Front Neurol. 2024 Feb 1;14:1331241. doi: 10.3389/fneur.2023.1331241. eCollection 2023.

ABSTRACT

Drug-induced tremor is a common side effect of lithium with an occurrence of approximately 25% of patients. Cessation of the offending drug can be difficult, and many medical treatments for drug-induced tremor are ineffective. Deep brain stimulation (DBS) has been shown in a limited number of case reports to effectively reduce drug-induced tremor, however, which remains an invasive therapeutic option. MR-guided focused ultrasound (MRgFUS) thalamotomy is an FDA-approved non-invasive treatment for essential tremor (ET). To the best of our knowledge, MRgFUS thalamotomy has never been reported to treat drug-induced tremor. Here, we present a case of a left-handed 55-year-old man with a progressive, medically refractory lithium-induced tremor of the bilateral upper extremities. The patient underwent MRgFUS thalamotomy targeting the right ventral intermediate nucleus (VIM) of the thalamus to treat the left hand. There was almost complete resolution of his left-hand tremor immediately following MRgFUS. There were no side effects. The patient continues to show excellent tremor control at 90-day follow-up and remains free from side effects. This case demonstrates MRgFUS thalamotomy as a possible novel treatment option to treat drug-induced tremor.

PMID:38362012 | PMC:PMC10867204 | DOI:10.3389/fneur.2023.1331241

Pharmacoepidemiol Drug Saf. 2024 Feb;33(2):e5735. doi: 10.1002/pds.5735.

ABSTRACT

BACKGROUND: Medication error (ME) surveillance in Danish healthcare relies on the mandatory national incident reporting system, the Danish Patient Safety Database (DPSD). Individual case reviews and descriptive statistics with frequency counts are the most often used approaches when analyzing MEs in incident reporting systems, including the DPSD. However, incident reporting systems often generate a large number of reports and may suffer from underreporting; consequently, additional approaches are needed to overcome these challenges. Disproportionality analysis (DPA) is a statistical tool used for signal detection of adverse drug reactions in pharmacovigilance reports, but the evidence for using DPA on ME analysis in safety reporting systems is limited.

OBJECTIVES: We aimed to test the feasibility of DPA by analysing harmful MEs reported to DPSD 2014-2018.

METHODS: We utilized proportional reporting ratios (PRR) to identify signals of diproportionality.

RESULTS: We identified well-known high-risk medicines, including anticoagulants, opioids, insulins, antiepileptic, and antipsychotic drugs, and their association with several ME types and stages in a medication process.

CONCLUSION: DPA might be suggested as an additional tool for screening MEs and identifying priority areas for further investigation in safety reporting systems.

PMID:38357842 | DOI:10.1002/pds.5735

Nurs Health Sci. 2024 Mar;26(1):e13084. doi: 10.1111/nhs.13084.

ABSTRACT

The COVID-19 pandemic deeply affected the lives of children and young people; studies report adverse effects on mental, physical, and social well-being. However, the impact of the pandemic on obesity care for children received little attention. The aim of this study was to gain insight into the challenges youth healthcare nurses experienced and to describe implications for future obesity care and policy. We conducted interviews, participant observations, and a group session with youth healthcare nurses during the pandemic in Amsterdam, the Netherlands. Youth healthcare nurses reported a deterioration in the problems of children and young people who were already in the highest classification for pediatric obesity, such as increased weight gain, mental health problems, and socio-economic problems. The nurses experienced immense challenges while trying to provide obesity care, such as a decrease in face-to-face contact with youth and their families, as well as loss of continuity of care. It is important to reconnect with these families, invest in a trusted relationship with youth receiving obesity care, and prioritize available and accessible obesity care for those who need it the most.

PMID:38356109 | DOI:10.1111/nhs.13084

Reg Anesth Pain Med. 2024 Feb 15:rapm-2023-104851. doi: 10.1136/rapm-2023-104851. Online ahead of print.

