Optimal Pharmacological Treatment Research Articles

Guilu Erxian Jiao remodels dendritic spine morphology through activation of the hippocampal TRPC6-CaMKIV-CREB signaling pathway and suppresses fear memory generalization in rats with post-traumatic stress disorder.

Guilu Erxian Jiao (GLEXJ) is a renowned traditional Chinese herbal formula used to tonify the kidney. It is employed to treat psychiatric disorders, and alleviate memory impairment, cognitive dysfunction, and behavioral disorders. Modern pharmacological studies have demonstrated GLEXJ's ability to significantly inhibit the fear response in post-traumatic stress disorder (PTSD) and facilitate the extinction of fear memory. However, the underlying pharmacological mechanisms remain elusive. Fear memory generalization, a fundamental characteristic of PTSD, remains poorly understood, and optimal pharmacological treatments are lacking. This study aimed to investigate GLEXJ's inhibitory effects on fear memory generalization in PTSD rats and elucidate its underlying mechanisms. PTSD rats were induced using the single prolonged stress and electrical stimulation (SPS&S) protocol and treated with GLEXJ or paroxetine (PRX). Fear memory generalization was assessed using a contextual fear memory test. Hippocampal dendritic spine morphology was analyzed using Golgi-Cox staining. The chemical composition of GLEXJ was determined using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Network pharmacology was employed to predict GLEXJ's therapeutic mechanism in PTSD treatment. Western blotting and immunofluorescence were used to measure indicators of the transient receptor potential channel 6 (TRPC6)-mediated calcium/calmodulin-dependent protein kinase IV-cAMP response element-binding protein (CaMKIV-CREB) signaling pathway. In vitro, TRPC6 was suppressed in rat adrenal pheochromocytoma (PC12) cells using lentiviral vectors, and phalloidin staining was employed to examine changes in Fibros actin (F-actin), elucidating the mechanistic effects of GLEXJ-containing serum. GLEXJ significantly mitigated fear memory generalization in PTSD rats, even with repeated stress exposure. It also alleviated abnormal hippocampal dendritic spine morphology. Network pharmacology analysis confirmed that GLEXJ was closely related to the Ca2+ signaling pathway in PTSD treatment. PTSD rats exhibited disrupted TRPC6-mediated CaMKIV-CREB signaling and impaired synaptic plasticity. GLEXJ upregulated TRPC6 expression, reactivated the CaMKIV-CREB pathway, and promoted synaptic remodeling. In vitro studies confirmed that TRPC6 suppression reduced F-actin levels while GLEXJ-containing serum increased TRPC6 expression and F-actin content. GLEXJ activates CaMKIV-CREB signaling by upregulating TRPC6 in the hippocampus of PTSD rats, leading to the positive modulation of dendritic spine morphology and synaptic remodeling. This mechanism contributes to the attenuation of fear memory generalization. Given the limitations of current PTSD treatments, these findings offer potential avenues for developing more effective therapeutic strategies.

Therapeutic Approach to Primary Tic Disorders and Associated Psychiatric Comorbidities.

