Prevalence of Opioid Use in Nursing Homes Over the Last Decade: A Systematic Literature Review.

Background: Despite global concerns of an opioid epidemic, there is no systematic literature review on how frequently these drugs are used in nursing home (NH) populations, including those living with dementia. Objective: This systematic review aims to describe the prevalence and incidence of opioid use in NHs. A secondary objective is to describe the use of these drugs in a subset of NH residents, namely among persons living with dementia. Methods: A systematic literature review was carried out using MEDLINE and Scopus (PROSPERO registration number CRD42021254210). Screening of title and abstract was carried out by 2 persons independently for studies published between January 1, 2011 and May 19, 2021. The main outcomes were annual prevalence, period prevalence, and duration of opioid use. Results: From a total of 178 identified studies, 29 were considered eligible for inclusion. The annual prevalence of any opioid use among all NH residents without any selection criteria ranged from 6.3% to 50% with a median annual prevalence of 22.9% (Q25-Q75: 19.5%-30.2%), based on 17 studies. Five studies measured the annual prevalence in NH residents living with dementia, finding that this ranged from 10% to 39.6%. Conclusions: More evidence is needed quantifying opioid use in NH, especially among persons living with dementia. Given that opioid use in NH is still a problem, implementation of a pain management protocol in NH or nationally would help improve clinical outcomes.

Nivolumab Safety in Renal Cell Carcinoma: A Case Report.

Nivolumab is used to treat several different types of cancers. Although it is generally considered to be effective and well-tolerated, it has been associated with adverse effects requiring discontinuation of treatment, like many other drugs used for cancer. A 70-year-old male was switched from sunitinib to nivolumab for renal cell carcinoma. The patient developed persistent hypothyroidism, onycholysis, and pneumonitis at nivolumab cycle 6, 10, and 11, respectively. Using the Naranjo causality method, the likelihood of causality was deemed "probable" for pneumonitis and hypothyroidism and "possible" for onycholysis. Nivolumab was eventually discontinued due to disease progression, rather than safety concerns. Eudravigilance, the European pharmacovigilance database, was searched for all nivolumab-related individual case safety reports from Malta, up to September 4, 2023. Six reports were identified in Malta, although the 3 events identified in this case report were not reported, suggesting under-reporting in Malta. This case report identified an uncommon nivolumab adverse drug reaction (ADR), onycholysis and showed how, despite the occurrence of 3 ADRs, it was its lack of efficacy rather than its safety which led to its discontinuation in this particular patient.

Overview of the European post-authorisation study register post-authorization studies performed in Europe from September 2010 to December 2018.

BACKGROUND: The European post-authorisation study (EU PAS) register is a repository launched in 2010 by the European Medicines Agency (EMA). All EMA-requested PAS, commonly observational studies, must be recorded in this register. Multi-database studies (MDS) leveraging secondary data have become an important strategy to conduct PAS in recent years, as reflected by the type of studies registered in the EU PAS register. OBJECTIVES: To analyse and describe PAS in the EU PAS register, with focus on MDS. METHODS: Studies in the EU PAS register from inception to 31st December 2018 were described concerning transparency, regulatory obligations, scope, study type (e.g., observational study, clinical trial, survey, systematic review/meta-analysis), study design, type of data collection and target population. MDS were defined as studies conducted through secondary use of >1 data source not linked at patient-level. Data extraction was carried out independently by 14 centres with expertise in pharmacoepidemiology, using publicly available information in the EU PAS register including study protocol, whenever available, using a standardised data collection form. For validation purposes, a second revision of key fields for a 15% random sample of studies was carried out by a different centre. The inter-rater reliability (IRR) was then calculated. Finally, to identify predictors of primary data collection-based studies/versus those based on secondary use of healthcare databases) or MDS (vs. non-MDS), odds ratios (OR) and 95% confidence intervals (CI) were calculated fitting univariate logistic regression models. RESULTS: Overall, 1426 studies were identified. Clinical trials (N = 30; 2%), systematic reviews/meta-analyses (N = 16; 1%) and miscellaneous study designs (N = 46; 3%) were much less common than observational studies (N = 1227; 86%). The protocol was available for 63% (N = 360) of 572 observational studies requested by a competent authority. Overall, 36% (N = 446) of observational studies were based fully or partially on primary data collection. Of 757 observational studies based on secondary use of data alone, 282 (37%) were MDS. Drug utilisation was significantly more common as a study scope in MDS compared to non-MDS studies. The overall percentage agreement among collaborating centres that collected the data concerning study variables was highest for study type (93.5%) and lowest for type of secondary data (67.8%). CONCLUSIONS: Observational studies were the most common type of studies in the EU PAS register, but 30% used primary data, which is more resource-intensive. Almost half of observational studies using secondary data were MDS. Data recording in the EU PAS register may be improved further, including more widespread availability of study protocols to improve transparency.

