-
Expert Opinion on Drug Safety Feb 2024Dyslipidaemia is a crucial risk factor for cardiovascular morbidity and mortality. A short interfering RNA called inclisiran diminishes circulating levels of PCSK9 and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dyslipidaemia is a crucial risk factor for cardiovascular morbidity and mortality. A short interfering RNA called inclisiran diminishes circulating levels of PCSK9 and LDL-C by hindering PCSK9 translation in the liver.
METHODS
RCTs were electronically searched on PubMed, Cochrane Central, and Clinicaltrials.gov to assess the safety and efficacy of inclisiran. Cochrane Review Manager 5 was used to conduct the pooled analysis. Risk of bias was assessed and GRADE pro-GDT was utilized, respectively, to estimate the methodological quality and overall quality of evidence.
RESULTS
Of 218 records screened, four studies were included with 2203 participants in inclisiran and 1949 participants in the placebo group. Inclisiran was related to non-significant elevated risk of total adverse events[RR = 1.05(0.98,1.12), = 0.16; I = 53%], non-serious adverse events[RR = 1.09(0.97,1.22), = 0.15;I = 61%] and all-cause mortality[RR = 1.01(0.60,1.70), = 0.97;I = 0%] whereas a lower risk of serious adverse events[RR = 0.94(0.70,1.25), = 0.67;I = 73%], cardiac disorders [RR = 0.87(0.66,1.15), = 0.33;I = 42%] and Major adverse cardiovascular events(MACE)[RR = 0.79(0.62,1.00), = 0.05; I = 0%] as compared to placebo. Inclisiran was also linked to a substantial decline in the percentage of LDL-C, PCSK9, total cholesterol, and Apo B.
CONCLUSION
The pooled analysis of the existing evidence shows that inclisiran showed reduced risk of MACE along with excellent efficacy in managing dyslipidemia.
CLINICAL TRIAL REGISTRATION
www.clinicaltrials.gov identifiers are NCT03399370, NCT03397121, NCT03400800, and NCT02597127.
Topics: Humans; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Dyslipidemias; Hyperlipidemias; Proprotein Convertase 9; RNA, Small Interfering
PubMed: 38063346
DOI: 10.1080/14740338.2023.2293201 -
Journal of Intensive Care Medicine Oct 2022Inhaled pulmonary vasodilators (IPVD) have been previously studied in patients with non-coronavirus disease-19 (COVID-19) related acute respiratory distress syndrome... (Meta-Analysis)
Meta-Analysis
Inhaled pulmonary vasodilators (IPVD) have been previously studied in patients with non-coronavirus disease-19 (COVID-19) related acute respiratory distress syndrome (ARDS). The use of IPVD has been shown to improve the partial pressure of oxygen in arterial blood (PaO), reduce fraction of inspired oxygen (FiO) requirements, and ultimately increase PaO/FiO (P/F) ratios in ARDS patients. However, the role of IPVD in COVID-19 ARDS is still unclear. Therefore, we performed this meta-analysis to evaluate the role of IPVD in COVID-19 patients. Comprehensive literature search of PubMed, Embase, Web of Science and Cochrane Library databases from inception through April 22, 2022 was performed for all published studies that utilized IPVD in COVID-19 ARDS patients. The single arm studies and case series were combined for a 1-arm meta-analysis, and the 2-arm studies were combined for a 2-arm meta-analysis. Primary outcomes for the 1-arm and 2-arm meta-analyzes were change in pre- and post-IPVD P/F ratios and mortality, respectively. Secondary outcomes for the 1-arm meta-analysis were change in pre- and post-IPVD positive end-expiratory pressure (PEEP) and lung compliance, and for the 2-arm meta-analysis the secondary outcomes were need for endotracheal intubation and hospital length of stay (LOS). 13 single arm retrospective studies and 5 case series involving 613 patients were included in the 1-arm meta-analysis. 3 studies involving 640 patients were included in the 2-arm meta-analysis. The pre-IPVD P/F ratios were significantly lower compared to post-IPVD, but there was no significant difference between pre- and post-IPVD PEEP and lung compliance. The mortality rates, need for endotracheal intubation, and hospital LOS were similar between the IPVD and standard therapy groups. Although IPVD may improve oxygenation, our investigation showed no benefits in terms of mortality compared to standard therapy alone. However, randomized controlled trials are warranted to validate our findings.
Topics: COVID-19; Humans; Oxygen; Respiratory Distress Syndrome; Retrospective Studies; Vasodilator Agents
PubMed: 35915994
DOI: 10.1177/08850666221118271 -
Physiotherapy Canada. Physiotherapie... 2021A systematic review was conducted to investigate the effect of respiratory physiotherapy on mortality, quality of life, functional recovery, intensive care length of...