The treatment of tics and psychiatric comorbidities is crucial when they affect the patient's well-being and relationships. However, the optimal pharmacological treatment (PT) tailored to each patient's phenotype remains unclear. The primary objective of this study is to describe the clinical characteristics and treatment received for tics and psychiatric comorbidities in our cohort of children and adult patients with tic disorders. Additionally, a further aim was to quantify the severity of tics, comorbidities and overall severity, and the overall clinical changes observed during the follow-up. Retrospective descriptive study of patients with tic disorders under follow-up at our Tic Functional Unit from January 2022 to March 2024. Two independent neurologists retrospectively applied the Clinical Global Impression of Change (CGI-C) and the Clinical Global Impression of Severity (CGI-S) scales at baseline and at last assessment. A total of 36 individuals were included (63.8% males, median age = 18 years, IQR 19): 94.4% with Tourette syndrome (TS), 2.8% with chronic tic disorder (CTD), and 2.8% with provisional tic disorder (PTD). A total of 86% had at least one psychiatric comorbidity, the most common being obsessive-compulsive symptomatology (OCS) (52%), anxiety (52%), and attention deficit hyperactivity disorder (ADHD) (35%). At last assessment, 26 patients (72.2%) were on undergoing PT for tics and 3 were receiving additional botulinum toxin. The most used medication for tics were aripiprazole (46.2%) and clonazepam (46.2%), and for psychiatric comorbidities, SSRIs (42.9%), methylphenidate (19%), and benzodiazepines (57.1%). Overall improvement according to the CGI-C scale was mild (CGI-C 3). Children and adolescents showed greater improvement than adults (CGI-C 2 vs. 3; p = 0.005). Aripiprazole and clonazepam produced similar outcomes in reducing CGI-C. We observed a favorable clinical course in patients treated with aripiprazole and clonazepam, which appear to be better than that obtained with other treatments. We consider that clonazepam may be useful as a first-line monotherapy and as an adjuvant for both tics and comorbidities in selected cases.

Optimizing triple therapy in patients with metastatic hormone-sensitive prostate cancer

Triple therapy with docetaxel, androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs) has demonstrated survival benefits in patients with metastatic hormone-sensitive prostate cancer (mHSPC), especially in those with high-risk disease. However, once the use of ADT and docetaxel is established, guidelines do not clearly specify which ARPI is most appropriate. In this work, a literature review to identify phase III clinical trials, systematic reviews, meta-analyses, and clinical practice guidelines on triple therapy in mHSPC was carried out. Evidence and recommendations were qualitatively reviewed to provide guidelines on the most suitable ARPI based on patient risk, disease volume, and nature of metastases (synchronous or metachronous). This review aims to update the previously published consensus on the optimal pharmacological treatment for mHSPC and to expose the opinions of hospital pharmacy, urology and medical and radiation oncology experts.

Optimización de la triple terapia en el tratamiento del cáncer de próstata hormonosensible metastásico

Triple therapy with docetaxel, androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs) has demonstrated survival benefits in patients with metastatic hormone-sensitive prostate cancer (mHSPC), especially in those with high-risk disease. However, once the use of ADT and docetaxel is established, guidelines do not clearly specify which ARPI is most appropriate. In this work, a literature review to identify phase III clinical trials, systematic reviews, meta-analyses, and clinical practice guidelines on triple therapy in mHSPC was carried out. Evidence and recommendations were qualitatively reviewed to provide guidelines on the most suitable ARPI based on patient risk, disease volume, and nature of metastases (synchronous or metachronous). This review aims to update the previously published consensus on the optimal pharmacological treatment for mHSPC and to expose the opinions of hospital pharmacy, urology and medical and radiation oncology experts.

Exploration of Management Strategies for Type 2 Diabetes among Wounded Patients: A Review

The management of type 2 diabetes mellitus (T2DM) in patients with wounds posed a complex challenge, requiring a multifaceted approach to optimize glycemic control and improve healing outcomes. T2DM impaired the body’s natural healing processes, increasing the risk of chronic wounds, particularly diabetic foot ulcers (DFUs), which can lead to severe complications such as infections and amputations. This review explored various management strategies tailored for wounded patients with T2DM, including the importance of maintaining optimal glycemic levels, dietary interventions, pharmacological treatments, and multidisciplinary care approaches. The review was conducted by synthesizing current research findings, clinical studies, and systematic reviews on glycemic control, dietary interventions, pharmacological treatments, and multidisciplinary approaches in managing wounds among patients with T2DM. Key findings indicate that tight glycemic control, particularly with target hemoglobin A1c (HbA1c) levels between 7.0% and 8.0%, enhances wound healing, while overly aggressive management may have adverse effects. Nutritional strategies like Mediterranean and low-carbohydrate diets improve insulin sensitivity and reduce inflammation, while pharmacological treatments like metformin, GLP-1 receptor agonists, and SGLT-2 inhibitors improve glycemic control and overall health outcomes. A multidisciplinary team (MDT) approach is highlighted as a critical factor in improving patient care, with evidence showing significant reductions in HbA1c levels among patients treated by MDTs. Future research should focus on standardizing protocols, leveraging emerging technologies, and assessing the long-term effects of integrated management strategies on wound healing and quality of life. Keywords: Type 2 Diabetes Management, Glycemic Control, Wound Healing, Dietary Interventions, Multidisciplinary Care.