Direct healthcare costs of chronic kidney disease management in Italy: What cost-savings can be achieved with higher biosimilar uptake and more appropriate use of erythropoiesis-stimulating agents?

PURPOSE: Erythropoiesis-stimulating agents (ESAs), are used for treating chronic kidney disease (CKD)-related anemia, contributing to CKD costs. The study was aimed at investigating direct healthcare costs of CKD patients treated with ESAs and the potential savings achievable by increasing the use of biosimilars and preventing inappropriate ESA use. METHODS: A multi-center, cohort study was conducted using claims databases of five large Italian geographic areas. Yearly mean direct healthcare costs per patient were estimated, stratifying by CKD stage. The total yearly cost and potential savings related to ESA use were estimated: (a) considering 25/50/75% of originator ESA substitution with biosimilars; (b) eliminating inappropriate ESA dispensing. RESULTS: During the study period, the ESA-related yearly mean cost represented 17% of total yearly costs in stage I-III, decreasing to 13% in stage IV-V and 6% in dialysis. Among originator users, assuming a 25% of biosimilar uptake, the annual cost-savings of ESA treatment would represent 10.5% of total ESA costs in CKD stage I-V and 7.7% in dialysis. Among incident ESA users for which hemoglobin levels were available, 9% started inappropriately ESA treatment, increasing to 62.0% during the first year of maintenance therapy. Hypothesizing prevention of the first inappropriate ESA dispensing, the total yearly cost-savings would amount to €35 772, increasing to €167 641 eliminating the inappropriate dispensing during maintenance therapy. CONCLUSIONS: Higher use of lowest cost ESA, prevention of inappropriate ESA use as well as other strategies aimed at slowing down the progressive renal impairment are essential for minimizing clinical and economic burden of CKD.

Anti-hypertensive drugs deprescribing: an updated systematic review of clinical trials.

BACKGROUND: Polypharmacy is defined as the prescription of at least 5 different medicines for therapeutic or prophylactic effect and is a serious issue among elderly patients, who are frequently affected by multi-morbidity. Deprescribing is one of the proposed approaches to reduce the number of administered drugs, by eliminating those that are inappropriately prescribed. The aim of this systematic review is to provide an updated and systematic assessment of the benefit-risk profile of deprescribing of anti-hypertensive drugs, which are among the most commonly used drugs. METHODS: MEDLINE, EMBASE and The Cochrane Library were searched for studies assessing the efficacy and safety of anti-hypertensive drugs deprescribing in the period between January, 12,016 and December, 312,019. The quality of randomized clinical trials (RCTs) was assessed using the GRADE approach for the evaluation of the main outcomes. The risk of bias assessment was carried out using the Cochrane risk-of-bias tool. RESULTS: Overall, two RCTs were identified. Despite summarized evidence was in favor of anti-hypertensive deprescribing, the overall risk of bias was rated as high for each RCT included. According to the GRADE approach, the overall quality of the RCTs included was moderate regarding the following outcomes: systolic blood pressure < 150 mmHg after 12 weeks of follow-up, quality of life, frailty and cardiovascular risk. CONCLUSIONS: This updated systematic review of the efficacy and safety of anti-hypertensive treatment deprescribing found two recently published RCTs, in addition to the previous guideline of the National Institute for Health and Care Excellence (NICE). Evidence points towards non-inferiority of anti-hypertensive deprescribing as compared to treatment continuation, despite the quality of published studies is not high. High quality experimental studies are urgently needed to further assess the effect of deprescribing for this drug class in specific categories of patients.

