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Clinical and Translational Allergy Nov 2022Several risk factors for asthma have been proposed; however, the causality of these associations is sometimes unclear. Mendelian randomization is a powerful... (Review)
Review
BACKGROUND
Several risk factors for asthma have been proposed; however, the causality of these associations is sometimes unclear. Mendelian randomization is a powerful epidemiological approach that can help elucidate the causality of risk factors. The aim of the present study was to identify causal risk factors for asthma through Mendelian Randomization studies.
METHODS
A systematic search of PubMed and EMBASE was conducted, to identify studies investigating risk factors for asthma or respiratory allergies through Mendelian Randomization. When two or more studies investigated the same risk factor a meta-analysis was conducted. Of 239 studies initially identified, 41 were included.
RESULTS
A causal association between adiposity and adult asthma risk was found in 10 out of 12 studies with a summary risk ratio of 1.05 per kg/m increase in BMI (95% CI: 1.03-1.07). Puberty timing (n = 3), alcohol (n = 2), and linoleic acid (n = 1) had causal effects on asthma risk, while vitamins/minerals (n = 6) showed no consistent effect on asthma. The effect of smoking on adult asthma conflicted between studies. Several of the significant associations of asthma with immune related proteins (n = 5) and depression (n = 2) investigated through multiple traits analyses could generally benefit from replications in independent datasets.
CONCLUSION
This systematic review and meta-analysis found evidence for causal effects of adiposity, puberty timing, linoleic acid, alcohol, immune related proteins, and depression on risk of asthma.
PubMed: 36434743
DOI: 10.1002/clt2.12207 -
Brain Sciences Nov 2022Thyroid hormone (TH) augmentation, although commonly used for major depression, is sparingly used for bipolar disorder (BD) after the failure of mood-stabilizing agents.... (Review)
Review
Thyroid hormone (TH) augmentation, although commonly used for major depression, is sparingly used for bipolar disorder (BD) after the failure of mood-stabilizing agents. While the exact mechanisms of thyroid hormone action in BD remains unclear, central thyroid hormone deficit has been postulated as a mechanism for rapid cycling. This systematic review-conducted in accordance with the PRISMA guidelines-of eight studies synthesizes the evidence for TH augmentation in BD. A systematic search of the Ovid MEDLINE, Embase, PsycINFO, and Cochrane databases was conducted for randomized controlled trials (RCT), open-label trials, and observational studies of levothyroxine (LT4) and triiodothyronine (T3) for BD. Open-label studies of high dose LT4 augmentation for bipolar depression and rapid cycling showed improvement in depression outcomes and reduction in recurrence, respectively. However, an RCT of high-dose LT4 did not show benefit in contrast to placebo. An RCT comparing LT4, T3, and placebo showed benefit only in rapid-cycling bipolar women. A meta-analysis could not be completed due to significant differences in study designs, interventions, and outcomes. Our systematic review shows mixed evidence and a lack of high-quality studies. The initial promise of supratherapeutic LT4 augmentation from open-label trials has not been consistently replicated in RCTs. Limited data are available for T3. The studies did not report significant thyrotoxicosis, and TH augmentation were well tolerated. Therefore, TH augmentation, especially with supratherapeutic doses, should be reserved for highly treatment-resistant bipolar depression and rapid-cycling BD.
PubMed: 36421864
DOI: 10.3390/brainsci12111540 -
Journal of Sleep Research Jun 2023Lucid dreams are defined as dreams in which the dreamers are aware of the fact that they are dreaming as dreams continue. It has been ~12 years since the last review... (Review)
Review
Lucid dreams are defined as dreams in which the dreamers are aware of the fact that they are dreaming as dreams continue. It has been ~12 years since the last review of the efficiency of lucid dream induction techniques was conducted. Hence, the present study aimed to review the lucid dream induction techniques published in the past decade. The second aim was to propose a modified classification for the existing lucid dream induction techniques, including cognitive techniques, external stimulation, substance intervention, and cortical stimulation. The third aim was to assess the methodological quality of the studies included in the review. It was hypothesised that, comparing with the studies included in the last review, the studies included in the present review had better overall methodological quality. A total of 19 peer-reviewed studies were included and analysed in the present review, from which 14 lucid dream induction techniques were identified. The results indicated that the mnemonic induction of lucid dream technique was the most effective for inducing lucid dreams. Moreover, two new techniques, the senses-initiated lucid dream technique and galantamine intervention, might also be competitive candidates for lucid dream induction but further replications are needed. As hypothesised, the overall methodological quality of the studies included in the present review was higher than that of the studies included the previous review. In all, 17 studies had moderate methodological quality, whereas only three studies had poor methodological quality.