Designing and validating a clinical decision support algorithm for diabetic nephroprotection in older patients

BackgroundOlder patients with diabetic kidney disease (DKD) often do not receive optimal pharmacological treatment. Current clinical practice guidelines (CPGs) do not incorporate the concept of personalised care. Clinical decision support...

Evaluation of the Efficacy of Transcatheter Intervention, Surgery, and Pharmacological Treatment of Functional Mitral Regurgitation — A Bayesian Network Meta-Analysis with ≥12-Month Follow-up

Aim: Evaluate, using a Bayesian network meta-analysis system, the long-term prognosis of patients with functional mitral regurgitation (FMR) undergoing individual or combined treatment with percutaneous intervention, surgical intervention, or optimal medical therapy. Compare the prognostic outcomes of the different treatment modalities. Methods: Computerized searches of Embase, PubMed, and the Cochrane Library databases were performed. Randomized controlled trials (RCTs) and observational studies were searched to compare prognoses following transcatheter interventions, surgery, and optimal pharmacological treatment for FMR, all with a construction timeframe of 21 October 2023. The primary endpoint event was all-cause mortality. The secondary endpoint events were heart failure readmission rate, mitral regurgitation (MR) ≤2+ improvement rate, New York Heart Association (NYHA) improvement rate (improvement to I–II), and degree of left ventricular ejection fraction (LVEF) improvement. Results: Twenty-six (26) papers were included, comprising 10 RCTs and 16 observational studies involving 5443 patients. A network meta-analysis showed no significant difference in prognosis for all-cause mortality among transcatheter interventions, surgical procedures, and optimal pharmacological treatments. For heart failure readmission rates, mitral valve surgery was superior to MitraClip (odds ratio (OR) = 11.82; 95% confidence interval (CI): 1.67, 90.13). For NYHA (improvement to I–II) improvement rates, the results showed no significant differences for the various mitral interventions. For MR ≤2+ improvement rates, the MitraClip (OR = 3.07; 95% CI: 2.42, 3.76), MitraClip+Guideline-directed medical therapy (GDMT) (OR = 2.93; 95% CI: 2.38, 3.52), mitral valve surgery (OR = 3.01; 95% CI: 2.24, 3.8), and annuloplasty (OR = 4.31; 95% CI: 3.12, 5.58) were superior to GDMT, and mitral valve surgery (OR = 0.07; 95% CI: –0.45, 0.62) was superior to MitraClip+GDMT. For the degree of improvement in LVEF, Carillon+GDMT (mean difference (MD) = –0.97; 95% CI: –1.72, –0.22) was superior to GDMT, mitral valve surgery was superior to Carillon+GDMT (MD = 4.67; 95% CI: 0.92, 8.39); MitraClip+GDMT (MD = 4.01; 95% CI: 1.28, 6.66), GDMT (MD = 3.71; 95% CI: 0.04, 7.35), and annuloplasty were superior to mitral valve surgery (MD = –6.42; 95% CI: –11.96, –0.78). Conclusion: There were no significant differences among the three treatment modalities of transcatheter intervention, surgery, and optimal drug therapy in improving all-cause mortality hard endpoint events, and no significant differences were seen in the rates of heart failure readmission and NYHA improvement (improvement to I–II). However, surgery was superior to transcatheter intervention and optimal drug therapy in terms of improvement in the degree of regurgitation and LVEF.

A Delphi consensus among experts on assessment and treatment of disruptive mood dysregulation disorder.

