Overcoming Methodological Challenges for Advancing Stem Cell Therapies in Parkinson's Disease.

The quest for new and improved therapies for Parkinson's disease (PD) remains of paramount importance, despite previous trial failures. There is a current debate regarding the potential of stem cell research as a therapeutic approach for PD. The studies of dopaminergic fetal stem cells for PD treatment, their design, and the results of the initial surgical placebo-controlled trials were reviewed in this study. Some of the fundamental methodological challenges and possible strategies to resolve them were proposed. In this article, we argue that the most important impact lies in the proof-of-principle demonstrated by clinical trials for cell replacement strategies in reconstructing the human brain. While some researchers argue that the considerable technical challenges associated with cell therapies for PD warrant the discontinuation of further development using stem cells, we believe that the opposing viewpoints are instrumental in identifying a series of methodological misunderstandings. Here, we propose to expose key challenges to ensure the advancement of the field and unlock the potential of stem cell therapies in PD treatment. Overall, this review underscores the need for further research and innovation to overcome the hurdles in realizing the potential of stem cell-based therapies for PD.

Effect of implementation strategies on the routine provision of antenatal care addressing smoking in pregnancy: study protocol for a non-randomised stepped-wedge cluster controlled trial.

INTRODUCTION: Globally, guideline-recommended antenatal care for smoking cessation is not routinely delivered by antenatal care providers. Implementation strategies have been shown to improve the delivery of clinical practices across a variety of clinical services but there is an absence of evidence in applying such strategies to support improvements to antenatal care for smoking cessation in pregnancy. This study aims to determine the effectiveness and cost effectiveness of implementation strategies in increasing the routine provision of recommended antenatal care for smoking cessation in public maternity services. METHODS AND ANALYSIS: A non-randomised stepped-wedge cluster-controlled trial will be conducted in maternity services across three health sectors in New South Wales, Australia. Implementation strategies including guidelines and procedures, reminders and prompts, leadership support, champions, training and monitoring and feedback will be delivered sequentially to each sector over 4 months. Primary outcome measures will be the proportion of: (1) pregnant women who report receiving a carbon monoxide breath test; (2) smokers or recent quitters who report receiving quit/relapse advice; and (3) smokers who report offer of help to quit smoking (Quitline referral or nicotine replacement therapy). Outcomes will be measured via cross-sectional telephone surveys with a random sample of women who attend antenatal appointments each week. Economic analyses will be undertaken to assess the cost effectiveness of the implementation intervention. Process measures including acceptability, adoption, fidelity and reach will be reported. ETHICS AND DISSEMINATION: Ethics approval was obtained through the Hunter New England Human Research Ethics Committee (16/11/16/4.07; 16/10/19/5.15) and the Aboriginal Health and Medical Research Council (1236/16). Trial findings will be disseminated to health policy-makers and health services to inform best practice processes for effective guideline implementation. Findings will also be disseminated at scientific conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry-ACTRN12622001010785.

A systematic review of the efficacy of group social skills interventions on social functioning and social participation in children with acquired brain injury or cerebral palsy.

AIM: The aim of this study was to evaluate the efficacy of Group social skills interventions (GSSIs) versus any comparator on social functioning in children aged 5-12 years with acquired brain injury or cerebral palsy. BACKGROUND: GSSIs are an evidence-based approach to foster social skills development in children with autism spectrum disorder. Currently, limited literature exploring GSSIs in children with acquired brain injury and cerebral palsy is available. RESULTS: MEDLINE, SCOPUS, Embase, CINAHL, Cochrane Library, PsycINFO, clinicaltrials.gov, ICTRP and ProQuest Dissertations and Theses were systematically searched. Study screening, risk-of-bias, Grading of Recommendations Assessment, Development and Evaluation and data extraction were performed in duplicate. Six studies were included in the narrative synthesis (one randomised controlled trial and five nonrandomised studies). Results indicate that GSSIs may increase children's social skills as measured on the Social Skills Rating System and Social Skills Questionnaire. Very low certainty evidence was found for improvements in social functioning and competence. CONCLUSIONS: There is low certainty evidence that participation in GSSI may lead to gains in social functioning for children with acquired brain injury or cerebral palsy. Given the certainty of the evidence, these results must be interpreted with caution. Only one randomised controlled trial of GSSIs for children with acquired brain injury was identified, underscoring the need for additional high-quality studies.