ABSTRACT

Hallucinogen exposure in patients in the perioperative period presents challenges for anesthesiologists and other anesthesia providers. Acute and chronic exposure to these substances can cause physiological impacts that can affect the function of anesthetic and analgesic medications used during perioperative care. The objective of this narrative review is to educate readers on the wide array of hallucinogens and psychedelics that may influence the perioperative management of patients exposed to these substances. A narrative review of the literature surrounding hallucinogens and psychedelics was completed. Hallucinogens and psychedelics are quite varied in their mechanisms of action and therefore present a variety of perioperative implications and perioperative considerations. Many of these substances increase serotonin levels or act directly at serotonergic receptors. However, there are other relevant actions that may include varied mechanisms from N-methyl-D-aspartate receptor antagonism to stimulation of muscarinic receptors. With hallucinogen exposure rates on the rise, understanding the effects of hallucinogens is important for optimizing management and reducing risks perioperatively for patients with acute or chronic exposure.

PMID:38359966 | DOI:10.1136/rapm-2023-104851

Int Immunopharmacol. 2024 Feb 14;129:111606. doi: 10.1016/j.intimp.2024.111606. Online ahead of print.

ABSTRACT

INTRODUCTION: Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) immune checkpoint inhibitors (ICIs) are used for a variety of cancers and are associated with a risk of developing immune-related adverse events, most commonly dermatitis, colitis, hepatitis, and pneumonitis. Immune-mediated hematologic toxicities have been reported, but are less well-described in the literature. Immune thrombocytopenia (ITP) is a rare autoimmune, hematologic adverse event that has been reported with PD-1/PD-L1 inhibitors.

METHODS: We performed a retrospective observational analysis of the United States Food and Drug Administration Adverse Event Reporting System (FAERS) data. We searched for cases of ITP reported with exposure to PD-1/PD-L1 inhibitors from initial FDA approval for each agent to September 30, 2022. Disproportionality signal analysis was done by calculating the reporting odds ratio (ROR). Oxaliplatin was used as a positive control for sensitivity analysis as it is an anticancer therapy that has been associated with drug-induced ITP. A systematic review of the PubMed database was also conducted to identify published cases of PD-1/PD-L1 inhibitor-induced ITP.

RESULTS: There were 329 reports of ITP with ICIs in the FAERS database that were reviewed for a disproportionality signal, including atezolizumab (n = 27), durvalumab (n = 17), nivolumab (n = 160), and pembrolizumab (n = 125). The ROR was significant for atezolizumab (ROR 5.39, 95 % CI 3.69-7.87), avelumab (ROR 10.32, 95 % CI 4.91-21.69), durvalumab (ROR 7.91, 95 % CI 4.91-12.75), nivolumab (ROR 9.76, 95 % CI 8.34-11.43), and pembrolizumab (ROR 12.6, 95 % CI 10.55-15.06). In our systematic review, we summated 57 cases of ICI-induced ITP. Nivolumab and pembrolizumab had the most reported cases of ITP in the literature. Most cases reported (53 %) included ITP-directed therapies beyond corticosteroids for the management of ICI-induced ITP.

CONCLUSION: There is a significant reporting signal of ITP with several ICI agents. Clinicians should be aware of and monitor for signs of this potentially serious adverse event.

PMID:38359661 | DOI:10.1016/j.intimp.2024.111606

Adv Ther. 2024 Feb 15. doi: 10.1007/s12325-024-02795-z. Online ahead of print.

ABSTRACT

INTRODUCTION: This article aimed to assess the efficacy and tolerability of adjunctive brivaracetam (BRV) in adults with focal-onset seizures on specific concomitant antiseizure medications (ASMs) taken as part of their treatment regimen.

METHODS: This was a post hoc analysis of pooled data from double-blind, placebo-controlled trials (N01252/NCT00490035, N01253/NCT00464269, and N01358/NCT01261325) in patients with uncontrolled focal-onset seizures randomized to BRV (50-200 mg/day) or placebo on the most common concomitant ASMs at trial initiation.

