UNASSIGNED: The standard of care in patients with solitary brain metastasis involves surgical resection and postoperative whole-brain radiotherapy (WBRT). However, WBRT is associated with adverse effects, mainly neurocognitive deterioration. Stereotactic radiosurgery (SRS) is a more targeted form of radiation therapy that could be as effective as WBRT without the detrimental neurocognitive decline.
UNASSIGNED: We performed the first systematic review and meta-analysis comparing postoperative SRS versus postoperative WBRT in patients with one resected brain metastasis. PubMed, Scopus, and Cochrane library were systematically searched for studies comparing the efficacy of the two radiation modalities in terms of local and distant brain control, leptomeningeal disease control, and overall survival. Additionally, we extracted patients\' neurocognitive function and quality of life after each postoperative radiation form.
UNASSIGNED: Four studies with 248 patients (128: WBRT, 120: SRS) were included in our analysis. There was no difference between SRS and WBRT in the risk of local recurrence (RR = 0.92, CI = 0.51-1.66, p = 0.78, I2 = 0%) and leptomeningeal disease (RR = 1.21, CI = 0.49-2.98, p = 0.67, I2 = 18%), neither in the patients\' overall survival (HR = 1.06, CI = 0.61-1.85, p = 0.83, I2 = 63%). Nevertheless, SRS appeared to increase the risk of distant brain failure (RR = 2.03, CI = 0.94-4.40, p = 0.07, I2 = 61%). Neurocognitive function and quality of life in the SRS group were equal or superior to the WBRT group.
UNASSIGNED: Although SRS may increase the risk of distant brain failure, it appears to be as effective as WBRT in terms of local control, risk of leptomeningeal disease, and overall survival while sparing the patients of the detrimental, WBRT-associated cognitive deterioration.

UNASSIGNED: Positive pressure ventilation via a facemask is critical in neonatal resuscitation, but frequently results in mask leak, obstruction, and inadequate respiratory support. This systematic review aimed to determine whether the display of respiratory function monitoring improved resuscitation or clinical outcomes.
UNASSIGNED: Randomized controlled trials comparing outcomes when respiratory function monitoring was displayed versus not displayed for newborns requiring positive pressure ventilation at birth were selected and from databases (last search August 2022), and assessed for risk of bias using Cochrane Risk of Bias Tools for randomized control trials. The study was registered in the Prospective Register of Systematic Reviews. Grading of Recommendations, Assessment, Development and Evaluations was used to assess the certainty of evidence. Treatment recommendations were approved by the Neonatal Life Support Task Force of the International Liaison Committee on Resuscitation. Results reported primary and secondary outcomes and included resuscitation and clinical outcomes.
UNASSIGNED: Of 2294 unique articles assessed for eligibility, three randomized controlled trials were included (observational studies excluded) (n = 443 patients). For predefined resuscitation and clinical outcomes, these studies either did not report the primary outcome (time to heart rate ≥ 100 bpm from birth), had differing reporting methods (achieving desired tidal volumes, significant mask leak) or did not find significant differences (intubation rate, air leaks, death before hospital discharge, severe intraventricular hemorrhage, chronic lung disease). Limitations included limited sample size for critical outcomes, inconsistent definitions amongst studies and unreported long-term outcomes.
UNASSIGNED: Although respiratory function monitoring has been utilized in clinical care, there is currently insufficient evidence to suggest its benefit for newborn infants receiving respiratory support for resuscitation at birth.
UNASSIGNED: PROSPERO CRD42021278169 (registered November 27, 2021).
UNASSIGNED: The International Liaison Committee on Resuscitation provided support that included access to software platforms and teleconferencing.