A systematic review was conducted to investigate the effect of respiratory physiotherapy on mortality, quality of life, functional recovery, intensive care length of stay, duration of ventilation, oxygenation, secretion clearance, and pulmonary mechanics for invasively ventilated adults with pneumonia. Five databases were searched for randomized trials published between January 1995 and November 2018. Study quality was assessed using a standardized Joanna Briggs Institute critical appraisal tool, and Review Manager software was used to pool the studies. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the level of certainty of the evidence. A total of 14 studies of moderate quality included 251 subjects with pneumonia. Eight studies were pooled for meta-analysis. Interventions that increased inspiratory volume appeared to benefit secretion clearance by nearly 2 grams (mean difference [MD] 1.97; 95% CI: 0.80, 3.14; very low GRADE evidence) and increase static lung compliance immediately after treatment by more than 5 millilitres/centimetre H0 (MD 5.40 mL/cm HO; 95% CI: 2.37, 8.43; very low GRADE evidence) or by more than 6 millilitres/centimetre HO after a 20- to 30-minute delay (MD 6.86 mL/cm HO; 95% CI: 2.86, 10.86; very low GRADE evidence). No adverse events were found. Respiratory physiotherapy that increases tidal volume may benefit secretion clearance and lung compliance in invasively ventilated adults with pneumonia, but its impact on other outcomes, including mortality, length of stay, and other patient-centred outcomes, is unclear, and further research is required.
PubMed: 35106019
DOI: 10.3138/ptc-2019-0025 -
Physiotherapy Research International :... Apr 2022Manual hyperinflation (MHI) or with a mechanical ventilator (VHI) are alternatives in bronchial hygiene therapy, in recent years several studies have emerged with the... (Review)
Review
INTRODUCTION
Manual hyperinflation (MHI) or with a mechanical ventilator (VHI) are alternatives in bronchial hygiene therapy, in recent years several studies have emerged with the objective of verifying the effectiveness and safety of the techniques.
OBJECTIVE
Systematically review and analyze the most recent studies in the literature on MHI and VHI, compare both techniques and demonstrate their effectiveness in bronchial hygiene therapy in mechanically ventilated patients.
METHODS
We conducted this systematic review based on the PICO strategy and used the databases Ovid, LILACS, CINAHL, Pubmed and CENTRAL. Search, selection and analysis of randomized controlled trials on MHI, VHI or comparing both techniques. We performed a comparison on secretion elimination, static and dynamic compliance, oxygenation and clinical outcomes. The studies were analyzed by two independent evaluators.
RESULTS
Nine articles were selected comparing MHI with usual care, demonstrating improved compliance in the MHI group, but with no impact on secretion removal. Four studies compared VHI with usual care, with three showing increased secretion elimination and compliance in the HVM group. Another four articles compared MHI with VHI but none of the studies showed superiority in terms of elimination of secretion and three studies found improvement in static compliance.
CONCLUSION
Both techniques have proven to be effective alternatives to bronchial hygiene therapy.
Topics: Adult; Home Care Services; Humans; Lung; Respiration, Artificial; Ventilators, Mechanical
PubMed: 35060664
DOI: 10.1002/pri.1936 -
The Cochrane Database of Systematic... Feb 2023People with cystic fibrosis (CF) experience chronic airway infections as a result of mucus buildup within the lungs. Repeated infections often cause lung damage and... (Review)
Review
BACKGROUND
People with cystic fibrosis (CF) experience chronic airway infections as a result of mucus buildup within the lungs. Repeated infections often cause lung damage and disease. Airway clearance therapies aim to improve mucus clearance, increase sputum production, and improve airway function. The active cycle of breathing technique (ACBT) is an airway clearance method that uses a cycle of techniques to loosen airway secretions including breathing control, thoracic expansion exercises, and the forced expiration technique. This is an update of a previously published review.
OBJECTIVES
To compare the clinical effectiveness of ACBT with other airway clearance therapies in CF.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched clinical trials registries and the reference lists of relevant articles and reviews. Date of last search: 29 March 2021.
SELECTION CRITERIA
We included randomised or quasi-randomised controlled clinical studies, including cross-over studies, comparing ACBT with other airway clearance therapies in CF.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened each article, abstracted data and assessed the risk of bias of each study. We used GRADE to assess our confidence in the evidence assessing quality of life, participant preference, adverse events, forced expiratory volume in one second (FEV) % predicted, forced vital capacity (FVC) % predicted, sputum weight, and number of pulmonary exacerbations.