Antipsychotic utilization patterns among patients with schizophrenic disorder: a cross-national analysis in four countries.

PURPOSE: The aim of the present study was to describe antipsychotic utilization patterns among patients with schizophrenic disorder in Italy, Spain, the UK, and the USA. METHODS: A retrospective cohort study was conducted. Patients aged 15 and over with schizophrenic disorder were identified in the Caserta claims database (Italy), the Valencia electronic medical record (EMR) database (Spain), in The Health Improvement Network EMR database (UK), and in databases of publicly and privately insured populations in the United States (US). RESULTS: The frequency of first-generation or second-generation antipsychotic use and of long-acting or other formulations was described. Persistence to antipsychotics was estimated. Overall, 1,403,240 patients with schizophrenic disorder having a total of 765,573 new antipsychotic treatment episodes were identified. The median follow-up time ranged from 0.8 (IQR 0.2-1.9) years in the US commercially-insured population to 1.2 (IQR 0.1-1.7) years in the Spanish population. Second-generation antipsychotics were more frequently used than first-generation antipsychotics in all countries (on average, from 64.4% in the UK to 87% in US): the use of this class increased over time in Italy, Spain, and US (Medicaid). The use of long-acting formulations was heterogeneous across countries, but generally much lower than other formulations. Persistence to antipsychotic treatment at 1 year was low in all countries, ranging from 40 in Spain to 30% in Italy. CONCLUSIONS: Antipsychotic utilization was heterogeneous among persons with schizophrenic disorder. Nevertheless, low persistence was an issue in all the countries, as less than half of the patients continued their treatment beyond 1 year.

Use of azithromycin and risk of ventricular arrhythmia.

BACKGROUND: There are conflicting findings from observational studies of the arrhythrogenic potential of azithromycin. Our aim was to quantify the association between azithromycin use and the risk of ventricular arrhythmia. METHODS: We conducted a nested case-control study within a cohort of new antibiotic users identified from a network of 7 population-based health care databases in Denmark, Germany, Italy, the Netherlands and the United Kingdom for the period 1997-2010. Up to 100 controls per case were selected and matched by age, sex and database. Recency of antibiotic use and type of drug (azithromycin was the exposure of interest) at the index date (occurrence of ventricular arrhythmia) were identified. We estimated the odds of ventricular arrhythmia associated with current azithromycin use relative to current amoxicillin use or nonuse of antibiotics (≥ 365 d without antibiotic exposure) using conditional logistic regression, adjusting for confounders. RESULTS: We identified 14 040 688 new antibiotic users who met the inclusion criteria. Ventricular arrhythmia developed in 12 874, of whom 30 were current azithromycin users. The mean age of the cases and controls was 63 years, and two-thirds were male. In the pooled data analyses across databases, azithromycin use was associated with an increased risk of ventricular arrhythmia relative to nonuse of antibiotics (adjusted odds ratio [OR] 1.97, 95% confidence interval [CI] 1.35-2.86). This increased risk disappeared when current amoxicillin use was the comparator (adjusted OR 0.90, 95% CI 0.48-1.71). Database-specific estimates and meta-analysis confirmed results from the pooled data analysis. INTERPRETATION: Current azithromycin use was associated with an increased risk of ventricular arrhythmia when compared with nonuse of antibiotics, but not when compared with current amoxicillin use. The decreased risk with an active comparator suggests significant confounding by indication.

Indications of newer and older anti-epileptic drug use: findings from a southern Italian general practice setting from 2005-2011.

