Ugeskr Laeger. 2023 Jun 26;185(26):V02230097.

ABSTRACT

This review summarises the effect of common medication on sleep patterns. Evaluation of current medication status is an important part of the assessment in case of complaints of disturbed sleep. Medication may affect sleep continuity and sleep architecture directly via effects on wake or sleep promoting neurotransmitter systems and indirectly via beneficial therapeutic effects or unwanted side effects. It is important for clinicians to be aware of potentially sleep disturbing effects of prescribed medication, especially in case of polypharmacy, and to adjust treatment accordingly to avoid disrupted sleep patterns and the resulting impairment of daytime functioning.

PMID:37381871

Sr Care Pharm. 2023 Jul 1;38(7):276-287. doi: 10.4140/TCP.n.2023.276.

ABSTRACT

Objective The objective of this systematic review was to evaluate adverse effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors in older people. Data Sources Articles in PubMed and EBSCOhost-Medline databases between January 2011 and 2021 were analyzed. Search terms were SGLT2 inhibitor, SGLT2 inhibitors, geriatric/elderly/older people, and safety/ adverse drug reaction/tolerability. Meta-analyses, systematic reviews, review articles, journal clubs, articles that did not address the research question, excluded patients 65 years of age and older, had an updated article available, did not stratify by age group, or were a commentary on a cohort study were excluded. Data Synthesis The search resulted in 113 articles. There were 62 duplicates removed, and 30 excluded based on the abstract. Of the 32 articles remaining, 19 were removed for not meeting the research question or meeting exclusion criteria. A total of 13 studies, including randomized controlled trials, cohort studies, and case reports, were assessed. Conclusion Current evidence demonstrates that patients taking SGLT2 inhibitors and diuretics were more likely to experience volume depletion. Findings suggest that risk of UTI was highest when the patient's age is 75 years or older. Some studies indicated that risk of genital mycotic infection is prevalent in older people. Use of SGLT2 inhibitors in the older population was not associated with a higher risk of developing diabetic ketoacidosis. Use of SGLT2 inhibitors appears to be relatively safe in older people. The risk of side effects may be decreased by considering concomitant medications. Randomized controlled trials assessing safety of SGLT2 inhibitors in the older population is still warranted.

PMID:37381139 | DOI:10.4140/TCP.n.2023.276

Sr Care Pharm. 2023 Jul 1;38(7):300-304. doi: 10.4140/TCP.n.2023.300.

ABSTRACT

Prevalence of dementia continues to increase with limited pharmacotherapy options available. Acetylcholinesterase inhibitors remain a mainstay of treatment. The US FDA has approved three oral medications within this class- donepezil, galantamine, and rivastigmine. In 2022, the US Food and Drug Administration approved a novel patch formulation for donepezil that could be beneficial for patients with dysphagia as well as potentially decreasing the side effect burden. The purpose of this analysis is to review the efficacy, safety, tolerability, and clinical considerations related to this novel formulation.

PMID:37381137 | DOI:10.4140/TCP.n.2023.300

J Clin Oncol. 2023 Jun 29:JCO2300152. doi: 10.1200/JCO.23.00152. Online ahead of print.

ABSTRACT

PURPOSE: Although several agents targeting epidermal growth factor receptor (EGFR) exon 20 insertions (ex20ins) have recently been approved by the US Food and Drug Administration, toxicities related to the inhibition of wild-type (WT) EGFR are common with these agents and affect overall tolerability. Zipalertinib (CLN-081, TAS6417) is an oral EGFR tyrosine kinase inhibitor (TKI) with a novel pyrrolopyrimidine scaffold leading to enhanced selectivity for EGFR ex20ins-mutant versus WT EGFR with potent inhibition of cell growth in EGFR ex20ins-positive cell lines.

METHODS: This phase 1/2a study of zipalertinib enrolled patients with recurrent or metastatic EGFR ex20ins-mutant non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy.