UNASSIGNED: Although heart failure with preserved ejection fraction (HFpEF) is a serious disease, only limited options are available for its treatment. Recent studies have analyzed the effects of phosphodiesterase (PDE) inhibitors, especially PDE5 and PDE3 inhibitors, in patients with HFpEF, with mixed outcomes.
UNASSIGNED: We searched PUBMED and EMBASE databases up to August 2021. Randomized controlled trials (RCTs) and clinical trials that tested the effects of PDE inhibitors on patients with HFpEF were included as eligible studies. Indicators of left ventricular (LV) function, pulmonary arterial pressure (PAP), right ventricular (RV) function, exercise capacity, and quality of life (QOL) were used to evaluate the efficacy of PDE inhibitors in HFpEF.
UNASSIGNED: Six RCTs that reported in 7 studies were included to evaluate the efficiency of PDE inhibitors on HFpEF patients. In the pooled analysis, PDE inhibitors showed insignificant changes in the ratio of early diastolic mitral inflow to annular velocities, left atrial volume index, pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR), peak oxygen uptake, 6-minute walking test distance, as well as Kansas City Cardiomyopathy Questionnaire score. However, substantial improvement was observed in the tricuspid annular plane systolic excursion (TAPSE). Additionally, the regression analysis showed that PDE inhibitor administration time is a critical factor for the decrease in PASP.
UNASSIGNED: PDE inhibitors did not effectively improve LV function, PAP, exercise capacity, and QOL in patients with HFpEF. However, they improved RV function with significant difference, suggesting that PDE inhibitors might be a promising option for HFpEF patients with RV dysfunction.

SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) is the most dangerous form of the coronavirus, which causes COVID-19. In patients with severe COVID-19, the immune system becomes markedly overactive. There is evidence that supplementation with select micronutrients may play a role in maintaining immune system function in this patient population. Throughout the COVID-19 pandemic, significant emphasis has been placed on the importance of supplementing critical micronutrients such as Vitamin C and Zinc (Zn) due to their immunomodulatory effects. Viral infections, like COVID-19, increase physiological demand for these micronutrients. Therefore, the purpose of this review was to provide comprehensive information regarding the potential effectiveness of Vitamin C and Zn supplementation during viral infection and specifically COVID-19. This review demonstrated a relation between Vitamin C and Zn deficiency and a reduction in the innate immune response, which can ultimately make patients with COVID-19 more vulnerable to viral infection. As such, adequate intake of Vitamin C and Zn, as an adjunctive therapeutic approach with any necessary pharmacological treatment(s), may be necessary to mitigate the adverse physiological effects of COVID-19. To truly clarify the role of Vitamin C and Zn supplementation in the management of COVID-19, we must wait for the results of ongoing randomized controlled trials. The toxicity of Vitamin C and Zn should also be considered to prevent over-supplementation. Over-supplementation of Vitamin C can lead to oxalate toxicity, while increased Zn intake can reduce immune system function. In summary, Vitamin C and Zn supplementation may be useful in mitigating COVID-19 symptomology.

BACKGROUND: The current guidelines recommend targeted temperature management (TTM) as part of the post-resuscitation care for comatose patients following out-of-hospital cardiac arrest. These recommendations are based on the weak evidence of benefit seen in the early clinical trials. Recent large multicentered trials have failed to show a meaningful clinical benefit of hypothermia, unlike the earlier studies. Thus, to fully appraise the available data, we sought to perform this systematic review and meta-analysis of randomized controlled trials.
METHODS: We searched four databases for randomized controlled trials comparing therapeutic hypothermia (32-34 °C) with normothermia (≥36 °C with control of fever) in adult patients resuscitated after out-of-hospital cardiac arrest. Independent reviewers did the title and abstract screening, full-text screening, and extraction. The primary outcome was mortality six months after cardiac arrest, and secondary outcomes were neurological outcomes and adverse effects.
UNASSIGNED: Six randomized controlled trials were included in this review. There was no significant difference between the hypothermia and normothermia groups in mortality till 6 months follow up after out-of-hospital cardiac arrest (OR 0.88, 95% CI 0.67-1.16; n = 3243; I2 = 51%), or favorable neurological outcome (OR 1.31, 95% CI 0.93-1.84; n = 3091; I2 = 68%). Rates of arrhythmias were notably higher in the hypothermia group than the normothermia group (OR 1.43, 95% CI 1.20-1.71; n = 3029; I2 = 4%). However, odds for development of pneumonia showed no significant differences across two groups (OR 1.13, 95% CI 0.98-1.31; n = 3056; I2 = 22%). Therefore, targeted hypothermia with a target temperature of 32-34 °C does not provide mortality benefit or better neurological outcome in patients resuscitated after the out-of-hospital cardiac arrest when compared with normothermia.