AIMS: The aim of the study was to analyze the prescribing pattern of both newer and older AEDs. METHODS: A population of almost 150 000 individuals registered with 123 general practitioners was included in this study. Patients who received at least one AED prescription over 2005-2011 were identified. The 1 year prevalence and cumulative incidence of AED use, by drug class and individual drug, were calculated over the study period. Potential predictors of starting therapy with newer AEDs were also investigated. RESULTS: The prevalence of use per 1000 inhabitants of older AEDs increased from 10.7 (95% CI10.1, 11.2) in 2005 to 13.0 (95% CI12.4, 13.6) in 2011, while the incidence remained stable. Newer AED incidence decreased from 9.4 (95% CI 8.9, 9.9) in 2005 to 7.0 (95% CI 6.6, 7.5) in 2011, with a peak of 15.5 (95% CI 14.8, 16.1) in 2006. Phenobarbital and valproic acid were the most commonly prescribed AEDs as starting therapy for epilepsy. Gabapentin and pregabalin accounted for most new pain-related prescriptions, while valproic acid and lamotrigine were increasingly used for mood disorders. Female gender (OR 1.36, 95% CI 1.20, 1.53), age ranging between 45-54 years (OR 1.39, 95% CI 1.16, 1.66) and pain as an indication (OR 16.7, 95% CI, 13.1, 21.2) were associated with newer AEDs starting therapy. CONCLUSIONS: Older AEDs were mainly used for epileptic and mood disorders, while newer drugs were preferred for neuropathic pain. Gender, age, indication of use and year of starting therapy influenced the choice of AED type. The decrease of newer AED use during 2007 is probably related to the restricted reimbursement criteria for gabapentin and pregabalin.

Changes in the prescribing pattern of antidepressant drugs in elderly patients: an Italian, nationwide, population-based study.

BACKGROUND: Despite the high use of antidepressants (ADs) among the elderly, there is limited information about the prescribing pattern of these drugs in the Italian elderly population. The aim of this study was to analyze the trend in the use of ADs in the Italian elderly patients in the years 2003-2009, and specifically, to evaluate rates and predictors of AD treatment discontinuation in depressed older patients. METHODS: The nationwide general practice Health Search Database (HSD) was used to identify AD users aged 65 years old and over from 2003 to 2009. ADs were categorized as (1) selective serotonin reuptake inhibitors (SSRIs); (2) serotonin-norepinephrine reuptake inhibitors (SNRIs); (3) tricyclic antidepressants (TCAs); (4) noradrenergic and specific serotonergic antidepressants (NaSSAs); and (5) other ADs. Incidence and prevalence of AD use per 1,000 inhabitants was calculated by drug class and single compound. We also measured rates and predictors of AD discontinuation (i.e., treatment gap ≥ 60 days) during the first year of therapy. RESULTS: Overall, 39,557 AD users ≥65 years (17 % of the total HSD elderly population) were included in the study. SSRIs were increasingly and most frequently prescribed ADs (102.7-195.3 per 1,000 over seven years). The most common indications for AD use were depression and anxiety. Overall, 14 % of AD users continued their AD medication without treatment gaps, 27 % were intermittent AD users and 58 % discontinued their ADs during the first year of follow-up. Specific AD classes such as TCAs and 'other ADs were found to be predictors of discontinuation. In depressed patients, the use of NaSSas, TCAs and 'other ADs as well the concomitant use of >5 drugs (other than ADs) and living in Southern Italy were more likely to predict discontinuation. CONCLUSION: ADs, especially SSRIs, are widely and increasingly prescribed in elderly Italian patients in recent years. The observed high AD discontinuation rates are likely to impact the achievement of a therapeutic endpoint in depressed patients. Patients who are at high risk of AD discontinuation such as those receiving multi-drug therapy or living in Southern Italy should be monitored more closely to improve benefits of AD treatments.

Safety of drugs used for the treatment of migraine during pregnancy: a narrative review.

INTRODUCTION: Migraine is common in females of childbearing age and negatively impacts quality of life. The majority of those with migraine who become pregnant see an improvement in their condition but not all do. Providing evidence-based recommendations for the pharmacological management of migraine in pregnancy is challenging. AREAS COVERED: This narrative review provides an update on the safety of drugs used for migraine in pregnancy. National and international guidelines on the management of episodic migraine in adults were used to select the drugs of relevance to pregnant women. The final list of drugs was chosen by a pain specialist who categorized them according to drug class and use in acute management or prevention. PubMed was searched from inception to 31st July 2022 for evidence on drug safety. EXPERT OPINION: Obtaining high-quality drug safety data in pregnant migraineurs is difficult not least because exposing a fetus to research-related risks is often considered unethical. There is reliance on observational studies which often group drugs together and lack specificities pertinent to drug prescribing like timing, dosing and duration. Improved statistical tools, study designs and the creation of international collaborative frameworks are ways to advance knowledge on drug safety in pregnancy.