RESULTS: Seventy-three patients were treated with zipalertinib at dose levels including 30, 45, 65, 100, and 150 mg orally twice a day. Patients were predominantly female (56%), had a median age of 64 years, and were heavily pretreated (median previous systemic therapies 2, range 1-9). Thirty six percent of patients had received previous non-ex20ins EGFR TKIs and 3/73 (4.1%) patients received previous EGFR ex20ins TKIs. The most frequently reported treatment-related adverse events of any grade included rash (80%), paronychia (32%), diarrhea (30%), and fatigue (21%). No cases of grade 3 or higher drug-related rash or diarrhea were observed at 100 mg twice a day or below. Objective responses occurred across all zipalertinib dose levels tested, with confirmed partial response (PR) observed in 28/73 (38.4%) response-evaluable patients. Confirmed PRs were seen in 16/39 (41%) response-evaluable patients at the dose of 100 mg twice a day.

CONCLUSION: Zipalertinib has encouraging preliminary antitumor activity in heavily pretreated patients with EGFR ex20ins-mutant NSCLC, with an acceptable safety profile, including low frequency of high-grade diarrhea and rash.

PMID:37384848 | DOI:10.1200/JCO.23.00152

J Liver Cancer. 2020 Mar;20(1):84-89. doi: 10.17998/jlc.20.1.84. Epub 2020 Mar 31.

ABSTRACT

The efficacy and safety of sequential systemic therapy for the treatment of recurrent hepatocellular carcinoma (HCC) after liver transplantation (LT) are not well established. This study describes a successful experience where sequential therapy with sorafenib followed by regorafenib was used to treat recurrent HCC in a 54-year old male LT recipient. After HCC recurred in both lungs 10 months after LT, sorafenib was administered with radiation therapy to treat pulmonary metastases. However, after 4 months of sorafenib treatment showed progressive pulmonary metastases, sequential regorafenib treatment was started. After 3 months (cycles) of regorafenib treatment, tumor response was partial, and after 6 months (cycles), disease status remained stable without signs of progression or drug-related serious adverse events. This case suggests that sequential systemic therapy is feasible in patient with recurrent HCC after LT.

PMID:37383051 | PMC:PMC10035698 | DOI:10.17998/jlc.20.1.84

Neurol Ther. 2023 Jun 29. doi: 10.1007/s40120-023-00496-3. Online ahead of print.

ABSTRACT

Cladribine tablets (CladT) is a highly active oral disease-modifying therapy (DMT) for the management of relapsing multiple sclerosis (RMS). CladT acts as an immune reconstitution therapy, in that two short courses of treatment 1 year apart have been shown to suppress disease activity for a prolonged period in most patients, without need for continued DMT. Each course of CladT induces a profound reduction in B lymphocytes that recovers over months, and serious lymphopenia (Grade 3-4) is uncommon. Smaller reductions in levels of T lymphocytes occur slightly later: on average, these remain within the normal range and repopulate progressively. A larger effect occurs on CD8 vs. CD4 cells. Reactivation of latent or opportunistic infections (e.g. varicella zoster, tuberculosis) is mostly associated with very low lymphocyte counts (< 200/mm3). Screening and managing pre-existing infections, vaccinating non-exposed patients and delaying the 2nd year of treatment with CladT to allow lymphocytes to recover to > 800/mm3 (if necessary) are important for avoiding infections and higher-grade lymphopenia. There was no demonstrable or apparent effect of CladT on the efficacy of vaccinations, including against Covid-19. Adverse events consistent with drug-induced liver injury (DILI) represent a rare but potentially serious complication of CladT therapy in spontaneous adverse event reporting; patients should be screened for liver dysfunction before starting treatment. Ongoing hepatic monitoring is not required, but CladT must be withdrawn if signs and symptoms of DILI develop. There was a numerical imbalance for malignancies when comparing cladribine to placebo in the clinical programme, particularly in short-term data, but recent evidence shows that the risk of malignancy with CladT is similar to the background rate in the general population and to that with other DMTs. Overall, CladT is well tolerated with a favorable safety profile appropriate for the management of RMS.

PMID:37382841 | DOI:10.1007/s40120-023-00496-3

Reprod Health. 2023 Jun 29;20(1):98. doi: 10.1186/s12978-023-01642-8.

