PLoS One. 2023 May 23;18(5):e0285736. doi: 10.1371/journal.pone.0285736. eCollection 2023.

ABSTRACT

BACKGROUND: The response to the vaccine may vary among individuals. Hence, it is important to know how often individuals experience side effects after immunization against COVID-19.

OBJECTIVE: This study aimed to assess the incidence of side effects following COVID-19 vaccination across different vaccine recipients in Southern Pakistan and identify the potential factors associated with these side effects in the population.

METHODS: The survey was conducted across Pakistan through Google-forms Links from August to October 2021. The questionnaire included demographic information and COVID-19 vaccine information. Chi-square (x2) was performed for comparative analysis to check the significance level with P <0.05. The final analysis included 507 participants who had received COVID-19 vaccines.

RESULTS: Of the total 507 COVID-19 vaccines recipients, 24.9% received CoronaVac, 36.5% received BBIBP-CorV, 14.2% received BNT162b2, 13.8% received AZD1222, and 10.7% received mRNA-1273. The most prominent side effects after the first dose were fever, weakness, lethargy, and pain at the site of injection. Moreover, the most commonly reported side effects after the second dose were pain at the injection site, headache, body ache, lethargy, fever, chills, flu-like symptoms, and diarrhea.

CONCLUSION: Our results suggested that the side effects due to COVID-19 vaccination can vary between the first and second doses and type of COVID-19 vaccine. Our findings suggest continuing monitoring of vaccine safety and the importance of individualized risk-benefit assessment for COVID-19 immunization.

PMID:37220099 | PMC:PMC10204992 | DOI:10.1371/journal.pone.0285736

Cochrane Database Syst Rev. 2023 May 22;5(5):CD002283. doi: 10.1002/14651858.CD002283.pub5.

ABSTRACT

BACKGROUND: Without a phase of retention after successful orthodontic treatment, teeth tend to 'relapse', that is, to return to their initial position. Retention is achieved by fitting fixed or removable retainers to provide stability to the teeth while avoiding damage to teeth and gums. Removable retainers can be worn full- or part-time. Retainers vary in shape, material, and the way they are made. Adjunctive procedures are sometimes used to try to improve retention, for example, reshaping teeth where they contact ('interproximal reduction'), or cutting fibres around teeth ('percision'). This review is an update of one originally published in 2004 and last updated in 2016.

OBJECTIVES: To evaluate the effects of different retainers and retention strategies used to stabilise tooth position after orthodontic braces.

SEARCH METHODS: An information specialist searched Cochrane Oral Health Trials Register, CENTRAL, MEDLINE, Embase and OpenGrey up to 27 April 2022 and used additional search methods to identify published, unpublished and ongoing studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) involving children and adults who had retainers fitted or adjunctive procedures undertaken to prevent relapse following orthodontic treatment with braces. We excluded studies with aligners.

DATA COLLECTION AND ANALYSIS: Two review authors independently screened eligible studies, assessed risk of bias and extracted data. Outcomes were stability or relapse of tooth position, retainer failure (i.e. broken, detached, worn out, ill-fitting or lost), adverse effects on teeth and gums (i.e. plaque, gingival and bleeding indices), and participant satisfaction. We calculated mean differences (MD) for continuous data, risk ratios (RR) or risk differences (RD) for dichotomous data, and hazard ratios (HR) for survival data, all with 95% confidence intervals (CI). We conducted meta-analyses when similar studies reported outcomes at the same time point; otherwise results were reported as mean ranges. We prioritised reporting of Little's Irregularity Index (crookedness of anterior teeth) to measure relapse, judging the minimum important difference to be 1 mm.

