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Therapeutic Advances in... 2024Long-acting injectable antipsychotics (LAIs) have advantages over oral antipsychotics (OAPs) in preventing relapse and hospitalization in chronically ill patients with...
Efficacy and safety of long-acting injectable oral antipsychotics in the treatment of patients with early-phase schizophrenia-spectrum disorders: a systematic review and meta-analysis.
BACKGROUND
Long-acting injectable antipsychotics (LAIs) have advantages over oral antipsychotics (OAPs) in preventing relapse and hospitalization in chronically ill patients with schizophrenia-spectrum disorders (SSDs), but evidence in patients with first-episode/recent-onset, that is, early-phase-SSDs is less clear.
OBJECTIVES
To assess the relative medium- and long-term efficacy and safety of LAIs OAPs in the maintenance treatment of patients with early-phase SSDs.
METHOD
We searched major electronic databases for head-to-head randomized controlled trials (RCTs) comparing LAIs and OAPs for the maintenance treatment of patients with early-phase-SSDs.
DESIGN
Pairwise, random-effects meta-analysis. Relapse/hospitalization and acceptability (all-cause discontinuation) measured at study-endpoint were co-primary outcomes, calculating risk ratios (RRs) with their 95% confidence intervals (CIs). Subgroup analyses sought to identify factors moderating differences in efficacy or acceptability between LAIs and OAPs.
RESULTS
Across 11 head-to-head RCTs ( = 2374, median age = 25.2 years, males = 68.4%, median illness duration = 45.8 weeks) lasting 13-104 (median = 78) weeks, no significant differences emerged between LAIs and OAPs for relapse/hospitalization prevention (RR = 0.79, 95%CI = 0.58-1.06, = 0.13) and acceptability (RR = 0.92, 95%CI = 0.80-1.05, = 0.20). The included trials were highly heterogeneous regarding methodology and patient populations. LAIs outperformed OAPs in preventing relapse/hospitalization in studies with stable patients (RR = 0.65, 95%CI = 0.45-0.92), pragmatic design (RR = 0.67, 95%CI = 0.54-0.82), and strict intent-to-treat approach (RR = 0.64, 95%CI = 0.52-0.80). Furthermore, LAIs were associated with better acceptability in studies with schizophrenia patients only (RR = 0.87, 95%CI = 0.79-0.95), longer illness duration (RR = 0.88, 95%CI = 0.80-0.97), unstable patients (RR = 0.89, 95%CI = 0.81-0.99) and allowed OAP supplementation of LAIs (RR = 0.90, 95%CI = 0.81-0.99).
CONCLUSION
LAIs and OAPs did not differ significantly regarding relapse prevention/hospitalization and acceptability. However, in nine subgroup analyses, LAIs were superior to OAPs in patients with EP-SSDs with indicators of higher quality and/or pragmatic design regarding relapse/hospitalization prevention (four subgroup analyses) and/or reduced all-cause discontinuation (five subgroup analyses), without any instance of OAP superiority LAIs. More high-quality pragmatic trials comparing LAIs with OAPs in EP-SSDs are needed.
TRIAL REGISTRATION
CRD42023407120 (PROSPERO).
PubMed: 38831918
DOI: 10.1177/20451253241257062 -
Hypertension Research : Official... Jun 2024The efficacy of renal denervation (RDN) has been controversial, but recent randomized sham-controlled trials demonstrated significant blood pressure reductions after RDN...
