WHO Database Research Articles

Immune checkpoint inhibitor rechallenge after immune-related adverse events: a retrospective study from VigiBase update in 2024 looking for emergent safety signals

ObjectivesLimited information is available on the safety of a rechallenge with an immune checkpoint inhibitor (ICI) after occurrence of an immune-related adverse event (irAE). We aim to identify potential emergent...

Artificial intelligence in respiratory pandemics-ready for disease X? A scoping review.

This study aims to identify repeated previous shortcomings in medical imaging data collection, curation, and AI-based analysis during the early phase of respiratory pandemics. Based on the results, it seeks to highlight essential steps for improving future pandemic preparedness. We searched PubMed/MEDLINE, Scopus, and Cochrane Reviews for articles published from January 1, 2000, to December 31, 2021, using the terms "imaging" or "radiology" or "radiography" or "CT" or "x-ray" combined with "SARS," "MERS," "H1N1," or "COVID-19." WHO and CDC Databases were searched for case definitions. Over the last 20 years, the world faced several international health emergencies caused by respiratory diseases such as SARS, MERS, H1N1, and COVID-19. During the same period, major technological advances enabled the analysis of vast amounts of imaging data and the continual development of artificial intelligence algorithms to support radiological diagnosis and prognosis. Timely availability of data proved critical, but so far, data collection attempts were initialized only as individual responses to each outbreak, leading to long delays and hampering unified guidelines and data-driven technology to support the management of pandemic outbreaks. Our findings highlight the multifaceted role of imaging in the early stages of SARS, MERS, H1N1, and COVID-19, and outline possible actions for advancing future pandemic preparedness. Advancing international cooperation and action on these topics is essential to create a functional, effective, and rapid counteraction system to future respiratory pandemics exploiting state of the art imaging and artificial intelligence. Question What has been the role of radiological data for diagnosis and prognosis in early respiratory pandemics and what challenges were present? Findings International cooperation is essential to developing an effective rapid response system for future respiratory pandemics using advanced imaging and artificial intelligence. Clinical relevance Strengthening global collaboration and leveraging cutting-edge imaging and artificial intelligence are crucial for developing rapid and effective response systems. This approach is essential for improving patient outcomes and managing future respiratory pandemics more effectively.

Serious adverse events reported with benzimidazole derivatives: A disproportionality analysis from the World Health Organization's pharmacovigilance database.

Benzimidazole derivatives are widely used anthelmintic drugs, particularly in mass campaigns for intestinal parasitosis treatment. Despite their generally good safety profile, serious adverse reactions have been reported. This study aims to identify potential pharmacovigilance signals for benzimidazole derivatives using disproportionality analysis in the WHO database. A case/non-case study was conducted using data from the WHO VigiBase database (2000-2023). Cases were individual case safety reports (ICSRs) where at least one suspected serious adverse event of interest was reported, while non-cases were ICSRs reporting any adverse events other than the serious adverse events of interest. Reporting Odds Ratios (RORs) and 95% confidence intervals were calculated to assess disproportionate reporting. Analyses were adjusted for potential confounding factors and a sensitivity analysis with imputed missing data was performed. Among 19,068 serious reports analyzed, significant disproportionality signals were found for benzimidazole derivatives compared to other anthelmintic drugs, notably for bone marrow failure and hypoplastic anemia (adjusted ROR 9.44 [5.01-18.9]), serious leukopenia (3.89 [2.64-5.76]), serious hepatic disorders (3.10 [2.59-3.71]), hepatitis (2.88, 95% CI 2.29-3.63) and serious urticaria (2.02, 95% CI 1.36-2.99). We have also highlighted a new signal not mentioned in the summaries of product characteristics for seizures with benzimidazole derivatives. Secondary analysis revealed these signals were primarily reported with albendazole. This study identified potential pharmacovigilance signals for serious hematological and hepatic adverse events for benzimidazole derivatives, particularly albendazole. New signal for benzimidazole derivatives has been described for seizures. These findings underscore the need for vigilant monitoring during benzimidazole derivatives use and warrant further pharmacoepidemiologic studies to confirm these signals and investigate underlying mechanisms.