ABSTRACT

BACKGROUND: Worldwide, there is limited knowledge regarding women's views of future fertility in relation to contraceptive use. Few studies include material where women share their experiences at peer-written public domain websites, in spite of a larger portion of women discontinuing use of contraceptives. The objective of this study was to explore women's experiences of contraceptive methods based on data gathered from individual blog posts.

METHODS: Explorative qualitative study including 123 individual blog posts as the data source analysed with inductive thematic analysis.

RESULTS: Two themes were identified. Theme 1, 'Seeking control over reproduction and optimise fertility' including the sub-themes; Having the possibility to decide if, and when, to become pregnant, The value of effective contraceptive methods and the impact of women's sexuality, A wish to understand the body's normal fertility function and Limited knowledge-sharing information about the menstrual cycle during counselling and Theme 2, 'Making the complex decision on their own' including the sub- themes; Limited or subpar guidance in counselling and need for information from social media, Relational and environmental factors influencing contraceptive decision making and Considering beneficial effects and fears of adverse health effects when using hormonal contraceptive methods.

CONCLUSIONS: During counselling, women desired an extended dialogue regarding effectiveness, health effects of different methods and an increased understanding of their menstrual cycle. Insufficient understanding of contraceptive methods can lead to use of methods not providing the expected level of protection. Hormonal contraceptives, especially Long-acting reversible contraception (LARC) were believed to inhibit fertility long after ending treatment.

PMID:37381022 | PMC:PMC10308677 | DOI:10.1186/s12978-023-01642-8

Clin Exp Rheumatol. 2023 Jun;41(6):1301-1309. doi: 10.55563/clinexprheumatol/i7kod6. Epub 2023 Jun 28.

ABSTRACT

OBJECTIVES: The COVID-19 pandemic, along with the associated restrictions and changes, has had a far-reaching impact on the mental health and well-being of people around the world. The most serious impact can arguably be observed in vulnerable populations, such as chronic pain patients. Using a pre-test/post-test design with pre-pandemic comparative data, the present study sought to investigate how the pandemic impacted chronic pain and well-being in individuals with fibromyalgia (FM) (N = 109).

METHODS: We assessed longitudinal changes of various clinical parameters, such as pain severity, disability, FM impact, depressive mood and several items assessing the individual experience of the pandemic as well as self-perceived changes of pain, anxiety, depression and physical activity levels.

RESULTS: Results suggested a significant self-perceived worsening of pain, depressive mood, anxiety as well as reduced physical activity due to the pandemic. Interestingly, these self-perceived changes were not reflected in longitudinal increases of test values (T1-T2). Pain severity at T1 was the strongest predictor of pain severity at T2, while COVID-related outcomes showed no critical importance, with COVID-related fear being the only significant predictor of T2 pain. The general perceived negative impact of the pandemic was the only predictor of self-perceived worsening of pain. Finally, patients with less severe pre-pandemic pain symptoms displayed greater longitudinal worsening of pain.

CONCLUSIONS: These findings emphasise the importance of addressing the specific needs of chronic pain suffers during a pandemic.

PMID:37378488 | DOI:10.55563/clinexprheumatol/i7kod6

J Appl Biomed. 2023 Jun;21(2):59-66. doi: 10.32725/jab.2023.010. Epub 2023 Jun 21.

ABSTRACT

BACKGROUND: The core motive of pharmacovigilance is the detection and prevention of adverse drug reactions (ADRs), to improve the risk-benefit balance of the drug. However, the causality assessment of ADRs remains a major challenge among clinicians, and none of the available tools of causality assessment used for assessing ADRs have been universally accepted.

OBJECTIVE: To provide an up-to-date overview of the different causality assessment tools.

METHODS: We conducted electronic searches in MEDLINE, EMBASE, and the Cochrane database. The eligibility of each tool was screened by three reviewers. Each eligible tool was then scrutinized for its domains (the reported specific set of questions/areas used for calculating the likelihood of cause-and-effect relation of an ADR) to discover the most comprehensive tool. Finally, we subjectively assessed the tool's ease-of-use in a Canadian, Indian, Hungarian, and Brazilian clinical context.

