-
Transplant Infectious Disease : An... Aug 2023Cytomegalovirus (CMV) is a frequent infectious complication following solid organ transplantation (SOT). Considering significant differences in healthcare systems, a...
Epidemiology, management, and burden of cytomegalovirus in solid organ transplant recipients in selected countries outside of Europe and North America: A systematic review.
BACKGROUND
Cytomegalovirus (CMV) is a frequent infectious complication following solid organ transplantation (SOT). Considering significant differences in healthcare systems, a systematic review was conducted to describe the epidemiology, management, and burden of CMV post-SOT in selected countries outside of Europe and North America.
METHODS
MEDLINE, Embase, and Cochrane databases were searched for observational studies in SOT recipients across 15 countries in the regions of Asia, Pacific, and Latin America (search period: January 1, 2011 to September 17, 2021). Outcomes included incidence of CMV infection/disease, recurrence, risk factors, CMV-related mortality, treatment patterns and guidelines, refractory and/or resistant CMV, patient-reported outcomes, and economic burden.
RESULTS
Of 2708 studies identified, 49 were eligible (n = 43/49; 87.8% in adults; n = 34/49, 69.4% in kidney recipients). Across studies, selection of CMV preventive strategy was based on CMV serostatus. Overall, rates of CMV infection (within 1 year) and CMV disease post-SOT were respectively, 10.3%-63.2% (9 studies) and 0%-19.0% (17 studies). Recurrence occurred in 35.4%-41.0% cases (3 studies) and up to 5.3% recipients died of CMV-associated causes (11 studies). Conventional treatments for CMV infection/disease included ganciclovir (GCV) or valganciclovir. Up to 4.4% patients were resistant to treatment (3 studies); no studies reported on refractory CMV. Treatment-related adverse events with GCV included neutropenia (2%-29%), anemia (13%-48%), leukopenia (11%-37%), and thrombocytopenia (13%-24%). Data on economic burden were scarce.
CONCLUSION
Outside of North America and Europe, rates of CMV infection/disease post-SOT are highly variable and CMV recurrence is frequent. CMV resistance and treatment-associated adverse events, including myelosuppression, highlight unmet needs with conventional therapy.
Topics: Adult; Humans; Cytomegalovirus; Cytomegalovirus Infections; Europe; North America; Ganciclovir; Organ Transplantation; Leukopenia
PubMed: 37254966
DOI: 10.1111/tid.14070 -
Annals of Neurology Sep 2023We sought to better understand the workflow, outcomes, and complications of deep brain stimulation (DBS) for pediatric status dystonicus (SD). We present a systematic...
OBJECTIVE
We sought to better understand the workflow, outcomes, and complications of deep brain stimulation (DBS) for pediatric status dystonicus (SD). We present a systematic review, alongside a multicenter case series of pediatric patients with SD treated with DBS.
METHODS
We collected individual data regarding treatment, stimulation parameters, and dystonia severity for a multicenter case series (n = 8) and all previously published cases (n = 77). Data for case series were used to create probabilistic voxelwise maps of stimulated tissue associated with dystonia improvement.
RESULTS
In our institutional series, DBS was implanted a mean of 25 days after SD onset. Programming began a mean of 1.6 days after surgery. All 8 patients in our case series and 73 of 74 reported patients in the systematic review had resolution of their SD with DBS, most within 2 to 4 weeks of surgery. Mean follow-up for patients in the case series was 16 months. DBS target for all patients in the case series and 68 of 77 in our systematic review was the globus pallidus pars interna (GPi). In our case series, stimulation of the posterior-ventrolateral GPi was associated with improved dystonia. Mean dystonia improvement was 32% and 51% in our institutional series and systematic review, respectively. Mortality was 4% in the review, which is lower than reported for treatment with pharmacotherapy alone (10-12.5%).
INTERPRETATION
DBS is a feasible intervention with potential to reverse refractory pediatric SD and improve survival. More work is needed to increase awareness of DBS in this setting, so that it can be implemented in a timely manner. ANN NEUROL 2023.
