 adverse events, 222 (22.7%) were judged to be preventable and 316 (32.3%) had a severity level of serious (i.e., caused harm that resulted in substantial intervention or prolonged recovery) or higher. A preventable adverse event occurred in 191 (6.8%) of all admissions, and a preventable adverse event with a severity level of serious or higher occurred in 29 (1.0%). There were seven deaths, one of which was deemed to be preventable. Adverse drug events were the most common adverse events (accounting for 39.0% of all events), followed by surgical or other procedural events (30.4%), patient-care events (which were defined as events associated with nursing care, including falls and pressure ulcers) (15.0%), and health care-associated infections (11.9%).

CONCLUSIONS: Adverse events were identified in nearly one in four admissions, and approximately one fourth of the events were preventable. These findings underscore the importance of patient safety and the need for continuing improvement. (Funded by the Controlled Risk Insurance Company and the Risk Management Foundation of the Harvard Medical Institutions.).

PMID:36630622 | DOI:10.1056/NEJMsa2206117

Pediatrics. 2023 Jan 11:e2022059574. doi: 10.1542/peds.2022-059574. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: All US Food and Drug Administration-approved medications for Tourette syndrome are antipsychotics, and their use is limited by the risk of weight gain, metabolic changes, and drug-induced movement disorders. Several small trials suggest that ecopipam, a first-in-class, selective dopamine 1 receptor antagonist, reduces tics with a low risk for these adverse events. This trial sought to further evaluate the efficacy, safety, and tolerability of ecopipam in children and adolescents with moderate to severe Tourette syndrome.

METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, phase 2b trial. Subjects aged ≥6 to <18 years with a baseline Yale Global Tic Severity Score Total Tic Score of ≥20 were randomly assigned 1:1 to ecopipam (n = 76) or placebo (n = 77). The primary endpoint was mean change over 12 weeks in the Yale Global Tic Severity Score Total Tic Score. The Clinical Global Impression of Tourette Syndrome Severity was the secondary endpoint. Safety and tolerability were evaluated at each study visit.

RESULTS: Total tic scores were significantly reduced from baseline to 12 weeks in the ecopipam group compared with placebo (least squares mean differences -3.44, 95% confidence interval -6.09 to -0.79, P = .01). Improvement in Clinical Global Impression of Tourette Syndrome Severity was also greater in the ecopipam group (P = .03). More weight gain was seen in subjects assigned to placebo. No metabolic or electrocardiogram changes were identified. Headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%) were the most common adverse events.

CONCLUSIONS: Among children and adolescents with TS, ecopipam reduces tics to a greater extent than placebo, without observable evidence of common antipsychotic-associated side effects.

PMID:36628546 | DOI:10.1542/peds.2022-059574

BMC Complement Med Ther. 2023 Jan 10;23(1):9. doi: 10.1186/s12906-023-03836-w.

ABSTRACT

BACKGROUND: Tripterygium wilfordii Hook. F. (TwHF), a traditional Chinese medicine, is widely used in the treatment of rheumatoid arthritis. Due to multiorgan toxicity, particularly hepatotoxicity, the application of TwHF is restricted. To clarify the hepatotoxic substances, zebrafish, hepatocytes and macrophages were used for screening based on hepatotoxic injury patterns. This study provides a basis for further elucidation of the hepatotoxic mechanism of TwHF.

METHODS: First, 12 compounds were selected according to the chemical categories of TwHF. The fluorescence area and fluorescence intensity of zebrafish livers were observed and calculated. The viability of two hepatocyte lines was detected by CCK8 assay. TNF-α and IL-1β mRNA expression in bone marrow-derived macrophages was used to evaluate macrophage activation, a factor of potential indirect hepatotoxicity. Finally, the hepatotoxic characteristics of 4 representative components were verified in mice in vivo.