RESULTS: Twenty-one eligible causality assessment tools were retrieved. Naranjo's tool and De Boer's tool appeared the most comprehensive among all the tools, covering 10 domains each. Regarding "ease-of-use" in a clinical setting, we judged that many tools were hard to implement in a clinical context because of their complexity and/or lengthiness. Naranjo's tool, Jones's tool, Danan and Benichou's tool, and Hsu and Stoll's tool appeared to be the easiest to implement into various clinical contexts.

CONCLUSION: Among the many tools identified, 1981 Naranjo's scale remains the most comprehensive and easy to use for performing causality assessment of ADRs. Upcoming analysis should compare the performance of each ADR tool in clinical settings.

PMID:37376882 | DOI:10.32725/jab.2023.010

Viruses. 2023 May 25;15(6):1235. doi: 10.3390/v15061235.

ABSTRACT

Since the COVID-19 outbreak began, an association between COVID-19 and thrombotic diseases has been underlined. Although this association is more frequent with venous thromboembolism, ischaemic stroke has also been reported as a thrombotic complication in several cohorts of affected patients. Furthermore, the association between ischaemic stroke and COVID-19 has been considered a risk factor for early mortality. On the other hand, after the successful vaccination campaign, the incidence and the virulence of SARS-CoV-2 decreased, though it has been observed that COVID-19 may induce a severe infection in specific cohorts of frail subjects. For this reason, different drugs have been introduced of an antiviral action in order to improve the disease outcome of frail patients. In this field, with the arrival of a neutralizing monoclonal antibody against SARS-CoV-2, in particular, sotrovimab, a further chance to treat high-risk patients with mild-to-moderate COVID-19 arrived, achieving a concrete reduction in the risk of disease progression. We here report our clinical experience of an ischaemic stroke occurring a few minutes after the administration of sotrovimab for the treatment of moderate COVID-19 in a frail patient with chronic lymphocytic leukaemia. Other causes of ischaemic stroke were ruled out, and in order to evaluate the probability of a rare side effect, the Naranjo probability scale has also been utilized. In conclusion, among several side effects that have been described during the treatment of COVID-19 with sotrovimab, ischaemic stroke was not reported. Therefore, we here report a rare case of ischaemic stroke with early clinical manifestation after the administration of sotrovimab for the treatment of moderate COVID-19 in an immunocompromised patient for the first time.

PMID:37376535 | PMC:PMC10305374 | DOI:10.3390/v15061235

Nutrients. 2023 Jun 8;15(12):2666. doi: 10.3390/nu15122666.

ABSTRACT

The aim of this study was to assess the available evidence regarding the effect of a variety of fasting-like regimens on preventing chemotherapy-related side effects. PubMed, Scopus and Embase were used to select the studies for this review, which concluded on 24 November 2022. All types of clinical trials and case series reporting chemotherapy toxicity associated with fasting regimens and any comparison were considered. A total of 283 records were identified, of which 274 were excluded, leaving only nine studies that met the inclusion criteria. Five of these trials were randomized. Overall, moderate to high-quality evidence showed that several fasting regimens did not provide benefits compared to a conventional diet or other comparators in reducing the risk of adverse events. The overall pooled estimate for a variety of fasting regime when compared to non-fasting, indicated no significant difference in the side effects (RR = 1.10; 95% CI: 0.77-1.59; I2 = 10%, p = 0.60), including neutropenia alone (RR = 1.33; 95% CI: 0.90-1.97; I2 = 0%, p = 0.15). A sensitivity analysis confirmed these results. Based on our systematic review and meta-analysis, there is currently no evidence supporting the superiority of therapeutic fasting over non-fasting in preventing chemotherapy toxicity. The development of cancer treatment that do not entail toxicities remains imperative.

PMID:37375570 | PMC:PMC10303481 | DOI:10.3390/nu15122666

Medicina (Kaunas). 2023 Jun 2;59(6):1075. doi: 10.3390/medicina59061075.