Topics: Humans; Dreams; Awareness; Memory
PubMed: 36408823
DOI: 10.1111/jsr.13786 -
Asian Spine Journal Feb 2023Routinely, adolescent idiopathic scoliosis (AIS) curves that progress beyond 40° in skeletally immature adolescents require surgery. However, some adolescents with AIS...
Routinely, adolescent idiopathic scoliosis (AIS) curves that progress beyond 40° in skeletally immature adolescents require surgery. However, some adolescents with AIS and their parents utterly refuse surgery and insist on wearing a brace. Debate continues regarding the appropriateness of bracing for AIS curves exceeding 40° in patients who have rejected surgical intervention. This systematic review and meta-analysis was conducted to review the literature on the effectiveness of bracing and its predictive factors in largermagnitude AIS curves ≥40°. This study replicated the search strategy used by the PICOS system for formulating study questions, which include consideration of the patient/population (P), intervention (I), comparison (C), outcome (O), and study design (S). The search was conducted up to January 2022 in the following bibliographic online databases only in the English language: PubMed, Google Scholar, Scopus, and Web of Science. Two assessors reviewed the articles for qualification. Eligible studies were assessed for risk of bias at the study level using the Newcastle-Ottawa Scale. The effect size across the studies was determined using standardized mean differences (Cohen's d) and 95% confidence intervals for the meta-analysis. Among the eight included moderate quality studies, evidence of potential publication bias (p <0.05) for the trials included was found in the Cobb angle outcome. Results obtained through meta-analysis indicated that the effectiveness of bracing in controlling Cobb angle progression in curves ≥40° is significantly positive. Additionally, initial curve severity, Risser stage, in-brace curve correction, curve type, and apical vertebral rotation were considered risk factors associated with brace effectiveness. This systematic review revealed that bracing could alter the normal course of AIS curves ≥40° in patients refusing posterior spinal fusion (PSF). However, the suggested course for patients refusing PSF remains unclear because of the significant heterogeneity in the risk factors associated with bracing failure.
PubMed: 36382367
DOI: 10.31616/asj.2022.0162 -
International Journal of Environmental... Oct 2022This study showed the effectiveness of biomedical interventions in obesity, diabetes and hypertension (NCDs), but innovative and intersectoral elements in the fight... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
This study showed the effectiveness of biomedical interventions in obesity, diabetes and hypertension (NCDs), but innovative and intersectoral elements in the fight against obesity, type 2 diabetes and hypertension were rare.
BACKGROUND
Is it possible to find effective and innovative actions to promote health and prevent NCDs in Brazilian municipalities? Can they be replicated?
OBJECTIVE
Our objectives were to identify innovative and effective intersectoral actions for promoting and preventing NCDs in Brazilian municipalities.
METHODS
This is a systematic review in an exploratory theoretical essay with a qualitative and quantitative approach. It is descriptive and analytical in terms of reporting findings and results. Inclusion and exclusion criteria favored health promotion work. Bias risk assessments was performed using the Cochrane GRADE and bias risk, with meta-analyses using RevMan and Iramuteq.
RESULTS
Meta-analysis of biometric markers resulted in -4.46 [95% IC; -5.42, -3.49], = 0.00001, indicating a reduction in NCD risk rates. The textual meta-analysis revealed P(r) ≈ 83% (Reinert), meaning low connectivity between the 'halos'.
CONCLUSIONS
There is evidence of the effectiveness in interventions, but innovative and intersectoral elements to combat and prevent NCDs were barely seen. While evidence of intervention effectiveness was observed, innovative and intersectoral elements to combat and prevent NCDs were barely noticed.
Topics: Humans; Brazil; Cities; Health Promotion; Diabetes Mellitus, Type 2; Hypertension; Obesity
PubMed: 36293640
DOI: 10.3390/ijerph192013059 -
International Journal of Molecular... Aug 2022Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral agent that causes Coronavirus disease 2019 (COVID-19), a disease that causes flu-like symptoms... (Review)
Review
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral agent that causes Coronavirus disease 2019 (COVID-19), a disease that causes flu-like symptoms that, when exacerbated, can have life-threatening consequences. COVID-19 has been linked to persistent symptoms, sequelae, and medical complications that can last months after the initial infection. This systematic review aims to elucidate the innate and adaptive immune mechanisms involved and identify potential characteristics of COVID-19 pathology that may increase symptom duration. We also describe he three different stages of COVID-19-viral replication, immune hyperactivation, and post-acute sequelae-as well as each phase's corresponding immune response. Finally, we use this multiphasic approach to describe different treatment approaches for each of the three stages-antivirals, immunosuppressants and monoclonal antibodies, and continued immunosuppressants-to fully curate the treatment to the stage of disease.