The aim of this study was to explore consensus among clinicians and researchers on how to assess and treat Disruptive Mood Dysregulation Disorder (DMDD). The Delphi method was used to organize data collected from an initial sample of 23 child psychiatrists and psychologists. Three rounds of closed/open questions were needed to achieve the objective. Fifteen experts in the field completed the whole study. Finally, 122 proposals were validated and 5 were rejected. Globally, consensus was more easily reached on items regarding assessment than on those regarding treatment. Specifically, experts agreed that intensity, frequency, and impact of DMDD symptoms needed to be measured across settings, including with parents, siblings, peers, and teachers. While a low level of consensus emerged regarding optimal pharmacological treatment, the use of psychoeducation, behavior-focused therapies (e.g., dialectical behavior therapy, chain analysis, exposure, relaxation), and systemic approaches (parent management training, family therapy, parent-child interaction therapy) met with a high degree of consensus. This study presents recommendations that reached a certain degree of consensus among researchers and clinicians regarding the assessment and treatment of youths with DMDD. These findings may be useful to clinicians working with this population and to researchers since they also highlight non-consensual areas that need to be further investigated.

Diversified applications of hepatocellular carcinoma medications: molecular-targeted, immunotherapeutic, and combined approaches.

Hepatocellular carcinoma (HCC) is one of the primary forms of liver cancer and is currently the sixth most prevalent malignancy worldwide. In addition to surgical interventions, effective drug treatment is essential for treating HCC. With an increasing number of therapeutic drugs for liver cancer undergoing clinical studies, the therapeutic strategies for advanced HCC are more diverse than ever, leading to improved prospects for HCC patients. Molecular targeted drugs and immunotherapies have become crucial treatment options for HCC. Treatment programs include single-agent molecular-targeted drugs, immunotherapies, combinations of immunotherapies with molecular-targeted drugs, and dual immune checkpoint inhibitors. However, further exploration is necessary to determine the optimal pharmacological treatment regimens, and the development of new effective drugs is urgently needed. This review provides an overview of the current globally approved drugs for liver cancer, as well as the latest advances in ongoing clinical research and drug therapies. Additionally, the review offers an outlook and discussion on the prospects for the development of drug therapy approaches for HCC.

Surgical and bronchoscopic pulmonary function-improving procedures in lung emphysema.

COPD is a highly prevalent, chronic and irreversible obstructive airway disease without curative treatment. Standard therapeutic strategies, both non-pharmacological and pharmacological, have only limited effects on lung function parameters of patients with severe disease. Despite optimal pharmacological treatment, many patients with severe COPD still have a high burden of dyspnoea and a poor quality of life. If these patients have severe lung emphysema, with hyperinflation as the driver of symptoms and exercise intolerance, lung volume reduction may be an effective treatment with a significant impact on lung function, exercise capacity and quality of life. Currently, different lung volume reduction approaches, both surgical and bronchoscopic, have shown encouraging results and have been implemented in COPD treatment recommendations. Nevertheless, choosing the optimal lung volume reduction strategy for an individual patient remains challenging. Moreover, there is still room for improving durability of effect and safety in all available procedures. Ongoing and innovative research is essential to push this field forwards. This review provides an overview of results and limitations of the current lung volume reduction options for patients with severe lung emphysema and hyperinflation.

Lipid-Lowering Therapy after Acute Coronary Syndrome in Outpatient Practice-How to Achieve Goal.

