Cureus. 2023 Jan 16;15(1):e33831. doi: 10.7759/cureus.33831. eCollection 2023 Jan.

ABSTRACT

Paxlovid (nirmatrelvir/ritonavir) is a game changer in the fight against COVID-19 due to its ease of administration and significant benefits of reducing progression to severe COVID-19, hospitalization, and death. Cardiac adverse events such as bradycardia and syncope are not known with this medication. We report a case of a 71-year-old patient who developed symptomatic bradycardia, syncopal episodes, and sinus pause after taking Paxlovid. Discontinuing medication and intravenous atropine helped to reverse the bradycardia and symptoms promptly. She did not require a pacemaker. We would like to report this possible association between Paxlovid and bradycardia. Until further information or studies are available, it is advised to promptly discontinue Paxlovid after any evidence of bradycardia and closely monitor for at least 40 hours in a hospital setting. The reported half-life (t 1/2) of the medication is 6.05 ± 1.79 hours and using 8 hours as a reference for the upper limit of t 1/2, around 97 % of the medication should be cleared off in about 40 hours (five half-lives).

PMID:36655157 | PMC:PMC9842109 | DOI:10.7759/cureus.33831

Innov Pharm. 2022 Dec 12;13(2). doi: 10.24926/iip.v13i2.4541. eCollection 2022.

ABSTRACT

Drug-induced Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson Syndrome (SJS), and Toxic Epidermal Necrolysis (TEN) are rare but life-threatening immune-mediated drug reactions known as Severe Cutaneous Adverse Reactions (SCARs). These severe drug reactions have been associated with many commonly prescribed medications, including sulfonamides, allopurinol, carbamazepine, and several antiepileptic drugs including lamotrigine.1 Although the risk of these adverse events is recognized by many medical providers, the risk may be overlooked when prescribing lamotrigine for mood disorders. Review of the literature and the experience of these cases suggest that the risk of lamotrigine-associated SCARs is increased when starting lamotrigine at high initial doses. Here we present and discuss two cases of SCARs attributed to high-dose lamotrigine prescribed for mood disorders. A third patient also presented with a SCAR related to high-dose lamotrigine prescribed for a mood disorder during this time but was lost to follow-up and was not reachable. All three patients presented to our hospital system from 2019-2020. Due to this clinical experience, we recommend that pharmacists and prescribers alike be alerted of the risk of severe cutaneous drug reactions when lamotrigine is prescribed, particularly at initial doses greater than 25 mg.

PMID:36654707 | PMC:PMC9836753 | DOI:10.24926/iip.v13i2.4541

J Dermatol. 2023 Jan 17. doi: 10.1111/1346-8138.16715. Online ahead of print.

ABSTRACT

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous drug adverse reaction characterized by various cutaneous and systemic manifestations. However, reports on the various patterns of alopecia after DRESS are lacking. Thus, we aimed to describe cases of alopecia after DRESS and review the literature. This multicentric retrospective study reviewed the records of 182 patients diagnosed with DRESS from 2009 to 2021; of these, 10 who had alopecia after DRESS were included. Patients were diagnosed with permanent alopecia (n = 4), telogen effluvium (n = 5), and alopecia areata (n = 1), and were treated with topical minoxidil or alfatradiol (6; 60%), topical corticosteroids (3; 30%), dietary supplements (6; 60%), systemic corticosteroids (1; 10%), and intralesional corticosteroid injection (2; 20%). Although patients with permanent alopecia did not show hair regrowth after 6 months, those with telogen effluvium and alopecia areata experienced marked clinical improvement within 6 months. Various types of alopecia can persist over an extended period, even after the resolution of an acute episode of DRESS.

PMID:36651019 | DOI:10.1111/1346-8138.16715

Sci Rep. 2023 Jan 17;13(1):934. doi: 10.1038/s41598-022-27238-z.

ABSTRACT

Although numerous studies have reported the association between sarcopenia and the prognosis of hepatocellular carcinoma (HCC) patients, there is lack of a newer and more comprehensive meta-analysis. Herein, a comprehensive literature search was performed on PubMed, Web of Science, the Cochrane Library, and Embase databases to identify relevant studies published up to February 2022. The outcomes were overall survival (OS), recurrence, progression-free survival, tumor response, severe postoperative complications, and toxicity of drugs. A total of 57 studies involving 9790 HCC patients were included in the meta-analysis. The pooled prevalence of sarcopenia in HCC patients was 41.7% (95% CI 36.2-47.2%). Results demonstrated that sarcopenia was significantly associated with impaired OS (HR: 1.93, 95% CI 1.73-2.17, P < 0.001), higher risk of tumor recurrence (HR: 1.75, 95% CI 1.56-1.96, P < 0.001), lower objective response rate (OR: 0.37 95% CI 0.17-0.81, P = 0.012), and more drug-related adverse events (OR: 2.23, 95% CI 1.17-4.28, P = 0.015) in HCC patients. The subgroup analyses revealed that the OS of patients at the early stage of tumor was more severely affected by sarcopenia than for patients at other stages. Moreover, the presence of cirrhosis and Child Pugh class B increased the hazard of mortality from sarcopenia. This study has shown that sarcopenia is highly associated with poor prognosis in HCC patients. In addition, cirrhosis and poor liver functional reserve increase the danger of sarcopenia. OS was more impaired in HCC patients with sarcopenia at early stage of tumor than at other tumor stages.

