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Journal of the American Academy of... Jul 2023New evidence has emerged since the 2014 guidelines that further informs the management of atopic dermatitis (AD) with topical therapies. These guidelines update the 2014...
BACKGROUND
New evidence has emerged since the 2014 guidelines that further informs the management of atopic dermatitis (AD) with topical therapies. These guidelines update the 2014 recommendations for management of AD with topical therapies.
OBJECTIVE
To provide evidence-based recommendations related to management of AD in adults using topical treatments.
METHODS
A multidisciplinary workgroup conducted a systematic review and applied the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach for assessing the certainty of evidence and formulating and grading recommendations.
RESULTS
The workgroup developed 12 recommendations on the management of AD in adults with topical therapies, including nonprescription agents and prescription topical corticosteroids (TCS), calcineurin inhibitors (TCIs), Janus kinase (JAK) inhibitors, phosphodiesterase-4 inhibitors (PDE-4), antimicrobials, and antihistamines.
LIMITATIONS
The pragmatic decision to limit the literature review to English-language randomized trials may have excluded data published in other languages and relevant long-term follow-up data.
CONCLUSIONS
Strong recommendations are made for the use of moisturizers, TCIs, TCS, and topical PDE-4 and JAK inhibitors. Conditional recommendations are made for the use of bathing and wet wrap therapy and against the use of topical antimicrobials, antiseptics, and antihistamines.
Topics: Adult; Humans; Dermatitis, Atopic; Calcineurin Inhibitors; Dermatologic Agents; Administration, Topical; Glucocorticoids; Anti-Infective Agents, Local; Histamine Antagonists
PubMed: 36641009
DOI: 10.1016/j.jaad.2022.12.029 -
International Journal of Sports... Apr 2021Proximal hamstring tendinopathy affects athletic and non-athletic populations and is associated with longstanding buttock pain. The condition is common in track and...
BACKGROUND
Proximal hamstring tendinopathy affects athletic and non-athletic populations and is associated with longstanding buttock pain. The condition is common in track and field, long distance running and field-based sports. Management options need to be evaluated to direct appropriate clinical management.
PURPOSE/HYPOTHESIS
To evaluate surgical and non-surgical interventions used in managing proximal hamstring tendinopathy.
STUDY DESIGN
Systematic review.
METHODS
Electronic databases were searched to January 2019. Studies (all designs) investigating interventions for people with proximal hamstring tendinopathy were eligible. Outcomes included symptoms, physical function, quality of life and adverse events. Studies were screened for risk of bias. Reporting quality was assessed using the Cochrane Risk of Bias Tool (Randomized Controlled Trials [RCT]) and the Joanna Briggs Institute Checklist (Case Series). Effect sizes (Standard mean difference or Standard paired difference) of 0.2, 0.5 and 0.8 were considered as small, medium and large respectively. Overall quality of evidence was rated according to GRADE guidelines.
RESULTS
Twelve studies (2 RCTs and 10 case series) were included (n=424; males 229). RCTs examined the following interventions: platelet-rich plasma injection (n=1), autologous whole-blood injection (n=1), shockwave therapy (n=1) and multi-modal intervention (n=1). Case series included evaluation of the following interventions: platelet-rich plasma injection (n=3), surgery (n=4), corticosteroid injection (n=2), multi-modal intervention + platelet-rich plasma injection (n=1). Very low-level evidence found shockwave therapy was more effective than a multi-modal intervention, by a large effect on improving symptoms (-3.22 SMD; 95% CI -4.28, -2.16) and physical function (-2.42 SMD; 95% CI-3.33, -1.50) in the long-term. There was very low-level evidence of no difference between autologous whole-blood injection and platelet-rich plasma injection on physical function (0.17 SMD; 95% CI -0.86, 1.21) to (0.24 SMD; 95% CI -0.76, 1.24) and quality of life (-0.04 SMD; 95%CI -1.05, 0.97) in the medium-term. There was very low-quality evidence that surgery resulted in a large reduction in symptoms (-1.89 SPD; 95% CI -2.36, -1.41) to (-6.02 SPD; 95% CI -8.10, -3.94) and physical function (-4.08 SPD; 95%CI -5.53, -2.63) in the long-term.