Secondary prevention of cardiovascular disease involves the use of optimal pharmacological treatment and modification of risk factors through lifestyle changes. Recent evidence demonstrates that the major initiating event in atherogenesis is the storage of low-density lipoproteins. We aimed to compare the efficacy in achieving the therapeutic lipid target in relation to the frequency of follow-up at selected time points and to determine the safety and tolerability of cholesterol-lowering drugs (statins, ezetimibe). This was a prospective analysis of 72 consecutive patients hospitalized for acute coronary syndrome: ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). Patients were consecutively divided into two groups: first, with follow-up and laboratory tests at 1, 3, 6 and 12 months after hospital discharge, including 32 patients; second, including 40 patients with follow-up and laboratory tests 12 months after hospital discharge. A significant reduction in LDL-C level was observed at 12 months in both groups. LDL-C level was significantly lower in group 1 than in group 2 after 12 months (p = 0.02). Total cholesterol level was significantly lower in group 1 than in group 2 after 12 months. After 12 months of therapy, 21 (65.6%) patients in group 1 and 17 (42.5%) in group 2 had LDL-C < 1.4 mmol/L. In group 1, we observed a significant decrease in LDL-C, triglyceride, and total cholesterol levels at 1, 3, 6 and 12 months (p < 0.05). The group of patients with more frequent follow-up visits showed a greater reduction in LDL-C level than the group with only one visit after a 12-month hospital discharge.

What determines the optimal pharmacological treatment of atrial fibrillation? Insights from in silico trials in 800 virtual atria.

The best pharmacological treatment for each atrial fibrillation (AF) patient is unclear. We aim to exploit AF simulations in 800 virtual atria to identify key patient characteristics that guide the optimal selection of anti-arrhythmic drugs. The virtual cohort considered variability in electrophysiology and low voltage areas (LVA) and was developed and validated against experimental and clinical data from ionic currents to ECG. AF sustained in 494 (62%) atria, with large inward rectifier K+ current (IK1 ) and Na+ /K+ pump (INaK ) densities (IK1 0.11±0.03 vs. 0.07±0.03 SmF-1 ; INaK 0.68±0.15 vs. 0.38±26 SmF-1 ; sustained vs. un-sustained AF). In severely remodelled left atrium, with LVA extensions of more than 40% in the posterior wall, higher IK1 (median density 0.12±0.02 SmF-1 ) was required for AF maintenance, and rotors localized in healthy right atrium. For lower LVA extensions, rotors could also anchor to LVA, in atria presenting short refractoriness (median L-type Ca2+ current, ICaL , density 0.08±0.03 SmF-1 ). This atrial refractoriness, modulated by ICaL and fast Na+ current (INa ), determined pharmacological treatment success for both small and large LVA. Vernakalant was effective in atria presenting long refractoriness (median ICaL density 0.13±0.05 SmF-1 ). For short refractoriness, atria with high INa (median density 8.92±2.59 SmF-1 ) responded more favourably to amiodarone than flecainide, and the opposite was found in atria with low INa (median density 5.33±1.41 SmF-1 ). In silico drug trials in 800human atria identify inward currents as critical for optimal stratification of AF patient to pharmacological treatment and, together with the left atrial LVA extension, for accurately phenotyping AF dynamics. KEY POINTS: Atrial fibrillation (AF) maintenance is facilitated by small L-type Ca2+ current (ICaL ) and large inward rectifier K+ current (IK1 ) and Na+ /K+ pump. In severely remodelled left atrium, with low voltage areas (LVA) covering more than 40% of the posterior wall, sustained AF requires higher IK1 and rotors localize in healthy right atrium. For lower LVA extensions, rotors can also anchor to LVA, if the atria present short refractoriness (low ICaL ) Vernakalant is effective in atria presenting long refractoriness (high ICaL ). For short refractoriness, atria with fast Na+ current (INa ) up-regulation respond more favourably to amiodarone than flecainide, and the opposite is found in atria with low INa . The inward currents (ICaL and INa ) are critical for optimal stratification of AF patient to pharmacological treatment and, together with the left atrial LVA extension, for accurately phenotyping AF dynamics.

Determinants and treatments of heart failure after transcatheter aortic valve implantation: moving up a notch.