Suicidal behaviour and CFTR modulators: A case series and WHO database disproportionality analysis

BackgroundA highly effective therapy involving elexacaftor, tezacaftor, and ivacaftor (ETI) for cystic fibrosis (CF) patients has recently raised safety concerns regarding potential psychiatric disorders. The manuscript reports cases of suicide attempts in patients receiving ETI and investigates putative causality using the WHO spontaneous reporting database. MethodsFirst, four cases of suicide attempts/self-injury are described. Second, a disproportionality analysis was conducted using spontaneous reports collected in Vigibase through the standardised MedDRA Query (narrow version) "Suicide/Self-injury" and ETI exposure. Reporting Odds Ratio (ROR) was calculated for the main and subgroup (i/suicide attempt, ii/suicidal ideation) analyses. Sensitivity analyses were performed with variations in exposure, to ivacaftor/lumacaftor to assess the intrinsic psychiatric risk of CF patients, and paracetamol as a positive control for suicide attempt and a negative one for suicidal ideation. Exposure to reduced-dose ETI was studied to evaluate the dose-gradient effect. ResultsFour cases of suicide attempt/self-injury occurred 3 to 13 months after ETI initiation in CF patients and were reported to the Bordeaux Pharmacovigilance centre. Aside, in Vigibase, ETI is associated with an increased likelihood of reporting suicidal behaviour (ROR 2.5, 95 % CI[2.1; 2.8]). A signal of disproportionate reporting was found for the subgroup of suicide attempts (1.4, 95 % CI[1.2; 1.8]), unlike ivacaftor/lumacaftor, which was associated only with the risk of reporting suicidal ideation. Significant ROR values were also found for reduced-dose ETI for all psychiatric effects studied except suicide attempt. ConclusionsETI exposure is related with increased reporting of suicidal behaviour. A potential dose-dependent effect merits further investigation.

Rheumatic adverse effects with biologics targeting type 2 inflammation in severe asthma: a VigiBase study

Biologics in severe asthma are associated with an excess reporting of rheumatic diseases and rheumatic symptoms in the WHO database. The profile of rheumatic adverse events varies according to biologics and their mechanisms of action.

Anticoagulant use before COVID-19 diagnosis prevent COVID-19 associated acute venous thromboembolism or not: A systematic review and meta-analysis.

Coagulopathy and thromboembolic events are associated with poor outcomes in coronavirus disease 2019 (COVID-19) patients. There is conflicting evidence on the effects of chronic anticoagulation on mortality and severity of COVID-19 disease. To summarize the body of evidence on the effects of pre-hospital anticoagulation on outcomes in COVID-19 patients. A Literature search was performed on LitCovid PubMed, WHO, and Scopus databases from inception (December 2019) till June 2023 for original studies reporting an association between prior use of anticoagulants and patient outcomes in adults with COVID-19. The primary outcome was the risk of thromboembolic events in COVID-19 patients taking anticoagulants. Secondary outcomes included COVID-19 disease severity, in terms of intensive care unit admission or invasive mechanical ventilation/intubation requirement in patients hospitalized with COVID-19 infection, and mortality. The random effects models were used to calculate crude and adjusted odds ratios (aORs) with 95% confidence intervals (95%CIs). Forty-six observational studies met our inclusion criteria. The unadjusted analysis found no association between prior anticoagulation and thromboembolic event risk [n = 43851, 9 studies, odds ratio (OR)= 0.67 (0.22, 2.07); P = 0.49; I 2 = 95%]. The association between prior anticoagulation and disease severity was non-significant [n = 186782; 22 studies, OR = 1.08 (0.78, 1.49); P = 0.64; I 2 = 89%]. However, pre-hospital anticoagulation significantly increased all-cause mortality risk [n = 207292; 35 studies, OR = 1.72 (1.37, 2.17); P < 0.00001; I 2 = 93%]. Pooling adjusted estimates revealed a statistically non-significant association between pre-hospital anticoagulation and thromboembolic event risk [aOR = 0.87 (0.42, 1.80); P = 0.71], mortality [aOR = 0.94 (0.84, 1.05); P = 0.31], and disease severity [aOR = 0.96 (0.72, 1.26); P = 0.76]. Prehospital anticoagulation was not significantly associated with reduced risk of thromboembolic events, improved survival, and lower disease severity in COVID-19 patients.