Topics: Antiviral Agents; Humans; Immunosuppressive Agents; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35955740
DOI: 10.3390/ijms23158606 -
International Journal of Molecular... Jul 2022Ovarian cancer is the most lethal gynecologic malignancy in the United States. Some patients affected by ovarian cancers often present genome instability with one or... (Review)
Review
Ovarian cancer is the most lethal gynecologic malignancy in the United States. Some patients affected by ovarian cancers often present genome instability with one or more of the defects in DNA repair pathways, particularly in homologous recombination (HR), which is strictly linked to mutations in breast cancer susceptibility gene 1 (BRCA 1) or breast cancer susceptibility gene 2 (BRCA 2). The treatment of ovarian cancer remains a challenge, and the majority of patients with advanced-stage ovarian cancers experience relapse and require additional treatment despite initial therapy, including optimal cytoreductive surgery (CRS) and platinum-based chemotherapy. Targeted therapy at DNA repair genes has become a unique strategy to combat homologous recombination-deficient (HRD) cancers in recent years. Poly (ADP-ribose) polymerase (PARP), a family of proteins, plays an important role in DNA damage repair, genome stability, and apoptosis of cancer cells, especially in HRD cancers. PARP inhibitors (PARPi) have been reported to be highly effective and low-toxicity drugs that will tremendously benefit patients with HRD (i.e., BRCA 1/2 mutated) epithelial ovarian cancer (EOC) by blocking the DNA repair pathways and inducing apoptosis of cancer cells. PARP inhibitors compete with NAD at the catalytic domain (CAT) of PARP to block PARP catalytic activity and the formation of PAR polymers. These effects compromise the cellular ability to overcome DNA SSB damage. The process of HR, an essential error-free pathway to repair DNA DSBs during cell replication, will be blocked in the condition of BRCA 1/2 mutations. The PARP-associated HR pathway can also be partially interrupted by using PARP inhibitors. Grossly, PARP inhibitors have demonstrated some therapeutic benefits in many randomized phase II and III trials when combined with the standard CRS for advanced EOCs. However, similar to other chemotherapy agents, PARP inhibitors have different clinical indications and toxicity profiles and also face drug resistance, which has become a major challenge. In high-grade epithelial ovarian cancers, the cancer cells under hypoxia- or drug-induced stress have the capacity to become polyploidy giant cancer cells (PGCCs), which can survive the attack of chemotherapeutic agents and start endoreplication. These stem-like, self-renewing PGCCs generate mutations to alter the expression/function of kinases, p53, and stem cell markers, and diploid daughter cells can exhibit drug resistance and facilitate tumor growth and metastasis. In this review, we discuss the underlying molecular mechanisms of PARP inhibitors and the results from the clinical studies that investigated the effects of the FDA-approved PARP inhibitors olaparib, rucaparib, and niraparib. We also review the current research progress on PARP inhibitors, their safety, and their combined usage with antiangiogenic agents. Nevertheless, many unknown aspects of PARP inhibitors, including detailed mechanisms of actions, along with the effectiveness and safety of the treatment of EOCs, warrant further investigation.
Topics: Antineoplastic Agents; Carcinoma, Ovarian Epithelial; Clinical Trials, Phase II as Topic; Female; Genes, BRCA2; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Randomized Controlled Trials as Topic
PubMed: 35897700
DOI: 10.3390/ijms23158125 -
The Cochrane Database of Systematic... Jun 2022Ivermectin, an antiparasitic agent, inhibits the replication of viruses in vitro. The molecular hypothesis of ivermectin's antiviral mode of action suggests an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ivermectin, an antiparasitic agent, inhibits the replication of viruses in vitro. The molecular hypothesis of ivermectin's antiviral mode of action suggests an inhibitory effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in early stages of infection. Currently, evidence on ivermectin for prevention of SARS-CoV-2 infection and COVID-19 treatment is conflicting.
OBJECTIVES
To assess the efficacy and safety of ivermectin plus standard of care compared to standard of care plus/minus placebo, or any other proven intervention for people with COVID-19 receiving treatment as inpatients or outpatients, and for prevention of an infection with SARS-CoV-2 (postexposure prophylaxis).