The efficacy of renal denervation (RDN) has been controversial, but recent randomized sham-controlled trials demonstrated significant blood pressure reductions after RDN in patients with hypertension. We conducted a systematic review and updated meta-analysis to evaluate the effects of RDN on ambulatory and office blood pressures in patients with hypertension. Databases were searched up to 15 November 2023 to identify randomized, sham-controlled trials of RDN. The primary endpoint was change in 24 h ambulatory systolic blood pressure (SBP) with RDN versus sham control. The secondary endpoints were changes in 24 h ambulatory diastolic blood pressure, daytime and nighttime blood pressure (BP), office BP, and home BP. A sub-analysis determined outcomes by medication, procedure, and device. From twelve trials, 2222 patients with hypertension were randomized to undergo RDN (n = 1295) or a sham procedure (n = 927). At 2-6 months after treatment, RDN significantly reduced 24 h ambulatory SBP by 2.81 mmHg (95% confidence interval: -4.09, -1.53; p < 0.001) compared with the sham procedure. RDN also reduced daytime SBP by 3.17 mmHg (- 4.75, - 1.58; p < 0.001), nighttime SBP by 3.41 mmHg (- 4.69, - 2.13; p < 0.001), office SBP by 4.95 mmHg (- 6.37, - 3.54; p < 0.001), and home SBP by 4.64 mmHg (- 7.44, - 1.84; p = 0.001) versus the sham control group. There were no significant differences in the magnitude of BP reduction between first- and second-generation trials, between devices, or between with or without medication. These data from randomized sham-controlled trials showed that RDN significantly reduced all blood pressure metrics in medicated or unmedicated patients with hypertension, including resistant/uncontrolled hypertension.
PubMed: 38831091
DOI: 10.1038/s41440-024-01739-y -
Clinical Nutrition (Edinburgh, Scotland) Jul 2024The AHA/ASA guidelines for primary stroke prevention are almost a decade old. The current recommendation regarding folic acid supplementation is based on only 8 clinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
The AHA/ASA guidelines for primary stroke prevention are almost a decade old. The current recommendation regarding folic acid supplementation is based on only 8 clinical trials, and an additional 13 folate trials have been published since then. This meta-analysis aims to fill in critical evidence gaps by comprehensively evaluating 21 published trials with particular attention given to identifying the true influences through stratification.
METHODS
PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched from inception to April 4, 2023. This study included all randomized controlled trials (RCTs) of folic acid with stroke as one of the reporting endpoints. Relative risks and 95% confidence intervals were used to assess the association between folic acid supplementation and the risk of stroke in a random-effects model.
RESULTS
Results from the 21 pooled RCTs totaling 115,559 participants showed that folic acid supplementation significantly reduced the risk of stroke by 10% (RR 0.90, 95%CI 0.83 to 0.98). Subgroup analyses showed that folic acid efficacy was greater in areas without fortified grain or with partially-fortified grain (RR = 0.83, 95% CI 0.75 to 0.93; RR = 1.04 in areas with grain fortification, P-interaction = 0.003). In this group, folic acid supplementation was most efficacious in those without a history of stroke or myocardial infarction (RR = 0.77, 95% CI 0.68 to 0.86; RR = 0.94 for participants with a history of stroke or myocardial infarction, P-interaction = 0.008). The efficacy of folic acid remained consistent regardless of baseline folate levels, folic acid dosage, baseline vitamin B12 levels, vitamin B12 dosage, homocysteine reduction, intervention duration, and whether folic acid was taken alone or in combination (all P-interaction>0.05). All 21 trials were free of attrition bias and reporting bias, and there was no significant publication bias.
CONCLUSIONS
This is by far the largest meta-analysis of RCTs regarding folic acid supplementation and stroke, demonstrating the overall benefit of folic acid for stroke prevention. Grain fortification and history of stroke or myocardial infarction may be the most important influences on the efficacy of folic acid for stroke prevention.
Topics: Folic Acid; Humans; Stroke; Dietary Supplements; Randomized Controlled Trials as Topic
PubMed: 38824900
DOI: 10.1016/j.clnu.2024.05.034 -
Clinical Microbiology and Infection :... May 2024Current guidelines recommend at least two weeks duration of antibiotic therapy (DOT) for patients with uncomplicated Staphylococcus aureus bacteraemia (SAB) but the... (Review)
Review
BACKGROUND
Current guidelines recommend at least two weeks duration of antibiotic therapy (DOT) for patients with uncomplicated Staphylococcus aureus bacteraemia (SAB) but the evidence for this recommendation is unclear.