DO ORAL CARE AND REHABILITATION IMPROVE COGNITIVE FUNCTION? A SYSTEMATIC REVIEW OF CLINICAL STUDIES.

OBJECTIVES: An increasing number of studies have identified an association between oral health status and cognitive function. However, the effect of oral interventions, including oral health care, dental treatment and oral motor exercises, on cognitive function remains unclear. This systematic review examined whether oral interventions contribute to the long-term improvement of cognitive status. METHODS: Four databases were searched (MEDLINE, Web of Science, Cochrane Library, and ICHUSHI Web) to identify randomized and nonrandomized controlled trial studies and prospective cohort studies from inception until 1 September 2023, published in English or Japanese. The Cochrane risk of bias tool for randomized controlled trials and the risk of bias assessment tool for nonrandomized studies were used to assess bias risk. RESULTS: A total of 20 articles were included in the qualitative analysis; 13 articles were published in English, and 7 were published in Japanese. The implemented interventions were oral care in 8 studies, dental treatment in 8 studies, and oral motor exercise in 4 studies. One study found a significant effect on attention following oral care intervention. Some dental treatments influenced cognitive function, although a clear positive effect was not determined. In 1 study, attention and working memory improved in the chewing exercise group. CONCLUSIONS: Several studies verified the improvement effects of oral interventions, such as oral care, dental treatment, and oral motor exercise, on cognitive function or impairment. However, there was still a lack of conclusive evidence that such an intervention clearly improved cognitive function. To clarify the effects of oral interventions on cognitive function, it is necessary to examine participants, interventions, and outcome measures in detail.

Percutaneous electrical nerve field stimulation for adolescents with irritable bowel syndrome: Cost-benefit and cost-minimization analysis.

Abdominal pain drives significant cost for adolescents with irritable bowel syndrome (IBS). We performed an economic analysis to estimate cost-savings for patients' families and healthcare insurance, and health outcomes, based on abdominal pain improvement with percutaneous electrical nerve field stimulation (PENFS) with IB-Stim® (Neuraxis). We constructed a Markov model with a 1-year time horizon comparing outcomes and costs with PENFS versus usual care without PENFS. Clinical outcomes were derived from a sham-controlled double-blind trial of PENFS for adolescents with IBS. Costs/work-productivity impact for parents were derived from appropriate observational cohorts. PENFS was associated with 18 added healthy days over 1 year of follow-up, increased annual parental wages of $5,802 due to fewer missed work days to care for the child, and $4744 in cost-savings to insurance. Percutaneous electrical field nerve stimulation for adolescents with IBS appears to yield significant cost-savings to patients' families and insurance.

Psychological and attentional outcomes following acute mindfulness induction among high anxiety individuals: A systematic review and meta-analysis.

BACKGROUND: Training outcomes of mindfulness interventions for anxiety have been extensively researched. Less is known about the acute effects of mindfulness induction and associated mechanisms. This systematic review aimed to identify 1) the effect of mindfulness induction on pre-post measures of state anxiety and attention among adults experiencing high levels of anxiety; and 2) the impact of predictors, mediators and moderators on post-induction changes in anxiety and attention. State distress and mindfulness were included as secondary outcomes. METHODS: A systematic search was conducted in November 2021 in electronic databases using relevant search terms. Five studies (four randomised controlled trials and one non-randomised controlled trial) were included, comprising a total of 277 participants with elevated trait/generalised anxiety. Each study used a brief audio-based mindfulness induction exercise. RESULTS: The meta-analysis indicated mindfulness induction had medium and large effects on state anxiety (k = 3, n = 100, g = -0.60, 95%CI [-1.04, -0.16]; p = .008) and state mindfulness (k = 2, n = 110, g = 0.91, 95%CI [0.52, 1.30], p < .001), respectively, when compared with non-therapeutic control conditions. Furthermore, two studies showed small and moderate effects of mindfulness on state anxiety when compared to therapeutic active controls, but were not pooled in a meta-analysis. While results could not be pooled for attention, there was limited evidence of behavioural improvements on tasks measuring aspects of attention following mindfulness induction. However, one study found an increase in Low Beta to High Beta ratio and a reduction in Beta activity in the Anterior Cingulate Cortex following mindfulness induction. Moreover, another study found aspects of state mindfulness mediated reductions in state anxiety. LIMITATIONS: A small number of studies were included in the review, with high risk of bias and low certainty of evidence present. CONCLUSION: The findings support the use of mindfulness induction to reduce state anxiety in anxious individuals but suggest gains in state mindfulness may be a more realistic expected outcome. Further controlled trials are needed to delineate the relative effects of objectively assessed anxiety outcomes from mindfulness induction in clinically defined samples.