A scoping review of legibility of hand-written prescriptions and drug-orders: the writing on the wall.

INTRODUCTION: Prescription and drug order writing are key components of patient care allowing physicians communicate their therapeutic plans. Although electronic prescriptions are becoming more common, handwritten prescriptions are still quite prevalent and a persistent issue with handwritten prescriptions is the illegibility of physician handwritings. Prescriptions have to be legible to avoid delays in healthcare provision and consequences as serious as patient death. AREAS COVERED: We did a scoping review of multiple articles that assessed the legibility of prescriptions in different settings (inpatient, outpatient, and pharmacies) and countries, ranging from 1997 to 2020. Studies also elaborated on possible reasons for these suboptimal prescriptions and ways to address them. EXPERT OPINION: While the degree of legibility of prescriptions varies widely, it remains a concern because a single incorrectly read prescription can have severe consequences. Various measures exist to possibly minimize illegible prescriptions and while none alone is probably sufficient, combining is likely to yield great results. One is the sensitization and education of physicians and physicians-in-training. Another option is audits and a third and very potent option is the use of computerized provider order entry (CPOE) system which will help improve patient safety by reducing errors due to inappropriately read prescriptions.

Risk management of medication errors: a novel conceptual framework.

BACKGROUND: Medication error is a common cause of patient harm. The study aims to propose a way to manage the risk of medication errors in a novel way, by identifying practice areas where mitigating patient harm should be prioritized using a risk management approach. METHODS: Suspected Adverse Drug Reactions (sADRs) in Eudravigilance database over three years were reviewed to identify preventable medication errors. These were classified using a new method based upon the root cause underlying pharmacotherapeutic failure. The correlation between severity of harm and type of medication error, and other clinical parameters was investigated. RESULTS: Overall, 2294 medication errors were identified from Eudravigilance, of which 1300 (57%) were due to pharmacotherapeutic failure. Most cases of preventable medication error involved prescribing (41%) and administration (39%). The variables which significantly predicted severity of medication errors were pharmacological group, patient age, number of drugs prescribed, and route of administration. The drug classes most strongly associated with harm included cardiac drugs, opioids, hypoglycaemics, antipsychotics, sedatives, and antithrombotic agents. CONCLUSION: The findings of this study highlight the feasibility of using a novel conceptual framework to identify areas of practice at risk of pharmacotherapeutic failure where Interventions by healthcare professionals in these areas are most likely to improve medication safety.

The pharmacological treatment of granulomatosis with polyangiitis: a review of clinical trials registered in clinicaltrials.gov and the International Clinical Trials Registry Platform.

To date, there is no published overview of the drug pipeline in granulomatosis with polyangiitis (GPA), a rare disease. The aim of this study was to identify clinical trials from two study repositories. A review of clinical trials was conducted using publicly available data. Clinicaltrials.gov and International Clinical Trials Registry Platform were searched from inception until 25 September 2022. Only GPA-specific studies were included; these were described in detail. A total of 137 studies were identified in the trial repositories, of which 108 (79%) studies were found to concern GPA. Of these 108 studies, 67 enrolled GPA patients to investigate pharmacotherapy in this disease (62%). Most studies included all severity types (n = 51; 76%); the scope of almost half of the studies was remission induction (n = 33; 49%). The drug class which was by the most widely investigated in trials was the non-corticosteroid immunosuppressant drug class (46; 68.7%), monoclonal antibodies (32; 47.8%), and corticosteroids (31; 46.3%). There is a need for more GPA trials to generate evidence on effectiveness in terms of severity-specificity and maintenance of remission.