OBJECTIVES
To perform a systematic literature review assessing current evidence for recommended DOT for patients with SAB.
METHODS
Data sources: We searched MEDLINE, ISI Web of Science, the Cochrane Database and clinicaltrials.gov from inception to March 30, 2024. References of eligible studies were screened and experts in the field contacted for additional articles.
STUDY ELIGIBILITY CRITERIA
All clinical studies, regardless of design, publication status and language.
PARTICIPANTS
Adult patients with uncomplicated SAB.
INTERVENTIONS
Long (>14; >18; 11-16 days) vs. short (≤14; 10-18; 6-10 days, respectively) DOT with the DOT being defined as the first until the last day of antibiotic therapy.
ASSESSMENT OF RISK OF BIAS
Risk of bias was assessed using the ROBINS-I-tool.
METHODS OF DATA SYNTHESIS
The primary outcome was 90-day all-cause mortality. Only studies presenting results of adjusted analyses for mortality were included. Data synthesis could not be performed.
RESULTS
Eleven non-randomized studies were identified that fulfilled the predefined inclusion criteria, of which three studies reported adjusted effect ratios. Only these were included in the final analysis. We did not find any RCT. Two studies with 1,230 patients reported the primary endpoint 90-day all-cause mortality. Neither found a statistically significant superiority for longer (>14; 11-16 days) or shorter DOT (≤14; 6-10 days, respectively) for patients with uncomplicated SAB. Two studies investigated the secondary endpoint 30-day all-cause mortality (>18; 11-16 days vs. 10-18; 6-10 days, respectively) and did not find a statistically significant difference. All included studies had a moderate risk of bias.
CONCLUSIONS
Sound evidence that supports any duration of antibiotic treatment for patients with uncomplicated SAB is lacking.
PubMed: 38823452
DOI: 10.1016/j.cmi.2024.05.015 -
Neurosurgical Focus Jun 2024The purpose of this systematic review was to evaluate empirical outcomes of studies in the literature that investigated effectiveness of intrathecal baclofen (ITB) in...
OBJECTIVE
The purpose of this systematic review was to evaluate empirical outcomes of studies in the literature that investigated effectiveness of intrathecal baclofen (ITB) in the treatment of multiple sclerosis (MS)-related spasticity (MSRS) based on various metrics. Since the first description of this route of baclofen delivery for MS patients by Penn and Kroin in 1984, numerous studies have contributed to the medical community's knowledge of this treatment modality. The authors sought to add to the literature a systematic review of studies over the last 2 decades that elucidates the clinical impact of ITB in treating MSRS with the following endpoints: impact on patient-centered outcomes, such as spasticity reduction (primary), complications (secondary), and dosing (secondary).
METHODS
The authors queried three databases (PubMed, Scopus, and Cochrane Library) using the following search terms: (intrathecal baclofen) AND (multiple sclerosis). The set inclusion criteria were as follows: 1) original, full-text article; 2) written in the English language; 3) published between and including the years 2000 and 2023; 4) discussion of pre- and post-ITB pump implantation outcomes (e.g., reduction in spasticity and improved comfort) in MSRS patients with long-term ITB treatment; and 5) contained a minimum of 5 MS patients. Data on study type, patient demographics, follow-up periods, primary outcomes, and secondary outcomes were extracted from the included studies.
RESULTS
The authors' search yielded 465 studies, of which 17 met inclusion criteria. Overall, they found evidence for the effectiveness of ITB in treating MSRS patients whose condition was refractory to oral medications, with significant reported changes in spasm frequency from pre- to postimplantation. They also found evidence supporting the positive impact of ITB on MSRS patients' quality of life. Moreover, the authors found that most complications were surgical rather than pharmacological. In addition, the average 1-year dose of ITB (reported in 7 of the included studies) was 191.93 μg/day, which is substantially lower than ITB doses reported in the literature for patients with central (non-MS) or spinal origins of spasticity at 1-year follow-up.
