The utilisation of primary health care system concepts positively impacts the assistance of patients with rare diseases despite limited knowledge and experience by health care professionals: A qualitative synopsis of the evidence including approximately 78 000 individuals.

Background: Individuals with rare diseases (RD) have been historically understudied. Previous publications reported that existing primary health care (PHC) workforces and associated infrastructure had been shown to improve their access and health-related outcomes in low- and middle-income countries (LMICs). As current evidence about the impact of PHC on patients diagnosed with RD is yet highly dispersed, this scoping review aimed to collate available evidence of the impact of PHC on patients with RD and summarize published information from multiple stakeholders about the perceived usefulness and barriers to effective use of the PHC system. Methods: We searched Embase, Health System Evidence, PubMed, LILACS / BVS, and The Cochrane Library, from inception to September 1, 2022, for publications providing clear expert- or experience-based insights or data from patients living with RD at the PHC level of care. We included publications highlighting barriers to integrated care of patients with RD, reported by multiple social actors involved in caring for patients with RD. Two investigators screened publications, extracted data, and clustered information among records deemed eligible for inclusion. Data synthesis was performed using narrative and thematic-based analysis. Major findings identified and coded through a semantic-driven analysis were processed in vosViewer software and reported using descriptive statistics. Findings: Eighty publications were included in this review. Quali-quantitative analyses evidenced that the PHC level is essential for approaching patients with RD, mainly due to its longitudinal, multidisciplinary, and coordinated care delivery. In addition, several publications highlighted that the medical curriculum is inappropriate for preparing health care providers to deal with patients presenting unusual signs and symptoms and being diagnosed with RD. PHC teams are essential in orienting patients and families on emergency events. Technology-related concepts were reported in 19 publications, emphasizing their effectiveness on early diagnosis, optimal treatment definition, improvement of quality of life, and long-lasting follow-up. Conclusions: We provided valuable information on the effectiveness of the PHC in fostering a creative, integrative, and supportive environment for patients living with RD. Our results can be helpful to several stakeholders in deciding what actions are still pending to achieve a solid and positive experience for patients with RD in the PHC. Registration: PROSPERO (CRD42022332347).

Need for evidence synthesis for quality control of healthcare decision-making.

Systematic reviews that are out-of-date delay policymaking, create controversy, and can erode trust in research. To avoid this issue, it is preferable to keep summaries of the study evidence. Living evidence is a synthesis approach that provides up-to-date rigorous research evidence summaries to decision-makers. This strategy is particularly useful in rapidly expanding research domains, uncertain existing evidence, and new research that may impact policy or practice, ensuring that physicians have access to the most recent evidence. Addressing global challenges - ranging from public health crises to climate change or political instability - requires evidence-based judgements. An obsolete, biased, or selective information poses risks of poor decisions and resource misallocation. The relatively nascent practice of living evidence proves invaluable in maintaining continuous interest and team engagement. The concept of living evidence has been particularly relevant during the COVID-19 pandemic due to the rapidly evolving nature of the virus, the urgent need for timely information, and the continuous emergence of new research findings. Although the COVID-19 pandemic accelerated the adoption of evidence systems, researchers and funders of research should rigorously test the living-evidence model across diverse domains to further advance and optimize its methodology.

Quarantine, physical distancing and social isolation measures in individuals potentially exposed to SARS-CoV-2 in community settings and health services: a scoping review.

To provide a synthesis of diverse evidence on the impact of the non-therapeutic preventive measures, specifically quarantine, physical distancing and social isolation, on the control of COVID-19. A scoping review conducted in the PubMed, Embase, LILACS, CENTRAL and SCOPUS databases between 2019 and August 28th, 2020. The descriptors used were the following: "quarantine", "physical distancing", "social isolation", "COVID-19" and "SARS-Cov2". Studies that addressed the non-therapeutic preventive measures in people exposed to SARs-CoV-2 in community settings and health services were included. A total of 14,442 records identified through a database search were reduced to 346 studies and, after a standardized selection process, a total of 68 articles were selected for analysis. A total of 35 descriptive, cross-sectional or longitudinal observational studies were identified, as well as 3 reviews, in addition to 30 studies with mathematical modeling. The main intervention assessed was social distancing (56.6%), followed by lockdown (25.0%) and quarantine (18.4%). The main evidence analyzed points to the need for rapid responses to reduce the number of infections, deaths and hospital admissions, especially in intensive care unit beds.The current review revealed consistent reports that the quarantine, physical distancing and social isolation are effective strategies to contain spread of the new coronavirus.