Antagonist enamel tooth wear produced by different dental ceramic systems: A systematic review and network meta-analysis of controlled clinical trials.

OBJECTIVES: The aim of this study was to evaluate the amount of enamel tooth wear induced by different antagonistic ceramic crown materials in the posterior area within a follow-up period up to 24 months in function. A network meta-analysis was performed to assess the effect of the materials on the mean vertical loss (MVL) of the antagonist enamel tooth surface. DATA: Main search terms used in combination: ceramic, dental materials, metal ceramic, tooth wear and dental enamel. SOURCES: An electronic search was conducted in PubMed/Medline, Embase, and Cochrane CENTRAL plus hand-searching. STUDY SELECTION: Eligibility criteria included clinical studies reporting on MVL on antagonist's tooth up to 24 months following the permanent crown placement. From a total of 5697 articles, 7 studies reporting on 261 crowns for 177 subjects with 3 ceramic materials (Lithium disilicate, metal-ceramic, monolithic zirconia) were included. Among all, metal-ceramic and zirconia caused significantly higher enamel tooth wear on antagonist teeth, representing 82.5 µm [54.4; 110.6]) and 40.1 µm [22.2; 58.0]) more MVL than natural teeth group. In contrast, lithium disilicate showed only 5.0 µm [-48.2; 58.1]) more MVL than occurs on opposing natural teeth. CONCLUSIONS: This systematic review demonstrated that prosthodontic ceramic materials produced significantly more antagonist enamel tooth wear than opposing natural enamel tooth wear, and ceramic material type was correlated to the degree of enamel tooth wear. Additional well-conducted, randomized controlled trials with homogeneous specimens are required due to inadequate sample size and number of the clinical studies included in the analyses. CLINICAL SIGNIFICANCE: The amount of wear caused by different restorative materials has a high influence on the antagonistic natural teeth and should therefore be evaluated intensively by the dentist.

Self-reported MeasUrement of Physical and PsychosOcial Symptoms Response Tool (SUPPORT-dialysis): systematic symptom assessment and management in patients on in-centre haemodialysis - a parallel arm, non-randomised feasibility pilot study protocol.

INTRODUCTION: Patients with kidney failure experience symptoms that are often under-recognised and undermanaged. These symptoms negatively impact health-related quality of life and are associated with adverse clinical outcomes. Regular symptom assessment, using electronic patient reported outcomes measure (ePROMs) linked to systematic symptom management, could improve such outcomes. Clinical implementation of ePROMs have been successful in routine oncology care, but not used for patients on dialysis. In this study, we describe a pilot study of ePROM-based systematic symptom monitoring and management intervention in patients treated with in-centre haemodialysis. METHODS AND ANALYSIS: This is a parallel-arm, controlled pilot of adult patients receiving in-centre maintenance haemodialysis. Participants in the intervention arm will complete ePROMs once a month for 6 months. ePROMs will be scored real time and the results will be shared with participants and with the clinical team. Moderate-severe symptoms will be flagged using established cut-off scores. Referral options for those symptoms will be shared with the clinical team, and additional symptom management resources will also be provided for both participants and clinicians. Participants in the control arm will be recruited at a different dialysis unit, to prevent contamination. They will receive usual care, except that they will complete ePROMs without the presentation of results to participants of the clinical team. The primary objectives of the pilot are to assess (1) the feasibility of a larger, randomised clinical effectiveness trial and (2) the acceptability of the intervention. Interviews conducted with participants and staff will be assessed using a content analysis approach. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained from the University Health Network (REB#21-5199) and the William Osler Health System (#23-0005). All study procedures will be conducted in accordance with the standards of University Health Network research ethics board and with the 1964 Helsinki declaration and its later amendments. Results of this study will be shared with participants, patients on dialysis and other stakeholders using lay language summaries, oral presentations to patients and nephrology professionals. We will also be publishing the results in a peer-reviewed journal and at scientific meetings. PROTOCOL VERSION: 4 (16 November 2022). TRIAL REGISTRATION NUMBER: NCT05515991.

Tezepelumab decreases airway epithelial IL-33 and T2-inflammation in response to viral stimulation in patients with asthma.