CONCLUSIONS
The evidence supports ITB as a clinically effective treatment for MSRS, particularly in patients in whom oral antispasmodics and physiotherapy have failed. This systematic review contributes a comprehensive synthesis of clinical benefits, complications, and dosing of ITB reported over the past 2 decades, which furthers an understanding of ITB's clinical utility in practice.
Topics: Baclofen; Humans; Multiple Sclerosis; Injections, Spinal; Muscle Spasticity; Muscle Relaxants, Central; Treatment Outcome
PubMed: 38823049
DOI: 10.3171/2024.3.FOCUS2464 -
Minerva Urology and Nephrology May 2024The optimal temperature of irrigation solution in patients undergoing PCNL is still unclear. Accordingly, this study aims to investigate the effects of different...
Effect of irrigation solution temperature on complications of percutaneous nephrolithotomy: a systematic review of the literature, meta-analysis and trial sequential analysis of randomized clinical trials.
INTRODUCTION
The optimal temperature of irrigation solution in patients undergoing PCNL is still unclear. Accordingly, this study aims to investigate the effects of different irrigation solution temperatures (cold/room temperature irrigation fluid versus warm/body temperature fluid). Our primary endpoint was hypothermia rate. Secondary outcomes were shivering rate, mean temperature decrease, mean patient final temperature, blood loss, and operative time.
EVIDENCE ACQUISITION
This systematic review was conducted in accordance with PRISMA guidelines. Multiple databases were searched in November 2023. Among 299 studies screened, eight were selected for full-text review, resulting in four randomized clinical trials that fit inclusion criteria and desired outcomes. Studies selection and data extraction were performed by multiple reviewers and a random-effects model was used for pooling of data.
EVIDENCE SYNTHESIS
The primary outcome, hypothermia rate, showed a significant statistical difference between groups, occurring less frequently in the experimental group (35-37 ºC) than in the cold/room temperature irrigation group (RR 0.64;95%CI 0.46, 0.89; P<0.008; I=33%). Secondary outcomes such as shivering rate (RR 0.46; 95%CI 0.31, 0.67; P<0.0001; I=0%) and mean final temperatures (MD 0.43; 95%CI 0.12, 0.75; I=82%) also showed statistically significant differences between groups, favoring the irrigation with heated fluid.
CONCLUSIONS
There was a decreased rate of hypothermia and shivering among patients undergoing PCNL with warm irrigation fluid. Mean final temperatures were also higher in the experimental group. As to blood loss, mean hemoglobin decrease showed no statistically significant difference between groups, prompting further investigation of the influence of Irrigation solution temperature on blood loss volume.
PubMed: 38819387
DOI: 10.23736/S2724-6051.24.05731-8 -
The British Journal of Dermatology May 2024Primary endpoint measures in clinical trials are typically measures of disease severity, with patient reported outcome measures (PROMs) relegated as secondary endpoints....
BACKGROUND
Primary endpoint measures in clinical trials are typically measures of disease severity, with patient reported outcome measures (PROMs) relegated as secondary endpoints. However validation of some PROMs may be more rigorous than that of disease severity measures, arguing for a primary role for PROMs.
OBJECTIVES
This study reports on 24 peer reviewed journal articles that used the Dermatology Life Quality Index (DLQI) as primary outcome, derived from a systematic review of randomised controlled trials (RCTs) utlising DLQI covering all diseases and interventions.