PMID:36650190 | DOI:10.1038/s41598-022-27238-z

J Oral Rehabil. 2023 Jan 17. doi: 10.1111/joor.13414. Online ahead of print.

ABSTRACT

BACKGROUND: The nocebo response refers to the phenomenon where nonspecific factors, including negative verbal suggestion and treatment expectations, cause adverse events (AE) following a placebo treatment. Nonspecific factors are also likely to influence AE occurrence following administration of active pharmacological treatments.

OBJECTIVE: This meta-analysis aimed to estimate the nocebo response in dentistry by assessing the AEs prevalence in placebo- and active arms of randomised controlled trials (RCTs) assessing analgesic treatment following third molar (M3) surgery.

METHODS: A systematic search was performed in PubMed, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials. Eligible studies had to report the number of patients experiencing at least one drug-related AE (patients with AE ≥ 1) separately for the active and placebo arms. The proportion of patients with AE ≥ 1 and drug-related dropouts were pooled, and risk differences (RDs) between patients in the placebo- and active arm were calculated.

RESULTS: In 50 independent RCTs of 47 identified articles, the pooled rates of patients with AE ≥ 1 were 22.8% in the placebo arm and 20.6% in the active arm. The pooled rates of drug-related dropout were 0.24% in the placebo arm and 0.08% in the active arm. There were no significant RDs in patients with AE ≥ 1 and drug-related dropouts.

CONCLUSION: These results show that patients in the placebo arm reported AEs to the same extent as patients receiving active treatment, suggesting that most AEs in analgesic medication following M3 surgery may be attributed to the nocebo phenomenon.

PMID:36648379 | DOI:10.1111/joor.13414

Eur J Anaesthesiol. 2023 Jan 18. doi: 10.1097/EJA.0000000000001799. Online ahead of print.

ABSTRACT

BACKGROUND: HSK3486 (ciprofol) is a 2,6-disubstituted phenol derivative that acts like propofol as an agonist at the gamma-aminobutyric acid-A (GABAA) receptor.

OBJECTIVE: To investigate the efficacy and safety of HSK3486 for general anaesthesia induction and maintenance.

DESIGN: A single-blinded, randomised, parallel-group, phase 3 trial.

SETTING: Involving 10 study centres, from November 24, 2020 to January 25, 2021.

PATIENTS: A total of 129 patients undergoing nonemergency, noncardiothoracic, and nonbrain elective surgery.

INTERVENTION: Patients were randomly assigned at a 2:1 ratio into HSK3486 or propofol groups, to receive HSK3486 (0.4 mg kg-1) or propofol (2.0 mg kg-1) for induction before a maintenance infusion at initial rates of 0.8 and 5.0 mg kg-1 h-1, and were adjusted to maintain a bispectral index (BIS) of 40-60 until the end of surgery.

MAIN OUTCOME MEASURES: Noninferiority between the drugs was evaluated as the lower limit of the 95% confidence interval (CI) for the between-group difference in the success rate of anesthetic maintenance (primary outcome) >-8%. Secondary outcomes included successful anaesthetic induction, full alertness and spontaneous breathing recovery, time until leaving the postanaesthesia care unit and changes in BIS. Safety profiles were also measured.

RESULTS: Of 129 enrolled patients, 128 completed the trial, with 86 in the HSK3486 group and 42 in the propofol group. The success rate for the maintenance of general anaesthesia was 100% for both groups, and noninferiority of HSK3486 was confirmed (95% CI -4.28% to 8.38%). No significant differences were found between the two groups of patients with regard to secondary outcomes (all P > 0.05). There appeared to be a comparable incidence of treatment for emergency adverse events (TEAEs) (80.2% vs. 81.0%, P = 1.000) and drug-related TEAEs (57.0% vs. 64.3%, P = 0.451) in the HSK3486 and propofol groups.

CONCLUSION: HSK3486 had a noninferior efficacy profile compared to propofol, exhibiting excellent tolerance.

TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT04511728.

PMID:36647565 | DOI:10.1097/EJA.0000000000001799

JMIR Public Health Surveill. 2023 Jan 16;9:e40080. doi: 10.2196/40080.

ABSTRACT

BACKGROUND: Adverse drug reactions (ADRs) are unintended consequences of medication use and may result in hospitalizations or deaths. Timely reporting of ADRs to regulators is essential for drug monitoring, research, and maintaining patient safety, but it has not been standardized in Australia.

OBJECTIVE: We sought to explore the ways that ADRs are monitored or reported in Australia. We reviewed how consumers and health care professionals participate in ADR monitoring and reporting.

METHODS: The Arksey and O'Malley framework provided a methodology to sort the data according to key themes and issues. Web of Science, Scopus, Embase, PubMed, CINAHL, and Computer & Applied Sciences Complete databases were used to extract articles published from 2010 to 2021. Two reviewers screened the papers for eligibility, extracted key data, and provided descriptive analysis of the data.