CONCLUSIONS
There is insufficient evidence to recommend any one intervention over another. A pragmatic approach would be to initially trial approaches proven successful in other tendinopathies.
LEVEL OF EVIDENCE
Level 2a.
PubMed: 33842025
DOI: 10.26603/001c.21250 -
The Cochrane Database of Systematic... Jan 2022Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to... (Review)
Review
BACKGROUND
Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to manage upper GI bleeding. However, there is conflicting evidence regarding the clinical efficacy of proton pump inhibitors initiated before endoscopy in people with upper gastrointestinal bleeding.
OBJECTIVES
To assess the effects of PPI treatment initiated prior to endoscopy in people with acute upper GI bleeding.
SEARCH METHODS
We searched the CENTRAL, MEDLINE, Embase and CINAHL databases and major conference proceedings to October 2008, for the previous versions of this review, and in April 2018, October 2019, and 3 June 2021 for this update. We also contacted experts in the field and searched trial registries and references of trials for any additional trials.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) that compared treatment with a PPI (oral or intravenous) versus control treatment with either placebo, histamine-2 receptor antagonist (HRA) or no treatment, prior to endoscopy in hospitalised people with uninvestigated upper GI bleeding.
DATA COLLECTION AND ANALYSIS
At least two review authors independently assessed study eligibility, extracted study data and assessed risk of bias. Outcomes assessed at 30 days were: mortality (our primary outcome), rebleeding, surgery, high-risk stigmata of recent haemorrhage (active bleeding, non-bleeding visible vessel or adherent clot) at index endoscopy, endoscopic haemostatic treatment at index endoscopy, time to discharge, blood transfusion requirements and adverse effects. We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included six RCTs comprising 2223 participants. No new studies have been published after the literature search performed in 2008 for the previous version of this review. Of the included studies, we considered one to be at low risk of bias, two to be at unclear risk of bias, and three at high risk of bias. Our meta-analyses suggest that pre-endoscopic PPI use may not reduce mortality (OR 1.14, 95% CI 0.76 to 1.70; 5 studies; low-certainty evidence), and may reduce rebleeding (OR 0.81, 95% CI 0.62 to 1.06; 5 studies; low-certainty evidence). In addition, pre-endoscopic PPI use may not reduce the need for surgery (OR 0.91, 95% CI 0.65 to 1.26; 6 studies; low-certainty evidence), and may not reduce the proportion of participants with high-risk stigmata of recent haemorrhage at index endoscopy (OR 0.80, 95% CI 0.52 to 1.21; 4 studies; low-certainty evidence). Pre-endoscopic PPI use likely reduces the need for endoscopic haemostatic treatment at index endoscopy (OR 0.68, 95% CI 0.50 to 0.93; 3 studies; moderate-certainty evidence). There were insufficient data to determine the effect of pre-endoscopic PPI use on blood transfusions (2 studies; meta-analysis not possible; very low-certainty evidence) and time to discharge (1 study; very low-certainty evidence). There was no substantial heterogeneity amongst trials in any analysis.
AUTHORS' CONCLUSIONS
There is moderate-certainty evidence that PPI treatment initiated before endoscopy for upper GI bleeding likely reduces the requirement for endoscopic haemostatic treatment at index endoscopy. However, there is insufficient evidence to conclude whether pre-endoscopic PPI treatment increases, reduces or has no effect on other clinical outcomes, including mortality, rebleeding and need for surgery. Further well-designed RCTs that conform to current standards for endoscopic haemostatic treatment and appropriate co-interventions, and that ensure high-dose PPIs are only given to people who received endoscopic haemostatic treatment, regardless of initial randomisation, are warranted. However, as it may be unrealistic to achieve the optimal information size, pragmatic multicentre trials may provide valuable evidence on this topic.
Topics: Acute Disease; Endoscopy; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Proton Pump Inhibitors
PubMed: 34995368
DOI: 10.1002/14651858.CD005415.pub4 -
Ultrasound in Obstetrics & Gynecology :... Jul 2019Primary studies and systematic reviews provide estimates of varying accuracy for different factors in the prediction of pre-eclampsia. The aim of this study was to...