MATERIALS AND METHOD
The study protocol was prospectively published on the PROSPERO database, and the study followed PRISMA guidelines. Searches were made with Medline, Cochrane library, EMBASE, Web of Science, SCOPUS, CINAHL(EBSCO) and PsycINFO databases and records combined into an Endnote database. Records were filtered for duplicates and selected by study inclusion/exclusion criteria. Full text articles were sourced and data was extracted by two reviewers into a bespoke REDCap database, with a third reviewer adjudicating differences. The Jadad scoring method was used to determine risk of bias.
RESULTS
Of the 3,220 publications retrieved from online searching, 457 articles met eligibility criteria and included 198,587 patients. DLQI scores were primary outcomes in 24 (5.3%) of these studies comprising 15 different diseases and 3,436 patients. Most study interventions (17/24 studies, 68%) were systemic drugs with biologics (liraglutide, alefacept, secukinumab, ustekinumab, adalimumab) accounting for five out of 25 pharmacological interventions (20%). Topical treaments comprised 32% (8 studies) whereas non-pharmacological interventions (8) were 24% of the total interventions (33). Three studies used non-traditional medicines. Eight studies were multicentred (33.3%), with trials conducted in at least 14 different countries, and four (16.7%) were conducted in multiple countries. The Jadad risk of bias scale showed that bias was uncertain or low, as 87.5% of studies had Jadad scores of ≥3.
CONCLUSIONS
This study provides evidence for use of the DLQI as primary outcome in clinical trials to inform researchers' and clinicians' decisions for its further use.
PubMed: 38819233
DOI: 10.1093/bjd/ljae228 -
BJS Open May 2024Postoperative pancreatic fistulas remain a driver of major complications after partial pancreatectomy. It is unclear whether coverage of the anastomosis or pancreatic... (Meta-Analysis)
Meta-Analysis
Effect of artificial or autologous coverage of the pancreatic remnant or anastomosis on postoperative pancreatic fistulas after partial pancreatectomy: meta-analysis of randomized clinical trials.
BACKGROUND
Postoperative pancreatic fistulas remain a driver of major complications after partial pancreatectomy. It is unclear whether coverage of the anastomosis or pancreatic remnant can reduce the incidence of postoperative pancreatic fistulas. The aim of this study was to evaluate the effect of autologous or artificial coverage of the pancreatic remnant or anastomosis on outcomes after partial pancreatectomy.
METHODS
A systematic literature search was performed using MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL) up to March 2024. All RCTs analysing a coverage method in patients undergoing partial pancreatoduodenectomy or distal pancreatectomy were included. The primary outcome was postoperative pancreatic fistula development. Subgroup analyses for pancreatoduodenectomy or distal pancreatectomy and artificial or autologous coverage were conducted.
RESULTS
A total of 18 RCTs with 2326 patients were included. In the overall analysis, coverage decreased the incidence of postoperative pancreatic fistulas by 29% (OR 0.71, 95% c.i. 0.54 to 0.93, P < 0.01). This decrease was also seen in the 12 RCTs covering the remnant after distal pancreatectomy (OR 0.69, 95% c.i. 0.51 to 0.94, P < 0.02) and the 4 RCTs applying autologous coverage after pancreatoduodenectomy and distal pancreatectomy (OR 0.53, 95% c.i. 0.29 to 0.96, P < 0.04). Other subgroup analyses (artificial coverage or pancreatoduodenectomy) showed no statistically significant differences. The secondary endpoints of mortality, reoperations, and re-interventions were each affected positively by the use of coverage techniques. The certainty of evidence was very low to moderate.
CONCLUSION
The implementation of coverage, whether artificial or autologous, is beneficial after partial pancreatectomy, especially in patients undergoing distal pancreatectomy with autologous coverage.