MAIN RESULTS: We included 47 studies, with 4377 participants. The studies evaluated: removable versus fixed retainers (8 studies); different types of fixed retainers (22 studies) or bonding materials (3 studies); and different types of removable retainers (16 studies). Four studies evaluated more than one comparison. We judged 28 studies to have high risk of bias, 11 to have low risk, and eight studies as unclear. We focused on 12-month follow-up. The evidence is low or very low certainty. Most comparisons and outcomes were evaluated in only one study at high risk of bias, and most studies measured outcomes after less than a year. Removable versus fixed retainers Removable (part-time) versus fixed One study reported that participants wearing clear plastic retainers part-time in the lower arch had more relapse than participants with multistrand fixed retainers, but the amount was not clinically significant (Little's Irregularity Index (LII) MD 0.92 mm, 95% CI 0.23 to 1.61; 56 participants). Removable retainers were more likely to cause discomfort (RR 12.22; 95% CI 1.69 to 88.52; 57 participants), but were associated with less retainer failure (RR 0.44, 95% CI 0.20 to 0.98; 57 participants) and better periodontal health (Gingival Index (GI) MD -0.34, 95% CI -0.66 to -0.02; 59 participants). Removable (full-time) versus fixed One study reported that removable clear plastic retainers worn full-time in the lower arch did not provide any clinically significant benefit for tooth stability over fixed retainers (LII MD 0.60 mm, 95% CI 0.17 to 1.03; 84 participants). Participants with clear plastic retainers had better periodontal health (gingival bleeding RR 0.53, 95% CI 0.31 to 0.88; 84 participants), but higher risk of retainer failure (RR 3.42, 95% CI 1.38 to 8.47; 77 participants). The study found no difference between retainers for caries. Different types of fixed retainers Computer-aided design/computer-aided manufacturing (CAD/CAM) nitinol versus conventional/analogue multistrand One study reported that CAD/CAM nitinol fixed retainers were better for tooth stability, but the difference was not clinically significant (LII MD -0.46 mm, 95% CI -0.72 to -0.21; 66 participants). There was no evidence of a difference between retainers for periodontal health (GI MD 0.00, 95% CI -0.16 to 0.16; 2 studies, 107 participants), or retainer survival (RR 1.29, 95% CI 0.67 to 2.49; 1 study, 41 participants). Fibre-reinforced composite versus conventional multistrand/spiral wire One study reported that fibre-reinforced composite fixed retainers provided better stability than multistrand retainers, but this was not of a clinically significant amount (LII MD -0.70 mm, 95% CI -1.17 to -0.23; 52 participants). The fibre-reinforced retainers had better patient satisfaction with aesthetics (MD 1.49 cm on a visual analogue scale, 95% CI 0.76 to 2.22; 1 study, 32 participants), and similar retainer survival rates (RR 1.01, 95% CI 0.84 to 1.21; 7 studies; 1337 participants) at 12 months. However, failures occurred earlier (MD -1.48 months, 95% CI -1.88 to -1.08; 2 studies, 103 participants; 24-month follow-up) and more gingival inflammation at six months, though bleeding on probing (BoP) was similar (GI MD 0.59, 95% CI 0.13 to 1.05; BoP MD 0.33, 95% CI -0.13 to 0.79; 1 study, 40 participants). Different types of removable retainers Clear plastic versus Hawley When worn in the lower arch for six months full-time and six months part-time, clear plastic provided similar stability to Hawley retainers (LII MD 0.01 mm, 95% CI -0.65 to 0.67; 1 study, 30 participants). Hawley retainers had lower risk of failure (RR 0.60, 95% CI 0.43 to 0.83; 1 study, 111 participants), but were less comfortable at six months (VAS MD -1.86 cm, 95% CI -2.19 to -1.53; 1 study, 86 participants). Part-time versus full-time wear of Hawley There was no evidence of a difference in stability between part-time and full-time use of Hawley retainers (MD 0.20 mm, 95% CI -0.28 to 0.68; 1 study, 52 participants).

AUTHORS' CONCLUSIONS: The evidence is low to very low certainty, so we cannot draw firm conclusions about any one approach to retention over another. More high-quality studies are needed that measure tooth stability over at least two years, and measure how long retainers last, patient satisfaction and negative side effects from wearing retainers, such as tooth decay and gum disease.

PMID:37219527 | PMC:PMC10202160 | DOI:10.1002/14651858.CD002283.pub5

J Pak Med Assoc. 2023 May;73(5):1168. doi: 10.47391/JPMA.7940.

NO ABSTRACT

PMID:37218272 | DOI:10.47391/JPMA.7940

Rev Alerg Mex. 2023 Apr 19;69(4):195-213. doi: 10.29262/ram.v69i4.1181.

ABSTRACT

BACKGROUND: Any substance used as a treatment for any disease can produce harmful or unpleasant events called adverse drug reactions (ADRs). They are due to inherent biological effects of the drug and are caused by immunological and non-immunological mechanisms.