OBJECTIVE
Primary studies and systematic reviews provide estimates of varying accuracy for different factors in the prediction of pre-eclampsia. The aim of this study was to review published systematic reviews to collate evidence on the ability of available tests to predict pre-eclampsia, to identify high-value avenues for future research and to minimize future research waste in this field.
METHODS
MEDLINE, EMBASE and The Cochrane Library including DARE (Database of Abstracts of Reviews of Effects) databases, from database inception to March 2017, and bibliographies of relevant articles were searched, without language restrictions, for systematic reviews and meta-analyses on the prediction of pre-eclampsia. The quality of the included reviews was assessed using the AMSTAR tool and a modified version of the QUIPS tool. We evaluated the comprehensiveness of search, sample size, tests and outcomes evaluated, data synthesis methods, predictive ability estimates, risk of bias related to the population studied, measurement of predictors and outcomes, study attrition and adjustment for confounding.
RESULTS
From 2444 citations identified, 126 reviews were included, reporting on over 90 predictors and 52 prediction models for pre-eclampsia. Around a third (n = 37 (29.4%)) of all reviews investigated solely biochemical markers for predicting pre-eclampsia, 31 (24.6%) investigated genetic associations with pre-eclampsia, 46 (36.5%) reported on clinical characteristics, four (3.2%) evaluated only ultrasound markers and six (4.8%) studied a combination of tests; two (1.6%) additional reviews evaluated primary studies investigating any screening test for pre-eclampsia. Reviews included between two and 265 primary studies, including up to 25 356 688 women in the largest review. Only approximately half (n = 67 (53.2%)) of the reviews assessed the quality of the included studies. There was a high risk of bias in many of the included reviews, particularly in relation to population representativeness and study attrition. Over 80% (n = 106 (84.1%)) summarized the findings using meta-analysis. Thirty-two (25.4%) studies lacked a formal statement on funding. The predictors with the best test performance were body mass index (BMI) > 35 kg/m , with a specificity of 92% (95% CI, 89-95%) and a sensitivity of 21% (95% CI, 12-31%); BMI > 25 kg/m , with a specificity of 73% (95% CI, 64-83%) and a sensitivity of 47% (95% CI, 33-61%); first-trimester uterine artery pulsatility index or resistance index > 90 centile (specificity 93% (95% CI, 90-96%) and sensitivity 26% (95% CI, 23-31%)); placental growth factor (specificity 89% (95% CI, 89-89%) and sensitivity 65% (95% CI, 63-67%)); and placental protein 13 (specificity 88% (95% CI, 87-89%) and sensitivity 37% (95% CI, 33-41%)). No single marker had a test performance suitable for routine clinical use. Models combining markers showed promise, but none had undergone external validation.
CONCLUSIONS
This review of reviews calls into question the need for further aggregate meta-analysis in this area given the large number of published reviews subject to the common limitations of primary predictive studies. Prospective, well-designed studies of predictive markers, preferably randomized intervention studies, and combined through individual-patient data meta-analysis are needed to develop and validate new prediction models to facilitate the prediction of pre-eclampsia and minimize further research waste in this field. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Adult; Biomarkers; Body Mass Index; Female; Humans; Mass Screening; Meta-Analysis as Topic; Placenta Growth Factor; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Complications; Prospective Studies; Pulsatile Flow; Risk Factors; Sensitivity and Specificity; Ultrasonography; Uterine Artery
PubMed: 30267475
DOI: 10.1002/uog.20117 -
The Cochrane Database of Systematic... Jan 2023Diabetic kidney disease (DKD) continues to be the leading cause of kidney failure across the world. For decades dietary protein restriction has been proposed for... (Review)
Review
BACKGROUND
Diabetic kidney disease (DKD) continues to be the leading cause of kidney failure across the world. For decades dietary protein restriction has been proposed for patients with DKD with the aim to retard the progression of chronic kidney disease (CKD) towards kidney failure. However, the relative benefits and harms of dietary protein restriction for slowing the progression of DKD have not been addressed.