EP354 - Acute pancreatitis – an unusual cause

Abstract Introduction Drugs are responsible for only 0.1%-2% of acute pancreatitis. Whilst the link between some drugs and pancreatitis is well-established, (steroids, azathioprine), we found only one previous case-report linking testosterone replacement therapy (TRT) to pancreatitis. We report a case of acute pancreatitis secondary to TRT. Case Report A 55-year-old man presented with history of upper abdominal pain. He denied alcohol/illicit drug use, no recent infection/changes to medication. His amylase was raised; CT scan confirmed acute pancreatitis. When interrogating his past medical history for a cause, we learned of his bilateral orchidectomy, radiotherapy and chemotherapy for seminoma in 1993, following which, he was on Testogel. He was managed conservatively, with success. Discussion Although drug-related causes of pancreatitis are uncommon, management is easy with identification/cessation of the causative agent. Therefore, a detailed medical history (including exposure to toxins and medication changes) is important. In our patient, an extensive surgical, medical and social history, CT and bloods excluded other main causes of acute pancreatitis i.e. alcohol, gallstones/infection, hypertriglyceridemia, toxins and trauma. The WHO database of “drugs suspected to cause pancreatitis” includes evidence from published literature, mostly case reports. Testosterone does not feature amongst the 525 drugs mentioned. Conclusion Our anecdotal evidence may provide a possible link between TRT and pancreatitis, however further research is needed to ascertain a definite causality. Reporting such potential links is important due to increased TRT use recently as treatment for female-to-male sex transition and young adults for performance enhancement, as well as remaining the primary treatment for hypogonadism.

Analysis of the structure and efficiency of national health care systems

It was noted that the right to health care is a key topic of discussion around the world, and ensuring the realization of this right and the opportunity to access the necessary medical care is in the spotlight. The realization of the right to health care in each country directly depends on the national health policy. The analysis is focused on assessing the effectiveness of health care systems of states according to several models. The data for this study were obtained from the existing WHO database, which provides accumulated data for groups of countries. Thus, it was possible to compare different countries, whose state health statistics may have their own characteristics. For data processing, an input-oriented analysis model of a dynamic network data shell was used. The analysis combines the use of traditional and non-traditional methods for measuring health performance. The analysis shows that there are no pure health systems financing models, most states use mixed funding models. The only way to reduce dependence on direct payments is for the government to encourage the use of a prepayment and risk pooling approach.

Risk Factors and Preventive Measures for Breast Cancer.

Background: Breast cancer is the most common cancer in women in many countries. Breast cancer is a multifactorial disease. This study investigates the possible influencing factors and preventive measures for breast cancer. Methods: The data for this study were obtained from WHO databases. First, age standardization was performed, followed by a correlation analysis. Relationships between the mortality rates of breast cancer and the possible influencing factors were analyzed. The significant results from the correlation analysis were analyzed using a stepwise regression analysis. In order to find out whether the application of a uniform screening program can reduce breast cancer mortality, the countries were divided into groups according to the time of initiation of the screening program, and breast cancer mortality was compared. Results: The correlation analysis showed a significant relationship with breast cancer mortality for 15 of 30 potential influencing factors. A stepwise multivariate regression analysis was performed with these 15 factors, which revealed 13 relevant factors. Two factors were more relevant: the number of radiotherapy units per 100,000 inhabitants and the proportion of the population (over 50 years of age) with a social network. These were followed by the proportion of general practitioners and obstetricians, as well as healthcare expenses. Breast cancer mortality differed between the countries that introduced the screening program in the 1990s and those that did so in the 2020s. Conclusions: A country's healthcare system influences breast cancer mortality through prevention, diagnosis. and treatment. Regular screening, counseling for socially disadvantaged women, and prompt treatment are important factors. In the future, prevention measures should also aim to strengthen the social environment. The prescription of social activities should be used as preventive care.