PubMed: 37714824
DOI: 10.1002/ana.26799 -
Cureus Oct 2023The optimal fluid management strategy for patients with sepsis remains a topic of debate. This meta-analysis aims to evaluate the impact of restrictive versus liberal... (Review)
Review
The optimal fluid management strategy for patients with sepsis remains a topic of debate. This meta-analysis aims to evaluate the impact of restrictive versus liberal fluid regimens on mortality, adverse events, and other clinical outcomes in patients with sepsis. We systematically reviewed 11 randomized controlled trials published between 2008 and 2023, comprising a total of 4,121 participants. The studies assessed 90-day mortality, 30-day mortality, adverse events, hospital length of stay, ICU admission rate, mechanical ventilation, ventilator-free days, ICU-free days, and vasopressor-free days. Quality assessments indicated minimal bias across the studies. The meta-analysis showed no statistically significant difference in 90-day mortality between restrictive and liberal fluid regimens (OR, 0.93; 95% CI, 0.80 to 1.70; P=0.30). Similar results were observed for 30-day mortality (OR, 0.73; 95% CI, 0.30 to 1.80; P=0.50). Adverse events were comparable between the two groups (OR, 0.81; 95% CI, 0.55 to 1.19; P=0.28). Furthermore, there were no significant differences in hospital length of stay (OR, 0.47; 95% CI, -0.85 to 1.80; P=0.48) or ICU admission rate (OR, 1.09; 95% CI, 0.66 to 1.77; P=0.75) between the restrictive and liberal fluid regimens. Regarding mechanical ventilation and ventilator-free days, no significant distinctions were observed (OR, 0.87; 95% CI, 0.65 to 1.17; P=0.48; OR, 0.99; 95% CI, -0.17 to 2.15; P=0.09, respectively). ICU-free days and vasopressor-free days also showed no significant differences between the two groups (OR, 0.97; 95% CI, -0.28 to 2.21; P=0.13; OR, -0.38; 95% CI, -1.14 to 0.37; P=0.32, respectively). This comprehensive meta-analysis of clinical trials suggests that restrictive and liberal fluid management strategies have comparable outcomes in patients with sepsis, including mortality, adverse events, and various clinical parameters. However, most studies favored restrictive fluid regimen over liberal approach regarding the number of vasopressor-free days, need for mechanical ventilation, adverse events, 30-day mortality, and 90-day mortality in sepsis patients.
PubMed: 37899903
DOI: 10.7759/cureus.47783 -
Advances in Rheumatology (London,... Jul 2023Our aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi... (Meta-Analysis)
Meta-Analysis
Compared efficacy of rituximab, abatacept, and tocilizumab in patients with rheumatoid arthritis refractory to methotrexate or TNF inhibitors agents: a systematic review and network meta-analysis.
BACKGROUND
Our aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi agents.
METHODS
We searched 6 databases until January 2023 for phase 2-4 RCTs evaluating patients with RA refractory to MTX or TNFi therapy treated with rituximab, abatacept, and tocilizumab (intervention arm) compared to controls. Study data were independently assessed by two investigators. The primary outcome was considered as achieving ACR70 response.
RESULTS
The meta-analysis included 19 RCTs, with 7,835 patients and a mean study duration of 1.2 years. Hazard ratios for achieving an ACR70 response at six months were not different among the bDMARDs, however, we found high heterogeneity. Three factors showing a critical imbalance among the bDMARD classes were identified: baseline HAQ score, study duration, and frequency of TNFi treatment in control arm. Multivariate meta-regression adjusted to these three factors were conducted for the relative risk (RR) for ACR70. Thus, heterogeneity was attenuated (I2 = 24%) and the explanatory power of the model increased (R2 = 85%). In this model, rituximab did not modify the chance of achieving an ACR70 response compared to abatacept (RR = 1.773, 95%CI 0.113-10.21, p = 0.765). In contrast, abatacept was associated with RR = 2.217 (95%CI 1.554-3.161, p < 0.001) for ACR70 compared to tocilizumab.
CONCLUSION
We found high heterogeneity among studies comparing rituximab, abatacept, and tocilizumab. On multivariate metaregressions, if the conditions of the RCTs were similar, we estimate that abatacept could increase the chance of reaching an ACR70 response by 2.2-fold compared to tocilizumab.