The des-Arg9-bradykinin/B1R axis: Hepatic damage in COVID-19.

Patients infected by the SARS-CoV-2 virus are commonly diagnosed with threatening liver conditions associated with drug-induced therapies and systemic viral action. RNA-Seq data from cells in bronchoalveolar lavage fluid from COVID-19 patients have pointed out dysregulation of kallikrein-kinin and renin-angiotensin systems as a possible mechanism that triggers multi-organ damage away from the leading site of virus infection. Therefore, we measured the plasma concentration of biologically active peptides from the kallikrein-kinin system, bradykinin and des-Arg9-bradykinin, and liver expression of its proinflammatory axis, bradykinin 1 receptor (B1R). We measured the plasma concentration of bradykinin and des-Arg9-bradykinin of 20 virologically confirmed COVID-19 patients using a liquid chromatography-tandem mass spectrometry-based methodology. The expression of B1R was evaluated by immunohistochemistry from post-mortem liver specimens of 27 COVID-19 individuals. We found a significantly higher blood level of des-Arg9-bradykinin and a lower bradykinin concentration in patients with COVID-19 compared to a healthy, uninfected control group. We also observed increased B1R expression levels in hepatic tissues of patients with COVID-19 under all hepatic injuries analyzed (liver congestion, portal vein dilation, steatosis, and ischemic necrosis). Our data indicate that des-Arg9-bradykinin/B1R is associated with the acute hepatic dysfunction induced by the SARS-CoV-2 virus infection in the pathogenesis of COVID-19.

The effects of exercise training on inflammatory biomarkers in patients with breast cancer: A systematic review and meta-analysis.

OBJECTIVE: Despite several studies on the effects of exercise training on inflammatory biomarkers in patients with breast cancer, no earlier study has systematically summarized their findings. Current systematic review and meta-analysis has been done on earlier clinical trials in this topic. METHOD: Relevant studies published up to August 2021 were searched through PubMed, MEDLINE, SCOPUS, EMBASE, and Google Scholar using predefined keywords. Studies that examined the effect of exercise training on inflammatory biomarkers in adult women with breast cancer were included. RESULT: A total of 18 studies were included. Combining 11 effect sizes, exercise training significantly reduced CRP level (WMD: -0.55; 95% CI: -1.10, -0.01). However, it had no significant influence on serum TNF-α (WMD: -0.40; 95% CI: -1.30, 0.50) and IL-6 concentrations (WMD: -0.05, 95% CI: -0.53, 0.43) in 8 and 15 studies, respectively. Pooling 7 effect sizes, we failed to find significant changes in IL-8 following exercise training (WMD: -0.65, 95% CI: -1.57, 0.28). Moreover, we reached no significant findings for serum levels of INF-É£ (WMD: -2.66, 95% CI: -7.67, 2.36), IL-1ß (WMD: 0.03, 95% CI: -0.26, 0.21), and IL-10 (WMD: -0.70, 95% CI: -2.92, 1.52). Based on subgroup analyses, best findings were reached in long-term intervention and after concurrent training. DISCUSSION: Chronic inflammation is hypothesized to be associated with breast cancer development. We found significant reduction in CRP level following exercise training, which was more considerable after concurrent aerobic and resistance training and in long-term intervention. No significant changes were seen in serum levels of TNF-α, IL-6, IL-8, IL-10, INF-É£, IL-1ß following exercise training. Further studies are needed to find more details.

Epidemiologic characteristics, clinical management, and public health implications of Coronavirus Disease 2019 (COVID-19) in pregnancy: A Systematic Review and Meta-analysis.