BACKGROUND: Respiratory virus infections are main triggers of asthma exacerbations. Tezepelumab, an anti-TSLP mAb, reduces exacerbations in patients with asthma, but the effect of blocking TSLP on host epithelial resistance and tolerance to virus infection is not known. AIM: To examine effects of blocking TSLP in patients with asthma on host resistance (IFNß, IFNλ, and viral load) and on the airway epithelial inflammatory response to viral challenge. METHODS: Bronchoalveolar lavage fluid (BALF, n = 39) and bronchial epithelial cells (BECs) were obtained from patients with uncontrolled asthma before and after 12 weeks of tezepelumab treatment (n = 13) or placebo (n = 13). BECs were cultured in vitro and exposed to the viral infection mimic poly(I:C) or infected by rhinovirus (RV). Alarmins, T2- and pro-inflammatory cytokines, IFNß IFNλ, and viral load were analyzed by RT-qPCR and multiplex ELISA before and after stimulation. RESULTS: IL-33 expression in unstimulated BECs and IL-33 protein levels in BALF were reduced after 12 weeks of tezepelumab. Further, IL-33 gene and protein levels decreased in BECs challenged with poly(I:C) after tezepelumab whereas TSLP gene expression remained unaffected. Poly(I:C)-induced IL-4, IL-13, and IL-17A release from BECs was also reduced with tezepelumab whereas IFNß and IFNλ expression and viral load were unchanged. CONCLUSION: Blocking TSLP with tezepelumab in vivo in asthma reduced the airway epithelial inflammatory response including IL-33 and T2 cytokines to viral challenge without affecting anti-viral host resistance. Our results suggest that blocking TSLP stabilizes the bronchial epithelial immune response to respiratory viruses.

Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: a multicenter, retrospective, real-world experience with 200 cases outside of controlled clinical trials.

In the ELOQUENT-3 trial, the combination of elotuzumab, pomalidomide and dexamethasone (EloPd) proved to have a superior clinical benefit over pomalidomide and dexamethasone with a manageable toxicity profile, leading to its approval for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. We report here a real-world experience of 200 cases of RRMM treated with EloPd in 35 Italian centers outside of clinical trials. In our dataset, the median number of prior lines of therapy was two, with 51% of cases undergoing autologous stem cell transplant and 73% having been exposed to daratumumab. After a median follow-up of 9 months, 126 patients had stopped EloPd, most of them (88.9%) because of disease progression. The overall response rate was 55.4%, a finding in line with the pivotal trial results. Regarding adverse events, the toxicity profile in our cohort was similar to that in the ELOQUENT-3 trial, with no significant differences between younger (<70 years) and older patients. The median progression-free survival was 7 months, which was shorter than that observed in ELOQUENT-3, probably because of the different clinical characteristics of the two cohorts. Interestingly, International Staging System stage III disease was associated with worse progression-free survival (hazard ratio=2.55). Finally, the median overall survival of our series was shorter than that observed in the ELOQUENT-3 trial (17.5 vs. 29.8 months). In conclusion, our real-world study confirms that EloPd is a safe and possible therapeutic choice for patients with RRMM who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.

Implementation outcomes in psychosocial intervention studies for children and adolescents living in low- and middle-income countries: A systematic review.

Psychosocial interventions play a key role in addressing mental health and substance use needs for children and adolescents living in low- and middle-income countries (LMICs). While research efforts have primarily focused on their effectiveness, implementation outcomes also require examining. We conducted a systematic review of qualitative, quantitative, and mixed-methods studies (PROSPERO: CRD42022335997) to synthesize the literature on implementation outcomes for psychosocial interventions for children and adolescents in LMICs. We searched Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Web of Science, PsychINFO, and Global Health through April 2023. Data were extracted and quality appraised through the Mixed Methods Appraisal Tool (MMAT) independently by two reviewers. A total of 13,380 records were screened, and 87 studies met inclusion criteria. Feasibility was the most reported implementation outcome (69, 79%), followed by acceptability (60, 69%), and fidelity (32, 37%). Appropriateness was assessed in 11 studies (13%), implementation costs in 10 (11%), and sustainability in one (1%). None of the included studies reported on penetration or adoption. Despite a growing body of evidence for implementation research in child and adolescent global mental health, most research focused on earlier-stage implementation outcomes, assessing them in research-controlled settings. To overcome this, future efforts should focus on assessing interventions in routine care, assessing later-stage implementation outcomes through standardized tools.