OBJECTIVES
To determine the efficacy and safety of low protein diets (LPD) (0.6 to 0.8 g/kg/day) in preventing the progression of CKD towards kidney failure and in reducing the incidence of kidney failure and death (any cause) in adult patients with DKD. Moreover, the effect of LPD on adverse events (e.g. malnutrition, hyperglycaemic events, or health-related quality of life (HRQoL)) and compliance were also evaluated.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 17 November 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) or quasi-RCTs in which adults with DKD not on dialysis were randomised to receive either a LPD (0.6 to 0.8 g/kg/day) or a usual or unrestricted protein diet (UPD) (≥ 1.0 g/kg/day) for at least 12 months.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies and extracted data. Summary estimates of effect were obtained using a random-effects model. Results were summarised as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised MD (SMD) with 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
We identified eight studies involving 486 participants with DKD. The prescribed protein intake in the intervention groups ranged from 0.6 to 0.8 g/kg/day. The prescribed protein intake in the control groups was ≥ 1.0 g/kg/day, or a calculated protein intake ≥ 1.0 g/kg/day if data on prescribed protein intake were not provided. The mean duration of the interventions was two years (ranging from one to five years). Risks of bias in most of the included studies were high or unclear, most notably for allocation concealment, performance and detection bias. All studies were considered to be at high risk for performance bias due to the nature of the interventions. Most studies were not designed to examine death or kidney failure. In low certainty evidence, a LPD may have little or no effect on death (5 studies, 358 participants: RR 0.38, 95% CI 0.10 to 1.44; I² = 0%), and the number of participants who reached kidney failure (4 studies, 287 participants: RR 1.16, 95% CI 0.38 to 3.59; I² = 0%). Compared to a usual or unrestricted protein intake, it remains uncertain whether a LPD slows the decline of glomerular filtration rate over time (7 studies, 367 participants: MD -0.73 mL/min/1.73 m²/year, 95% CI -2.3 to 0.83; I² = 53%; very low certainty evidence). It is also uncertain whether the restriction of dietary protein intake impacts on the annual decline in creatinine clearance (3 studies, 203 participants: MD -2.39 mL/min/year, 95% CI -5.87 to 1.08; I² = 53%). There was only one study reporting 24-hour urinary protein excretion. In very low certainty evidence, a LPD had uncertain effects on the annual change in proteinuria (1 study, 80 participants: MD 0.90 g/24 hours, 95% CI 0.49 to 1.31). There was no evidence of malnutrition in seven studies, while one study noted this condition in the LPD group. Participant compliance with a LPD was unsatisfactory in nearly half of the studies. One study reported LPD had no effect on HRQoL. No studies reported hyperglycaemic events.
AUTHORS' CONCLUSIONS
Dietary protein restriction has uncertain effects on changes in kidney function over time. However, it may make little difference to the risk of death and kidney failure. Questions remain about protein intake levels and compliance with protein-restricted diets. There are limited data on HRQoL and adverse effects such as nutritional measures and hyperglycaemic events. Large-scale pragmatic RCTs with sufficient follow-up are required for different stages of CKD.
Topics: Adult; Humans; Kidney Failure, Chronic; Diet, Protein-Restricted; Diabetic Nephropathies; Renal Insufficiency, Chronic; Malnutrition; Hyperglycemia; Diabetes Mellitus; Randomized Controlled Trials as Topic
PubMed: 36594428
DOI: 10.1002/14651858.CD014906.pub2 -
The Cochrane Database of Systematic... Oct 2020Electromechanical- and robot-assisted gait-training devices are used in rehabilitation and might help to improve walking after stroke. This is an update of a Cochrane... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Electromechanical- and robot-assisted gait-training devices are used in rehabilitation and might help to improve walking after stroke. This is an update of a Cochrane Review first published in 2007 and previously updated in 2017.