BACKGROUND: The novel Coronavirus Disease 2019 (COVID-19) outbreak, caused by the pathogenic severe acute respiratory syndrome-2 (SARS-CoV-2) virus, is exponentially spreading across the globe. METHODS: The current systematic review was performed utilising the following electronic databases PubMed, MEDLINE and EMBASE. We searched for the keywords "COVID-19 AND "pregnancy" between January 1, 2020 until December 31, 2020. RESULTS: Out of 4005 records which were identified, 36 original studies were included in this systematic review. Pooled prevalence of vertical transmission was 10%, 95% CI: 4-17%. Pooled prevalence of neonatal mortality was 7%, 95% CI: 0-21%. CONCLUSION: The contemporary evidence suggests that the incubation period of COVID-19 is 2-14 days, and this infection could be transmitted even from the infected asymptomatic individuals. It is found that the clinical presentation of pregnant women with COVID-19 infection is comparable with the infected non-pregnant females, and the frequent symptoms were fever, cough, myalgia, sore throat and malaise. Some cases have severe maternal morbidity and perinatal deaths secondary to COVID-19 infection. Under these circumstances, pregnant women should focus on maintaining personal hygiene, proper nutrition and extreme social distancing to reduce the risk of COVID-19. Therefore, systematic data reporting for evidence based clinical assessment, management and pregnancy outcomes is essential for preventing of COVID-19 infection among pregnant women.

Physical Exercise and Quality of Life of Patients Diagnosed with Colorectal Cancer: Systematic Literature Review.

BACKGROUND: Colorectal cancer decrease quality of life, due to treatment and disease, and physical exercise can improve the quality of life of patients with cancer, but it is still uncertain whether physical exercise can improve quality of life in these patients. AIM: To determine if there is an improvement in the quality of life in patients diagnosed with colorectal cancer undergoing physical exercise. METHODS: A systematic literature review was carried out; non-randomized clinical trials of any year were included from PubMed, Embase, Cochrane, and VHL platforms, without specific language delimitation, and analyzed the influence of physical exercise on the quality of life of patients diagnosed with colorectal cancer, and for analysis of bias, the Cochrane Manual for the Development of Systematic Intervention Reviews was used. RESULTS: Four studies were analyzed in full to produce the results; of these, three intervened with unsupervised aerobic exercises and one with semi-supervised aerobic exercises, all used the FACT-C as a questionnaire to assess quality of life, some even used FACT-G and/or SF-12, and only one author found significance values in the variables of physical well-being, emotional well-being, and functional well-being of the questionnaire, compared with the control group. CONCLUSION: There were no significant increases in the quality of life of patients diagnosed with colorectal cancer compared with the control group.

Effect of Oral Minoxidil for Alopecia: Systematic Review.

Patients with major presentations of alopecia experience physically harmful effects and psychological comorbidities, such as depression and anxiety. Oral minoxidil (OM) has been suggested by dermatologists as a potential remedy; however, its effectiveness remains unclear. This systematic review aims to collate published studies and to analyze the effect of OM among patients diagnosed with any type of alopecia. For this systematic review, Medline/PubMed, Cochrane Central, EMBASE, Web of Sciences, and Latin American and Caribbean Health Sciences Information System were searched for relevant studies from inception to September 21, 2019. Of 1960 studies retrieved in several electronic databases and three additional records identified though reference list from potentially eligible studies, nine studies (one randomized controlled trial and eight nonrandomized controlled trials) met the requirements and were used in our analysis. Although we found positive effects in favor of OM, this should be interpreted cautiously due to very low quality of the evidence of outcomes in the selected studies. Definitive conclusions are not possible without high-quality trials. This review has highlighted the absence of high-quality randomized controlled trials evaluating OM in the treatment of various types of alopecia. Given the mild adverse events of OM, future studies should also analyze doses and duration to maximize efficacy and decrease side effects.

Impact of COVID-19 on clinical trials and clinical research: A systematic review.