Transcatheter aortic valve implantation (TAVI) has become an alternative to surgical aortic valve replacement for patients with symptomatic severe aortic stenosis in elderly and comorbid population. Significant improvement in heart function has been observed in patients undergoing TAVI, but numerous patients are readmitted to hospital for heart failure (HF). Moreover, repeat HF hospitalization is strongly associated with an adverse prognosis and increases the financial burden of health care. Although studies have identified pre-existing and post-procedural factors that contribute to HF hospitalization after TAVI, there is a paucity of data regarding optimal post-procedural pharmacological treatments. This review aims to provide an overview of the current understanding of mechanisms, determinants, and potential treatments of HF following TAVI. We first review the pathophysiology of left ventricular (LV) remodelling, coronary microcirculation disorder, and endothelial dysfunction in patients with aortic stenosis and then examine the impact of TAVI on these conditions. We then present evidence of various factors and complications that may interplay with LV remodelling and contribute to HF events after TAVI. Next, we describe the triggers and predictors of early and late HF rehospitalizations following TAVI. Lastly, we discuss the potential of conventional pharmacological treatments, including renin-angiotensin blockers, beta-blockers, and diuretics in TAVI patients. The paper explores the potential of newer drugs, including sodium-glucose co-transporter 2 inhibitors, anti-inflammatory drugs, and ion supplementation. Comprehensive knowledge in this field may aid in recognizing successful existing therapies, developing effective new treatments, and establishing dedicated patient care strategies during follow-up after TAVI.

Protocol of a randomized controlled trial investigating Deep Brain Stimulation for MOtor symptoms in patients with Parkinson’s disease DEmentia (DBS-MODE)

BackgroundDeep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for disabling motor symptoms of Parkinson’s disease (PD) that persist despite optimal pharmacological treatment. Currently, DBS is not performed if there is concomitant significant cognitive impairment based on concerns of cognitive deterioration, higher complication rate and less functional improvement. However, this has not been investigated so far.MethodsA single center, prospective, randomized, open-label, blinded end-point (PROBE design) pilot clinical trial is being performed. Patients are eligible for the trial if they have PD dementia (PDD), are able to provide informed consent, and experience disabling motor response fluctuations, bradykinesia, dyskinesia, or painful dystonia, despite optimal pharmacological treatment. In total 44 patients will be randomized to either STN-DBS accompanied by best medical treatment (DBS group) or to best medical treatment alone (BMT group). The primary outcome measure is the change from baseline to 30 weeks on the Movement Disorder Society—Unified Parkinson’s Disease Rating Scale part III score in a standardized off-drug phase. The main secondary outcome measures consist of scales assessing cognitive aspects of daily living, neuropsychiatric symptoms and impulsive compulsive disorders. Additional secondary outcome measures include motor signs during on-drug phase, dyskinesia, motor fluctuations, cognitive performance, (severe) adverse events, treatment satisfaction, and caregiver burden. Patients will be followed during 52 weeks after randomization.DiscussionThe Deep Brain Stimulation for MOtor symptoms in patients with Parkinson’s disease DEmentia (DBS-MODE) trial directly compares the effectiveness and safety of DBS with BMT in patients with PDD.Trial registrationThe DBS-MODE trial has been registered in the International Clinical Trial Registry Platform (NL9361) on the 24th of March 2021 (https://trialsearch.who.int/Trial2.aspx?TrialID=NL9361).

Wewnątrzsercowe urządzenia wszczepialne w niewydolności serca

With widespread access to intracardiac implantable devices, the number of people with heart failure (HF) who underwent primary or secondary prophylaxis has increased. Technological progress has made it possible to construct modern high-energy intracardiac devices, allowing them to achieve the intended therapeutic goals. However, it should be considered that implantation of the device may be associated with complications, the frequency of which varies depending on the experience of the operator, the age of the patient, the degree of multi-organ failure and the patient’s coexisting conditions. Implantation of cardioverter-defibrillator or cardiac resynchronisation therapy, in a properly qualified patient and experienced team of interventional cardiologists, is associated with the risk of a relatively low percentage of early and distant complications. An important element of patient management is striving to eliminate inadequate interventions that adversely affect both the patient’s functioning and quality of life. It is important to educate the patient, as well as highlight the risks associated with alcohol and medication abuse, illegal sports and non-compliance with pharmacotherapy recommendations. Optimal pharmacological treatment of HF and co-existing diseases and systematic control of the device during visits to the clinic or using remote monitoring is necessary.