OBJECTIVES: To describe the immunological mechanisms of hypersensitivity reactions (HSR) to drugs, their epidemiology, risk factors, classification, clinical manifestations, diagnosis, treatment, and prognosis.

METHODS: A review of the most current literature in English and Spanish was carried out, in the main databases, related to the HSR of various drug groups.

RESULTS: This study describes the terms used to define ADRs and HSRs, their classification and clinical manifestations, current diagnostic tools, treatment algorithms and prognosis of the most frequently used medications and with the highest prevalence of reported adverse events.

CONCLUSION: ADRs are a challenging entity, with a complex pathophysiology that has not been fully understood. Its approach requires a careful consideration since not all drugs have validated tests for their diagnosis nor a specific treatment. When indicating the use of any drug, the severity of the disease, the availability of other treatments and the potential risks of developing future adverse events should always be taken into consideration.

PMID:37218047 | DOI:10.29262/ram.v69i4.1181

Drug Metab Rev. 2023 May 22:1-15. doi: 10.1080/03602532.2023.2215478. Online ahead of print.

ABSTRACT

Tuberculosis (TB) remains a major global health burden. Antitubercular drugs (ATDs) such as isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), and ethambutol are used as first-line therapy in TB patients. Drug-induced liver injury is one of the common side effects that leads to the discontinuation of ATDs in TB patients. Therefore, this review discusses the molecular pathogenesis of ATDs induced liver injury. The biotransformation of INH, RIF, and PZA in the liver liberates several reactive intermediates, leading to peroxidation of the hepatocellular membrane and oxidative stress. INH + RIF administration decreased the expression of bile acid transporters such as the bile salt export pump and multidrug resistance-associated protein 2 and induced liver injury by sirtuin 1 and farnesoid X receptor pathway. INH inhibits the nuclear translocation of Nrf2 by interfering with its nuclear importer, karyopherin β1, thereby inducing apoptosis. INF + RIF treatments alter Bcl-2 and Bax homeostasis, mitochondrial membrane potential, and cytochrome c release, thereby triggering apoptosis. RIF administration enhances the expression of genes involved in fatty acid synthesis and hepatocyte fatty acid uptake (CD36). RIF induces the expression of peroxisome proliferator-activated receptor -γ and its downstream proteins and perilipin-2 by activating the pregnane X receptor in the liver to increase fatty infiltration into the liver. ATDs administration induces oxidative stress, inflammation, apoptosis, cholestasis, and lipid accumulation in the liver. However, ATDs toxic potentials are not elaborately studied at the molecular level in clinical samples. Therefore, future studies are warranted to explore ATDs induced liver injuries at the molecular level in clinical samples whenever possible.

PMID:37218081 | DOI:10.1080/03602532.2023.2215478

CNS Drugs. 2023 May;37(5):453-465. doi: 10.1007/s40263-023-01001-y. Epub 2023 May 22.

ABSTRACT

BACKGROUND AND OBJECTIVE: OnabotulinumtoxinA (BoNTA) is a relatively safe and effective treatment for chronic migraine. The local mode of action of BoNTA favors the combination of oral treatments with systemic action. However, little is known about the possible interactions with other preventive treatments. The objective of the study was to describe the use of oral preventive treatments in patients with chronic migraine treated with BoNTA in routine clinical care and discuss the tolerability and efficacy according to the presence or absence of concomitant oral treatments.

METHODS: In this multicenter, observational, retrospective, cohort study, we collected data from patients with chronic migraine receiving prophylactic treatment with BoNTA. Patients were eligible if aged ≥18 years, diagnosed with chronic migraine according to the International Classification of Headache Disorders, Third Edition criteria, and treated with BoNTA according to the PREEMPT paradigm. We documented the proportion of patients with at least one concomitant treatment prescribed specifically for migraine (CT+M) and their side effects during four BoNTA treatment cycles. Additionally, we collected monthly headache days and monthly acute medication days from the patients' headache diaries. Patients with CT+M were compared to those without concomitant treatment (CT-) using a nonparametric approach.