OBJECTIVES
Primary • To determine whether electromechanical- and robot-assisted gait training versus normal care improves walking after stroke Secondary • To determine whether electromechanical- and robot-assisted gait training versus normal care after stroke improves walking velocity, walking capacity, acceptability, and death from all causes until the end of the intervention phase SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched 6 January 2020); the Cochrane Central Register of Controlled Trials (CENTRAL; 2020 Issue 1), in the Cochrane Library; MEDLINE in Ovid (1950 to 6 January 2020); Embase (1980 to 6 January 2020); the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 20 November 2019); the Allied and Complementary Medicine Database (AMED; 1985 to 6 January 2020); Web of Science (1899 to 7 January 2020); SPORTDiscus (1949 to 6 January 2020); the Physiotherapy Evidence Database (PEDro; searched 7 January 2020); and the engineering databases COMPENDEX (1972 to 16 January 2020) and Inspec (1969 to 6 January 2020). We handsearched relevant conference proceedings, searched trials and research registers, checked reference lists, and contacted trial authors in an effort to identify further published, unpublished, and ongoing trials.
SELECTION CRITERIA
We included all randomised controlled trials and randomised controlled cross-over trials in people over the age of 18 years diagnosed with stroke of any severity, at any stage, in any setting, evaluating electromechanical- and robot-assisted gait training versus normal care.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, assessed methodological quality and risk of bias, and extracted data. We assessed the quality of evidence using the GRADE approach. The primary outcome was the proportion of participants walking independently at follow-up.
MAIN RESULTS
We included in this review update 62 trials involving 2440 participants. Electromechanical-assisted gait training in combination with physiotherapy increased the odds of participants becoming independent in walking (odds ratio (random effects) 2.01, 95% confidence interval (CI) 1.51 to 2.69; 38 studies, 1567 participants; P < 0.00001; I² = 0%; high-quality evidence) and increased mean walking velocity (mean difference (MD) 0.06 m/s, 95% CI 0.02 to 0.10; 42 studies, 1600 participants; P = 0.004; I² = 60%; low-quality evidence) but did not improve mean walking capacity (MD 10.9 metres walked in 6 minutes, 95% CI -5.7 to 27.4; 24 studies, 983 participants; P = 0.2; I² = 42%; moderate-quality evidence). Electromechanical-assisted gait training did not increase the risk of loss to the study during intervention nor the risk of death from all causes. Results must be interpreted with caution because (1) some trials investigated people who were independent in walking at the start of the study, (2) we found variation between trials with respect to devices used and duration and frequency of treatment, and (3) some trials included devices with functional electrical stimulation. Post hoc analysis showed that people who are non-ambulatory at the start of the intervention may benefit but ambulatory people may not benefit from this type of training. Post hoc analysis showed no differences between the types of devices used in studies regarding ability to walk but revealed differences between devices in terms of walking velocity and capacity.
AUTHORS' CONCLUSIONS
People who receive electromechanical-assisted gait training in combination with physiotherapy after stroke are more likely to achieve independent walking than people who receive gait training without these devices. We concluded that eight patients need to be treated to prevent one dependency in walking. Specifically, people in the first three months after stroke and those who are not able to walk seem to benefit most from this type of intervention. The role of the type of device is still not clear. Further research should consist of large definitive pragmatic phase 3 trials undertaken to address specific questions about the most effective frequency and duration of electromechanical-assisted gait training, as well as how long any benefit may last. Future trials should consider time post stroke in their trial design.