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register, Web of Science (Emerging Citation Index and Science Citation Index), WHO COVID-19 Global literature on coronavirus disease, and HTA database weekly to identify completed and ongoing trials without language restrictions to 16 December 2021. Additionally, we included trials with > 1000 participants up to April 2022.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing ivermectin to standard of care, placebo, or another proven intervention for treatment of people with confirmed COVID-19 diagnosis, irrespective of disease severity or treatment setting, and for prevention of SARS-CoV-2 infection. Co-interventions had to be the same in both study arms. For this review update, we reappraised eligible trials for research integrity: only RCTs prospectively registered in a trial registry according to WHO guidelines for clinical trial registration were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
We assessed RCTs for bias, using the Cochrane RoB 2 tool. We used GRADE to rate the certainty of evidence for outcomes in the following settings and populations: 1) to treat inpatients with moderate-to-severe COVID-19, 2) to treat outpatients with mild COVID-19 (outcomes: mortality, clinical worsening or improvement, (serious) adverse events, quality of life, and viral clearance), and 3) to prevent SARS-CoV-2 infection (outcomes: SARS-CoV-2 infection, development of COVID-19 symptoms, admission to hospital, mortality, adverse events and quality of life).
MAIN RESULTS
We excluded seven of the 14 trials included in the previous review version; six were not prospectively registered and one was non-randomized. This updated review includes 11 trials with 3409 participants investigating ivermectin plus standard of care compared to standard of care plus/minus placebo. No trial investigated ivermectin for prevention of infection or compared ivermectin to an intervention with proven efficacy. Five trials treated participants with moderate COVID-19 (inpatient settings); six treated mild COVID-19 (outpatient settings). Eight trials were double-blind and placebo-controlled, and three were open-label. We assessed around 50% of the trial results as low risk of bias. We identified 31 ongoing trials. In addition, there are 28 potentially eligible trials without publication of results, or with disparities in the reporting of the methods and results, held in 'awaiting classification' until the trial authors clarify questions upon request. Ivermectin for treating COVID-19 in inpatient settings with moderate-to-severe disease We are uncertain whether ivermectin plus standard of care compared to standard of care plus/minus placebo reduces or increases all-cause mortality at 28 days (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.14 to 2.51; 3 trials, 230 participants; very low-certainty evidence); or clinical worsening, assessed by participants with new need for invasive mechanical ventilation or death at day 28 (RR 0.82, 95% CI 0.33 to 2.04; 2 trials, 118 participants; very low-certainty evidence); or serious adverse events during the trial period (RR 1.55, 95% CI 0.07 to 35.89; 2 trials, 197 participants; very low-certainty evidence). Ivermectin plus standard of care compared to standard of care plus placebo may have little or no effect on clinical improvement, assessed by the number of participants discharged alive at day 28 (RR 1.03, 95% CI 0.78 to 1.35; 1 trial, 73 participants; low-certainty evidence); on any adverse events during the trial period (RR 1.04, 95% CI 0.61 to 1.79; 3 trials, 228 participants; low-certainty evidence); and on viral clearance at 7 days (RR 1.12, 95% CI 0.80 to 1.58; 3 trials, 231 participants; low-certainty evidence). No trial investigated quality of life at any time point. Ivermectin for treating COVID-19 in outpatient settings with asymptomatic or mild disease Ivermectin plus standard of care compared to standard of care plus/minus placebo probably has little or no effect on all-cause mortality at day 28 (RR 0.77, 95% CI 0.47 to 1.25; 6 trials, 2860 participants; moderate-certainty evidence) and little or no effect on quality of life, measured with the PROMIS Global-10 scale (physical component mean difference (MD) 0.00, 95% CI -0.98 to 0.98; and mental component MD 0.00, 95% CI -1.08 to 1.08; 1358 participants; high-certainty evidence). Ivermectin may have little or no effect on clinical worsening, assessed by admission to hospital or death within 28 days (RR 1.09, 95% CI 0.20 to 6.02; 2 trials, 590 participants; low-certainty evidence); on clinical improvement, assessed by the number of participants with all initial symptoms resolved up to 14 days (RR 0.90, 95% CI 0.60 to 1.36; 2 trials, 478 participants; low-certainty evidence); on serious adverse events (RR 2.27, 95% CI 0.62 to 8.31; 5 trials, 1502 participants; low-certainty evidence); on any adverse events during the trial period (RR 1.24, 95% CI 0.87 to 1.76; 5 trials, 1502 participants; low-certainty evidence); and on viral clearance at day 7 compared to placebo (RR 1.01, 95% CI 0.69 to 1.48; 2 trials, 331 participants; low-certainty evidence). None of the trials reporting duration of symptoms were eligible for meta-analysis.