RESULTS: Nine concomitant ASMs were analyzed: carbamazepine (CBZ), lamotrigine (LTG), valproate (VPA), oxcarbazepine (OXC), topiramate (TPM), phenytoin (PHT), lacosamide (LCM), clobazam (CLB), and phenobarbital (PHB). Reduction over placebo in focal-onset seizure frequency per 28 days with BRV ranged from 11.7% (concomitant OXC) to 33.5% (concomitant PHB). The median percentage reduction from baseline in focal-onset seizure frequency per 28 days ranged from 25.5% to 42.8% in patients on BRV (placebo 4.4-21.2%); 50% responder rates ranged from 31.9% to 44.9% in patients on BRV (placebo 11.4-25.2%). In patients on BRV, seizure freedom ranged from 1.4% (concomitant PHT) to 12.5% (concomitant LCM); seizure freedom ranged from 0% to 1.2% in patients on placebo. All efficacy endpoints analyzed were consistently numerically higher in patients on BRV versus placebo. The overall incidence of treatment-emergent adverse events (TEAEs) was generally similar across subgroups by specific concomitant ASMs in patients on BRV (range 60.8-74.5%) or placebo (range 53.8-66.7%). Drug-related TEAEs were numerically higher across all subgroups by concomitant ASM in patients on BRV (range 35.2-48.3%) versus placebo (range 23.9-37.1%). Discontinuations due to TEAEs ranged from 2.9% to 13.3% in patients on BRV and was 0-5.7% for patients taking placebo across subgroups.

CONCLUSION: BRV was efficacious and well tolerated regardless of the specific concomitant ASMs used as part of their treatment regimen. These data show that in patients with focal-onset seizures, BRV provides additional efficacy to a broad range of ASMs.

PMID:38356105 | DOI:10.1007/s12325-024-02795-z

J Med Chem. 2024 Feb 22;67(4):2264-2286. doi: 10.1021/acs.jmedchem.3c01892. Epub 2024 Feb 13.

ABSTRACT

Delamanid, bedaquiline, and pretomanid have been recently added in the anti-tuberculosis (anti-TB) treatment regimens and have emerged as potential solutions for combating drug-resistant TB. These drugs have proven to be effective in treating drug-resistant TB when used in combination. However, concerns have been raised about the eventual loss of these drugs due to evolving resistance mechanisms and certain adverse effects such as prolonged QT period, gastrointestinal problems, hepatotoxicity, and renal disorders. This Perspective emphasizes the properties of these first-in-class drugs, including their mechanism of action, pharmacokinetics/pharmacodynamics profiles, clinical studies, adverse events, and underlying resistance mechanisms. A brief coverage of efforts toward the generation of best-in-class leads in each class is also provided. The ongoing clinical trials of new combinations of these drugs are discussed, thus providing a better insight into the use of these drugs while designing an effective treatment regimen for resistant TB cases.

PMID:38351709 | DOI:10.1021/acs.jmedchem.3c01892

J Neural Transm (Vienna). 2024 Mar;131(3):253-266. doi: 10.1007/s00702-024-02738-6. Epub 2024 Feb 14.

ABSTRACT

Edema as an adverse drug reaction is a commonly underestimated yet potentially debilitating condition. This study analyzes the incidence of severe psychotropic drug-induced edema (e.g., edema affecting the face, legs, or multiple body parts and lasting for more than 1 week, or in any case necessitating subsequent diuretic use) among psychiatric inpatients. The cases under examination are derived from an observational pharmacovigilance program conducted in German-speaking countries ("Arzneimittelsicherheit in der Psychiatrie", AMSP) from 1993 to 2016. Among the 462,661 inpatients monitored, severe edema was reported in 231 cases, resulting in an incidence of 0.05%. Edema occurred more frequently in women (80% of all cases) and older patients (mean age 51.8 years). Pregabalin had the highest incidence of severe edema, affecting 1.46‰ of patients treated with pregabalin, followed by mirtazapine (0.8‰). The majority of edema cases showed a positive response to appropriate countermeasures, such as dose reduction and drug discontinuation, and resolved by the end of the observation period. While most instances of drug-induced edema are reversible, they can have a significant impact on patient well-being and potentially result in decreased treatment adherence. It is, therefore, crucial to remain vigilant regarding risk-increasing circumstances during treatment with psychotropic drugs.