RESULTS: Parthenolide, triptolide, triptonide, triptobenzene H, celastrol, demethylzeylasteral, wilforlide A, triptotriterpenic acid A and regelidine significantly reduced the fluorescence area and fluorescence intensity of zebrafish livers. The viability of L-02 or AML-12 cells was significantly inhibited by parthenolide, triptolide, triptonide, celastrol, demethylzeylasteral, and triptotriterpenic acid A. Parthenolide, triptolide, triptonide, celastrol, demethylzeylasteral and triptobenzene H significantly increased TNF-α and IL-1β mRNA levels in macrophages, while triptophenolide, hypodiolide and wilforine significantly reduced TNF-α and IL-1β mRNA levels. Triptotriterpenic acid A, celastrol and triptobenzene H at a dose of 10 mg/kg significantly increased the levels of mouse serum alanine aminotransferase and aspartate aminotransferase and aggravated liver inflammation.

CONCLUSIONS: Parthenolide, triptolide, triptonide, celastrol, demethylzeylasteral, triptotriterpenic acid A and triptobenzene H might be the main hepatotoxic components of TwFH. Among them, only triptotriterpenic acid A presents direct hepatotoxicity. Triptobenzene H exerts indirect liver damage by activating macrophages. Parthenolide, triptolide, triptonide, celastrol, and demethylzeylasteral can directly and indirectly cause liver injury.

PMID:36627617 | DOI:10.1186/s12906-023-03836-w

BMC Prim Care. 2023 Jan 10;24(1):7. doi: 10.1186/s12875-022-01960-z.

ABSTRACT

BACKGROUND: Team-based primary care reforms aim to improve care coordination by involving multiple interdisciplinary health professionals in patient care. Team-based primary care may support improved medication management for older adults with polypharmacy and multiple points of contact with the healthcare system. However, little is known about this association. This study compares sociodemographic and prescribing trends among older adults in team-based vs. traditional primary care models in Ontario and Quebec.

METHODS: We constructed two provincial cohorts using population-level health administrative data from 2006-2018. Our primary exposure was enrollment in a team-based model of care. Key endpoints included adverse drug events (ADEs), potentially inappropriate prescriptions (PIPs), and polypharmacy. We plotted prescribing trends across the observation period (stratified by model of care) in each province. We used standardized mean differences to compare characteristics of older adults and providers, as well as prescribing endpoints.

RESULTS: Formal patient/physician enrollment increased in both provinces since the time of policy implementation; team-based enrollment among older adults was higher in Quebec (47%) than Ontario (33%) by the end of our observation period. The distribution of sociodemographic characteristics was reasonably comparable between team-based and non-team-based patients in both provinces, aside from a persistently higher share of rural patients in team-based care. Most PIPs assessed either declined or remained relatively steady over time, regardless of model of care and province. Several PIPs were more common among team-based patients than non-team-based patients, particularly in Quebec. We did not detect notable trends in ADEs or polypharmacy in either province.

CONCLUSIONS: Our findings offer encouraging evidence that many PIPs are declining over time in this population, regardless of patients' enrollment in team-based care. Rates of decline appear similar across models of care, suggesting these models may not meaningfully influence prescribing endpoints. Additional efforts are needed to understand the impact of team-based care among older adults and improve primary care prescribing practices.

PMID:36627566 | PMC:PMC9832790 | DOI:10.1186/s12875-022-01960-z

Ther Drug Monit. 2023 Feb 1;45(1):102-109. doi: 10.1097/FTD.0000000000001035.

ABSTRACT

PURPOSE: Tacrolimus is an immunosuppressant widely used in transplantations requiring mandatory concentration-controlled dosing to prevent acute rejection or adverse effects, including new-onset diabetes mellitus (NODM). However, no relationship between NODM and tacrolimus exposure has been established. This study aimed to evaluate the relationship between cumulative tacrolimus exposure and NODM occurrence.

METHODS: A total of 452 kidney transplant patients were included in this study. Sixteen patients developed NODM during the first 3 months after transplant. We considered all tacrolimus concentration (C0) values collected until the diagnosis of NODM in these patients and until 3 months after transplant in the others. New tacrolimus cumulative exposure metrics were derived from the time profile of the tacrolimus morning predose concentration, C0: the percentage of C0 values > cutoff, the average of C0 values above the cutoff, and the percentage of the area under C0 versus time curve, AUCC0, above the cutoff. The cutoff chosen was 15 ng/mL, corresponding to the higher end of the therapeutic range for the early post-transplant period. The influence of these metrics on NODM and other clinical and biological characteristics was investigated using the Cox models.