Cardiovascular Side Effects of COVID‑19 Vaccination

Background: The COVID-19 pandemic has had a profound impact on global health, with vaccination playing a crucial role in mitigating the spread of the virus and reducing the severity of illness. However, the potential cardiovascular side effects associated with COVID-19 vaccination have raised concerns. Myocarditis, an inflammation of the heart muscle, is one of the most widely reported side effects, particularly among male adolescents and young adults, following the second dose of mRNA vaccines. The incidence of myocarditis post-vaccination ranges from 150 to 4,000 cases per 100,000 individuals, higher than the pre-pandemic estimate of 1-10 cases per 100,000. Other cardiovascular complications such as pericarditis and stroke have also been reported in a small subset of vaccine recipients. Although these side effects are often acute and transient, they can be severe and even fatal in some cases. Understanding the incidence, clinical presentation, and long-term outcomes of these cardiovascular side effects is crucial for informing healthcare professionals and the public about the potential risks and benefits of the COVID-19 vaccination. Ongoing research and surveillance are essential to better understand the underlying mechanisms, identify risk factors, and develop strategies for preventing and managing adverse events, while maintaining public trust in the safety and efficacy of COVID-19 vaccines.Search Methods: This review was conducted by searching the WHO database and other relevant medical literature for studies published from 2000 to 2024 that reported on cardiovascular side effects of COVID-19 vaccination. Conclusion: Several studies have investigated the incidence of myocarditis, pericarditis, and stroke in individuals who received the COVID‑19 vaccines. Although the overall risk appears relatively low, cardiovascular complications have been reported in a small subset of vaccine recipients, particularly among younger individuals. These effects are often acute and transient but can be severe and even fatal in a few cases. Herein, we have provided a comprehensive review of documents reporting cardiovascular side effects of COVID-19 vaccines in international databases from 2000 to 2024 and discussed the possible causes of these disorders.

A real-world data analysis of ocular adverse events linked to anti-VEGF drugs: a WHO-VigiAccess study.

Vascular endothelial growth factor (VEGF) is key to wet age-related macular degeneration (wAMD). Anti-VEGF drugs are the main treatment in clinics. This study assessed ocular adverse events (AE) from anti-VEGF drugs in VigiAccess, WHO's database, and compared adverse drug reaction (ADR) profiles of four drugs to aid personalized treatment choices for optimal benefit and safety. The design was a descriptive retrospective study. We observed four anti-VEGF drugs commonly used in the clinical treatment of wAMD, and their ADR reports came from WHO-VigiAccess. The collected data included the age group, gender, and regional data, as well as the data of disease systems and symptoms caused by ADR recorded in the annual ADR reports and reports received by the WHO. We observed the overall characteristics of the ADR reports of these drugs, then explored the distribution of 27 SOCs of these drugs. Subsequently, we compared the most common ocular ADRs of the drugs. Finally, we compared the commonalities and differences of ocular ADRs related to the drugs. Overall, 57,779 AE associated with the four anti-VEGF drugs were reported. The results showed that the number of females experiencing ADRs (67.83%) was significantly higher than males (32.17%), the age group with the highest reported incidence was over 75years old. More than half of the ADR reports came from the Americas (50.86%). The five most common types of AE were: eye disorders (43.56%), general disorders and administration site conditions (34.47%), injury poisoning and procedural complications (13.36%), infections and infestations (11.61%), nervous system disorders (9.99%). Compared with the other three inhibitors, brolucizumab had a significantly higher rate of ocular ADR reports. The most common ocular ADRs of these four anti-VEGF drugs were mostly related to visual impairment, vision blurred, and blindness. However, there is still a disparity of ADRs between different drugs. The presence of ocular AEs when using anti-VEGF drugs to treat wAMD in clinical practice should attract clinical attention. Clinicians should use these expensive drugs more rationally based on the characteristics of ADRs and develop personalized treatment plans for patients.