Topics: Humans; Abatacept; Rituximab; Methotrexate; Tumor Necrosis Factor Inhibitors; Antirheumatic Agents; Network Meta-Analysis; Arthritis, Rheumatoid
PubMed: 37415193
DOI: 10.1186/s42358-023-00298-z -
European Journal of Neurology Aug 2023Treatment options for chronic inflammatory demyelinating polyneuropathy (CIDP) are intravenous immunoglobulin, plasmapheresis, corticosteroids and immunosuppressive... (Meta-Analysis)
Meta-Analysis Review
Efficacy of hematopoietic stem cell transplantation treatment in refractory chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review and meta-analysis.
BACKGROUND AND PURPOSE
Treatment options for chronic inflammatory demyelinating polyneuropathy (CIDP) are intravenous immunoglobulin, plasmapheresis, corticosteroids and immunosuppressive drugs. However, a substantial proportion of patients with CIDP remain refractory to treatment and develop severe functional disability. A systematic review and a meta-analysis of the efficacy of hematopoietic stem cell transplantation (HSCT) treatment in refractory CIDP patients was performed.
METHODS
The study is based on queries in the PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science and clinicaltrials.gov databases on 4 December 2022. Articles that met our eligibility criteria were included after screening. Patients' characteristics, treatment regime and outcome measures were extracted.
RESULTS
Eighty-nine patients in 11 studies were included. The pooled estimate of responsiveness amongst the four included studies was 87.04% (95% confidence interval 66.7%-99.5%) and the pooled estimate of freedom of all immune modulating or suppressive drugs was 80.75% (95% confidence interval 71.2%-90.2%).
CONCLUSION
This meta-analysis and systematic review suggested that HSCT can be effective in the treatment of refractory CIDP. Whilst there are risks involved, HSCT may be a beneficial and viable therapy for refractory CIDP when carefully evaluated.
Topics: Humans; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Immunoglobulins, Intravenous; Immunosuppressive Agents; Adrenal Cortex Hormones; Hematopoietic Stem Cell Transplantation
PubMed: 37170791
DOI: 10.1111/ene.15857 -
Psychopharmacology Oct 2023Clozapine is a unique medication with a potential role in the treatment of severe borderline personality disorder (BPD). (Review)
Review
RATIONALE
Clozapine is a unique medication with a potential role in the treatment of severe borderline personality disorder (BPD).
OBJECTIVES
The review examines the effectiveness of clozapine as a medication for management for severe BPD with high risk of suicide, violence or imprisonment, and aims to help guide clinical practice in managing severe BPD.
METHODS
A database search of the terms "Clozapine" AND "BPD"; "Antipsychotics" AND "BPD"; "Clozapine" AND "Borderline Personality Disorder"; and "Antipsychotics" AND "Borderline Personality Disorder" were performed in CINAHL, Cochrane Library, Embase, Medline, PsychINFO, PubMed, and Web of Science. Full-text articles of clinical clozapine use for BPD were included for review.
RESULTS
A total of 24 articles consisting of 1 randomised control trial, 10 non-controlled trials, and 13 case reports were identified. Most of the studies reported benefits from clozapine when used for severe BPD. Many of the studies focused on clozapine use in BPD patients at high risk of suicide. Results from these non-controlled and case reports support the use of clozapine in patients with severe BPD at high risk of suicide.
CONCLUSION
There may be a role for clozapine in treating severe treatment refractory BPD, especially for those patients at high risk of suicide and frequent hospitalisations.
Topics: Humans; Clozapine; Antipsychotic Agents; Suicide; Borderline Personality Disorder; Randomized Controlled Trials as Topic
PubMed: 37572113
DOI: 10.1007/s00213-023-06431-6 -
Expert Opinion on Pharmacotherapy Apr 2024Ganaxolone has exhibited potential in managing seizures for epilepsy. This systematic review and meta-analysis aim to assess both the safety and efficacy of Ganaxolone... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Ganaxolone has exhibited potential in managing seizures for epilepsy. This systematic review and meta-analysis aim to assess both the safety and efficacy of Ganaxolone for refractory epilepsy.
METHODS
A thorough search of electronic databases was conducted to identify relevant randomized controlled trials involving patients with drug-resistant focal epilepsy and CDKL5 deficiency disorder. Efficacy and safety outcomes were extracted from the selected studies. Cochrane Review Manager was utilized for data synthesis and analysis, with risk ratios and mean differences calculated to evaluate the efficacy and safety profile of Ganaxolone.