AUTHORS' CONCLUSIONS
For outpatients, there is currently low- to high-certainty evidence that ivermectin has no beneficial effect for people with COVID-19. Based on the very low-certainty evidence for inpatients, we are still uncertain whether ivermectin prevents death or clinical worsening or increases serious adverse events, while there is low-certainty evidence that it has no beneficial effect regarding clinical improvement, viral clearance and adverse events. No evidence is available on ivermectin to prevent SARS-CoV-2 infection. In this update, certainty of evidence increased through higher quality trials including more participants. According to this review's living approach, we will continually update our search.
Topics: COVID-19; Humans; Ivermectin; Randomized Controlled Trials as Topic; Respiration, Artificial; SARS-CoV-2; Severity of Illness Index
PubMed: 35726131
DOI: 10.1002/14651858.CD015017.pub3 -
International Journal of Environmental... Dec 2023The outbreak of coronavirus disease in 2019 has become a serious threat to human health. Whether meteorological conditions could influence the transmission and virulence... (Review)
Review
The outbreak of coronavirus disease in 2019 has become a serious threat to human health. Whether meteorological conditions could influence the transmission and virulence of COVID-19 remains controversial. In this study, we systematically reviewed the impact of temperature and humidity on the replication, morbidity, and mortality of COVID-19. We also discussed the main factors underlying the inconsistency across studies. Pubmed, Web of Science, Embase, and Scopus were used to identify papers published up to 7 December 2020. We initially identified 3515 papers, and 28 articles met the inclusion criteria after screening. Most studies showed high temperature and high humidity can partly reduce the reproduction, morbidity, and mortality of COVID-19. But the rest papers failed to identify a significant association. The discrepant results may be related to the difference in the climate context, study design, exposure assessment, policy intervention, socioeconomic status, and public health service.
Topics: Humans; COVID-19; SARS-CoV-2; Temperature; Climate; Meteorological Concepts
PubMed: 35674116
DOI: 10.1080/09603123.2022.2083090 -
Nephrology, Dialysis, Transplantation :... Jan 2023Adolescence is a time of significant change for patients, guardians and clinicians. The paediatrician must ensure patients develop the necessary skills and knowledge...
BACKGROUND
Adolescence is a time of significant change for patients, guardians and clinicians. The paediatrician must ensure patients develop the necessary skills and knowledge required to transition and to function as an independent entity, with autonomy over their own care. The transfer from paediatric to adult care carries an increased risk of graft-related complications attributable to a multitude of reasons, particularly non-adherence to immunosuppressive medicines and poor attendance at scheduled appointments. This systematic review was conducted to ascertain the transitional care models available to clinicians caring for kidney transplant recipients and to compare the approach in each respective case.
METHODS
A systematic review was performed, in a methodology outlined by the PRISMA guidelines. OVID MEDLINE and EMBASE databases were searched for studies that outlined valid, replicable models pertaining to transitional care of paediatric kidney transplant recipients between 1946 and Quarter 3 of 2021. The reference lists of selected articles were also perused for further eligible studies and experts in the field were consulted for further eligible articles. Two investigators assessed all studies for eligibility and independently performed data extraction. Any discrepancies were settled by consensus.
RESULTS
A total of 1121 abstracts were identified, which was reduced to 1029 upon removal of duplicates. A total of 51 articles were deemed appropriate for full-text review and critical appraisal. A total of 12 articles that described models for transition pertaining to kidney transplant patients were included in qualitative synthesis. Every paper utilized a different transition model. All but one model included a physician and nurse at minimum in the transition process. The involvement of adult nephrologists, medical social work, psychology and psychiatry was variable. The mean age for the initiation of transition was 13.4 years (range: 10-17.5 years). The mean age at transfer to adult services was 18.3 years (range: 16-20.5 years).
CONCLUSIONS
Despite the well-established need for good transitional care for paediatric solid-organ transplant recipients, models tailored specifically for kidney transplant recipients are lacking. Further research and validation studies are required to ascertain the best method of providing effective transitional care to these patients. Transitional care should become a standardized process for adolescents and young adults with kidney transplants.
Topics: Young Adult; Humans; Child; Adolescent; Adult; Kidney Transplantation; Transition to Adult Care; Transitional Care
PubMed: 35554567
DOI: 10.1093/ndt/gfac175