PMID:38353811 | PMC:PMC10874320 | DOI:10.1007/s00702-024-02738-6

Sci Rep. 2024 Feb 14;14(1):3759. doi: 10.1038/s41598-024-53684-y.

ABSTRACT

Adjuvant Temozolomide is considered the front-line Glioblastoma chemotherapeutic treatment; yet not all patients respond. Latest trends in clinical trials usually refer to Doxorubicin; yet it can lead to severe side-effects if administered in high doses. While Glioblastoma prognosis remains poor, little is known about the combination of the two chemotherapeutics. Patient-derived spheroids were generated and treated with a range of Temozolomide/Doxorubicin concentrations either as monotherapy or in combination. Optical microscopy was used to monitor the growth pattern and cell death. Based on the monotherapy experiments, we developed a probabilistic mathematical framework in order to describe the drug-induced effect at the single-cell level and simulate drug doses in combination assuming probabilistic independence. Doxorubicin was found to be effective in doses even four orders of magnitude less than Temozolomide in monotherapy. The combination therapy doses tested in vitro were able to lead to irreversible growth inhibition at doses where monotherapy resulted in relapse. In our simulations, we assumed both drugs are anti-mitotic; Temozolomide has a growth-arrest effect, while Doxorubicin is able to cumulatively cause necrosis. Interestingly, under no mechanistic synergy assumption, the in silico predictions underestimate the in vitro results. In silico models allow the exploration of a variety of potential underlying hypotheses. The simulated-biological discrepancy at certain doses indicates a supra-additive response when both drugs are combined. Our results suggest a Temozolomide-Doxorubicin dual chemotherapeutic scheme to both disable proliferation and increase cytotoxicity against Glioblastoma.

PMID:38355655 | DOI:10.1038/s41598-024-53684-y

Rev Prat. 2023 Oct;73(8):885-889.

ABSTRACT

NOCEBO PLACEBO, THE HIDDEN SIDE OF OUR TREATMENTS. Our knowledge of the placebo effect and its opposite, the nocebo effect, has changed dramatically in the last 20 years. Any treatment activity induces this type of effect. The placebo groups in clinical studies have biases that profoundly alter their neutrality. The nocebo effect is omnipresent in daily practice, it contributes to induce many of the adverse drug effects. The use of «impure» placebos is also widespread in daily practice. The placebo effect has an objectivable and reproducible neurobiological substrate. Its therapeutic effects are well documented. Disorders, symptoms involving the central nervous system (CNS) respond more easily to placebo. These new data make it possible to improve clinical practices by developing the quality of relationships with patients and families as well as the methodology of clinical trials.

PMID:38354014

J Gastroenterol Hepatol. 2024 Feb 14. doi: 10.1111/jgh.16486. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: Healing rates of severe erosive esophagitis (EE; Los Angeles [LA] Grade C/D) in patients treated with a proton pump inhibitor (PPI) is suboptimal (~60-70%). Vonoprazan, a potassium-competitive acid blocker, is suggested to have better healing rates in patients with severe EE. This meta-analysis compares the efficacy and safety of vonoprazan 20 mg versus lansoprazole 30 mg daily in healing EE, specifically in those with LA Grade C/D.

METHODS: We searched MEDLINE, Embase, and CENTRAL on May 24, 2023. Studies that randomized EE patients to vonoprazan 20 mg daily or lansoprazole 30 mg daily and compared healing rates were included. The risk of bias was assessed using Cochrane's Risk of Bias 2 tool. The fixed-effect model was used to obtain the pooled efficacy and safety outcomes. Subgroup analysis was done to compare healing rates in mild (LA Grade A/B) versus severe EE and based on study location.