RESULTS: Seven articles met the inclusion criteria. The Adverse Medicine Events Line (telephone reporting service) was introduced in 2003 to support consumer reporting of ADRs; however, only 10.4% of consumers were aware of ADR reporting schemes. Consumers who experience side effects were more likely to report ADRs to their doctors or pharmacists than to the drug manufacturer. The documentation of ADR reports in hospital electronic health records showed that nurses and pharmacists were significantly less likely than doctors to omit the description of the drug reaction, and pharmacists were significantly more likely to enter the correct classification of the drug reaction than doctors. Review and analysis of all ADR reports submitted to the Therapeutic Goods Administration highlighted a decline in physician contribution from 28% of ADR reporting in 2003 to 4% in 2016; however, within this same time period, hospital and community pharmacists were a major source of ADR reporting (ie, 16%). In 2014, there was an increase in ADR reporting by community pharmacists following the introduction of the GuildLink ADR web-based reporting system; however, a year later, the reporting levels dropped. In 2018, the Therapeutic Goods Administration introduced a black triangle scheme on the packaging of newly approved medicines, to remind and encourage ADR reporting on new medicines, but this was only marginally successful at increasing the quantity of ADR reports.

CONCLUSIONS: Despite the existence of national and international guidelines for ADR reporting and management, there is substantial interinstitutional variability in the standards of ADR reporting among individual health care facilities. There is room for increased ADR reporting rates among consumers and health care professionals. A thorough assessment of the barriers and enablers to ADR reporting at the primary health care institutional levels is essential. Interventions to increase ADR reporting, for example, the black triangle scheme (alert or awareness) or GuildLink (digital health), have only had marginal effects and may benefit from further improvement revisions and awareness programs.

PMID:36645706 | DOI:10.2196/40080

Lakartidningen. 2023 Jan 12;120:22097.

NO ABSTRACT

PMID:36644956

F1000Res. 2022 Apr 19;11:434. doi: 10.12688/f1000research.110268.2. eCollection 2022.

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines efficacy and safety have been tested in phase 3 studies in which cancer patients were not included or were underrepresented. Methods: The objective of this study is to evaluate the safety profile of the mRNA-1273 vaccine across cancer patients and its relationship to patients' demographics. We selected from our records all 18-years or older solid cancer patients under active treatment vaccinated with the complete three-dose schedule mRNA-1273 vaccine whose adverse drug reactions (ADRs) after each dose were recorded. Medical records were reviewed retrospectively to collect data between April 19, 2021, and December 31, 2021. Patients with documented previous infection by SARS-Cov-2 were excluded. Results: A total of 93 patients met the inclusion criteria. Local ADRs were reported more frequently after the first and second dose than after the third (41.9%, 43% and 31.1% of the patients respectively), while systemic ADRs followed the opposite pattern (16.1%, 34.4% and 52.6% of the patients respectively). We found a statistically significant association between sex and systemic adverse reactions after the third dose, p < 0.001 and between systemic adverse reactions after the second dose and systemic adverse reactions after the third dose, p = 0.001 A significant linear trend, p = 0.012, with a higher Eastern Cooperative Oncology Group (ECOG) score associated with a lower proportion of patients suffering from systemic side effects was found. Women had 5.79 times higher odds to exhibit systemic ADRs after the third dose (p=0.01) compared to males. Increasing age was associated with a decreased likelihood of exhibiting ADRs (p=0.016). Conclusion: The mRNA-1273 vaccine shows a tolerable safety profile. The likelihood of ADRs appears to be associated with gender and age. Its association with ECOG scores is less evident. Further studies are needed to elucidate this data in cancer patients.

PMID:36636471 | PMC:PMC9816496 | DOI:10.12688/f1000research.110268.2

Naunyn Schmiedebergs Arch Pharmacol. 2023 Jan 16. doi: 10.1007/s00210-023-02382-z. Online ahead of print.

ABSTRACT

Drug-induced cardiotoxicity is a life-threatening side effect of doxorubicin (DOX) treatment that impacts patient prognosis and survival. In the majority of cases, the acute clinical form often remains asymptomatic, with few patients presenting rather nonspecific electrocardiographic abnormalities. While chronic toxicity has been more widely studied, the alterations appearing in acute cardiotoxicity are much less investigated. Thus, our in vivo study aimed to evaluate the process of DOX-induced acute myocardial toxicity by investigating oxidative stress and autophagy markers as mechanisms of myocardial toxicity in correlation with echocardiography and electrocardiography findings. Our results show that both autophagy and oxidative homeostasis were disrupted as soon as 7 days after DOX treatment, alterations that occurred even before the significant increase of NT-proBNP, a clinical marker for cardiac suffering. Moreover, we found a large number of alterations in the electrocardiography and echocardiography of treated rats. These findings suggest that DOX-induced myocardial toxicity started early after treatment initiation, possibly marking the initial phase of the unfolding process of cardiac damage. Further studies are required to completely decipher the mechanisms of DOX-induced cardiotoxicity.

PMID:36645429 | DOI:10.1007/s00210-023-02382-z

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