MAIN RESULTS
Our search identified 99 studies, of which 22 (559 participants) met the inclusion criteria. Eight randomised controlled studies (259 participants) were included in the analysis; five were of cross-over design. The 14 remaining studies were cross-over studies with inadequate reports for complete assessment. The study size ranged from seven to 65 participants. The age of the participants ranged from six to 63 years (mean age 18.7 years). In 13 studies follow up lasted a single day. However, there were two long-term randomised controlled studies with follow up of one to three years. Most of the studies did not report on key quality items, and therefore, have an unclear risk of bias in terms of random sequence generation, allocation concealment, and outcome assessor blinding. Due to the nature of the intervention, none of the studies blinded participants or the personnel applying the interventions. However, most of the studies reported on all planned outcomes, had adequate follow up, assessed compliance, and used an intention-to-treat analysis. Included studies compared ACBT with autogenic drainage, airway oscillating devices (AOD), high-frequency chest compression devices, conventional chest physiotherapy (CCPT), positive expiratory pressure (PEP), and exercise. We found no difference in quality of life between ACBT and PEP mask therapy, AOD, other breathing techniques, or exercise (very low-certainty evidence). There was no difference in individual preference between ACBT and other breathing techniques (very low-certainty evidence). One study comparing ACBT with ACBT plus postural exercise reported no deaths and no adverse events (very low-certainty evidence). We found no differences in lung function (forced expiratory volume in one second (FEV) % predicted and forced vital capacity (FVC) % predicted), oxygen saturation or expectorated sputum between ACBT and any other technique (very low-certainty evidence). There were no differences in the number of pulmonary exacerbations between people using ACBT and people using CCPT (low-certainty evidence) or ACBT with exercise (very low-certainty evidence), the only comparisons to report this outcome.
AUTHORS' CONCLUSIONS
There is little evidence to support or reject the use of the ACBT over any other airway clearance therapy and ACBT is comparable with other therapies in outcomes such as participant preference, quality of life, exercise tolerance, lung function, sputum weight, oxygen saturation, and number of pulmonary exacerbations. Longer-term studies are needed to more adequately assess the effects of ACBT on outcomes important for people with cystic fibrosis such as quality of life and preference.
Topics: Humans; Adolescent; Child; Young Adult; Adult; Middle Aged; Cystic Fibrosis; Quality of Life; Respiratory Therapy; Mucus; Chest Wall Oscillation
PubMed: 36727723
DOI: 10.1002/14651858.CD007862.pub5 -
Journal of the American Heart... Apr 2022Background Pulmonary arterial end-diastolic forward flow (EDFF) following repaired tetralogy of Fallot has been thought to represent right ventricular (RV) restrictive... (Meta-Analysis)
Meta-Analysis Review
Background Pulmonary arterial end-diastolic forward flow (EDFF) following repaired tetralogy of Fallot has been thought to represent right ventricular (RV) restrictive physiology, but is not fully understood. This systematic review and meta-analysis sought to clarify its physiological and clinical correlates, and to define a framework for understanding EDFF and RV restrictive physiology. Methods and Results PubMed/MEDLINE, Embase, Scopus, and reference lists of relevant articles were searched for observational studies published before March 2021. Random-effects meta-analysis was performed to identify factors associated with EDFF. Forty-two individual studies published between 1995 and 2021, including a total of 2651 participants (1132 with EDFF; 1519 with no EDFF), met eligibility criteria. The pooled estimated prevalence of EDFF among patients with repaired tetralogy of Fallot was 46.5% (95% CI, 41.6%-51.3%). Among patients with EDFF, the use of a transannular patch was significantly more common, and their stay in the intensive care unit was longer. EDFF was associated with greater RV indexed volumes and mass, as well as smaller E-wave velocity at the tricuspid valve. Finally, pulmonary regurgitation fraction was greater in patients with EDFF, and moderate to severe pulmonary regurgitation was more common in this population. Conclusions EDFF is associated with dilated, hypertrophied RVs and longstanding pulmonary regurgitation. Although several studies have defined RV restrictive physiology as the presence of EDFF, our study found no clear indicators of poor RV compliance in patients with EDFF, suggesting that EDFF may have multiple causes and might not be the precise equivalent of RV restrictive physiology.