RESULTS: Four randomized controlled trials (RCTs) with low risks of bias comprising 2208 participants were included. Vonoprazan 20 mg was superior to lansoprazole 30 mg daily in healing severe EE at all weeks (Week 2 RR 1.294 [95% CI 1.169-1.433], Week 4 1.160 [1.059-1.270], and Week 8 1.175 [95% CI 1.107-1.247]), but was similar for mild EE at all weeks (P-interaction < 0.01). Vonoprazan 20 mg was more efficacious than lansoprazole 30 mg at Week 8 in Western versus Asian studies (P-interaction < 0.01). Any, serious, and drug-related treatment-emergent adverse events were comparable between groups.

CONCLUSION: Vonoprazan 20 mg is superior to lansoprazole 30 mg for healing severe EE but not mild EE. Vonoprazan 20 mg daily has a similar safety profile to lansoprazole 30 mg daily.

PMID:38353152 | DOI:10.1111/jgh.16486

Cancer Rep (Hoboken). 2024 Feb;7(2):e1987. doi: 10.1002/cnr2.1987.

ABSTRACT

BACKGROUND: Mercaptopurine is an important component of acute lymphoblastic leukemia (ALL) and lymphoma (LLy) maintenance therapy. The 6-thioguanine nucleosides (6-TGN) are believed to be the primary contributor to myelosuppression and immunosuppressive effects, while 6-methylmercaptopurine (6-MMPN) is believed to be responsible for several toxicities including hepatotoxicity, pancreatitis, and hypoglycemia. Previous reports suggest the addition of allopurinol may reduce these toxicities.

AIMS: To assess the use of allopurinol to improve both safety and efficacy of mercaptopurine in pediatric patients with ALL and LLy during maintenance therapy. Secondary objectives included evaluating patient tolerability and skewed metabolism. In addition, we also analyzed mercaptopurine daily dose reduction upon allopurinol initiation.

METHODS AND RESULTS: The primary endpoint was time within goal ANC prior to and after initiation of allopurinol. Secondary endpoints included; improvement in selective toxicities (hepatotoxicity, pancreatitis, and hypoglycemia) and 6-MMPN to 6-TGN ratio prior to and after allopurinol initiation. In addition, an exploratory endpoint assessing mercaptopurine daily dose reduction prior to and after allopurinol initiation was included. Sixteen patients met inclusion criteria and 15 (94%) of which were included in this study. Median percent of maintenance days within goal ANC prior to and after initiation of allopurinol was 27.8 (IQR 22.6-44.9) and 41.6 (IQR 20.2-58.2) respectively. All patients experienced selective toxicities; 15 (100%) hepatotoxicity, 1 (7%) pancreatitis, and 3 (20%) hypoglycemia. Improvement of toxicities was seen in 13/15 (87%), 1/1 (100%), and 2/3 (67%) respectively. Average 6-MMPN:6-TGN ratio prior to allopurinol initiation was 304:1 and after, allopurinol initiation improved to 15:1, resulting in a 95% reduction. Average mercaptopurine dose prior to and after allopurinol initiation decreased by about 56% (63 to 28 mg/m2 /day).

CONCLUSION: Results suggest that the use of allopurinol in pediatric patients with ALL and LLy receiving mercaptopurine during maintenance therapy is both safe and effective.

PMID:38351548 | DOI:10.1002/cnr2.1987

Cardiorenal Med. 2024 Feb 13. doi: 10.1159/000537710. Online ahead of print.

ABSTRACT

INTRODUCTION: The role of curcuminoids, a striking antioxidant, in prevention of contrast-induced acute kidney injury (CI-AKI) remains unknown. We aim to evaluate the efficacy and safety of curcuminoids in preventing CI-AKI in patients undergoing elective coronary angiography (CAG) and/or percutaneous coronary intervention (PCI).

METHODS: We randomized 114 patients who were undergoing elective CAG and/or PCI to receive curcuminoids, 4 grams/day (1 day before, and 1 day after the procedure, n=56) or placebo (n=58). Serum creatinine was assessed at baseline, 12, 24 and 48 hours after contrast exposure. The primary endpoint was development of CI-AKI defined as serum creatinine increase ≥0.3 mg/dL within 48 hours after contrast exposure. The secondary endpoint was the occurrence of kidney injury defined by >30% increase in urine neutrophil gelatinase-associated lipocalin (NGAL).