The pharmacological treatment of granulomatosis with polyangiitis: a review of clinical trials To date, there is no published overview of the drug pipeline in granulomatosis with polyangiitis (referred to in this paper as GPA), a rare disease. The aim of this study was to identify such studies from two study archives. Clinicaltrials.gov and International Clinical Trials Registry Platform (ICTRP) were searched from inception until 25th September 2022. Studies recruiting GPA patients were included; these were described in detail. A total of 137 studies were identified in the trial repositories, of which 108 were found to concern GPA. Of these 108 studies, 67 enrolled GPA patients to investigate the treatment of this disease through the administration of drugs. Most studies included all severity types (n = 51); the scope of almost half of the studies was to induce remission (n = 33). The drug classes which were the most widely investigated in trials were non-corticosteroid immunosuppressant drugs (n = 46), monoclonal antibodies (n = 32), and corticosteroids (n = 31). There is a need for more GPA clinical trials to generate evidence on effectiveness of drugs in terms of severity-specificity and maintenance of remission.

An Exploratory Study of the Impact of COVID-19 Vaccine Spontaneous Reporting on Masking Signal Detection in EudraVigilance.

INTRODUCTION: During the signal detection process, statistical methods are used to identify drug-event combinations (DECs) which are disproportionately reported when compared with other drugs and events in the entire database. We hypothesise that the high volume of COVID-19 vaccine adverse drug reaction (ADR) reports transmitted to EudraVigilance may have affected the performance of disproportionality statistics used in routine signal detection, potentially resulting in signals either being masked, or false associations being flagged as potential signals. OBJECTIVE: Our aim was to study the impact of COVID-19 vaccine spontaneous reporting on statistical signal detection in EudraVigilance. METHODS: We recalculated the reporting odds ratio (ROR) for signals that were previously discussed at the level of the Pharmacovigilance Risk Assessment Committee, or signals that were retrieved from EudraVigilance, by omitting COVID-19 vaccine reports from the standard ROR calculation and then comparing the lower confidence interval (LCI) of the recalculated ROR to the LCI of the actual ROR in EudraVigilance. RESULTS: In total, 52 signals for 38 active substances were reviewed. For 35 signals, the LCI of the recalculated ROR value was lower than the LCI of the actual ROR (suggesting that COVID-19 vaccine ADR reporting had a positive effect on the strength of the signal) while for 15 signals the LCI of the recalculated ROR value was higher than the LCI of the actual ROR (suggesting that COVID-19 vaccine ADR reporting had an attenuating effect on the strength of the signal). For two signals, no change in the ROR was observed. In our analysis, six significant results were found. Five DECs were found to be masked: bleomycin and immune thrombocytopenia (actual ROR LCI = 0.94, recalculated ROR LCI = 1.02), vortioxetine and heavy menstrual bleeding (actual ROR LCI = 0.3, recalculated ROR LCI = 1.06), caplacizumab and heavy menstrual bleeding (actual ROR LCI = 0.98, recalculated ROR LCI = 3.47), ziprasidone and amenorrhoea (actual ROR LCI = 0.84, recalculated ROR LCI = 1.67), and azacitidine and pericarditis (actual ROR LCI = 0.81, recalculated ROR LCI = 2.01). For the DEC of adalimumab and immune reconstitution inflammatory syndrome, the LCI of the actual ROR value was 1.14 and removing COVID-19 vaccine reporting resulted in an LCI of the recalculated ROR value of 0.94 (below threshold). CONCLUSIONS: We demonstrated five cases of masking and one case of false-positive association due to the influence of COVID-19 vaccine spontaneous reporting on the ROR. This suggests that the high number of adverse drug reaction reports for COVID-19 vaccines in EudraVigilance has the potential to affect routine statistical signal detection activities. The impact of COVID-19 vaccine ADR reports on current signal detection practices requires further evaluation and solutions to tackle masking issues in EudraVigilance may need to be developed.

Maltese Allelic Variants in Corneal Dystrophy Genes in a Worldwide Setting.