Conventional water resources associated with climate change in the Southeast Mediterranean and the Middle East countries

Conventional water sources in the Southeast Mediterranean and the Middle East play a crucial role in driving the socio-economic progress of the region. This study aims to address the uncertainties, discrepancies, and gaps in knowledge regarding how to combat the climate crisis and extreme weather events impacting traditional water sources. These sources encompass rivers, lakes, reservoirs, and groundwater reservoirs that are vital for agriculture, industry, and daily household needs. The availability and upkeep of water resources in this area are influenced by factors like climate change, population growth, and competing demands from different sectors. The methodology involved an extensive review of research literature curetted from a wide array of international scientific studies and reports, drawing data from sources such as PubMed, EBSCO, Medline, EMBASE, CINAHL, Scopus, Web of Science, Science Direct, Google Scholar, and UNESCO, WHO databases. The findings underscore the importance of traditional water sources in these regions, underscoring their significance for agricultural, industrial, and domestic applications. The accessibility of water resources varies among nations, with some grappling with water scarcity issues. This research delves into the condition of traditional water sources in the Southeast Mediterranean and the Middle East, shining a spotlight on concerns like water scarcity, pollution, and governance, offering valuable insights into these critical resources.

Risk Factors and Preventive Measures for Cardiovascular Diseases.

Background: Cardiovascular diseases are the most frequent cause of death worldwide. The aim of this study was to identify and demonstrate correlations between mortality data and etiological factors in EU countries. The relationships presented could thus provide a better understanding of etiological factors and possible points for interventions to prevent cardiovascular diseases. The focus was on the following diseases: hypertensive heart disease, atrial flutter/atrial fibrillation, myocardial infarction, and ischemic heart disease, as well as heart failure. Methods: The data in this study come from WHO databases. Connections between the mortality rates and the possible influencing factors were analyzed. The significant factors from the correlation analysis were simultaneously evaluated using a stepwise multiple regression analysis. Results: Analysis of hypertensive heart disease in women reveals the following factors to be significant: drug expenses, health expenses on gross domestic product, and smoking. For men, population density, first admission to a drug treatment center, and drug expenses per person emerged as important factors. Admission to drug treatment centers and length of hospitalization were significant factors for atrial fibrillation and flutter. Fine dust pollution was the most important factor in heart failure. The most important influencing factor for myocardial infarction and ischemic heart disease is nitrogen dioxide concentration. For women, the second highest value is health expenses, followed by the number of outpatient contacts per year. For men, outpatient contacts are in second place. Conclusions: Prevention measures must be taken by the government. The extent to which population density has an influence on cardiovascular diseases should be examined in more detail. In order to reduce the number of initial admissions to drug treatment centers, behavioral prevention related to drug use could be improved.

Are Doctors Equally Distributed Throughout the World?

As the vital and scarce resource of the health system, physicians are responsible for treating patients and saving lives and the equitable distribution of physicians among the whole population is a prerequisite to achieving health for all. We aimed to investigate inequality in physician distribution in the world using the Gini coefficient. This descriptive-analytical study was conducted in 2021. The number of physicians and the population of countries were obtained from the WHO and United Nations (UN) databases. The Gini coefficient was calculated in three different modes and the distribution of physicians among countries in various Human Development Index (HDI) groups was determined using the physician ratio per 10,000 population. There were generally more than 13 million doctors in the world. About 43% of the world's physicians were available to 20% of the world's population in very high HDI countries, and 12% of the population had access to about 1% of physicians in low HDI countries. An average of 19.5 physicians are distributed per 10,000 population worldwide. The Gini coefficient between the four groups of HDI countries was 0.55, and that of all countries in the world was 0.640. There was a shortage and inequality in the distribution of physicians worldwide. Governments should eliminate inequality in the distribution of the medical workforce, in particular physicians, by redoubling their efforts and accurate planning.

Reporting of Progress toward Eliminating Viral Hepatitis B and C in the Central Asian Region

Eliminating viral hepatitis became a global goal and was targeted by countries worldwide. Using WHO, Google Scholar, PubMed, and other databases, the progress of Central Asian countries (Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan) in ending viral hepatitis B and C by 2030 was evaluated and reported. Collected data shows that countries have made significant efforts toward achieving goals in the Global Health Sector Strategy. All countries have national programs focused on hepatitis elimination and have reached the target vaccination coverage against hepatitis B. However, the available information requires regular updates, and public accessibility of data collected by governments should be enhanced. Additionally, countries are recommended to improve harm reduction and treatment services.

Parsonage-Turner Syndrome following COVID-19 Vaccination: A Systematic Review.