RESULTS: Baseline characteristics were comparable between the two groups. Seven (12.7%) in curcuminoids group and eight (14.0%) in placebo group developed CI-AKI (p=0.84). The incidence of increased urine NGAL was comparable in the placebo and curcuminoids groups (39.6% vs. 50%, respectively; p=0.34). None in both groups had drug-related adverse events.

CONCLUSION: This is a pilot study to demonstrate the safety and tolerability of curcuminoids in patients undergoing elective CAG and/or PCI. Curcuminoids have no protective effects against kidney injury after elective CAG and/or PCI.

PMID:38350427 | DOI:10.1159/000537710

AIDS. 2024 Feb 12. doi: 10.1097/QAD.0000000000003865. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of 96 weeks of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) treatment in participants switching from dolutegravir (DTG)-based therapy.

DESIGN: Studies 1489 (NCT02607930) and 1490 (NCT02607956) were phase 3 randomized, double-blind, active-controlled, first-line therapy trials in people with HIV-1. After 144 weeks of DTG-based or B/F/TAF treatment, participants could enter a 96-week open-label extension (OLE) of B/F/TAF.

METHODS: A pooled analysis evaluated viral suppression (HIV-1 RNA <50 copies/mL) and changes in CD4+ cell count at OLE Weeks 48 and 96, treatment-emergent resistance, safety and tolerability after switch from a DTG-based regimen to B/F/TAF. Outcomes by prior treatment were summarized using descriptive statistics and compared by two-sided Wilcoxon rank sum test.

RESULTS: At OLE Week 96, participants who switched to B/F/TAF (N=519) maintained high levels of virologic suppression (99.5% and 99.1% in those switching from DTG/abacavir/lamivudine and DTG+F/TAF, respectively) and CD4+ cell count, with no treatment-emergent resistance to B/F/TAF. Twenty-one participants experienced drug-related adverse events (AEs) after switching, with diarrhea, weight gain and headache occurring most commonly. There were no cases of proximal renal tubulopathy, drug-related Grade 4 AEs or serious AEs. Two participants discontinued B/F/TAF due to treatment-related AEs. Participants who switched from DTG/abacavir/lamivudine experienced statistically significant greater weight gain than those who switched from DTG+F/TAF; however, median weight change from the blinded phase baseline to OLE Week 96 was numerically similar across treatment groups.

CONCLUSIONS: This medium-term analysis demonstrates the safety and efficacy of switching to B/F/TAF from a DTG-containing regimen in people with HIV-1.

PMID:38349226 | DOI:10.1097/QAD.0000000000003865

Ann Pharmacother. 2024 Feb 12:10600280241231612. doi: 10.1177/10600280241231612. Online ahead of print.

ABSTRACT

BACKGROUND: People with gender dysphoria are treated with hormone therapy for gender reassignment. The indication of this therapy was initially for the opposite sex, and information on potential adverse drug reaction (ADR) is lacking.

OBJECTIVE: To describe ADR associated with gender transition medication in transgender individuals reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.

METHODS: Data from the FAERS database up to June 2023 were examined, focusing on reports of gender transition medication use in the context of gender dysphoria. The ADRs were categorized using the Medical Dictionary for Regulatory Activities at both Preferred Term and System Organ Class (SOC) levels. Descriptive statistics summarized report counts, medication types, indications, and ADR severity.

RESULTS: For individuals assigned female at birth undergoing gender transition to male (transgender men), 82 reports (230 ADRs) were analyzed, with an average age of 29.5 years. Transgender hormonal therapy was cited in 72% of reports, predominantly from the United States (67.1%). A striking 88% were categorized as serious ADRs, primarily SOC injury, poisoning, and procedural complications (26.5%), followed by psychiatric disorders (14.8%) and nervous system disorders (12.2%). Among those assigned sex male at birth transitioning to female (transgender women) (81 reports, 237 ADRs), mean age was 33.3 years, with 58% indicating use for gender dysphoria. A significant proportion (53.6%) were serious ADRs, primarily SOC: injury, poisoning, and procedural complications (26.6%).