Topics: Diastole; Humans; Pulmonary Valve Insufficiency; Tetralogy of Fallot; Tricuspid Valve; Ventricular Dysfunction, Right; Ventricular Function, Right
PubMed: 35301867
DOI: 10.1161/JAHA.121.024036 -
Journal of Medical Internet Research Feb 2024Virtual reality-based exercise rehabilitation (VRER) is a promising intervention for patients with cancer-related dysfunctions (CRDs). However, studies focusing on VRER... (Review)
Review
BACKGROUND
Virtual reality-based exercise rehabilitation (VRER) is a promising intervention for patients with cancer-related dysfunctions (CRDs). However, studies focusing on VRER for CRDs are lacking, and the results are inconsistent.
OBJECTIVE
We aimed to review the application of VRER in patients with CRDs.
METHODS
This scoping review was conducted following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist framework. Publications were included from the time of database establishment to October 14, 2023. The databases were PubMed, Embase, Scopus, Cochrane, Web of Science, ProQuest, arXiv, IEEE Xplore, MedRxiv, CNKI, Wanfang Data, VIP, and SinoMed. The population included patients with cancer. A virtual reality (VR) system or device was required to be provided in exercise rehabilitation as an intervention. Eligible studies focused on VRER used for CRDs. Study selection and data extraction were performed by 2 reviewers independently. Extracted data included authors, year, country, study type, groups, sample size, participant age, cancer type, existing or potential CRDs, VR models and devices, intervention programs and durations, effectiveness, compliance, satisfaction, and safety.
RESULTS
We identified 25 articles, and among these, 12 (48%) were randomized clinical trials, 11 (44%) were other experimental studies, and 2 (8%) were observational studies. The total sample size was 1174 (range 6-136). Among the 25 studies, 22 (88%), 2 (8%), and 1 (4%) included nonimmersive VR, immersive VR, and augmented reality, respectively, which are models of VRER. Commercial game programs (17/25, 68%) were the most popular interventions of VRER, and their duration ranged from 3 to 12 weeks. Using these models and devices, VRER was mostly applied in patients with breast cancer (14/25, 56%), leukemia (8/25, 32%), and lung cancer (3/25, 12%). Furthermore, 6 CRDs were intervened by VRER, and among these, postmastectomy syndromes were the most common (10/25, 40%). Overall, 74% (17/23) of studies reported positive results, including significant improvements in limb function, joint range of motion, edema rates, cognition, respiratory disturbance index, apnea, activities of daily living, and quality of life. The compliance rate ranged from 56% to 100%. Overall, 32% (8/25) of studies reported on patient satisfaction, and of these, 88% (7/8) reported satisfaction with VRER. Moreover, 13% (1/8) reported mild sickness as an adverse event.
CONCLUSIONS
We found that around half of the studies reported using VRER in patients with breast cancer and postmastectomy dysfunctions through nonimmersive models and commercial game programs having durations of 3-12 weeks. In addition, most studies showed that VRER was effective owing to virtualization and interaction. Therefore, VRER may be an alternate intervention for patients with CRDs. However, as the conclusions were drawn from data with acknowledged inconsistencies and limited satisfaction reports, studies with larger sample sizes and more outcome indictors are required.
Topics: Humans; Female; Breast Neoplasms; Activities of Daily Living; Quality of Life; Mastectomy; Medicine
PubMed: 38407951
DOI: 10.2196/49312 -
Journal of Clinical Monitoring and... Apr 2023The optimization of positive end-expiratory pressure (PEEP) according to respiratory mechanics [driving pressure or respiratory system compliance (Crs)] is a simple and... (Meta-Analysis)
Meta-Analysis Review
Individualized positive end-expiratory pressure guided by respiratory mechanics during anesthesia for the prevention of postoperative pulmonary complications: a systematic review and meta-analysis.
The optimization of positive end-expiratory pressure (PEEP) according to respiratory mechanics [driving pressure or respiratory system compliance (Crs)] is a simple and straightforward strategy. However, its validity to prevent postoperative pulmonary complications (PPCs) remains unclear. Here, we performed a meta-analysis to assess such efficacy. We searched PubMed, Embase, and the Cochrane Library to identify randomized controlled trials (RCTs) that compared personalized PEEP based on respiratory mechanics and constant PEEP to prevent PPCs in adults. The primary outcome was PPCs. Fourteen studies with 1105 patients were included. Compared with those who received constant PEEP, patients who received optimized PEEP exhibited a significant reduction in the incidence of PPCs (RR = 0.54, 95% CI 0.42 to 0.69). The results of commonly happened PPCs (pulmonary infections, hypoxemia, and atelectasis but not pleural effusion) also supported individualized PEEP group. Moreover, the application of PEEP based on respiratory mechanics improved intraoperative respiratory mechanics (driving pressure and Crs) and oxygenation. The PEEP titration method based on respiratory mechanics seems to work positively for lung protection in surgical patients undergoing general anesthesia.