Parsonage-Turner syndrome (PTS) is an inflammatory condition of the brachial plexus, with more than half of patients presenting a trigger, such as infection or vaccination. Our objective was to synthesize the clinical and paraclinical features, therapeutic responses, and outcomes of PTS post-COVID-19 vaccination. We systematically reviewed two databases (LitCOVID and the WHO database on COVID-19) up to January 2024 following a published protocol (OSF registries). We included 59 cases. PTS occurred more frequently in males (61.1% mRNA group, 83.3% viral vector group). Patients in the mRNA group were younger (41.7% between 41 and 50 years vs. 38.9% between 61 and 70 years). Most cases had sudden pain within two weeks. Unilateral PTS was present in 94.4% of mRNA and all viral vector-vaccinated cases. Symptoms included pain (97.1% and 92.3%, respectively), usually followed within two weeks by motor deficits (97.2% and 94.1%, respectively), amyotrophy (30% and 81.8%, respectively), paresthesia (50% and 27.3%, respectively), and sensory loss (33.3% and 38.5%, respectively). Viral vector vaccine recipients had nerve involvement outside the brachial plexus. Ancillary investigations revealed CSF albuminocytological dissociation (33.3% and 100%, respectively) and ipsilateral axillary lymphadenopathy. Two PTS cases worsened after the second mRNA dose, and another recurred after influenza vaccination. One patient well tolerated the second dose of the viral vector vaccine, but symptoms reemerged in another. Current evidence suggests PTS may occur after all COVID-19 vaccine types, with some subgroup differences. Also, PTS might recur with subsequent similar or unrelated vaccines.

Paediatric, maternal, and congenital mpox: a systematic review and meta-analysis

Although mpox has been detected in paediatric populations in central and west Africa for decades, evidence synthesis on paediatric, maternal, and congenital mpox, and the use of vaccines and therapeutics in these groups, is lacking. A systematic review is therefore indicated to set the research agenda. We conducted a systematic review and meta-analysis, searching articles in Embase, Global Health, MEDLINE, CINAHL, Web of Science, Scopus, SciELO, and WHO databases from inception to April 17, 2023. We included studies reporting primary data on at least one case of confirmed, suspected, or probable paediatric, maternal, or congenital mpox in humans or the use of third-generation smallpox or mpox vaccines, targeted antivirals, or immune therapies in at least one case in our population of interest. We included clinical trials and observational studies in humans and excluded reviews, commentaries, and grey literature. A pooled estimate of the paediatric case fatality ratio was obtained using random-effects meta-analysis. This study is registered with PROSPERO (CRD420223336648). Of the 61 studies, 53 reported paediatric outcomes (n=2123 cases), seven reported maternal or congenital outcomes (n=32 cases), two reported vaccine safety (n=28 recipients), and three reported transmission during breastfeeding (n=4 cases). While a subset of seven observational studies (21 children and 12 pregnant individuals) reported uneventful treatment with tecovirimat, there were no randomised trials reporting safety or efficacy for any therapeutic agent. Among children, the commonest clinical features included rash (86 [100%] of 86), fever (63 [73%] of 86), and lymphadenopathy (40 [47%] of 86). Among pregnant individuals, rash was reported in 23 (100%) of 23; fever and lymphadenopathy were less common (six [26%] and three [13%] of 23, respectively). Most paediatric complications (12 [60%] of 20) arose from secondary bacterial infections. The pooled paediatric case fatality ratio was 11% (95% CI 4-20), I2=75%. Data from 12 pregnancies showed half resulted in fetal death. Research on vaccine and immune globulin safety remains scarce for children and absent for pregnant individuals. Our review highlights critical knowledge gaps in the epidemiology, prevention, and treatment of mpox in children and pregnant individuals, especially those residing in endemic countries. Increased funding, international collaboration, and equitable research is needed to inform mpox control strategies tailored for at-risk communities in endemic countries. None. For the French, Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Withdrawal syndrome after antipsychotics discontinuation: an analysis of the WHO database of spontaneous reports (Vigibase) between 2000 and 2022.