RESULTS
The meta-analysis included a total of five randomized controlled trials. Ganaxolone exhibited significant efficacy in reducing seizure frequency by at least 50% from baseline [RR 0.90 (95% CI: 0.83, 0.98), = 0.02]. However, the results did not reach significance for reducing 28-day seizure frequency [Mean Difference -1.45 (95% CI: -3.39, 0.49), = 0.14]. Ganaxolone exhibited a positive safety profile, with no statistically significant occurrence of adverse events [RR 1.30 (95% CI: 0.93, 1.83), = 0.12] and adverse events leading to discontinuation of the study drug [RR 1.01 (95% CI: 0.42, 2.39), = 0.99] compared to placebo.
CONCLUSION
Ganaxolone presents itself as a viable therapeutic option for refractory epilepsy, showing efficacy in reducing seizure frequency and exhibited a favorable safety profile.
PROSPERO REGISTRATION NUMBER
CRD42023434883.
Topics: Humans; Anticonvulsants; Randomized Controlled Trials as Topic; Drug Resistant Epilepsy; Pregnanolone; Epilepsy; Treatment Outcome
PubMed: 38606458
DOI: 10.1080/14656566.2024.2342413 -
Neuromodulation : Journal of the... Oct 2023This study aimed to review the best evidence on the long-term efficacy of neurostimulation for chronic pain. (Review)
Review
OBJECTIVE
This study aimed to review the best evidence on the long-term efficacy of neurostimulation for chronic pain.
MATERIALS AND METHODS
We systematically reviewed PubMed, CENTRAL, and WikiStim for studies published between the inception of the data bases and July 21, 2022. Randomized controlled trials (RCTs) with a minimum of one-year follow-up that were of high methodologic quality as ascertained using the Delphi list criteria were included in the evidence synthesis. The primary outcome was long-term reduction in pain intensity, and the secondary outcomes were all other reported outcomes. Level of recommendation was graded from I to III, with level I being the highest level of recommendation.
RESULTS
Of the 7119 records screened, 24 RCTs were included in the evidence synthesis. Therapies with recommendations for their usage include pulsed radiofrequency (PRF) for postherpetic neuralgia, transcutaneous electrical nerve stimulation for trigeminal neuralgia, motor cortex stimulation for neuropathic pain and poststroke pain, deep brain stimulation for cluster headache, sphenopalatine ganglion stimulation for cluster headache, occipital nerve stimulation for migraine, peripheral nerve field stimulation for back pain, and spinal cord stimulation (SCS) for back and leg pain, nonsurgical back pain, persistent spinal pain syndrome, and painful diabetic neuropathy. Closed-loop SCS is recommended over open-loop SCS for back and leg pain. SCS is recommended over PRF for postherpetic neuralgia. Dorsal root ganglion stimulation is recommended over SCS for complex regional pain syndrome.
CONCLUSIONS
Neurostimulation is generally effective in the long term as an adjunctive treatment for chronic pain. Future studies should evaluate whether the multidisciplinary management of the physical perception of pain, affect, and social stressors is superior to their management alone.
PubMed: 37436342
DOI: 10.1016/j.neurom.2023.05.003 -
Internal and Emergency Medicine Oct 2023Extracorporeal cardiopulmonary resuscitation (ECPR) is currently recommended as a rescue therapy for selected patients in refractory out-of-hospital cardiac arrest... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Extracorporeal cardiopulmonary resuscitation (ECPR) is currently recommended as a rescue therapy for selected patients in refractory out-of-hospital cardiac arrest (OHCA). However, there is conflicting evidence regarding its effect on survival and neurological outcomes. We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) to evaluate whether ECPR is superior to standard CPR in refractory OHCA.
METHODS
We performed a systematic search of electronic databases (PubMed, CENTRAL, and Scopus) until March 2023. Studies were eligible if they a) were RCTs, and b) compared ECPR vs. standard CPR for OHCA. Outcomes were defined as survival with a favorable neurological status (cerebral performance category 1 or 2) at both the shortest follow-up and at 6 months, and in-hospital mortality. Meta-analyses using a random-effects model were undertaken.
