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International Journal of Impotence... Sep 2023The efficacy of many non-surgical treatments for Peyronie's disease is unclear. This systematic review aims to critically assess the currently available options and... (Review)
Review
The efficacy of many non-surgical treatments for Peyronie's disease is unclear. This systematic review aims to critically assess the currently available options and provide a recommendation for treatment based on this. A systematic literature search utilising the Medline (Pubmed), Embase, global health and Cochrane library databases was conducted up to May 2021. All randomised controlled trials assessing non-surgical treatment modalities for Peyronie's Disease were included. Individual study risk of bias was evaluated using the Cochrane tool and GRADE was used to assess evidence strength. Outcome measures were the change in penile curvature (degrees), plaque size (volume or size), International Index of Erectile Function score, pain scores and change in penile length. Prospero registration number: CRD42017064618. Amongst the 5549 articles identified, 41 studies (42 reports) were included. Seven different oral treatment options including vitamin E supplementation showed evidence for improving outcomes such as penile curvature and plaque size. Of the intralesional treatments, Collagenase Clostridium Histolyticum showed evidence for improving penile curvature (Range: 16.3-17 degrees, moderate level certainty of evidence). Intralesional Interferon demonstrated some improvement in curvature (Range: 12-13.5 degrees), plaque size (Range: 1.67-2.2 cm) and pain, whilst intralesional calcium channel blockers such as Verapamil showed variable evidence for changes in the plaque size and pain. Extracorporeal Shockwave Therapy consistently demonstrated evidence for improving penile pain in stable disease, and two mechanical traction devices improved curvature. Iontophoresis, topical medications, and combination therapies did not demonstrate any consistent improvements in outcome measures. Intralesional options demonstrate the best potential. Overall, results varied with few high-quality randomised trials present.
Topics: Male; Humans; Penile Induration; Treatment Outcome; Microbial Collagenase; Penis; Pelvic Pain
PubMed: 36289392
DOI: 10.1038/s41443-022-00633-w -
Medicine Oct 2022LCZ696 is a novel neuroendocrine inhibitor that has been widely used in heart failure (HF). However, its advantage over other neuroendocrine inhibitors, such as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
LCZ696 is a novel neuroendocrine inhibitor that has been widely used in heart failure (HF). However, its advantage over other neuroendocrine inhibitors, such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) has not been fully elucidated. This study aimed to provide the latest evidence regarding the efficacy and safety of LCZ696 as compared to other ACEis and ARBs with regards to the treatment of HF.
METHODS
We systematically searched databases, including PubMed, Embase, and the Cochrane Library, for relevant randomized controlled trials (RCTs). The outcome measures included all-cause mortality, rate of hospitalizations for HF, rate of death from cardiovascular causes, change in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and decline of renal function.
RESULTS
Five RCTs involving 19,078 patients were identified. The meta-analysis indicated that LCZ696 was associated with a significant reduction in all-cause mortality (hazard ratio [HR] = 0.84; 95% confidence interval [CI], 0.76-0.93; P = .0005), rate of hospitalizations for HF (HR = 0.80; 95% CI, 0.73-0.87; P < .00001), reduction in NT-proBNP levels (rate ratio = 0.78; 95% CI, 0.70-0.88; P < .0001), and decline in renal function (odds ratio = 0.77; 95% CI, 0.68-0.88; P < .0001) compared with ACEis and ARBs. However, there was no statistical difference in the rate of death from cardiovascular causes (HR = 0.86; 95% CI, 0.72-1.03; P = .09) between LCZ696 and ACEis and ARBs.
CONCLUSION
LCZ696 is superior to ACEis and ARBs in the treatment of HF. Hence, it should be more widely used clinically.
Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Antihypertensive Agents; Biphenyl Compounds; Drug Combinations; Heart Failure; Humans; Neprilysin; Randomized Controlled Trials as Topic; Receptors, Angiotensin; Valsartan
PubMed: 36254034
DOI: 10.1097/MD.0000000000030904 -
Heart Failure Reviews Jul 2023Several guidelines have recommended the use of angiotensin receptor neprilysin inhibitors (ARNIs) as replacement for angiotensin-converting enzyme inhibitors in the... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety profile of angiotensin receptor neprilysin inhibitors in the management of heart failure: a systematic review and meta-analysis of randomized controlled trials.