ABSTRACT

Background and Objectives: Solid organ transplant (SOT) recipients have a higher risk of suffering from severe Coronavirus (COVID-19) compared to the general population. Studies have shown impaired immunogenicity of mRNA vaccines in this high-risk population; thus, SOT recipients have been prioritized globally for primary and booster doses. Materials and Methods: We analyzed 144 SOT recipients who had previously received two doses of BNT162b2 or mRNA1273 vaccine, and who were subsequently vaccinated with a booster dose of the mRNA1273 vaccine. Humoral and cellular immune responses were measured 1 and 3 months after the second dose, and 1 month after the third dose. Results: One month after the second dose, 33.6% (45/134) of patients displayed a positive antibody response with a median (25th, 75th) antibody titer of 9 (7, 161) AU/mL. Three months after the second dose, 41.8% (56/134) tested positive with a median (25th, 75th) antibody titer of 18 (7, 251) AU/mL. After the booster dose, the seropositivity rate increased to 69.4% (93/134), with a median (25th, 75th) titer of 966 (10, 8027) AU/mL. The specific SARS-CoV-2 T-cell response was assessed in 44 randomly selected recipients 3 months after the second dose, and 11.4% (5/44) of them had a positive response. Following the third dose, 42% (21/50) tested positive. Side effects after the third dose were mild, with pain at the injection site being the most frequent adverse effect, reported by 73.4% of the recipients. Conclusion: Our study shows a mild delayed increase in antibody titer, three months after primary vaccination compared to one month after. It also shows a robust augmentation of humoral and specific T-cell responses after the booster dose, as well as the safety and tolerability of the mRNA vaccines in SOT recipients.

PMID:37374279 | PMC:PMC10304658 | DOI:10.3390/medicina59061075

Medicina (Kaunas). 2023 May 25;59(6):1022. doi: 10.3390/medicina59061022.

ABSTRACT

Metabolic syndrome is a multifaceted pathophysiologic condition that is largely caused by an imbalance between caloric intake and energy expenditure. The pathogenesis of metabolic syndrome is determined by an individual's genetic/epigenetics and acquired factors. Natural compounds, notably plant extracts, have antioxidant, anti-inflammatory, and insulin-sensitizing properties and are considered to be a viable option for metabolic disorder treatment due to their low risk of side effects. However, the limited solubility, low bioavailability, and instability of these botanicals hinder their performance. These specific limitations have prompted the need for an efficient system that reduces drug degradation and loss, eliminates unwanted side effects, and boosts drug bioavailability, as well as the percentage of the drug deposited in the target areas. The quest for an enhanced (effective) drug delivery system has led to the formation of green-engineered nanoparticles, which has increased the bioavailability, biodistribution, solubility, and stability of plant-based products. The unification of plant extracts and metallic nanoparticles has helped in the development of new therapeutics against metabolic disorders such as obesity, diabetes mellitus, neurodegenerative disorders, non-alcoholic fatty liver, and cancer. The present review outlines the pathophysiology of metabolic diseases and their cures with plant-based nanomedicine.

PMID:37374226 | PMC:PMC10302892 | DOI:10.3390/medicina59061022

Int J Mol Sci. 2023 Jun 20;24(12):10405. doi: 10.3390/ijms241210405.

ABSTRACT

SARS-CoV-2 vaccination offered the opportunity to emerge from the pandemic and, thereby, worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe, but side effects are being reported more frequently as more and more people around the world become treated. Myopericarditis is the major, but not the only cardiovascular complication of this vaccine; hence it is important not to underestimate other side effects. We report a case series of patients affected by cardiac arrhythmias post-mRNA vaccine from our clinical practice and the literature. Reviewing the official vigilance database, we found that heart rhythm disorders after COVID vaccination are not uncommon and deserve more clinical and scientific attention. Since the COVID vaccine is the only vaccination related to this side effect, questions arose about whether these vaccines could affect heart conduction. Although the risk-benefit ratio is clearly in favor of vaccination, heart rhythm disorders are not a negligible issue, and there are red flags in the literature about the risk of post-vaccination malignant arrhythmias in some predisposed patients. In light of these findings, we reviewed the potential molecular pathways for the COVID vaccine to impact cardiac electrophysiology and cause heart rhythm disorders.