RESULTS: Our cohort included 181 patients taking BoNTA, of whom 77 (42.5%) received a CT+M. The most frequently prescribed concomitant treatments were antidepressants and antihypertensive drugs. Side effects in the CT+M group occurred in 14 patients (18.2%). Only in three of them (3.9%), the side effects had a significant interference with the patient's functioning (all in topiramate 200-mg/day users). Both CT+M and CT- groups had a significant reduction in monthly headache days of respectively - 6 (95% confidence interval - 9, - 3; p < 0.001; w = 0.200) during cycle 4 compared with baseline versus - 9 (95% confidence interval - 13, -6; p < 0.001; w = 0.469). However, the reduction in monthly headache days was significantly smaller in patients with CT+M after the fourth treatment cycle compared with patients with CT- (p = 0.004).

CONCLUSIONS: Prescription of oral concomitant preventive treatment is common in patients with chronic migraine receiving BoNTA. We did not identify any unexpected safety or tolerability issues in patients receiving BoNTA and a CT+M. However, patients with a CT+M experienced a smaller reduction in monthly headache days when compared with those with CT-, which might be associated with a higher resistance to treatment in that subgroup of patients.

PMID:37212943 | PMC:PMC10212860 | DOI:10.1007/s40263-023-01001-y

J Matern Fetal Neonatal Med. 2023 Dec;36(1):2215377. doi: 10.1080/14767058.2023.2215377.

ABSTRACT

BACKGROUND: Therapeutic regimens for the treatment of toxoplasmosis are not standardized. Treatment strategy mainly at the end of the second and the beginning of the third trimester, especially in cases of negative prenatal diagnosis, is the least uniform. In some situations, the choice of treatment may be ambiguous, and adverse drug reactions of the therapy should be taken into consideration.

METHODS: Adverse drug reactions of anti-toxoplasma therapy with spiramycin (n = 77) versus pyrimethamine/sulfadiazine (n = 35) were compared in 112 pregnant women.

RESULTS: Up to 36.6% of women reported adverse reactions to the treatment overall (n = 41). Out of those 38.9% (n = 30) were treated with spiramycin and 31.4% (n = 11) with pyrimethamine/sulfadiazine. Toxic allergic reactions were the only indication for discontinuation of treatment in 8.9% of patients (n = 10), where 9.1% (n = 7) were reported in spiramycin and 8.6% (n = 3) in pyrimethamine/sulfadiazine cohort. Neurotoxic complications (acral paraesthesia) were significantly more frequent during the therapy with spiramycine in 19.5% (n = 15) compared to no cases in pyrimethamine/sulfadiazine group (p = .003). Other adverse drug reactions, such as gastrointestinal discomfort, nephrotoxicity, vaginal discomfort were reported, but the differences between the cohorts were not significant.

CONCLUSIONS: The superiority of one of the therapeutic regimens was not statistically demonstrated, since the differences in overall toxicity or incidence of toxic allergic reactions between the cohorts were not confirmed (p = .53 and p = 1.00, respectively). However, although the isolated neurotoxicity of spiramycin was the only significant adverse reaction demonstrated in this study, pyrimethamine/sulfadiazine therapy should be preferred, because it is known to be more effective and with limited adverse reactions.

PMID:37217458 | DOI:10.1080/14767058.2023.2215377

Prague Med Rep. 2023;124(2):172-176. doi: 10.14712/23362936.2023.13.

ABSTRACT

Generic medication is a product that contains the same active substance and pharmaceutical characteristics as brand-name medications. Generic medications are cost-effective and comparable to brand-name medications in terms of clinical endpoints. However, the use of generic medications instead of brand-name medications is a debatable issue among patients and healthcare providers. Two patients with essential hypertension experienced side effects after switching to different generic antihypertensives (one generic medication to another generic medication). Adverse drug reactions, including, hypersensitivity, side effects, and intolerance, should be identified through present and past medical history and clinical characteristics. The adverse drug reactions in both patients were more likely to be side effects of the medications after switching to different generic antihypertensives produced by different companies (patient 1: enalapril and patient 2: amlodipine). The side effects were possibly caused by the different inactive ingredients or excipients. These two case reports emphasise the importance of monitoring adverse drug reactions throughout the course of treatment and communicating with patients prior to switching to a new generic medication.