Background: The World Health Organization has reported more than 31,186,000 confirmed cases of coronavirus disease-19 (COVID-19), including 962,343 deaths, worldwide as on September 21, 2020. The current COVID-19 pandemic is affecting clinical research activities in most parts of the world. The focus on developing a vaccine for SARS-CoV-2 and the treatment of COVID-19 is, in fact, disrupting many upcoming and/or ongoing clinical trials on other diseases around the globe. On March 18, 2020, the United States Food and Drug Administration (FDA) issued an updated guideline for the conduct of clinical trials during the current health emergency situation. The potential challenges, such as social distancing and quarantines, result in study participants' inaccessibility and trial personnel for in-person scheduled study visits and/or follow-up. Due to the sudden onset and wide-spread impact of COVID-19, its influence on the management of clinical trials and research necessitates urgent attention. Therefore, our systematic review of the literature aims to assess the impact of the COVID-19 pandemic on the conduction of clinical trials and research. The search for the relevant articles for review included the keywords "COVID-19" AND "clinical trial" in PubMed, MEDLINE, Embase, Google scholar and Google electronic databases. Key findings include: delaying subject enrollment and operational gaps in most ongoing clinical trials, which in turn has a negative impact on trial programmes and data integrity. Globally, most sites conducting clinical trials other than COVID-19 are experiencing a delay in timelines and a complete halt of operations in lieu of this pandemic, thus affecting clinical research outcomes.

Opioids and alpha-2-agonists for analgesia and sedation in newborn infants: protocol of a systematic review.

BACKGROUND: Hospitalized newborn infants may require analgesia and sedation either for the management of procedural pain, during or after surgery, and other painful conditions. The benefits and harms of opioids administered at different doses and routes of administration have been reported in numerous trials and systematic reviews. The use of alpha-2-agonists such as clonidine and dexmedetomidine in newborn infants is more recent, and they might be prescribed to reduce the total amount of opioids which are thought to have more side effects. Moreover, alpha-2-agonists might play an important role in the management of agitation and discomfort. METHODS: We will conduct a systematic review and meta-analysis on the use of opioids, alpha-2-agonists, or the combination of both drugs. We will include randomized controlled trials to assess benefits and harms and observational studies to assess adverse events and pharmacokinetics; preterm and term infants; studies on any opioids or alpha-2-agonists administered for any indication and by any route except spinal, intraosseous, or administration for nerve blocks and wound infusions. The use of opioids or alpha-2-agonists will be compared to no intervention; placebo with normal saline or other non-sedative, non-analgesic drug; control with oral sugar solution or non-pharmacological intervention; same drug of different dose or route; or a different drug (not limiting to opioids and alpha-2-agonists) or combinations of such drugs. The primary outcomes for this review will be all-cause mortality during initial hospitalization and hypotension requiring medical therapy. We will conduct a search in the following databases: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, Embase, and CINAHL. Two review authors will independently screen records for inclusion, undertake data abstraction using a data extraction form and assess the risk of bias of all included trials using the Cochrane "Risk of bias" tool. DISCUSSION: This systematic review will summarize and update our knowledge about neonatal analgesia and sedation including pharmacokinetics/pharmacodynamics, and provide a platform for developing evidence-based guidelines that we can immediately apply to our clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2020 CRD42020170852.

The effect of zinc supplementation on blood pressure: a systematic review and dose-response meta-analysis of randomized-controlled trials.

PURPOSE: Despite previous investigations on the effects of zinc supplementation on blood pressure, inconsistent findings are available in this regard. Therefore, we conducted a systematic review and meta-analysis of randomized clinical trials on the effects of zinc supplementation on blood pressure (BP) in adults. METHODS: Relevant studies published up to September 2019 were searched through PubMed/Medline, Scopus, ISI Web of Science, and Google Scholar using suitable keywords. All randomized clinical trials (RCTs) that examined the effect of oral zinc supplementation on systolic blood pressure (SBP) or diastolic blood pressure (DBP) in adults were included. RESULTS: Overall, nine trials were included in our study. Zinc supplementation significantly reduced SBP compared to the control [weighted mean differences (WMD) - 1.49 mmHg; 95% CI - 2.85 to - 0.13; P = 0.03]. However, zinc supplementation had no significant effects on DBP (WMD - 0.88 mmHg; 95% CI - 2.04 to 0.29; P = 0.14). Nonlinear analysis failed to indicate a significant influence of supplementation dosage or duration on both SBP and DBP. Sensitivity analysis showed that no individual study had a significant impact on our final results. In addition, we found no evidence for the presence of small-study effects among studies for both SBP and DBP. CONCLUSION: We found a significant reduction in SBP following zinc supplementation. However, zinc supplementation had no significant effect on DBP. In addition, no nonlinear association was found between supplementation dosage and duration with changes in both SBP and DBP. Further RCTs using different dosages of zinc in various durations are required to confirm our conclusion.