Topics: Humans; Pancreatic Fistula; Pancreatectomy; Randomized Controlled Trials as Topic; Postoperative Complications; Anastomosis, Surgical; Pancreaticoduodenectomy; Pancreas
PubMed: 38814751
DOI: 10.1093/bjsopen/zrae059 -
Musculoskeletal Surgery May 2024The purpose of this study was to systematically review and meta-analyze randomized controlled trials (RCTs) reporting the comparative clinical and functional outcomes,... (Review)
Review
Transtibial versus anteromedial transportal femoral tunnel in single-bundle anterior cruciate ligament reconstruction: a systematic review and meta-analysis of prospective randomized controlled trials.
The purpose of this study was to systematically review and meta-analyze randomized controlled trials (RCTs) reporting the comparative clinical and functional outcomes, postoperative complications, and radiological outcomes of single-bundle anterior cruciate ligament reconstruction (ACLR) performed using the transtibial (TT) approach or anteromedial (AM) technique. A systematic review of the literature was performed according to Cochrane and PRISMA guidelines. RCTs comparing TT and AM techniques were considered only. The quality of the studies was defined using the GRADE system, and the risk of bias was assessed with the RoB 2 tool. The primary endpoint was to systematically review and meta-analyze the clinical outcomes, residual laxity and failure rate of both AM and TT techniques. In the current meta-analysis 13 RCTs involving 989 patients who underwent arthroscopic single-bundle ACLR (486 TT and 503 AM) were included. Patients undergoing AM technique resulted in higher objective-IKDC (p < 0.001) and Lysholm scores (p = 0.002), despite a lower incidence of pathological anterior tibial translation (p < 0.001) and positive pivot-shift test (p < 0.001). No differences were detected in IKDC subjective score (p = 0.26), Tegner activity scale (p = 0.18) and graft failure (p = 0.07). ACL reconstruction through AM portal technique provides better clinical outcomes and lower incidence of residual rotational and anteroposterior laxity in comparison with the TT technique. No statistically significant difference in subjective outcomes and graft failure was reported.
PubMed: 38814430
DOI: 10.1007/s12306-024-00823-3 -
Abdominal Radiology (New York) May 2024This review aims to provide a comprehensive summary of DECT techniques, acquisition workflows, and post-processing methods. By doing so, we aim to elucidate the...
PURPOSE
This review aims to provide a comprehensive summary of DECT techniques, acquisition workflows, and post-processing methods. By doing so, we aim to elucidate the advantages and disadvantages of DECT compared to conventional single-energy CT imaging.
METHODS
A systematic search was conducted on MEDLINE/EMBASE for DECT studies in liver imaging published between 1980 and 2024. Information regarding study design and endpoints, patient characteristics, DECT technical parameters, radiation dose, iodinated contrast agent (ICA) administration and postprocessing methods were extracted. Technical parameters, including DECT phase, field of view, pitch, collimation, rotation time, arterial phase timing (from injection), and venous timing (from injection) from the included studies were reported, along with formal narrative synthesis of main DECT applications for liver imaging.
RESULTS
Out of the initially identified 234 articles, 153 met the inclusion criteria. Extensive variability in acquisition parameters was observed, except for tube voltage (80/140 kVp combination reported in 50% of articles) and ICA administration (1.5 mL/kg at 3-4 mL/s, reported in 91% of articles). Radiation dose information was provided in only 40% of articles (range: 6-80 mGy), and virtual non-contrast imaging (VNC) emerged as a common strategy to reduce the radiation dose. The primary application of DECT post-processed images was in detecting focal liver lesions (47% of articles), with predominance of study focusing on hepatocellular carcinoma (HCC) (27%). Furthermore, a significant proportion of the articles (16%) focused on enhancing DECT protocols, while 15% explored metastasis detection.
CONCLUSION
Our review recommends using 80/140 kVp tube voltage with 1.5 mL/kg ICA at 3-4 mL/s flow rate. Post-processing should include low keV-VMI for enhanced lesion detection, IMs for tumor iodine content evaluation, and VNC for dose reduction. However, heterogeneous literature hinders protocol standardization.
PubMed: 38811447
DOI: 10.1007/s00261-024-04380-y