Background: Proton pump inhibitors (PPIs) are some of the most frequently prescribed medications, but they are often used inappropriately, either being prescribed without a clear indication or continued for longer than necessary. In such cases, deprescribing is recommended. However, despite its proven effectiveness, the implementation of deprescribing in clinical practice remains inconsistent and varied, making it challenging to identify the most effective strategies. The goal is to provide a comprehensive outline of deprescribing interventions for PPI therapy implemented across various settings and by different healthcare professionals. Methods: The study is designed to be a systematic review of the published literature. PubMed, Embase, and Web of Science databases were searched from 1 January 1989 (the first PPI on the market) to 30 September 2024 for articles assessing PPI deprescribing in adult patients, focusing on the implementation rate (primary outcome) or effects on symptoms (secondary outcome). Results: After screening, 66 studies were included, predominantly pragmatic trials (N = 32) or randomized controlled trials (N = 25). We found a variety of interventions promoting PPI deprescription. Collaborative efforts involving multiple healthcare professionals, the use of algorithms for clinical decision-making, and patient involvement have proven to be key elements in the most effective strategies. Discontinuing therapy may not be advisable in cases of recurrent symptoms, suggesting that on-demand therapy could be a recommended approach. Deprescribing is particularly relevant for individuals with mild illnesses and symptoms, where tapering can effectively mitigate the rebound symptoms often associated with abrupt discontinuation. Conclusions: Given the current prevalence of inappropriate PPI prescribing, it is imperative to raise awareness among both physicians and patients about the importance of the deprescribing process, which should be tailored to the specific needs of each patient, considering his/her medical history, current health status, and personal preferences.

Although larger trinucleotide expansions give rise to a neurodevelopmental disorder called fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by a “premutation” (55–200 CGG repeats) in the FMR1 gene. FXTAS is one of the more common single-gene forms of late-onset ataxia and tremor that may have a more complex development in women, with atypical presentations. After a brief presentation of the atypical case of an Italian woman with FXTAS, who had several paroxysmal episodes suggestive of acute cerebellar and/or brainstem dysfunction, this article will revise the phenotype of FXTAS in women. Especially in females, FXTAS has a broad spectrum of symptoms, ranging from relatively severe diseases in mid-adulthood to mild cases beginning in later life. Female FXTAS and male FXTAS have a different symptomatic spectrum, and studies on the fragile X premutation should be conducted separately on women or men. Hopefully, a better understanding of the molecular processes involved in the polymorphic features of FXTAS will lead to more specific and effective therapies for this complex disorder.

In the last ten years, the knowledge of the genetic basis of mitochondrial diseases has significantly advanced. However, the vast phenotypic variability linked to mitochondrial disorders and the peculiar characteristics of their genetics make mitochondrial disorders a complex group of disorders. Although specific genetic alterations have been associated with some syndromic presentations, the genotype–phenotype relationship in mitochondrial disorders is complex (a single mutation can cause several clinical syndromes, while different genetic alterations can cause similar phenotypes). This review will revisit the most common syndromic pictures of mitochondrial disorders, from a clinical rather than a molecular perspective. We believe that the new phenotype definitions implemented by recent large multicenter studies, and revised here, may contribute to a more homogeneous patient categorization, which will be useful in future studies on natural history and clinical trials.

The COVID-19 virus diffusion is, nowadays, global and any clinical trial is potentially affected by the direct and indirect consequences of the COVID-19 during the pandemic. Any step, from protocol design to result's disclosure, needs to be revised to assess the impact of the COVID-19 on the study, evaluate the potential risks, and establish a mitigation plan. We have developed a series of recommendations, belonging to our experience in any aspect of clinical trials. We hope that the Risk and Mitigation actions for clinical trials during COVID-19 Pandemic (RiMiCOPa) will help all clinical trial professionals, patients, auditors, and assessors to ensure effective data management, statistics, and medical writing standards while conducting clinical trials in the pandemic.