INTRODUCTION: This study aimed to establish which worldwide population cohorts have a genetic make-up closest to that of a large sample of the Maltese population with regard to corneal dystrophy (CD) genes. METHODS: Single nucleotide polymorphisms (SNPs) in the Maltese cohort were compared with worldwide cohorts. Fixation index (FST) values were calculated to evaluate population differentiation. The genetic prevalence of CD subtypes in worldwide and Maltese cohorts were calculated, and single nucleotide missense mutations present in the Maltese cohort were evaluated for potential pathogenicity. RESULTS: FST values showed that CD-related genes differ substantially among the studied cohorts. FST values for each SNP showed greatest differentiation between the Maltese and African cohorts and least differentiation with the Puerto Rican, Mexican, and Colombian cohorts. One TGFBI casual CD mutation, 502V, which causes a Bowman's layer CD/atypical Thiel-Behnke CD was identified in the Maltese cohort. The KRT3 NC_000012.11:g.53186088G>C mutation was potentially deleterious. CONCLUSION: Identifying populations with least genetic differentiation can facilitate and help guide future diagnostic and treatment strategies for Maltese individuals with CDs in the absence of comparable Maltese data. Analysing the previously unknown CD genetic pool present in a large Maltese cohort adds to the global genetic bank that researchers rely on for medical progress.

Corrigendum: Editorial: The mechanisms of action of anti-SARS-CoV-2 drugs.

[This corrects the article DOI: 10.3389/fphar.2022.894310.].

Identifying and categorizing compounds that reduce corneal transforming growth factor beta induced protein levels: a scoping review.

INTRODUCTION: Transforming growth factor beta induced (TGFBI) gene mutations have been reported as the cause of a group of genetically inherited, visually debilitating, corneal dystrophies (CD). A scoping literature review to identify and categorize compounds that inhibit corneal TGFBI expression and/or promote TGFBIp degradation was performed. Emphasis was given to their potential to be used as a cost-effective approach via drug repurposing. AREAS COVERED: We performed a thorough search of original peer-reviewed literature using electronic bibliographic databases and selected articles according to a set of criteria. The total number of articles retrieved from the search terms applied to the databases was 2344. The number of relevant full-text articles included added up to 19. We identified 16 compounds that can theoretically reduce the levels of mutant TGFBIp in human corneal cells. EXPERT OPINION: Currently, the only temporary treatments available for this condition are lubricant drops and surgery. Here, we explored the crosstalk between cascades that regulate TGFBI expression and identified compounds that target these pathways. Compounds that inhibit DNA synthesis and function, increase elimination of TGFBIp or bind to mutant TGFBIp were also explored with the aim of highlighting promising compounds that can be used in future cost-effective drug-repurposing studies.

RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia-an international Delphi consensus.

Drug repositioning and repurposing has proved useful in identifying new treatments for many diseases, which can then rapidly be brought into clinical practice. Currently, there are few effective pharmacological treatments for Lewy body dementia (which includes both dementia with Lewy bodies and Parkinson's disease dementia) apart from cholinesterase inhibitors. We reviewed several promising compounds that might potentially be disease-modifying agents for Lewy body dementia and then undertook an International Delphi consensus study to prioritise compounds. We identified ambroxol as the top ranked agent for repurposing and identified a further six agents from the classes of tyrosine kinase inhibitors, GLP-1 receptor agonists, and angiotensin receptor blockers that were rated by the majority of our expert panel as justifying a clinical trial. It would now be timely to take forward all these compounds to Phase II or III clinical trials in Lewy body dementia.

Assessing intravitreal anti-VEGF drug safety using real-world data: methodological challenges in observational research.

INTRODUCTION: It is generally acknowledged that the ocular safety profile of intravitreal anti-VEGF drugs is acceptable, while the burden of systemic safety of these intravitreal agents is still being debated. The evaluation of the systemic safety of these drugs using real-world data (RWD), such as spontaneous reporting systems (SRS), electronic medical records (EMRs) and claims databases has several advantages, including the capture of outcomes among real-world populations over long observation periods. Nevertheless, there is a relatively small body of research exploring the post-marketing safety of these drugs. AREAS COVERED: The aim of this scoping review is to outline and discuss some of the methodological challenges to be faced when investigating the systemic safety of intravitreal anti-VEGF drugs using different sources of RWD. EXPERT OPINION: Such challenges include the selection of the most suitable data source, taking into account how well drug utilization is captured and whether the outcomes and covariates of interest can be captured. The strengths and limitations of some analytic methods that can be used to quantify risk, such as the intention-to-treat approach and the as-treated approach, complement each other, and using these together provides a more balanced analysis.