Topics: Aged; Bias; Cause of Death; Combined Modality Therapy; Confidence Intervals; Electric Stimulation Therapy; Equipment Design; Exercise Therapy; Gait; Humans; Middle Aged; Odds Ratio; Orthotic Devices; Randomized Controlled Trials as Topic; Robotics; Stroke Rehabilitation; Walking; Walking Speed
PubMed: 33091160
DOI: 10.1002/14651858.CD006185.pub5 -
Journal of Clinical Medicine Oct 2021(1) Background: Acute neck pain is common and usually managed by medication and/or manual therapy. General practitioners (GPs) hesitate to refer to manual therapy due to... (Review)
Review
(1) Background: Acute neck pain is common and usually managed by medication and/or manual therapy. General practitioners (GPs) hesitate to refer to manual therapy due to uncertainty about the effectiveness and adverse events (AEs); (2) Method: To review original randomized controlled trials (RCTs) assessing the effect of spinal manipulative therapy (SMT) for acute neck pain. Data extraction was done in duplicate and formulated in tables. Quality and evidence were assessed using the Cochrane Back and Neck (CBN) Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria, respectively; (3) Results: Six studies were included. The overall pooled effect size for neck pain was very large -1.37 (95% CI, -2.41, -0.34), favouring treatments with SMT compared with controls. A single study that showed that SMT was statistically significantly better than medicine (30 mg ketorolac im.) one day post-treatment, ((-2.8 (46%) (95% CI, -2.1, -3.4) vs. -1.7 (30%) (95% CI, -1.1, -2.3), respectively; = 0.02)). Minor transient AEs reported included increased pain and headache, while no serious AEs were reported; (4) Conclusions: SMT alone or in combination with other modalities was effective for patients with acute neck pain. However, limited quantity and quality, pragmatic design, and high heterogeneity limit our findings.
PubMed: 34768531
DOI: 10.3390/jcm10215011 -
Journal of Thrombosis and Thrombolysis Feb 2023Tenecteplase (TNK) is a promising candidate to replace alteplase as the standard of care for acute ischemic stroke (AIS); however, the optimal dosage is still to be... (Meta-Analysis)
Meta-Analysis Review
The efficacy and safety of tenecteplase versus alteplase for acute ischemic stroke: an updated systematic review, pairwise, and network meta-analysis of randomized controlled trials.
Tenecteplase (TNK) is a promising candidate to replace alteplase as the standard of care for acute ischemic stroke (AIS); however, the optimal dosage is still to be investigated. Therefore, we aim to evaluate the safety and efficacy of TNK versus alteplase and to investigate the optimal TNK dosage. A systematic review, pairwise, and network meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, SCOPUS, EMBASE, and PubMed until July 26, 2022. We used the risk ratio (RR) for dichotomous outcomes presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022352038. Nine RCTs with a total of 3,707 patients were included. TNK significantly led to complete recanalization (RR: 1.27 with 95% CI [1.02, 1.57], P = 0.03); however, we found no difference regarding early neurological improvement (RR: 1.07 with 95% CI [0.94, 1.21], P = 0.33) and excellent neurological recovery (RR: 1.03 with 95% CI [0.96, 1.10], P = 0.42). Also, TNK was similar to alteplase regarding mortality (RR: 0.99 with 95% CI [0.82, 1.18], P = 0.88), intracranial haemorrhage (RR: 1.00 with 95% CI [0.85, 1.18], P = 0.99), and parenchymal hematoma (RR: 1.13 with 95% CI [0.83, 1.54], P = 0.44). TNK in the dose of 0.25 mg is a viable candidate to displace alteplase as the standard of care in patients with an AIS within 4.5 h of presentation due to its better rate of early neurological recovery and non-inferiority in terms of safety outcomes. However, the evidence regarding TNK's role in AIS presenting after 4.5 h from symptoms onset, wake-up stroke, and minor stroke/TIA is still lacking, necessitating further double-blinded pragmatic RCTs in this regard.
Topics: Humans; Tissue Plasminogen Activator; Tenecteplase; Fibrinolytic Agents; Network Meta-Analysis; Randomized Controlled Trials as Topic; Stroke; Ischemic Stroke; Treatment Outcome; Brain Ischemia
PubMed: 36449231
DOI: 10.1007/s11239-022-02730-5 -
Journal of the American Academy of... Oct 2021Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma.
BACKGROUND
Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma.
OBJECTIVE
This analysis examined the literature related to the management of AK to provide evidence-based recommendations for treatment. Grading, histologic classification, natural history, risk of progression, and dermatologic surveillance of AKs are also discussed.
METHODS
A multidisciplinary Work Group conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus.
RESULTS
Analysis of the evidence resulted in 18 recommendations.
LIMITATIONS
This analysis is based on the best available evidence at the time it was conducted. The pragmatic decision to limit the literature review to English language randomized trials may have excluded data published in other languages or limited identification of relevant long-term follow-up data.
CONCLUSIONS
Strong recommendations are made for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are made for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.