Wine, as any other alcoholic drink, should be consumed in moderate dosages. The scientific literature reports a huge number of articles describing the various health benefits of moderate wine drinking, but none have so far summarized the different types of evidence supporting these effects. Furthermore, there is no proof that any specific wine might be more or less beneficial than any other according to its content of specific nutrients and components. The aim of this article was to identify the individual components of wine that are known to have a potential to effect on health, in order to create a wine-specific index to grossly estimate the impact of moderate wine drinking on well-being. A deep search was performed on the medical literature to choose those articles that could explain the role of the main components of wine on health. The proper dosages and the instruments to evaluate the quality of wines were identified and are described herein. Evidence supporting the role of alcohol, acidity, sulfur dioxide, malic acid, metals, polyphenols, and other components of wine on health was identified and summarized, and the various links with health benefits are described. Then a Wine Index of Salubrity and Health (WISH) was developed which, as a rapidly available and effective instrument, will help to understand at a glance the potential beneficial effect of a specific wine. Keywords: wine, health, alcohol, polyphenols, sulfur dioxide, metal, wine quality

Observational trials are a relevant part of clinical research. Publishing their results can be chal lenging for scientists and writers. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement was the first guideline developed to identify the minimal information that should be included in articles reporting observational and epidemiological research. More than 50 ancillary guidelines tailored to specific needs are now available to assist authors in preparing successful articles on observational studies.

Background A significant percentage of patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) achieve clinically meaningful improvement when receiving placebo or tadalafil 5mg once daily. However, individual patient characteristics associated with treatment response are unknown. Methods This integrated clinical data mining analysis was designed to identify factors associated with a clinically meaningful response to placebo or tadalafil 5mg once daily in an individual patient with LUTS-BPH. Analyses were performed on pooled data from four randomized, placebo-controlled, double-blind, clinical studies, including about 1,500 patients, from which 107 baseline characteristics were selected and 8 response criteria. The split set evaluation method (1,000 repeats) was used to estimate prediction accuracy, with the database randomly split into training and test subsets. Logistic Regression (LR), Decision Tree (DT), Support Vector Machine (SVM) and Random Forest (RF) models were then generated on the training subset and used to predict response in the test subset. Prediction models were generated for placebo and tadalafil 5mg once daily Receiver Operating Curve (ROC) analysis was used to select optimal prediction models lying on the ROC surface. Findings International Prostate Symptom Score (IPSS) baseline group (mild/moderate vs. severe) for active treatment and placebo achieved the highest combined sensitivity and specificity of 70% and ~50% for all analyses, respectively. This was below the sensitivity and specificity threshold of 80% that would enable reliable allocation of an individual patient to either the responder or non-responder group Conclusions This extensive clinical data mining study in LUTS-BPH did not identify baseline clinical or demographic characteristics that were sufficiently predictive of an individual patient response to placebo or once daily tadalafil 5mg. However, the study reaffirms the efficacy of tadalalfil 5mg once daily in the treatment of LUTS-BPH in the majority of patients and the importance of evaluating individual patient need in selecting the most appropriate treatment.

EMWA members were surveyed in late 2012 and early 2013 about their current salary levels. A total of 320 individuals responded. Most were women, between 31 and 50 years of age, and native speakers of English or German. About half had 2–10 years of experience. Mean annual income was €61 505 (median €54 000), more than 10% higher than reported in 2006. Men earned more than women and income rose with work experience and responsibility. Highest academic degree and native language did not appear to influence income, but members with an EMWA Professional Development Programme certificate earned more than those who did not. The results suggest that salary depends more on professional skills and knowledge than on formal requirements and might be increased by gaining experience and expanding professional skills; however, formal conclusions about influencing factors cannot be made because statistical comparisons were not performed due to potential sample bias.