PMID:37212135 | DOI:10.14712/23362936.2023.13

Reg Anesth Pain Med. 2023 May 22:rapm-2023-104628. doi: 10.1136/rapm-2023-104628. Online ahead of print.

NO ABSTRACT

PMID:37217259 | DOI:10.1136/rapm-2023-104628

Blood. 2023 May 22:blood.2022018669. doi: 10.1182/blood.2022018669. Online ahead of print.

ABSTRACT

Targeted therapies for cutaneous T-cell lymphoma (CTCL) are limited and curative approaches are lacking. Furthermore, relapses and drug induced side effects are major challenges in the therapeutic management of CTCL patients creating an urgent need for new, effective therapies. Pathologic constitutive NF-κB activity leads to apoptosis resistance in CTCL cells and thus represents a promising therapeutic target in CTCL. In a preclinical study we showed the potential of dimethyl fumarate (DMF) to block NF-κB and specifically kill CTCL cells (Nicolay et al.: Blood 2016). To translate these findings into a clinical setting, we performed a multicentric phase II study evaluating oral DMF therapy in 25 patients with CTCL stage Ib-IV over 24 weeks (EudraCT number 2014-000924-11/NCT number NCT02546440). Endpoints were safety and efficacy. We evaluated skin involvement (mSWAT), pruritus, quality of life and blood involvement if applicable as well as translational data. In the skin, 7/23 patients (30.4%) showed a response with >50% reduction in mSWAT. Patients with high tumor burden in skin and blood responded best to DMF therapy. Although not generally significant, DMF also improved pruritus in several patients. Response in the blood was mixed, but we confirmed the NF-κB inhibiting mechanism of DMF in the blood. The overall tolerability of the DMF therapy was very favorable with mostly mild side effects. In conclusion, our study presents DMF as an effective and excellently tolerable therapeutic option in CTCL to be further evaluated in a phase III study or real-life patient care as well as in combination therapies.

PMID:37217183 | DOI:10.1182/blood.2022018669

World J Clin Cases. 2023 Apr 26;11(12):2657-2669. doi: 10.12998/wjcc.v11.i12.2657.

ABSTRACT

The long-term management of patients with inflammatory bowel disease (IBD) is still a matter of debate, and no clear guidelines have been issued. In clinical practice, gastroenterologists often have to deal with patients in prolonged remission after immunomodulatory or immunosuppressive therapies. When planning an exit strategy for drug withdrawal, the risk of disease relapse must be balanced against the risk of drug-related adverse events and healthcare costs. Furthermore, there is still a dearth of data on the withdrawal of novel biologics, such as the anti-α4β7 integrin antibody (vedolizumab) and anti-IL12/23 antibody (ustekinumab), as well as the small molecule tofacitinib. Models for estimating the risk of disease relapse and the efficacy of retreatment should be evaluated according to the patient's age and IBD phenotype. These models should guide clinicians in programming a temporary drug withdrawal after discussing realistic outcomes with the patient. This would shift the paradigm from an exit strategy to a holiday strategy.

PMID:37214561 | PMC:PMC10198103 | DOI:10.12998/wjcc.v11.i12.2657

Case Rep Dermatol Med. 2023 May 13;2023:6397272. doi: 10.1155/2023/6397272. eCollection 2023.

ABSTRACT

Confluent and reticulated papillomatosis (CARP) is a rare keratinization disorder that presents with asymptomatic, reticulated papules coalescing into plaques, which adversely affect, most often, young black persons. Minocycline is considered the drug of choice, but it is not without its host of potential side effects, including drug hypersensitivity, drug-induced lupus/vasculitis/hepatitis, blue-gray skin hyperpigmentation, acute eosinophilic pneumonia, pseudotumor cerebri, and vestibular instability, among others. Alternatively, doxycycline might be considered as another first-line agent for CARP as it can effectively clear lesions while offering a more favorable side effect profile in select patients. Herein, we present a case of CARP successfully resolved with doxycycline after a protracted treatment history of topical and oral antifungal medications for suspected tinea versicolor (TV).

PMID:37213468 | PMC:PMC10199796 | DOI:10.1155/2023/6397272

Pediatr Dermatol. 2023 May-Jun;40(3):540-543. doi: 10.1111/pde.15200. Epub 2022 Nov 22.