Topics: Diclofenac; Fluorouracil; Humans; Imiquimod; Keratosis, Actinic; Photochemotherapy
PubMed: 33820677
DOI: 10.1016/j.jaad.2021.02.082 -
CNS Drugs May 2021Long-acting injectable (LAI) antipsychotics, compared with oral antipsychotics (OA), have been found to significantly improve patient outcomes, including reduced... (Comparative Study)
Comparative Study Meta-Analysis
Real-World Evidence of the Clinical and Economic Impact of Long-Acting Injectable Versus Oral Antipsychotics Among Patients with Schizophrenia in the United States: A Systematic Review and Meta-Analysis.
BACKGROUND
Long-acting injectable (LAI) antipsychotics, compared with oral antipsychotics (OA), have been found to significantly improve patient outcomes, including reduced hospitalizations and emergency room (ER) admissions and increased medication adherence among adult patients with schizophrenia. In turn, the clinical benefits achieved may translate into lower economic burden. Real-world evidence of the comparative effectiveness of LAI is needed to understand the potential benefits of LAI outside of the context of clinical trials. This study aimed to provide a comprehensive synthesis of recent published real-world studies comparing healthcare utilization, costs, and adherence between patients with schizophrenia treated with LAI versus OA in the United States.
METHODS
In this systematic literature review, MEDLINE was searched for peer-reviewed, real-world studies (i.e., retrospective or pragmatic designs) published in English between January 1, 2010 and February 10, 2020. Comparative studies reporting hospitalizations, ER admissions, healthcare costs, or medication adherence (measured by proportion of days covered [PDC]) in adults with schizophrenia treated with LAI versus OA (or pre- vs post-LAI initiation) in the United States were retained. Random effects meta-analyses were conducted among eligible studies to evaluate the association of LAI versus OA use on hospitalizations, ER admissions, healthcare costs, and treatment adherence. A sensitivity analysis among the subset of studies that compared OA with paliperidone palmitate once monthly (PP1M), specifically, was conducted.
RESULTS
A total of 1083 articles were identified by the electronic literature search, and two publications were manually added subsequently. Among the 57 publications meeting the inclusion criteria, 25 provided sufficient information for inclusion in the meta-analyses. Compared with patients treated with OA, patients initiated on LAI had lower odds of hospitalization (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.54-0.71, n = 7), fewer hospitalizations (incidence rate ratio [IRR] [95% CI] 0.75 [0.65-0.88], n = 9), and fewer ER admissions (IRR [95% CI] 0.86 [0.77-0.97], n = 6). The initiation of LAI was associated with higher per-patient-per-year (PPPY) pharmacy costs (mean difference [MD] [95% CI] $5603 [3799-7407], n = 6), which was offset by lower PPPY medical costs (MD [95% CI] - $5404 [- 7745 to - 3064], n = 6), resulting in no significant net difference in PPPY total all-cause healthcare costs between patients treated with LAI and those treated with OA (MD [95% CI] $327 [- 1565 to 2219], n = 7). Patients initiated on LAI also had higher odds of being adherent to their medication (PDC ≥ 80%; OR [95% CI] 1.89 [1.52-2.35], n = 9). A sensitivity analysis on a subset of publications evaluating PP1M found results similar to those of the main analysis conducted at the LAI class level.
CONCLUSIONS
Based on multiple studies with varying sub-types of patient populations with schizophrenia in the United States published in the last decade, this meta-analysis demonstrated that LAI antipsychotics were associated with improved medication adherence and significant clinical benefit such as reduced hospitalizations and ER admissions compared with OA. The lower medical costs offset the higher pharmacy costs, resulting in a non-significant difference in total healthcare costs. Taken together, these findings provide strong evidence on the clinical and economic benefits of LAI compared with OA for the treatment of schizophrenia in the real world.
Topics: Antipsychotic Agents; Delayed-Action Preparations; Emergency Service, Hospital; Health Care Costs; Hospitalization; Humans; Injections; Medication Adherence; Schizophrenia; United States
PubMed: 33909272
DOI: 10.1007/s40263-021-00815-y