Withdrawal syndrome (WDS) has been described after discontinuation of antipsychotics. WDS could be the consequence of an over-activation of the dopaminergic pathway. Antipsychotics with a higher affinity for dopamine D2 receptors could be associated with a higher risk of WDS. This study aims to address this statement and evaluate the risk difference for withdrawal syndrome between antipsychotics based on pharmacovigilance data. We collected individual reports registered in Vigibase® between 01/01/2000 and 31/12/2022 of patients treated with antipsychotics and who had presented WDS. A disproportionality analysis was performed to evaluate the risk of reporting WDS with each antipsychotic compared to all other antipsychotics. We performed a correlation analysis to assess the correlation between the risk of reporting WDS for each antipsychotic in relation with their pKi for D2 and 5HT2A receptors. The most frequent psychiatric withdrawal symptoms after antipsychotic discontinuation were insomnia, anxiety and depression. Tremor, headache and dizziness were among the most frequently reported neurologic withdrawal symptoms. Tiotixene had the highest risk of reporting WDS (ROR 7.08; 95%CI 3.49 - 14.35) followed by pimozide (ROR 4.35; 95%CI 1.93 - 9.77), quetiapine (ROR 4.24; 95%CI 3.87 - 4.64), thioridazine (ROR 4.17; 95%CI 2.50-6.98) and ziprasidone (ROR 2.98; 95%CI 2.41-3.67). We found a poor correlation between D2/5HT2A binding affinity and the risk of reporting withdrawal syndrome (R2 = 0,094). Our results suggest that there might be a risk difference for WDS between antipsychotics. Tiotixene, pimozide and quetiapine were associated with a higher risk of reporting a WDS whereas this risk was lower with chlorpromazine, clozapine and fluphenazine. We could not address the issue of withdrawal psychosis, withdrawal dyskinesia, rebound psychosis or supersensitivity psychosis due to the lack of specific WHO medDRA coded terms to identify potential cases.

Glaucoma: A review of current management, patients’ adherence, direct and indirect cost, and barriers to drug delivery

Glaucoma is the world’s leading cause of permanent blindness, influenced by numerous variables, including socio-demographic factors. This review considered existing management practices and innovative methods of drug delivery, as well as how they relate to patient adherence and therapy costs. Literatures were compiled using search engines including ScienceDirect, PubMed, Google Scholar and WHO database. The eye is a complex organ with various anatomical barriers presenting significant challenges in treating glaucoma due to poor patient compliance with topical ocular medications. Advanced drug delivery systems like implants, nano or microparticles, punctal plugs, contact lenses, topical ring-type systems, gels, and other depot systems such as intracameral, supraciliary, and intravitreal applied in the extraocular, periocular, or intraocular sites, significantly enhance medication absorption, reduce adverse effects, and improve patient compliance. Poor treatment adherence, stemming from various reasons, lead to inadequate glaucoma management, increasing direct (34 to 45 %) and indirect costs (55 to 66 %) of therapy. As a result, a variety of treatments including enhanced drug delivery systems have been tested to address these concerns, and some modern pharmaceuticals and drug delivery technologies are being developed.

Challenges in Emerging Vaccines and Future Promising Candidates against SARS-CoV-2 Variants.

Since the COVID-19 outbreak, the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus has evolved into variants with varied infectivity. Vaccines developed against COVID-19 infection have boosted immunity, but there is still uncertainty on how long the immunity from natural infection or vaccination will last. The present study attempts to outline the present level of information about the contagiousness and spread of SARS-CoV-2 variants of interest and variants of concern (VOCs). The keywords like COVID-19 vaccine types, VOCs, universal vaccines, bivalent, and other relevant terms were searched in NCBI, Science Direct, and WHO databases to review the published literature. The review provides an integrative discussion on the current state of knowledge on the type of vaccines developed against SARS-CoV-2, the safety and efficacy of COVID-19 vaccines concerning the VOCs, and prospects of novel universal, chimeric, and bivalent mRNA vaccines efficacy to fend off existing variants and other emerging coronaviruses. Genomic variation can be quite significant, as seen by the notable differences in impact, transmission rate, morbidity, and death during several human coronavirus outbreaks. Therefore, understanding the amount and characteristics of coronavirus genetic diversity in historical and contemporary strains can help researchers get an edge over upcoming variants.