PMID:37373551 | DOI:10.3390/ijms241210405

Cancer Chemother Pharmacol. 2023 Jun 28. doi: 10.1007/s00280-023-04557-0. Online ahead of print.

ABSTRACT

PURPOSE: Rhabdomyolysis, which is primarily characterized by serum creatine kinase (CK) elevation, is a potentially fatal disease, and it can occur in a variety of etiologies, including drug-induced. Cabozantinib is one of the standard treatments for patients with renal cell carcinoma (RCC). This retrospective case series aimed to investigate the frequency of cabozantinib-induced CK elevation and rhabdomyolysis, and to reveal their detailed clinical features.

METHODS: To investigate the frequency of cabozantinib-induced serum CK elevation and rhabdomyolysis, we retrospectively reviewed the clinical information and laboratory data of the patients with advanced RCC who received cabozantinib monotherapy at our institution from April 2020 to April 2023. Data were retrieved from the electronic medical records and the RCC database of our institution. Primary endpoint of the current case series was the frequency of CK elevation and rhabdomyolysis.

RESULTS: Sixteen patients were retrieved form the database and 13 were included in the case series (excluded by clinical trial enrollment [n = 2] and short-term administration [n = 1]). Eight (61.5%) patients among them experienced serum CK elevation, including five patients who were classified into grade 1. CK elevation occurred a median of 14 days after initiation of cabozantinib. Two patients with grade 2 or 3 of CK elevation developed rhabdomyolysis with muscle weakness and/or acute kidney injury.

CONCLUSIONS: CK elevation may frequently happen during cabozantinib treatment, and in most cases, it may be asymptomatic and may not be clinically problematic. However, medical providers should be aware that symptomatic CK elevations suggestive of rhabdomyolysis may occasionally occur.

PMID:37380798 | DOI:10.1007/s00280-023-04557-0

Cancer Chemother Pharmacol. 2023 Jun 28. doi: 10.1007/s00280-023-04559-y. Online ahead of print.

ABSTRACT

PURPOSE: The objective of this study was to investigate the pharmacokinetic characteristics of pegylated liposomal doxorubicin (PLD) in Chinese female patients with advanced breast cancer by constructing population pharmacokinetic (popPK) models of liposome-encapsulated and free doxorubicin. Additionally, the relationship between pharmacokinetic parameters and drug-related adverse events (AEs) was explored through toxicity correlation analysis.

METHODS: A total of 20 patients with advanced breast cancer were selected from a PLD bioequivalence study. All patients received a single intravenous dose of 50 mg/m2 PLD. Plasma concentrations were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A popPK model was simultaneously built to characterize the pharmacokinetic profiles of liposome-encapsulated and free doxorubicin by non-linear mixed effects model (NONMEM). PLD-related toxicities were graded according to the common terminology criteria for adverse events (CTCAE) v5.0. The Spearman correlation analysis was conducted to explore the relationship between pharmacokinetic parameters and drug-related AEs of both liposome-encapsulated doxorubicin and free doxorubicin.

RESULTS: The concentration-time profiles of both liposome-encapsulated doxorubicin and free doxorubicin were well described by a one-compartment model. The most common AEs to PLD were nausea, vomiting, neutropenia, leukopenia, and stomatitis, most of which were grade I-II. The toxicity correlation analysis results indicated that stomatitis was related to the Cmax of liposome-encapsulated doxorubicin (P < 0.05). No other AEs were found to be correlated with the pharmacokinetic parameters of either free or liposome-encapsulated doxorubicin.

CONCLUSION: A one-compartment model adequately described the popPK characteristics of both liposome-encapsulated and free doxorubicin in Chinese female patients with advanced breast cancer. Most AEs to PLD were mild. Additionally, the occurrence of mucositis may be positively correlated with the Cmax of liposome-encapsulated doxorubicin.

PMID:37378676 | DOI:10.1007/s00280-023-04559-y

Int J Mol Sci. 2023 Jun 7;24(12):9871. doi: 10.3390/ijms24129871.