ABSTRACT

Morphea is a rare multifactorial autoimmune disorder characterized by a complex and dynamic interplay between Th1 and Th2 signaling. Active clinical trials are currently investigating the safety and efficacy of dupilumab for the treatment of primary morphea. Here, we present two cases of morphea that developed in pediatric atopic dermatitis patients treated with dupilumab. These findings may support a causal relationship between IL-4 receptor blockade and the development of the early inflammatory phase of morphea.

PMID:37212737 | DOI:10.1111/pde.15200

N Engl J Med. 2023 May 20. doi: 10.1056/NEJMoa2303765. Online ahead of print.

ABSTRACT

BACKGROUND: Transthyretin amyloid (ATTR) cardiomyopathy is a progressive and fatal disease caused by misfolded transthyretin. Despite advances in slowing disease progression, there is no available treatment that depletes ATTR from the heart for the amelioration of cardiac dysfunction. NI006 is a recombinant human anti-ATTR antibody that was developed for the removal of ATTR by phagocytic immune cells.

METHODS: In this phase 1, double-blind trial, we randomly assigned (in a 2:1 ratio) 40 patients with wild-type or variant ATTR cardiomyopathy and chronic heart failure to receive intravenous infusions of either NI006 or placebo every 4 weeks for 4 months. Patients were sequentially enrolled in six cohorts that received ascending doses (ranging from 0.3 to 60 mg per kilogram of body weight). After four infusions, patients were enrolled in an open-label extension phase in which they received eight infusions of NI006 with stepwise increases in the dose. The safety and pharmacokinetic profiles of NI006 were assessed, and cardiac imaging studies were performed.

RESULTS: The use of NI006 was associated with no apparent drug-related serious adverse events. The pharmacokinetic profile of NI006 was consistent with that of an IgG antibody, and no antidrug antibodies were detected. At doses of at least 10 mg per kilogram, cardiac tracer uptake on scintigraphy and extracellular volume on cardiac magnetic resonance imaging, both of which are imaging-based surrogate markers of cardiac amyloid load, appeared to be reduced over a period of 12 months. The median N-terminal pro-B-type natriuretic peptide and troponin T levels also seemed to be reduced.

CONCLUSIONS: In this phase 1 trial of the recombinant human antibody NI006 for the treatment of patients with ATTR cardiomyopathy and heart failure, the use of NI006 was associated with no apparent drug-related serious adverse events. (Funded by Neurimmune; NI006-101 ClinicalTrials.gov number, NCT04360434.).

PMID:37212440 | DOI:10.1056/NEJMoa2303765

Mov Disord. 2023 May 22. doi: 10.1002/mds.29426. Online ahead of print.

ABSTRACT

BACKGROUND: Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that protects dopamine neurons and improves motor function in animal models of Parkinson's disease (PD).

OBJECTIVE: The primary objectives of this study were to assess the safety and tolerability of both CDNF and the drug delivery system (DDS) in patients with PD of moderate severity.

METHODS: We assessed the safety and tolerability of monthly intraputamenal CDNF infusions in patients with PD using an investigational DDS, a bone-anchored transcutaneous port connected to four catheters. This phase 1 trial was divided into a placebo-controlled, double-blind, 6-month main study followed by an active-treatment 6-month extension. Eligible patients, aged 35 to 75 years, had moderate idiopathic PD for 5 to 15 years and Hoehn and Yahr score ≤ 3 (off state). Seventeen patients were randomized to placebo (n = 6), 0.4 mg CDNF (n = 6), or 1.2 mg CDNF (n = 5). The primary endpoints were safety and tolerability of CDNF and DDS and catheter implantation accuracy. Secondary endpoints were measures of PD symptoms, including Unified Parkinson's Disease Rating Scale, and DDS patency and port stability. Exploratory endpoints included motor symptom assessment (PKG, Global Kinetics Pty Ltd, Melbourne, Australia) and positron emission tomography using dopamine transporter radioligand [18 F]FE-PE2I.

RESULTS: Drug-related adverse events were mild to moderate with no difference between placebo and treatment groups. No severe adverse events were associated with the drug, and device delivery accuracy met specification. The severe adverse events recorded were associated with the infusion procedure and did not reoccur after procedural modification. There were no significant changes between placebo and CDNF treatment groups in secondary endpoints between baseline and the end of the main and extension studies.