COVID-19 caused devastating effects of human loss and suffering along with disruption in clinical research, forcing reconceptualization and modification of studies. This paper attempts to outline the steps followed and detail the modifications undertaken to deal with the impacts of the pandemic on the first ongoing randomized controlled trial on effectiveness of neuropsychological rehabilitation in adult patients with drug-resistant epilepsy in India. All modifications were based on evolving guidelines and circumstantial context and were planned, reviewed and approved by important stakeholders. Results obtained from the trial need to be interpreted and analysed within this context. These modifications have implications for wider outreach of neuropsychology services in India.

UNASSIGNED: To summarize the level of knowledge regarding the effects of microcurrent therapy (MCT) on musculoskeletal pain in adults.
UNASSIGNED: The PubMed, Physiotherapy Evidence Database, Cumulative Index to Nursing Allied Health Literature, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi database were searched from the time of their inception to December 2020.
UNASSIGNED: Randomized controlled trials (RCTs) investigating the effects of MCT on musculoskeletal pain were included. Additionally, non-RCTs were included to assess the adverse events.
UNASSIGNED: The primary outcomes were pain and adverse events related to MCT. To assess the reproducibility of MCT, we evaluated the completeness of treatment description using the Template for Intervention Description and Replication (TIDieR) checklist. We also assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).
UNASSIGNED: A comprehensive assessment of 4 RCTs and 5 non-RCTs that met the inclusion criteria revealed that MCT significantly improved shoulder pain (1 study, 40 patients) and knee pain (1 study, 52 patients) compared with sham MCT without any severe adverse events. MCT has clinically significant benefits for knee pain. This study also revealed a clinically significant placebo response in treating knee pain. This evidence highlights the substantial effect of placebo response in clinical care. These treatment effects on knee pain are further supported by the high quality of evidence in GRADE with high reproducibility in TIDieR.
UNASSIGNED: The findings of this meta-analysis highlight the effect of placebo response in treating knee pain. MCT is a potential, core nonpharmacologic treatment option in clinical care with minimal adverse events and should be further investigated. This study proposes a framework for the future investigation of the effect of MCT on musculoskeletal pain to enhance the study quality and reproducibility.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the composite of heart failure (HF) hospitalizations or cardiovascular mortality among patients with HF. However, the efficacy of SGLT2 inhibitors in secondary endpoints of randomized trials and in subgroups of HF patients is not well known.
METHODS: We performed a systematic review and meta-analysis of placebo-controlled, randomized trials of SGLT2 inhibitors in patients with HF. PubMed, Embase, and Cochrane databases were searched for trials published up to January 21, 2021. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. Hazard ratios (HRs) with 95% CI were pooled across trials. The primary endpoints of interest were all-cause and cardiovascular mortality.
RESULTS: Out of 3969 database results, 15 randomized trials and 20,241 patients were included; 10,594 (52·3%) received SGLT2 inhibitors. All-cause mortality (HR 0·86; 95% CI 0·79-0·94; p = 0·0007; I2=0%) and cardiovascular mortality (HR 0·86; 95% CI 0·78-0·96; p = 0·006; I2=0%) were significantly lower in patients treated with SGLT2 inhibitors compared with placebo. The composite of cardiovascular mortality, HF hospitalizations, or urgent visits for HF was significantly reduced with SGLT2 inhibitors in all the following subgroups: male, female, age < 65, age ≥ 65, race - Black and White, estimated glomerular filtration rate (eGFR) <60, eGFR ≥60, New York Heart Association (NYHA) class II, NYHA ≥III, and HF with preserved ejection fraction.
CONCLUSIONS: In patients with HF, SGLT2 inhibitors significantly reduce all-cause and cardiovascular mortality compared with placebo. In addition, the composite of cardiovascular mortality or HF hospitalizations/urgent visits is reduced with SGLT2 inhibitors across subgroups of sex, age, race, eGFR, HF functional class, and ejection fraction.