RESULTS
Three RCTs, with a total of four hundred and eighteen patients, were included. Compared with standard CPR, ECPR was associated with a non-statistically significant higher rate of survival with a favorable neurological outcome at the shortest follow-up (26.4% vs. 17.2%; RR 1.47 [95% CI 0.91-2.40], P = 0.12) and at 6 months (28.3% vs. 18.6%; RR 1.48 [95% CI 0.88-2.49], P = 0.14). The mean absolute rate of in-hospital mortality was not significantly lower in the ECPR group (RR 0.89 [95% CI 0.74-1.07], P = 0.23).
CONCLUSION
ECPR was not associated with a significant improvement in survival with favorable neurologic outcomes in refractory OHCA patients. Nevertheless, these results constitute the rationale for a well-conducted, large-scale RCT, aiming to clarify the effectiveness of ECPR compared to standard CPR.
Topics: Humans; Out-of-Hospital Cardiac Arrest; Cardiopulmonary Resuscitation; Extracorporeal Membrane Oxygenation; Time Factors; Randomized Controlled Trials as Topic; Retrospective Studies
PubMed: 37391493
DOI: 10.1007/s11739-023-03357-x -
Journal of Shoulder and Elbow Surgery Aug 2023Calcific tendinitis is a relatively common shoulder disorder, with 7%-17% of individuals with shoulder pain having rotator cuff calcium deposits. Several nonoperative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Calcific tendinitis is a relatively common shoulder disorder, with 7%-17% of individuals with shoulder pain having rotator cuff calcium deposits. Several nonoperative interventions, extracorporeal shockwave therapy (ESWT) and ultrasonography-guided needling (UGN), and surgical techniques have been described to treat calcific tendonitis with satisfactory outcomes. Clinical guidelines are lacking for surgical excision in cases refractory to nonoperative treatment. Several arthroscopic and open operative techniques have been described to treat calcific tendonitis with satisfactory clinical outcomes. The purpose of this systematic review of randomized controlled trials is to compare outcomes and complications of nonoperative vs. operative management of chronic calcific tendinitis of the rotator cuff, to provide evidence-based treatment guidelines for practitioners.
METHODS
EMBASE, PubMed, and OVID [MEDLINE] were searched from database inception until February 20, 2022, for randomized controlled trials reporting outcomes related to operative or nonoperative management for calcific tendonitis of the shoulder. Clinical outcomes including pain on visual analog scale (VAS), Constant-Murley Shoulder Outcome Score (CMS), and resolution of calcific deposits were evaluated. Continuous data at last follow-up was pooled into mean differences using a random effects model for meta-analysis.
RESULTS
A total of 27 studies (2212 nonoperative patients and 140 operative patients) met the final inclusion criteria. Pooled mean difference in VAS for ESWT was -3.83 (95% confidence interval [CI] -5.38, -2.27); P < .001), compared to -4.83 (95% CI -5.44, -4.22; P < .001) for UGN, and -4.65 (95% CI -5.47, -3.82; P < .001) for the operative interventions. Pooled mean difference in CMS score after ESWT was 18.30 (95% CI 10.95, 25.66; P < .001) compared to 22.01 (95% CI 8.17, 35.84; P = .002) for UGN, and 38.35 (95% CI 31.68, 45.02; P < .001) for the operative interventions. Eighty-five percent of patients receiving operative and 67% of patients receiving UGN management had complete radiographic resolution of calcific deposit.
CONCLUSIONS
Surgical treatment of chronic calcific tendonitis of the rotator cuff results in larger improvement in functional outcome scores and comparable pain reduction to nonoperative interventions, particularly UGN. Both operative and nonoperative treatment modalities are likely to have clinically significant improvements in function and pain, and thus it is reasonable to trial UGN and ESWT as first-line treatment. Cost-effectiveness analyses will be needed to support one treatment over the other. High-quality randomized controlled trials directly comparing nonoperative interventions to operative interventions in patients prior to failing conservative treatment are needed to establish high-quality evidence-based guidelines.
Topics: Humans; Rotator Cuff; Randomized Controlled Trials as Topic; Tendinopathy; Shoulder; Shoulder Pain; Rotator Cuff Injuries; Treatment Outcome
PubMed: 37080421
DOI: 10.1016/j.jse.2023.03.017