ABSTRACT

Aspirin (ASA) is a popular nonsteroidal anti-inflammatory drug (NSAID), which exerts its therapeutic properties through the inhibition of cyclooxygenase (COX) isoform 2 (COX-2), while the inhibition of COX-1 by ASA results in the formation of gastrointestinal side effects. Due to the fact that the enteric nervous system (ENS) is involved in the regulation of digestive functions both in physiological and pathological states, the aim of this study was to determine the influence of ASA on the neurochemical profile of enteric neurons in the porcine duodenum. Our research, conducted using the double immunofluorescence technique, proved an increase in the expression of selected enteric neurotransmitters in the duodenum as a result of ASA treatment. The mechanisms of the visualized changes are not entirely clear but are probably related to the enteric adaptation to inflammatory conditions resulting from aspirin supplementation. A detailed understanding of the role of the ENS in the development of drug-induced inflammation will contribute to the establishment of new strategies for the treatment of NSAID-induced lesions.

PMID:37373019 | DOI:10.3390/ijms24129871

CMAJ Open. 2023 Jun 27;11(3):E569-E578. doi: 10.9778/cmajo.20210291. Print 2023 May-Jun.

ABSTRACT

BACKGROUND: Previous research has shown that cocaine-associated deaths occur more frequently in hot weather, which has not been described for other illicit drugs or combinations of drugs. The study objective was to evaluate the relation between temperature and risk of death related to cocaine, opioids and amphetamines in British Columbia, Canada.

METHODS: We extracted data on all deaths with cocaine, opioid or amphetamine toxicity recorded as an underlying or contributing cause from BC vital statistics for 1998-2017. We used a time-stratified case-crossover design to estimate the effect of temperature on the risk of death associated with acute drug toxicity during the warmer months (May through September). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for each 10°C increase in the 2-day average maximum temperature at the residential location.

RESULTS: We included 4913 deaths in the analyses. A 10°C increase in the 2-day average maximum temperature was associated with an OR of 1.43 (95% CI 1.11-1.86) for deaths with only cocaine toxicity recorded (n = 561), an OR of 1.15 (95% CI 0.99-1.33) for deaths with opioids only (n = 1682) and an OR of 1.11 (95% CI 0.60-2.04) for deaths with amphetamines only (n = 133). There were also elevated effects when toxicity from multiple drugs was recorded. Sensitivity analyses showed differences in the ORs by sex, by climatic region, and when the location of death was used instead of the location of residence.

INTERPRETATION: Increasing temperatures were associated with higher odds of death due to drug toxicity, especially for cocaine alone and combined with other drugs. Targeted interventions are necessary to prevent death associated with toxic drug use during hot weather.

PMID:37369523 | DOI:10.9778/cmajo.20210291

Cochrane Database Syst Rev. 2023 Jun 23;6(6):CD006586. doi: 10.1002/14651858.CD006586.pub5.

ABSTRACT

BACKGROUND: Premenstrual syndrome (PMS) is a common problem. Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome. Combined oral contraceptives (COC), which provide both progestin and oestrogen, have been examined for their ability to relieve premenstrual symptoms. A combined oral contraceptive containing drospirenone and a low oestrogen dose has been approved for treating PMDD in women who choose combined oral contraceptives for contraception.

OBJECTIVES: To evaluate the effectiveness and safety of COCs containing drospirenone in women with PMS.

SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group trial register, CENTRAL (now containing output from two trials registers and CINAHL), MEDLINE, Embase, PsycINFO, LILACS, Google Scholar, and Epistemonikos on 29 June 2022. We checked included studies' reference lists and contacted study authors and experts in the field to identify additional studies.

SELECTION CRITERIA: We included randomised controlled trials (RCT) that compared COCs containing drospirenone with placebo or with another COC for treatment of women with PMS.

DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The primary review outcomes were effects on premenstrual symptoms that were prospectively recorded, and withdrawal due to adverse events. Secondary outcomes included effects on mood, adverse events, and response rate to study medications.