Evaluation of antimicrobial photodynamic therapy and minimal intervention associated with deproteinisation in permanent teeth with molar incisor hypomineralisation: study protocol for a clinical, controlled, blinded trial.

INTRODUCTION: Molar incisor hypomineralisation (MIH) is a qualitative defect of enamel development that occurs in the mineralisation phase. MIH affects one or more permanent molars and, occasionally, permanent incisors. The aim of the proposed study is to evaluate the clinical effect of antimicrobial photodynamic therapy (aPDT) on permanent teeth with MIH through decontamination and sensitivity control. METHODS AND ANALYSIS: Patients from 8 to 12 years of age with permanent molars will be randomly allocated to three groups. Group 1: selective chemical-mechanical removal of carious dentinal tissue around the walls of the cavity with Papacárie Duo and a curette followed by the application of aPDT and deproteinisation with Papacárie Duo; group 2: selective removal of carious dentinal tissue around the walls of the cavity with a curette, followed by the application of aPDT and deproteinisation with a 5% sodium hypochlorite solution; group 3: selective removal of carious dentinal tissue using a curette. The selected teeth must have a carious lesion in the dentin and posteruptive enamel breakdown on one or more surfaces with an indication for clinical restorative treatment. The teeth will subsequently be restored using a mixed technique with resin-modified glass ionomer cement and bulk-fill composite resin. The data will be submitted to descriptive statistical analysis. Associations with age and sex will be tested using either the χ2 test or Fisher's exact test. Pearson's correlation coefficients will be calculated to determine the strength of correlations between variables. Comparisons of the microbiological results (colony-forming units) will be performed using analysis of variance and the Kruskal-Wallis test. Kaplan-Meier survival analysis will be performed to assess the performance of the restorations. ETHICS AND DISSEMINATION: This protocol has been approved by the Human Research Ethics Committee of Nove de Julho University (certificate number: 61027522.0.0000.5511/approval date: 23 August 2022). The findings will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05443035.

The predictive role of proinflammatory and neuroendocrine factors in the acute phases of bipolar disorder: study protocol of a longitudinal controlled trial.

INTRODUCTION AND AIMS: Bipolar disorder (BD) is a severe and recurring mental illness associated with a significant personal and social burden. It has been recently hypothesized that increased levels of pro-inflammatory cytokines and cortisol, which is also associated with a reduced expression of the brain-derived neurotrophic factor (BDNF), may influence affective recurrences in BD. Our study aims to: 1) assess changes in the levels of peripheral cytokines, BDNF and salivary cortisol during acute and euthymic phases of bipolar disorder, compared to that of a sample oh healthy controls; 2) evaluate whether these changes represent a biosignature for the different phases of the illness. MATERIALS AND METHODS: Patients aged 18-65 years old, with a diagnosis of BD I or II types, will be enrolled during an acute episode, according to DSM-5 criteria, together with age- and gender-matched healthy controls. Blood and salivary samples will be collected at baseline and after 3 and 6 months. Validated assessment instruments will be administered to all participants for the evaluation of symptom severity, global functioning, suicidal risk, stress levels and physical comorbidities. EXPECTED RESULTS: We expect changes in inflammatory and neuroendocrine indices to be predictive of the onset of an acute phase of bipolar disorder and that overall levels of cytokines, cortisol and BDNF are overall significantly different between BD patients and healthy controls. CONCLUSIONS: The longitudinal design of the study will allow to assess whether the presence of acute affective symptoms in BD patients correlates with significantly higher levels of cytokines and salivary cortisol and with reduced BDNF levels compared to euthymic phases. Moreover, the comparison with healthy control subjects will allow to understand if inflammatory mediators as well as the hypothalamic-pituitary-adrenal (HPA) axis are chronically elevated in BD patients and are independent from mood swings.

Guidelines of the International Headache Society for Controlled Clinical Trials in Idiopathic Intracranial Hypertension.

The quality of clinical trials is essential to advance treatment, inform regulatory decisions and meta-analysis. With the increased incidence of idiopathic intracranial hypertension and the emergence of clinical trials for novel therapies in this condition, the International Headache Society Guidelines for Controlled Clinical Trials in Idiopathic Intracranial Hypertension aims to establish guidelines for designing state-of-the-art controlled clinical trials for idiopathic intracranial hypertension.