CONCLUSIONS AND RELEVANCE: The FAERS data reveal significant ADRs in transgender individuals using hormone therapy, sometimes unintended for their recipient gender. Population-level studies are crucial to enhance transgender health care. Spontaneous surveillance databases like FAERS illuminate off-label ADRs, urging health care providers to approach hormone therapies with informed caution.

PMID:38347713 | DOI:10.1177/10600280241231612

BMC Cancer. 2024 Feb 12;24(1):192. doi: 10.1186/s12885-024-11926-2.

ABSTRACT

BACKGROUND: Recent advances in the management of pancreatic neuroendocrine tumors (pNETs) highlight the potential benefits of temozolomide, an alkylating agent, for these patients. In this meta-analysis, we aimed to assess the outcome of temozolomide, alone or in combination with other anticancer medications in patients with advanced pNET.

METHODS: Online databases of PubMed, Web of Science, Embase, the Cochrane Library, and ClinicalTrials.gov were searched systematically for clinical trials that reported the efficacy and safety of temozolomide in patients with advanced pNET. Random-effect model was utilized to estimate pooled rates of outcomes based on Response Evaluation Criteria in Solid Tumors criteria, biochemical response, and adverse events (AEs).

RESULTS: A total of 14 studies, providing details of 441 individuals with advanced pNET, were included. The quantitative analyses showed a pooled objective response rate (ORR) of 41.2% (95% confidence interval, CI, of 32.4%-50.6%), disease control rate (DCR) of 85.3% (95% CI of 74.9%-91.9%), and a more than 50% decrease from baseline chromogranin A levels of 44.9% (95% CI of 31.6%-49.0%). Regarding safety, the results showed that the pooled rates of nonserious AEs and serious AEs were 93.8% (95% CI of 88.3%-96.8%) and 23.7% (95% CI of 12.0%-41.5%), respectively. The main severe AEs encompassed hematological toxicities.

CONCLUSIONS: In conclusion, our meta-analysis suggests that treatment with temozolomide, either as a monotherapy or in combination with other anticancer treatments might be an effective and relatively safe option for patients with advanced locally unresectable and metastatic pNET. However, additional clinical trials are required to further strengthen these findings. This study has been registered in PROSPERO (CRD42023409280).

PMID:38347461 | PMC:PMC10860315 | DOI:10.1186/s12885-024-11926-2

Sci Rep. 2024 Feb 12;14(1):3503. doi: 10.1038/s41598-024-53838-y.

ABSTRACT

In Thailand, resource limitations lead many multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients to use off-label immunosuppressants. This study assesses the efficacy and safety of rituximab (RTX) with a CD19-based reinfusion regimen among Thai MS and NMOSD patients. A retrospective review of patients at the Faculty of Medicine Siriraj Hospital from January 1994 to April 2023 was conducted. The primary outcome assessed was the change in annualized relapse rate (ARR) for patients using RTX for over a year. Secondary outcomes included changes in the Expanded Disability Status Scale (EDSS) scores, time to the first relapse after RTX initiation for patients using RTX for over a year, and an evaluation of the safety of RTX. The study encompassed 36 MS and 39 NMOSD patients. A majority of patients (91.7% of MS and 79.5% of NMOSD) experienced no relapses during a median follow-up of 30 months (Interquartile range [IQR] 20-46) and 31 months (IQR 23-41), respectively. The median ARR significantly decreased in both MS (from 0.77 [IQR 0.42-1.83] to 0 [IQR 0-0], p < 0.001) and NMOSD (from 0.92 [IQR 0.68-1.78] to 0 [IQR 0-0.17], p < 0.001) patients after switching to RTX, with no difference between those following a fixed 6-month time point regimen and a CD19-based reinfusion regimen. Median EDSS scores improved significantly at the last follow-up visit in both groups. The mean time to the first subsequent relapse was 8.3 ± 3.0 months in MS and 6.8 ± 1.7 months in NMOSD. Mild adverse drug reactions occurred in 44% of patients. RTX effectively prevents relapses in Thai MS and NMOSD patients, with no observed serious adverse drug reactions.