An Update of Pharmacological Management in Children with Functional Constipation.

Functional constipation is a common problem in childhood worldwide and has a great impact on social, physical, and emotional functioning of affected children and their caregivers. It is a clinical diagnosis based on the Rome IV criteria. Non-pharmacological treatment involves education, demystification, lifestyle advice, and toilet training. Pharmacological treatment consists of disimpaction, maintenance treatment, and eventually weaning if possible. Polyethylene glycol is considered as the first choice of laxative for both disimpaction and maintenance treatment. Different osmotic laxatives, stimulant laxatives, lubricants, and enemas are available as alternative pharmacological treatment options. Novel drugs are emerging but evidence to support the widespread application of these drugs in the pediatric population is often lacking and more high-quality research is needed in this field. If children remain symptomatic despite optimal pharmacological treatment, botulinum toxin injections in the anal sphincter can be considered as an alternative, more invasive treatment option. This review provides an update on currently available literature concerning the pharmacologic treatment of functional constipation in children.

Pharmacological Interventions for Sialorrhoea in People with Parkinson's Disease: A Systematic Review and Meta-Analysis.

Sialorrhoea is a common non motor complication experienced by people with Parkinson's disease (PD). Despite its prevalence there is conflicting evidence on how to effectively treat it. Our aim was to establish the efficacy and safety outcomes of pharmacological interventions used to treat sialorrhoea in people with idiopathic PD. We registered and conducted a systematic review and meta-analysis (PROSPERO: CRD42016042470). We searched seven electronic databases from inception until July 2022. Quantitative synthesis was performed where data allowed using random effects models. From 1374 records we included 13 studies (n=405 participants). Studies were conducted in Europe, North America and China. There was marked heterogeneity in the interventions used, follow up times and outcome measures investigated. The main source of risk of bias identified was reporting bias. Five studies were included in the quantitative synthesis. Summary estimates showed administration of botulinum toxin significantly reduced saliva production, improved patient reported functional outcomes and was associated with an increase in adverse events. Sialorrhoea in PD is an important condition, but current data does not allow for strong recommendations on optimal pharmacological treatments. There is significant heterogeneity in outcomes measures used to evaluate the burden of sialorrhoea with lack of consensus on what constitutes clinically meaningful change. More research is required to better understand the underlying mechanism and potential treatments of sialorrhoea in idiopathic PD.

An implantable cardioverter-defibrillator for primary prevention in non-ischemic cardiomyopathy: A systematic review and meta-analysis.

Recent data regarding the comparison of implantable cardioverter-defibrillator (ICD) therapy and optimal medical treatment in patients with non-ischemic cardiomyopathy has indicated no mortality benefit as a result of ICD therapy. Although the recommendations for ICD implantation did not change, it is worth noting that these findings significantly affected the daily practice of ICD implantation in Europe. To assess the effect of ICD implantation in comparison to pharmacotherapy in the non- -ischemic cardiomyopathy heart failure population through a systematic review and meta-analysis of the available carefully designed prospective randomized controlled trials. Only prospective randomized controlled trials comparing ICD implantation in primary prevention vs. optimal pharmacological therapy or placebo and reporting mortality results were included in the meta-analysis. The authors have chosen to include the following trials: CAT, AMIOVIRT, DEFINITE, and DANISH. A meta-analysis of pooled hazard ratios (HR) from all trials conducted on a total of 1789 patients found that ICD therapy decreased all-cause mortality in comparison to optimal pharmacological treatment, with a HR of 0.48 (95% confidence interval [CI] 0.67-1.01); p = 0.06. The data from the AMIOVIRT, DANISH, and DEFINITE trials, with a total of 1677 participants, showed a significant reduction of sudden cardiac deaths as a result of ICD implantation, with a HR of 0.48 (95% CI 0.31-0.67); p < 0.001. In comparison with optimal medical treatment, ICD implantation in patients with heart failure improves the long-term prognosis in terms of sudden cardiac death, with a strong tendency towards all-cause mortality reduction.