[Italian Society of Interventional Cardiology (GISE) and Italian Society of Arterial Hypertension (SIIA) Consensus document on the role of renal denervation in the management of the difficult to treat hypertension]. / Documento di consenso della Società Italiana di Cardiologia Interventistica (GISE) e della Società Italiana dell'Ipertensione arteriosa (SIIA) sul ruolo della denervazione renale nella gestione dell'ipertensione arteriosa difficile da trattare.

Arterial hypertension is the most prevalent cardiovascular risk factor worldwide. Despite the availability of many and effective antihypertensive medications, the prevalence of uncontrolled blood pressure (BP) remains high. As sympathetic hyperactivity has long been recognized as a major contributor to resistant hypertension, catheter-based renal denervation (RDN) has emerged as a new strategy to reduce BP. RDN aims to interrupt the activity of renal sympathetic nerves by applying radiofrequency (RF) energy, ultrasound (US) energy, or injection of alcohol in the perivascular space. The Symplicity HTN-3 trial, the largest sham-controlled trial using the first-generation RF-based RDN device, failed to significantly reduce BP. Since then, new devices and techniques have been developed and consequently many sham-controlled trials using second-generation RF or US-based RDN devices have demonstrated the BP lowering efficacy and safety of the procedure. A multidisciplinary team involving hypertension experts, interventionalists with expertise in renal interventions and anesthesiologists, plays a pivotal role from the selection of the patient candidate for the procedure to the post-procedural care. The aim of this consensus document is to summarize the current evidence about the use of RDN in difficult to treat hypertension and to propose a management strategy from the selection of the patient candidate for the procedure to the post-procedural care.

The effects of metformin on anti-Müllerian hormone levels in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

OBJECTIVE: To analyze whether metformin treatment in patients with polycystic ovary syndrome (PCOS) results in a decrease of anti-Müllerian hormone (AMH) levels, we reviewed and analyzed PCOS studies which evaluated serum AMH levels before and after metformin treatment. METHODS: This is a systematic review and meta-analysis of self-controlled clinical trials. Databases including PubMed, Embase, and Web of Science library were searched to identify eligible studies published before February 2023. Random-effects models were applied to assess standardized mean differences (SMDs) with 95% confidence intervals (95% CI). RESULTS: The electronic-based search retrieved 167 articles of which 14 studies (12 publications) involving 257 women with PCOS were included. In general, AMH levels decreased significantly after metformin treatment [SMD (95% CI) of -0.70 (-1.13 to -0.28); P = 0.001]. Metformin exhibited a strong inhibitory effect on AMH levels for PCOS patients with age less than 28 [SMD - 1.24, 95% CI - 2.15 to - 0.32, P = 0.008]. Additionally, AMH levels significantly slid down in PCOS patients with no more than 6 months metformin treatment [SMD - 1.38, 95% CI - 2.18 to - 0.58, P = 0.0007], or with no more than a dose of 2000 mg/day [SMD -0.70, 95% CI -1.11 to -0.28; P = 0.001]. Notably, suppressive effects of metformin treatment were merely observed in patients with AMH levels at baseline higher than 4.7 ng/ml [SMD - 0.66, 95% CI - 1.02 to - 0.31, P = 0.0003]. CONCLUSION: This meta-analysis provided quantitative evidence demonstrating that metformin significantly decreased AMH levels, especially for young patients and those with AMH levels at baseline higher than 4.7 ng/ml. TRIAL REGISTRATION: PROSPERO CRD42020149182.

Comparación de la eficacia y toxicidad del estibogluconato de sodio y antimoniato de meglumina en el tratamiento de leishmaniasis cutánea en Perú / Efficacy and safety of sodium stibogluconate compared to meglumine antimoniate in the treatment of cutaneous leishmaniasis in Peru