Introduction: Insulin lispro protamine suspension (ILPS) is a protamine-based insulin lispro formulation that allows 24-h coverage while limiting the number of daily injections. ILPS was developed to be the basal insulin component of premixed biphasic formulations with insulin lispro, i.e., the lispro/ILPS 25/75 and 50/50 mixed compounds, but has recently also been marketed as a basal insulin analog formulation, with an indication for the therapy of diabetic patients.Areas covered: This article reviews the available literature on pharmacokinetics/pharmacodynamics (PK/PD), efficacy and safety of ILPS administered as basal insulin, or in premixed biphasic formulations, in patients with type 1 and type 2 diabetes mellitus.Expert opinion: The results of this review suggest that ILPS may be associated with a favorable time-action profile, basal and postprandial glycemic control, and efficacy in terms of rates of patients reaching glycosylated hemoglobin targets; an increased risk of hypoglycemic episodes, compared to other basal insulins, seems to be related to the percentage of patients upgrading from once-to twice-daily injections. This increased risk might be linked with the concomitant use of insulin secretagogues in patients on higher daily dosages and is generally not observed in patients using one injection of ILPS a day. Thus, ILPS can be considered a valid option both as basal insulin and as basal component of the actual premixed formulations of lispro for the therapy of diabetic patients.

OBJECTIVE:Depression is a comorbidity affecting quality of life (QoL) in patients with Parkinson's disease (PD) and requires appropriate treatment. This study evaluated the tolerability, safety, and efficacy of duloxetine 60 mg once daily for 12 weeks in PD patients with major depressive disorder (MDD).RESEARCH AND DESIGN METHODS:Non-comparative, open-label, multi-center study.MAIN OUTCOME MEASURES:Tolerability was evaluated by discontinuation rate (acceptable if ≤ 19%) due to treatment-emergent adverse events (TEAEs) and motor symptoms (UPDRS). Safety measures were TEAEs, the UKU side effect rating scale, vital signs, weight, laboratory tests, and ECG. Efficacy measures included HAMD-17, BDI, CGI-S, PGI-I, and pain VAS. QoL was measured by PDQ-39.RESULTS:Of the 151 patients enrolled, 8.6% (95% upper CI: 13.3%) discontinued the study due to TEAEs. Worsening in PD-related tremor and rigidity was not observed, activities of daily living significantly improved and UKU subscales progressively decreased. Clinically significant abnormalities in laboratory findings were limited to four cases of hypercholesterolemia and one increase of total bilirubin, CPK, and fasting glucose. Blood pressure, weight, and ECG did not change from baseline. HAMD-17 and PDQ-39 total score and individual domains, BDI, CGI-S, and PGI-I total scores significantly improved.CONCLUSIONS:Duloxetine seems well tolerated and likely effective in the treatment of depression associated with PD, with no detrimental effects in PD signs and symptoms.

INTRODUCTION:Erectile dysfunction (ED) is a very common multidimensional disorder affecting men worldwide. Physical illness, reaction to life stresses, or an unhappy couple relationship influence clinical outcome. Phosphodiesterase type 5 (PDE5) inhibitors are recognized as efficacious and well tolerated, and are the first-line treatment for ED. Sildenafil, tadalafil, and vardenafil are the most widely used and studied PDE5 inhibitors. Data acquired during a routine diagnostic workup for ED should be taken into account when choosing the best PDE5 inhibitor for the individual patient, creating an individualized treatment plan, and going beyond "experience-based" subjective opinion and unfounded ideas and prejudice regarding currently available drugs.AIM:As the process of matching a given patient's profile to any selected PDE5 inhibitor often relies more on physician's personal convictions than on solid evidence, the aim of this review is to identify the main clinical, demographic, and relational factors influencing the choice of the PDE5 inhibitor to be used for the treatment of ED.METHODS:A systematic literature search and current treatment guidelines were evaluated in a systematic manner.MAIN OUTCOME MEASURES:The main clinical, cultural, and demographical factors to be considered for the treatment of ED have been identified.RESULTS:Main factors influencing the choice of the treatment for ED have been described. A short list of items that may help in choosing the right PDE5 inhibitor for the treatment of different patients in daily clinical practice has been prepared.CONCLUSIONS:The simple algorithms prepared should be a useful tool to be used in daily practice, which may help in choosing the right treatment for each subject affected by ED.