PMID:38347079 | PMC:PMC10861443 | DOI:10.1038/s41598-024-53838-y

Drug Ther Bull. 2024 Feb 12:dtb-2024-000012. doi: 10.1136/dtb.2024.000012. Online ahead of print.

NO ABSTRACT

PMID:38346850 | DOI:10.1136/dtb.2024.000012

PLoS One. 2024 Feb 12;19(2):e0297562. doi: 10.1371/journal.pone.0297562. eCollection 2024.

ABSTRACT

CONTEXT: Potentially inappropriate prescribing of medications in older adults, particular those with dementia, can lead to adverse drug events including falls and fractures, worsening cognitive impairment, emergency department visits, and hospitalizations. Educational mailings from health plans to patients and their providers to encourage deprescribing conversations may represent an effective, low-cost, "light touch", approach to reducing the burden of potentially inappropriate prescription use in older adults with dementia.

OBJECTIVES: The objective of the Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in Elderly with Alzheimer's Disease (D-PRESCRIBE-AD) trial is to evaluate the effect of a health plan based multi-faceted educational outreach intervention to community dwelling patients with dementia who are currently prescribed sedative/hypnotics, antipsychotics, or strong anticholinergics.

METHODS: The D-PRESCRIBE-AD is an open-label pragmatic, prospective randomized controlled trial (RCT) comparing three arms: 1) educational mailing to both the health plan patient and their prescribing physician (patient plus physician arm, n = 4814); 2) educational mailing to prescribing physician only (physician only arm, n = 4814); and 3) usual care (n = 4814) among patients with dementia enrolled in two large United States based health plans. The primary outcome is the absence of any dispensing of the targeted potentially inappropriate prescription during the 6-month study observation period after a 3-month black out period following the mailing. Secondary outcomes include dose-reduction, polypharmacy, healthcare utilization, mortality and therapeutic switching within targeted drug classes.

CONCLUSION: This large pragmatic RCT will contribute to the evidence base on promoting deprescribing of potentially inappropriate medications among older adults with dementia. If successful, such light touch, inexpensive and highly scalable interventions have the potential to reduce the burden of potentially inappropriate prescribing for patients with dementia. ClinicalTrials.gov Identifier: NCT05147428.

PMID:38346025 | PMC:PMC10861034 | DOI:10.1371/journal.pone.0297562

Clin Pharmacol Ther. 2024 Feb 12. doi: 10.1002/cpt.3201. Online ahead of print.

ABSTRACT

Electronic health records (EHRs) provide meaningful knowledge of drug-related adverse events (AEs) that are not captured in standard drug development and postmarketing surveillance. Using variables obtained from EHR data in the University of California San Francisco de-identified Clinical Data Warehouse, we aimed to evaluate the potential of machine learning to predict two hematological AEs, thrombocytopenia and anemia, in a cohort of patients treated with linezolid for 3 or more days. Features for model input were extracted at linezolid initiation (index), and outcomes were characterized from index to 14 days post-treatment. Random forest classification (RFC) was used for AE prediction, and reduced feature models were evaluated using cumulative importance (cImp) for feature selection. Grade 3+ thrombocytopenia and anemia occurred in 31% of 2,171 and 56% of 2,170 evaluable patients, respectively. Of the total 53 features, as few as 7 contributed at least 50% cImp, resulting in prediction accuracies of 70% or higher and area under the receiver operating characteristic curves of 0.886 for grade 3+ thrombocytopenia and 0.759 for grade 3+ anemia. Sensitivity analyses in strictly defined patient subgroups revealed similarly high predictive performance in full and reduced feature models. A logistic regression model with the same 50% cImp features showed similar predictive performance as RFC and good concordance with RFC probability predictions after isotonic calibration, adding interpretability. Collectively, this work demonstrates potential for machine learning prediction of AE risk in real-world patients using few variables regularly available in EHRs, which may aid in clinical decision making and/or monitoring.

PMID:38345264 | DOI:10.1002/cpt.3201