Objetivos : Comparar la eficacia y toxicidad del antimoniato de meglumina (AM) y estibogluconato sódico (EGS) en el tratamiento de leishmaniasis cutánea (LC) en un hospital general. Material y métodos : Serie de casos comparativa de 193 pacientes con LC tratados en tres ensayos clínicos con AM (n=69) y EGS (n=124) durante 2001-2010. La administración de ambas drogas fue vía endovenosa lenta de 20 mg Sb5+/kg/día por 20 días consecutivos siguiendo las normativas de la OPS y OMS. La información clínica, toxicidad y eficacia fue obtenida de las historias clínicas almacenadas en el centro de investigación según la normativa local e internacional. Resultados : Las características demográficas fueron similares entre grupos, pero el tamaño y número de lesiones fueron mayores en el grupo AM. La eficacia del tratamiento con AM fue 76,0% versus 68,4% con EGS (p=0,340) y 55,1% versus 50,8% (p=0,570) en el análisis por protocolo y de intención de tratar, respectivamente. No se observaron efectos adversos inmediatos. Los síntomas más frecuentemente reportados fueron disgeusia (37,0%), mareos (32,0%), cefalea (36,0%), artralgias (31,0%) y linfangitis (21,0%). Los tres primeros síntomas, así como elevación de transaminasas, leucopenia, trombocitopenia y QTc prolongado fueron frecuentes en el grupo EGS, pero clínica y estadísticamente no significativos. El tratamiento fue suspendido definitivamente por toxicidad severa únicamente con EGS por emesis refractaria (2 participantes) y QTc prolongado con extrasístoles (1 participante). Conclusiones : La eficacia del tratamiento con AM y EGS fue comparable. La administración endovenosa de ambos no produjo efectos adversos inmediatos, aunque sí alteraciones clínicas y laboratoriales usuales.

SUMMARY Objectives : To compare the efficacy and safety of sodium stibogluconate (SS) and meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL) in a general hospital. Methods: Case-series of 193 patients with CL treated in three clinical trials with MA (n=69) and SS (n=124) during 2001-2010. Both study drugs were administered intravenously at a slow speed at 20 mg Sb5+/kg/day for 20 consecutive days following WHO-PAHO recommendations. Clinical and safety data were gathered from clinical files. Results: Demographic characteristics were similar between the study groups, but the size and number of lesions were higher in the MA group. Efficacy was 76.0% in the MA vs. 68.4% in the SS group (p=0.340) and 55.1% vs. 50.8% (p=0.570) in the per protocol and intention to treat analysis. respectively. Side effects more frequently reported were dysgeusia (37.0%). dizziness (32.0%). headache (36.0%). arthralgia (31.0%) and lymphangitis (21.0%). These first three symptoms as well as elevation of transaminases, leukopenia, thrombocytopenia and prolonged QTc were numerically more frequent in the SS group but without reaching statistical significance. Treatment was stopped definitively for severe toxicity in the SS group due to refractory emesis (two patients) and prolonged QTc (one patient). Conclusions: The efficacy of MA and SS is comparable. The intravenous administration of these compounds did not produce immediate reactions, but it was associated with unusual clinical and laboratory abnormalities.

Biopsychosocial effects and experience of use of robotic and virtual reality devices in neuromotor rehabilitation: A study protocol.

BACKGROUND: Robot-assisted therapy (RAT) and virtual reality (VR)-based neuromotor rehabilitation have shown promising evidence in terms of patient's neuromotor recovery, so far. However, still little is known on the perceived experience of use of robotic and VR devices and the related psychosocial impact. The present study outlines a study protocol aiming to investigate the biopsychosocial effects and the experience of use of robotic and non-immersive VR devices in patients undergoing neuromotor rehabilitation. METHODS: Adopting a prospective, two-arm, non-randomized study design, patients with different neuromotor diseases (i.e., acquired brain injury, Parkinson's Disease, and total knee/hip arthroplasty) undergoing rehabilitation will be included. In a real-world clinical setting, short- (4 weeks) and long-term (6 months) changes in multiple patient's health domains will be investigated, including the functional status (i.e., motor functioning, ADLs, risk of falls), cognitive functioning (i.e., attention and executive functions), physical and mental health-related quality of life (HRQoL), and the psychological status (i.e., anxiety and depression, quality of life satisfaction). At post-intervention, the overall rehabilitation experience, the psychosocial impact of the robotic and VR devices will be assessed, and technology perceived usability and experience of use will be evaluated through a mixed-methods approach, including both patients' and physiotherapists' perspectives. Repeated measures within-between interaction effects will be estimated, and association analyses will be performed to explore the inter-relationships among the variables investigated. Data collection is currently ongoing. IMPLICATIONS: The biopsychosocial framework adopted will contribute to expanding the perspective on patient's recovery within the technology-based rehabilitation field beyond motor improvement. Moreover, the investigation of devices experience of use and usability will provide further insight into technology deployment in neuromotor rehabilitation programs, thereby maximising therapy engagement and effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05399043.