Historically, oral phosphodiesterase type 5 inhibitors (PDE5‐i) have been prescribed with an ‘as‐necessary’ regimen for treating erectile dysfunction (ED), thus addressing primarily symptom relief. However, ≈ 30% of patients are unresponsive to on‐demand PDE5‐i regimens due to both psychogenic and organic factors and, although it is difficult to estimate the proportion, discontinuation rates remain high. In recent years, a 2.5–5 mg daily dose of tadalafil has been proposed and was recently approved for treating ED. Chronic PDE‐5 inhibition has the advantage of potentially ‘curing’ ED, on a daily basis, by interfering with pathophysiological factors of both psychogenic (anxiety related to planning sexual activity) and organic (endothelial dysfunction, penile structural homeostasis) origin, although further research is needed to better address these hypotheses. Clinical studies showed that chronic PDE5‐i regimens are a safe and effective alternative to the classical on‐demand dosage, and might improve the outcomes in a selected group of patients.

SUMMARYBackground: In patients with bipolar disorder, medication is effective in preventing relapses. Unfortunately, adherence to treatment in bipolar disorder, as in other chronic or recurrent conditions, is not optimal. Estimates of nonadherence to prescribed treatment range from 30% to 60% in epidemiological studies, and are at around 30% in clinical trials. Adherence to treatment is a potent predictor of effectiveness, both in clinical trials and cohort studies, therefore is a very relevant area of investigation. This study will try to show a picture of the real life care where adherence is influenced by a wide range of variables. Methods: Prospective, observational, multicenter study in 650 adult patients with bipolar disorder, who had to initiate or change their treatment regimen, observed for 1 year. Adherence was measured by the Simplified Medication Adherence Questionnaire (SMAQ). Additional variables: Symptom severity, Montgomery‐Åsberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS), Clinical Global Impression–Bipolar Disorder (CGI‐BD), the Drug Attitude Inventory score (DAI‐30), and quality of life (EuroQoL 5 Dimensions). The variables were recorded every 3 months for the next year. Results: Most subjects were out‐patients (77.1%), female (58.8%), aged 31–50 years (50.1%) and overweight (41.8%) or obese (28.7%); 67.4% had type I bipolar disorder and 66.8% had depressive or mixed symptoms. Adherence was 39.9% at baseline (and increased up to 67.0% at completion. The main predictors of nonadherence were alcohol consumption, severe bipolar symptoms, young age at time of first treatment, negative attitude towards treatment. Conclusions: The patient population of this observational trial was representative of the patients changing their therapy for bipolar disorder seen in clinical practice in Italy. Lack of adherence to pharmacotherapy for bipolar disorder is a serious issue, which is more likely to arise in alcohol users and patients with severe symptoms, negative attitude towards medication and/or initiation of treatment early in life. The findings could lead to a more adequate approach of adherence in patients with bipolar disorders.

ObjectivesTo identify factors associated with suicide attempts using data from a large, 3-year, multinational follow-up study of schizophrenia (SOHO study).MethodsAll baseline characteristics of 8,871 adult patients with schizophrenia collected in patients included in the SOHO study were included in a GEE logistic regression post-hoc analysis comparing patients who attempted suicide during the study with those who did not.ResultsA total of 384 (4.3%) patients attempted or committed suicide. The risk factors that resulted statistically associated with suicide attempt were a lifetime history of suicide attempts (OR 3.6 [95% CI 2.8, 4.6; p< 0.0001]), suicide attempts in the last 6 months (OR 2.5 [95% CI 1.8, 3.4; p< 0.0001]), prolactin-related side effects (OR 2.0 [95%CI 1.4, 2.9; p=0.0002]), CGI depression (OR 1.2 [95% CI 1.1, 1.3; p=0.0004]) and history of hospitalization for schizophrenia (OR 1.4 [95% CI 1.1, 1.8; p=0.009]).ConclusionsIn view of the observational design of the study and the post-hoc nature of the analysis, the identified risk factors should be confirmed by ad-hoc specifically designed studies.