OBJECTIVE: Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS) which worsen patients\' health and increase healthcare spending. Aim of this study was to assess the clinical and economic effect of adding mepolizumab (MEP) for the treatment of these patients.
METHODS: Patients >18 years old, referred to 8 asthma clinics, starting MEP between May 2017 and December 2018, were enrolled and followed-up for 12 months. Information in the 12 months before mepolizumab were collected retrospectively. The evaluation parameters included: OCS use, number of exacerbations/hospitalizations, concomitant therapies, comorbidity, and annual number of working days lost due to the disease. The primary objective was to compare the annual total cost per patient pre- and post-MEP. Secondary outcomes included rates of exacerbations and number of OCS-dependent patients.
RESULTS: 106 patients were enrolled in the study: 46 male, median age 58 years. Mean annual cost pre- and post-MEP (cost of biologic excluded) was €3996 and €1,527, respectively. Total savings due to MEP resulted in €2469 (95%CI 1945-2993), 62% due to exacerbations reduction and 33% due to productivity increase. Such savings could fund about 22% of the total cost of MEP for one year. The introduction of MEP induced a clinical benefit by reducing both OCS-dependent patients (OR = 0.12, 95%CI 0.06-0.23) and exacerbation rate (RR = 0.19, 95%CI 0.15-0.24).
CONCLUSIONS: Patients with severe eosinophilic asthma experienced a clinical benefit in asthma control adding MEP to standard therapy. Biologic therapy can be, partially, funded by the savings produced by patients\' improvement.

UNASSIGNED: Data on mepolizumab in patients with severe eosinophilic asthma (EA) and comorbidities are needed to assess whether randomized controlled trial results are applicable in the real world.
UNASSIGNED: To evaluate real-life effectiveness and the presence/absence of predictors of treatment response in patients with one or more comorbidities (nasal polyps, allergic rhinitis, gastro-esophageal reflux disease, nonallergic rhinitis with eosinophilia syndrome, obesity, bronchiectasis) who received mepolizumab (MEPO) for the treatment of severe EA.
UNASSIGNED: We performed a single-center retrospective study in patients with severe asthma and presence of comorbidities treated with mepolizumab at the respiratory outpatient clinic, Policlinico-Vittorio Emanuele, Catania, Italy. Health records of 31 severe asthmatic patients were retrieved and analyzed. Asthma control test (ACT) score, blood eosinophil count, forced expiratory volume in 1 s (FEV1), FEV1% of predicted and FEV1/FVC (Forced Vital Capacity) ratio, oral corticosteroid (OCS) dosage, and exacerbations were recorded at baseline (T0), after 3 (T1), 6 (T3), 9 (T6), and 12 months (T12). Clinical response was defined when 3 of these 4 criteria were fulfilled: i) 30% exacerbation decrease; ii) 80% blood eosinophilia reduction; iii) 3 point ACT increase; iv) FEV1 increase ≥200 mL.
UNASSIGNED: 83.87% of patients were classified as responsive to MEPO treatment. Substantial depletion of the blood eosinophils (>80%) was found in 87.1% of patients, FEV1 > 200 mL was seen in 54.84% of patients, a 3-point ACT improvement from baseline was recorded in 80.65% 25 of patients and a 30% reduction of exacerbations rates was seen in 96.77% of patients. Moreover, the majority 38.71% of patients met 3/4 parameters after 12 months. Neither the comorbidities nor other characteristics (sex, BMI, age, smoking) influenced treatment response.
UNASSIGNED: MEPO in patients with severe EA is effective regardless of the presence of comorbidities.