CONCLUSIONS: Intraputamenally administered CDNF was safe and well tolerated, and possible signs of biological response to the drug were observed in individual patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

PMID:37212361 | DOI:10.1002/mds.29426

J Med Virol. 2023 May;95(5):e28771. doi: 10.1002/jmv.28771.

ABSTRACT

The recent reports of oral side effects (SEs) following COVID-19 vaccination warrant further investigation into their prevalence, severity, and aetiology. This study was conducted to synthesize the first-ever population-level evidence about oral SEs of COVID-19 vaccines in Europe. The European Union Drug Regulating Authorities Pharmacovigilance (EudraVigilance) database was accessed in August 2022 to extract summary data of all potential oral SEs reported after COVID-19 vaccination. The data were reported descriptively and cross-tabulated to facilitate sub-group analysis per vaccine type, sex, and age group. Dysgeusia was the most commonly reported oral SE (0.381 case per each 100 received reports), followed by oral paraesthesia (0.315%), ageusia (0.296%), lip swelling (0.243%), dry mouth (0.215%), oral hypoaesthesia (0.210%), swollen tongue (0.207%), and taste disorder (0.173%). Females had significantly (Sig. < 0.001) a higher prevalence of all most common (top 20) oral SEs, except for salivary hypersecretion, which was equally prevalent among females and males. The present study revealed a low prevalence of oral SEs, with taste-related, other sensory and anaphylactic SEs being the most common SEs in Europe, similar to what was found earlier among the US population. Future studies should explore the potential risk factors of oral sensory and anaphylactic SEs to verify whether they are causally linked to COVID-19 vaccines.

PMID:37212314 | DOI:10.1002/jmv.28771

Ceska Slov Farm. 2023 Spring;72(2):70-78.

ABSTRACT

The concept of pharmaceutical care (PC) has existed as a professional philosophy for more than 30 years. However, for a long period of time, little had been done for its integration into the regular practice of healthcare provision. The COVID-19 pandemic and the resulting increase in patient influx in the community pharmacies (CP) encouraged the exploration and establishment of new healthcare services provided within the CP. Nevertheless, these services of PC are still novel, and more can be done to expand the community pharmacists' current role in primary healthcare. This can be achieved by improving and expanding the newly established services, all while incorporating new ones, for the benefit of public health and the reduction of avoidable healthcare expenditures. This article reviews information about the benefits of this service regarding patient health and the reduction of financial expenses pertinent to adverse drug events within the setting of the CP. Adverse drug events account for significant healthcare expenses and patient distress due to relevant symptoms, emergency doctor visits, and increased hospitalization rates. Several studies conducted internationally have investigated the positive impact of PC practiced by community pharmacists. In spite of results sometimes presenting a non-continuous pattern, PC applied under specific conditions has tangible positive outcomes. Congestive heart failure and type 2 diabetes mellitus patients presented fewer hospital admissions, better symptom control, and higher adherence in comparison to control groups, while a study on asthma patients revealed improved inhalation techniques. All intervention groups reported psychological improvement and a better understanding of their treatment. Special reference is made to the importance of this service for patients receiving anti-cancer treatment and how community pharmacists can have a crucial role in designing, monitoring, and re-designing these therapeutic schemes whose complexity and related adverse drug events negatively affect patient adherence. The role of community pharmacists was very important, especially for primary care, for both patients and healthcare systems during the pandemic, and it seems that it will remain decisive in the post-COVID era as well. The increased complexity of therapy and polypharmacy creates the need for organized, active participation of pharmacists in healthcare provision so that they can use their knowledge and skills under continuous cooperation with other healthcare professionals, thus providing coordinated services for the benefit of the patient.

PMID:37211427

J Geriatr Oncol. 2023 May 19:101531. doi: 10.1016/j.jgo.2023.101531. Online ahead of print.

NO ABSTRACT

PMID:37211515 | DOI:10.1016/j.jgo.2023.101531

Am J Prev Med. 2023 Jun;64(6):834-843. doi: 10.1016/j.amepre.2023.01.011. Epub 2023 Apr 20.

ABSTRACT

INTRODUCTION: Emergency department visits and hospitalizations for unsupervised medication exposures among young children increased in the early 2000s. Prevention efforts were initiated in response.