MAIN RESULTS: We included five RCTs (858 women analysed, most diagnosed with PMDD). The evidence was very low to moderate quality; the main limitations were serious risk of bias due to poor reporting of study methods, and serious inconsistency and imprecision. COCs containing drospirenone and ethinylestradiol (EE) versus placebo COCs containing drospirenone and EE may improve overall premenstrual symptoms (standardised mean difference (SMD) -0.41, 95% confidence interval (CI) -0.59 to -0.24; 2 RCTs, N = 514; I2 = 64%; low-quality evidence); and functional impairment due to premenstrual symptoms in terms of productivity (mean difference (MD) -0.31, 95% CI -0.55 to -0.08; 2 RCTs, N = 432; I2 = 47%; low-quality evidence), social activities (MD -0.29, 95% CI -0.54 to -0.04; 2 RCTs, N = 432; I2 = 53%; low-quality evidence), and relationships (MD -0.30, 95% CI -0.54 to -0.06; 2 RCTs, N = 432; I2 = 45%; low-quality evidence). The effects from COCs containing drospirenone may be small to moderate. COCs containing drospirenone and EE may increase withdrawal from trials due to adverse effects (odds ratio (OR) 3.41, 95% CI 2.01 to 5.78; 4 RCT, N = 776; I2 = 0%; low-quality evidence). This suggests that if you assume the risk of withdrawal due to adverse effects from placebo is 3%, the risk from drospirenone plus EE will be between 6% and 16%. We are uncertain of the effect of drospirenone plus EE on premenstrual mood symptoms, when measured by validated tools that were not developed to assess premenstrual symptoms. COCs containing drospirenone may lead to more adverse effects in total (OR 2.31, 95% CI 1.71 to 3.11; 3 RCT, N = 739; I2 = 0%; low-quality evidence). This suggests that if you assume the risk of having adverse effects from placebo is 28%, the risk from drospirenone plus EE will be between 40% and 54%. It probably leads to more breast pain, and may lead to more nausea, intermenstrual bleeding, and menstrual disorder. Its effect on nervousness, headache, asthenia, and pain is uncertain. There was no report of any rare but serious adverse effects, such as venous thromboembolism in any of the included studies. COCs containing drospirenone may improve response rate (OR 1.65, 95% CI 1.13 to 2.40; 1 RCT, N = 449; I2 not applicable; low-quality evidence). This suggests that if you assume the response rate from placebo is 36%, the risk from drospirenone plus EE will be between 39% and 58%. We did not identify any studies that compared COCs containing drospirenone with other COCs.

AUTHORS' CONCLUSIONS: COCs containing drospirenone and EE may improve premenstrual symptoms that result in functional impairments in women with PMDD. The placebo also had a significant effect. COCs containing drospirenone and EE may lead to more adverse effects compared to placebo. We do not know whether it works after three cycles, helps women with less severe symptoms, or is better than other combined oral contraceptives that contain a different progestogen.

PMID:37365881 | PMC:PMC10289136 | DOI:10.1002/14651858.CD006586.pub5

Pharmacol Res Perspect. 2023 Aug;11(4):e01110. doi: 10.1002/prp2.1110.

ABSTRACT

Recently, post-marketing safety measures have been considered critical in Japan due to the globalization of drug development and the introduction of new drug approval systems. Pharmacists are expected to play an active role in ensuring the safety of drugs post-approval. Utilizing risk management plans (RMPs) to ensure safety throughout the development and post-marketing phases is becoming even more critical. In this study, we examine the relationship between the safety specifications (SSs) in RMPs at the time of drug approval and the adverse reactions (ARs) added to the clinically significant adverse reactions (CSARs) section of the package inserts (PIs) post-approval to determine whether SSs constitute useful drug information for pharmacists. The analysis included new active ingredient-containing drugs approved in Japan from FY2013 to 2019. A 2 × 2 contingency table was created and analyzed using odds ratios (ORs) and Fisher's exact test. The OR was 14.22 (95% CI: 7.85-24.77; p < .001), which indicates a strong relationship between the ARs being SSs at the time of approval and being added to the PIs as CSARs post-approval. The positive predictive value that SSs at the time of approval were added as CSARs to the PIs post-approval was 7.1%. In addition, a similar relationship was observed with the "approval in shorter-period drugs" reviewed for approval based on a limited number of clinical trials. Therefore, SSs in RMPs are important drug information for pharmacists in Japan.

PMID:37365794 | DOI:10.1002/prp2.1110