RESULTS: The percentage of C0 > 15 mcg/L was statistically different between patients with and without NODM (P = 0.01). Only these tacrolimus C0-derived metrics were significantly associated with an increased risk of NODM [HR: 1.73 (1.43-2.10, P < 0.001)].

CONCLUSION: This study shows that tacrolimus concentrations >15 mcg/L affect the incidence of NODM.

PMID:36624577 | DOI:10.1097/FTD.0000000000001035

Drug Ther Bull. 2023 Jan 10:dtb-2022-000078. doi: 10.1136/dtb.2022.000078. Online ahead of print.

ABSTRACT

Overview of: European Medicines Agency. EMA recommends measures to minimise risk of serious side effects with Janus kinase inhibitors for chronic inflammatory disorders November 2022.

PMID:36627180 | DOI:10.1136/dtb.2022.000078

Enferm Infecc Microbiol Clin (Engl Ed). 2023 Jan;41(1):65. doi: 10.1016/j.eimce.2022.05.011.

NO ABSTRACT

PMID:36621255 | PMC:PMC9817720 | DOI:10.1016/j.eimce.2022.05.011

Enferm Infecc Microbiol Clin (Engl Ed). 2023 Jan;41(1):65-66. doi: 10.1016/j.eimce.2022.05.012.

NO ABSTRACT

PMID:36621254 | PMC:PMC9817762 | DOI:10.1016/j.eimce.2022.05.012

Front Psychiatry. 2022 Dec 21;13:1096006. doi: 10.3389/fpsyt.2022.1096006. eCollection 2022.

ABSTRACT

BACKGROUND: Schizophrenia is considered one of the major risk factors for mortality from SARS-CoV-2 infection. Early antiviral treatment is important to decrease the risk of mortality. Currently, Paxlovid (nirmatrelvir-ritonavir) has been widely used in SARS-CoV-2 patients with risk factors. However, drug-drug interactions with anti-psychotics are prominent and complicated.

CASE PRESENTATION: We report a clozapine-treated patient with SARS-CoV-2 infection who developed neutropenia after coadministration with Paxlovid. In this case, clozapine was used for over 15 years, without neutropenia development. However, severe neutropenia (absolute neutrophil count = 523/μl) developed 3 days after the coadministration of Paxlovid 2 doses per day, valproic acid 1,000 mg per day and clozapine 100 mg per day. The development of neutropenia may be attributed to the complicated interaction among Paxlovid, SARS-CoV-2 infection, valproic acid, fluvoxamine and clozapine.

CONCLUSIONS: Neutropenia is a rare but life-threatening event if a concomitant infection occurs. The risk may increase during SARS-CoV-2 infection and the coadministration of clozapine and Paxlovid. Although the exact causes of neutropenia in this patient are not fully clear, the white blood cell count and absolute neutrophil count should be closely monitored during the administration of Paxlovid in clozapine-treated patients with SARS-CoV-2 infection.

PMID:36620672 | PMC:PMC9810620 | DOI:10.3389/fpsyt.2022.1096006

Middle East J Dig Dis. 2022 Apr;14(2):244-253. doi: 10.34172/mejdd.2022.279. Epub 2022 Apr 30.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) have promising clinical activity and are essential medications for patients with several malignancies. However, by deranging the immune system, these novel agents could lead to immune-related adverse events (IRAEs). Hepatotoxicity with checkpoint inhibitors usually results in acute hepatitis or drug-induced liver injury. METHODS: This review article discusses the recent clinical evidence available regarding checkpoint inhibitor-induced hepatitis and reviews an approach to their diagnosis and management. CONCLUSION: ICIs have improved patients' outcomes with different forms of malignancy; however, ICIs-related liver damage is a clinically significant entity in these patients. All patients should be monitored carefully for IRAEs while undergoing treatment with ICIs.

PMID:36619143 | PMC:PMC9489307 | DOI:10.34172/mejdd.2022.279