Importance of the field: Except for generalized anxiety disorder, few reports have been published on the efficacy, safety and tolerability of duloxetine in patients with anxiety disorders individually or in comorbidity with major depressive disorder (MDD).Areas covered in this review: The literature search in Medline (dating back to 1966) and Embase (dating back to 1988) databases was conducted using the OVID interface on 9 April 2009, restricted to any article or abstract in English, per title, reporting any information on the use of duloxetine in patients with any anxiety disorder with or without concomitant MDD. A systematic review approach was taken.What the reader will gain: The reader will gain knowledge of the current data available on the use of duloxetine to treat patients with anxiety disorders individually or in comorbidity with MDD.Take home message: Duloxetine could be considered an effective treatment option in the treatment of anxiety disorders individually or in comorbidity with each other, or with MDD; however, apart from the well-demonstrated efficacy, tolerability and safety of duloxetine in the treatment of MDD with or without anxiety and GAD, data on this subject are preliminary and very limited, and more research is warranted.

Attention-deficit hyperactivity disorder (ADHD) is one of the most common neurobehavioural disorders in children. It has been shown that as many as 85% of patients with ADHD have at least one psychiatric co-morbidity, and approximately 60% have at least two. Atomoxetine is a specific, noradrenergic reuptake inhibitor that provides an effective treatment option for patients with ADHD and co-morbid conditions. The efficacy of atomoxetine in treating ADHD appears to be unaffected by the presence of co-morbid conditions. Therapy with atomoxetine has been associated with statistically significant improvements in symptoms of oppositional defiant disorder in most, but not all, studies. Limited data suggest this agent may have potential in improving co-occurring symptoms of anxiety and may be useful in patients with co-morbid conditions such as tics or Tourette's syndrome. The tolerability profile of atomoxetine in patients with ADHD and co-morbid conditions was similar to that of patients with uncomplicated ADHD. Atomoxetine was well tolerated, with adverse events generally mild and transient; the most frequent adverse events in patients with ADHD included abdominal pain, decreased appetite, nausea and vomiting. The favourable safety and efficacy profile of atomoxetine makes it a promising treatment for patients with ADHD and associated co-morbidities.

Objective: This observational study examined the effects of insulin lispro protamine suspension (ILPS) given as basal insulin in intensive insulin regimens in patients with type 1 and type 2 diabetes mellitus who attended a reference outpatient centre for the treatment of diabetes due to poor glycaemic control, frequent hypoglycaemia or intolerance to previous therapy.Methods: The study population included 64 patients, 33 male and 31 female, mean age 59.6 years; 50 patients were receiving an insulin regimen, while 14 had previously been treated with oral antidiabetic drugs (OADs). The starting insulin dose for patients receiving OADs was 0.5-0.8 IU/kg which was titrated according to a standard algorithm. Patients also received an individualised programme for diet adjustment and physical activity. Fasting plasma glucose (FPG), glycosylated haemoglobin (HbA(1c)), hypoglycaemic events, lipid profile, body weight and blood pressure were measured at baseline and thereafter.Results: The mean duration of therapy was 229.3 days. Total insulin daily dosage did not change statistically in the observation period. FPG and HbA(1c) levels decreased significantly (p < 0.001) in this period, with no increase in hypoglycaemic episodes. Univariate analysis has shown that patients having higher HbA(1c) and FPG levels at baseline have higher improvement in HbA(1c) and FPG than those having better glycaemic control at baseline. Patients with concomitant pathologies at baseline had a significantly lower improvement in HbA(1c) and FPG, while females had a significantly higher improvement in HbA(1c). Frequency of hypoglycaemic episodes was significantly lower in those patients who had previously experienced hypoglycaemia, had previously used insulin therapy, had concomitant pathologies, had HbA(1c) above 6.5% at baseline and required higher total daily insulin doses. A significant improvement in total cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride levels, together with a significant decrease in the cardiovascular risk index, were also observed, with no significant variation in body weight and blood pressure.Conclusions: This study shows that the use of ILPS as basal insulin in intensive insulin therapy, improved glycaemic control with no significant increase in hypoglycaemic episodes in the 64 patients observed undergoing treatment at the Potenza outpatient clinic. Because of the nature of this study, these results have to be confirmed in further randomised, controlled clinical trials.