METHODS: Nationally representative data from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project collected from 2009 to 2020 were analyzed in 2022 to assess overall and medication-specific trends in emergency department visits for unsupervised exposures among children aged ≤5 years.

RESULTS: From 2009 to 2020, there were an estimated 677,968 (95% CI=550,089, 805,846) emergency department visits for unsupervised medication exposures among children aged ≤5 years in the U.S. Most visits involved children aged 1-2 years (2009-2012 [70.3%], 2017-2020 [67.4%]), and nearly one half involved prescription solid medications (2009-2012 [49.4%], 2017-2020 [48.1%]). The largest declines in estimated numbers of annual visits from 2009-2012 to 2017-2020 were for exposures involving prescription solid benzodiazepines (-2,636 visits, -72.0%) and opioids (-2,596 visits, -53.6%) and over-the-counter liquid cough and cold medications (-1,954 visits, -71.6%) and acetaminophen (-1,418 visits, -53.4%). The estimated number of annual visits increased for exposures involving over-the-counter solid herbal/alternative remedies (+1,028 visits, +65.6%), with the largest increase for melatonin exposures (+1,440 visits, +421.1%). Overall, the estimated number of visits for unsupervised medication exposures decreased from 66,416 in 2009 to 36,564 in 2020 (annual percentage change= -6.0%). Emergent hospitalizations for unsupervised exposures also declined (annual percentage change= -4.5%).

CONCLUSIONS: Declines in estimated emergency department visits and hospitalizations for unsupervised medication exposures from 2009 to 2020 coincided with renewed prevention efforts. Targeted approaches may be needed to achieve continued declines in unsupervised medication exposures among young children.

PMID:37210158 | DOI:10.1016/j.amepre.2023.01.011

Ann Clin Microbiol Antimicrob. 2023 May 19;22(1):42. doi: 10.1186/s12941-023-00594-y.

ABSTRACT

OBJECTIVES: This meta-analysis evaluated the Efficacy and Effectiveness of several COVID-19 vaccines, including AstraZeneca, Pfizer, Moderna, Bharat, and Johnson & Johnson, to better estimate their immunogenicity, benefits, or side effects.

METHODS: Studies reporting the Efficacy and Effectiveness of COVID-19 vaccines from November 2020 to April 2022 were included. The pooled Effectiveness/Efficacy with a 95% confidence interval (95% CI) with Metaprop order was calculated. The results were presented in forest plots. Predefined subgroup analyses and sensitivity analyses were also performed.

RESULTS: A total of twenty articles were included in this meta-analysis. After the first dose of the vaccine, the total effectiveness of all COVID-19 vaccines in our study was 71% (95% CI 0.65, 0.78). The total effectiveness of vaccines after the second dose was 91% (95% CI 0.88, 0.94)). The total efficacy of vaccines after the first and second doses was 81% (95% CI 0.70, 0.91) and 71% (95% CI 0.62, 0.79), respectively. The effectiveness of the Moderna vaccine after the first and second dose was the highest among other studied vaccines ((74% (95% CI, 0.65, 0.83) and 93% (95% CI, 0.89, 0.97), respectively). The highest first dose overall effectiveness of the studied vaccines was against the Gamma variant (74% (95% CI, 0.73, 0.75)), and the highest effectiveness after the second dose was observed against the Beta variant (96% (95% CI, 0.96, 0.96)). The Efficacy for AstraZeneca and Pfizer vaccines after the first dose was 78% (95% CI, 0.62, 0.95) and 84% (95% CI, 0.77, 0.92), respectively. The second dose Efficacy for AstraZeneca, Pfizer, and Bharat was 67% (95% CI, 0.54, 0.80), 93% (95% CI, 0.85, 1.00), and 71% (95% CI, 0.61, 0.82), respectively. The overall efficacy of first and second dose vaccination against the Alfa variant was 84% (95% CI, 0.84, 0.84) and 77% (95% CI, 0.57, 0.97), respectively, the highest among other variants.

CONCLUSION: mRNA-based vaccines against COVID-19 showed the highest total efficacy and effectiveness than other vaccines. In general, administering the second dose produced a more reliable response and higher effectiveness than a single dose.

PMID:37208749 | DOI:10.1186/s12941-023-00594-y