Secondary Pharmacological Prevention of Coronary Artery Disease among Patients Submitted to Clinical Management, Percutaneous Coronary Intervention, or Coronary Artery Bypass Graft Surgery.

Secondary prevention is recommended for patients with evidence of coronary artery disease (CAD) regardless of the indication for treatment by coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI). This study evaluated whether clinical treatment, PCI or CABG had an influence on adherence to the pharmacological secondary prevention in patients with stable CAD. This cohort included patients aged ≥40 years with stable CAD confirmed by coronary angiography. The decision for medical treatment alone, or additionally with PCI or CABG, was made by the attending physicians. Adherence to the prescribed drugs recommended by the guidelines for secondary prevention (optimal pharmacological treatment), including antiplatelet agents, lipid-lowering drugs, beta-blockers, and renin-angiotensin-aldosterone system blockers, was assessed at follow-up. Differences were considered significant for p values <0.05. From 928 patients enrolled at baseline, 415 had mild CAD and 66 moderate to severe CAD. The average follow-up was 5.2 ± 1.5 years. Patients submitted to CABG were more likely to receive the optimal pharmacological treatment than those submitted to PCI or treated clinically (63.5% versus 39.1% versus 45.7% respectively, p=0.003). Baseline factors independently associated with greater probability of having a prescription of optimal treatment at follow-up were CABG [39% higher (6% - 83%, p=0.017) and diabetes [25% higher (1% - 56%), p=0.042] than their counterparts treated by other methods and participants without diabetes, respectively. Patients with CAD submitted to CABG are more commonly treated with optimal pharmacological secondary prevention than patients treated by PCI or exclusively with medical therapy.

PCOS in Adolescents-Ongoing Riddles in Diagnosis and Treatment.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. A diagnosis of PCOS is established when a patient exhibits two of three Rotterdam criteria: oligoovulation or anovulation, excess androgen activity, and polycystic ovarian morphology. The pathogenesis of PCOS, as it affects adolescents, is often discussed in terms of a "two-hit" theory. This refers to a stepwise process in which the first "hit" is an inborn congenitally programmed predisposition, while the second "hit" arises from a provocative factor such as insulin resistance. The dynamic physiological and anatomical changes which occur in puberty make for a challenging diagnosis in this group of patients. It is important to be mindful of the physiological particularities in adolescence which often mimic the symptoms of PCOS. In their first-year post-menarche, approximately 75% of menstruating adolescents report their cycle to last between 21-45 days. Recent studies have shown that regular menstrual cyclicity is only achieved within 2-3 years post-menarche. Anovulation, as a crucial diagnostic element for PCOS, features in about half of early-post-menarchal adolescents. Hirsutism and acne are the most common clinical manifestations of hyperandrogenism, and mild features are developed by most adolescents as a result of elevated androgen levels. Distinguishing between a pathological sign and normal features of maturation is often difficult. A polycystic ovarian morphology (PCOM) through ultrasound has been found in up to 40%, 35%, and 33.3% of patients when assessed at 2, 3, and 4 years, respectively, after menarche. PCOM in adolescence is not associated with future abnormalities in ovulatory rate or menstrual cycle duration. For this reason, international guidelines recommend against the use of pelvic ultrasound until 8 years post-menarche. The primary aim of management is focused mainly on improving hormonal and metabolic status, the prevention of future comorbid complications, and generally improving the overall quality of life in young women with PCOS. Considerable controversy surrounds the choice of optimal pharmacological treatment to address PCOS in adolescents. Reliable studies, which include this sub-section of the population, are very limited. There is a lack of robust and reliable trials in the literature addressing the use of combined oral contraceptives. Further work needs to be undertaken in order to provide safe and effective care to the adolescent population in this regard.