Topics: Adult; Humans; Lung; Positive-Pressure Respiration; Pulmonary Atelectasis; Anesthesia, General; Postoperative Complications; Respiratory Mechanics
PubMed: 36607532
DOI: 10.1007/s10877-022-00960-9 -
Journal of Clinical Medicine Oct 2022Background: Lung-protective ventilation strategies are recommended for patients undergoing mechanical ventilation. However, there are currently no guidelines to follow... (Review)
Review
Background: Lung-protective ventilation strategies are recommended for patients undergoing mechanical ventilation. However, there are currently no guidelines to follow regarding recruitment maneuvers (RMs). We attempted to identify the effects of RMs on patients undergoing laparoscopic abdominal surgery. Methods: We searched for randomized controlled trials (RCTs) in PubMed, the Cochrane Library databases, Embase, Web of Science and the ClinicalTrials.gov registry for trials published up to December 2021. The primary outcome was postoperative pulmonary complications (PPCs). The secondary outcomes consisted of the static lung compliance, driving pressure (DP), intraoperative oxygenation index (OI), OI in the post-anesthesia care unit (PACU), mean arterial pressure (MAP) and heart rate (HR). Seventeen RCTs with a total of 3480 patients were examined. Results: Patients who received RMs showed a considerable reduction in PPCs (risk ratio (RR) = 0.70; 95% confidence interval (CI): 0.62 to 0.79; p < 0.01), lower DP (weighted mean difference (WMD) = −3.96; 95% CI: −5.97 to −1.95; p < 0.01), elevated static lung compliance (WMD = 10.42; 95% CI: 6.13 to 14.71; p < 0.01) and improved OI (intraoperative: WMD = 53.54; 95% CI: 21.77 to 85.31; p < 0.01; PACU: WMD = 59.40; 95% CI: 39.10 to 79.69; p < 0.01) without substantial changes in MAP (WMD = −0.16; 95% CI −1.35 to 1.03; p > 0.05) and HR (WMD = −1.10; 95% CI: −2.29 to 0.10; p > 0.05). Conclusions: Recruitment maneuvers reduce postoperative pulmonary complications and improve respiratory mechanics and oxygenation in patients undergoing laparoscopic abdominal surgery. More data are needed to elucidate the effect of recruitment maneuver on the circulatory system.
PubMed: 36233708
DOI: 10.3390/jcm11195841 -
The Journal of Allergy and Clinical... May 2024Poor adherence to asthma and chronic obstructive pulmonary disease maintenance therapies impairs health outcomes. Proven and cost-effective programs to promote adherence...
Cost-Effectiveness and Impact on Health Care Utilization of Interventions to Improve Medication Adherence and Outcomes in Asthma and Chronic Obstructive Pulmonary Disease: A Systematic Literature Review.
BACKGROUND
Poor adherence to asthma and chronic obstructive pulmonary disease maintenance therapies impairs health outcomes. Proven and cost-effective programs to promote adherence and persistence are not yet in regular widespread use. Implementation costs are a potential barrier to uptake of such programs.
OBJECTIVE
We undertook a systematic literature review and narrative synthesis of studies investigating the cost-effectiveness of treatment adherence-promoting programs or that determined their impact on health care budget directly or via health care resource use (HCRU).
METHODS
We identified relevant publications using Medline and PreMEDLINE (PubMed), Embase (Embase.com, Elsevier), and EconLit for publications between January 2000 and July 2021. We also searched clinical trial databases and selected conference proceedings.
RESULTS
Of 1,910 potentially relevant articles, 26 met prespecified inclusion criteria and underwent data extraction. Eleven reported a direct assessment of adherence, 15 included economic evaluations, and 17 described HCRU. None included an analysis of biologic medication use. When they were studied, interventions were often found to be highly cost-effective, with dominant incremental cost-effectiveness ratios in some cases. Reductions in direct costs and HCRU (health care visits, hospital admissions, and/or the use of medications, including add-on/reliever treatment and antibiotics) were frequently reported. Reported use of maintenance treatments improved in some studies. Counseling and/or digitally informed programs were used in all cases in which favorable outcomes were observed.
CONCLUSIONS
Adherence-promoting interventions are mostly cost-effective and often result in reduced HCRU and associated costs. Multidisciplinary care involving one-to-one advice and digitally enhanced communications appear to offer the greatest benefit.
Topics: Humans; Cost-Benefit Analysis; Asthma; Pulmonary Disease, Chronic Obstructive; Medication Adherence; Patient Acceptance of Health Care
PubMed: 38182099
DOI: 10.1016/j.jaip.2023.12.049