Several guidelines have recommended the use of angiotensin receptor neprilysin inhibitors (ARNIs) as replacement for angiotensin-converting enzyme inhibitors in the management of heart failure. Till date, there are no reviews done that comprehensively cover different aspects of efficacy and safety parameters. Hence, we have performed a comprehensive systematic review and meta-analysis on role of ARNIs for the management of heart failure patients. Searches were done in Embase, Scopus, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, PubMed Central, Cochrane Library, MEDLINE, Google Scholar, ScienceDirect and Clinicaltrials.gov until June 2022. Risk of bias assessment was done with Cochrane's risk of bias tool. Meta-analysis was carried out using random-effects model. Pooled standardized mean difference (SMD)/mean difference (MD) and/or risk ratio (RR) with 95% confidence intervals (CIs) was reported. In total, we analysed 34 studies, with almost all of them had a high risk of bias. Pooled RR was 0.88 (95% CI: 0.82-0.95) for all-cause mortality, 0.84 (95% CI: 0.77-0.92) for cardiovascular mortality and 0.78 (95% CI: 0.70-0.87) for hospitalization. Pooled MD was 3.74 (95% CI: 1.93-5.55) for left ventricular ejection fraction, -2.16 (95% CI: -3.58 to -0.74) for left atrial volume index, -3.80 (95% CI: -6.60 to -1.00) for left ventricular end-diastolic dimension and -1.16 (95% CI: -1.98 to -0.35) for E/E' ratio. Regarding adverse events, pooled RR was 1.55 (95% CI: 1.31-1.85) for symptomatic hypotension, 0.93 (95% CI: 0.78-1.11) for worsening renal function, 1.09 (95% CI: 0.94-1.26) for hyperkalaemia and 1.29 (95% CI: 0.67-2.50) for angioedema. ARNIs had beneficial efficacy and safety profile on the management of heart failure especially patients with reduced ejection fraction.
Topics: Humans; Neprilysin; Stroke Volume; Ventricular Function, Left; Randomized Controlled Trials as Topic; Heart Failure; Angiotensin Receptor Antagonists
PubMed: 36184714
DOI: 10.1007/s10741-022-10273-3 -
BMJ Open Ophthalmology Aug 2022Medial eyelid tumours may result in the loss of the proximal lacrimal system during staged excision and delayed reconstruction, to achieve tumour margin clearance. The...
OBJECTIVE
Medial eyelid tumours may result in the loss of the proximal lacrimal system during staged excision and delayed reconstruction, to achieve tumour margin clearance. The remnant canaliculus was marsupialised during reconstruction. The aim was to understand how many patients experienced symptomatic epiphora as a consequence of this.
METHODS AND ANALYSIS
A retrospective study including patients over a 15-year period with medial eyelid tumours, where the proximal lacrimal system was sacrificed to achieve tumour margin clearance. Included were all who had marsupialisation of the remnant distal stump as part of their delayed reconstruction. All who had pre-existing epiphora were excluded. The primary objective was the rate of epiphora following the procedure. A systematic literature review of postoperative epiphora occurring in patients with lid tumours requiring lacrimal system injury/sacrifice during tumour excision.
RESULTS
There were 22 eyes (22 patients). All were basal cell carcinomas except for 1 (4.5%) tarsal conjunctival squamous cell carcinoma. All cases involved the lower lid. There were two (9.1%) patients who developed epiphora. One patient underwent a superior three-snip punctoplasty, botulinum toxin to the lacrimal gland and conjunctivodacryocystorhinostomy with Lester Jones tube insertion. The other patient was not overly troubled and did not require further treatment. The literature review showed the median postoperative rate of epiphora in these patients was 12.5% (range 0%-100%).
CONCLUSION
Marsupialisation of the remnant canaliculus during delayed reconstruction is a straightforward and effective surgical option, which may help prevent postreconstruction epiphora when the proximal lacrimal system is sacrificed for tumour margin clearance.
TRIAL REGISTRATION NUMBER
10391.
Topics: Botulinum Toxins; Eyelid Neoplasms; Humans; Lacrimal Apparatus; Lacrimal Duct Obstruction; Retrospective Studies
PubMed: 36161857
DOI: 10.1136/bmjophth-2022-000985 -
The Journal of Headache and Pain Sep 2022Chronic migraine is a common neurovascular brain disorder with substantial economic costs. We performed a systematic review to identify economic evaluations of... (Review)
Review
BACKGROUND AND AIMS
Chronic migraine is a common neurovascular brain disorder with substantial economic costs. We performed a systematic review to identify economic evaluations of pharmacological treatments for adults with chronic migraine.
METHODS
We undertook systematic literature searches using terms for migraine/headache and prophylactic drug interventions, combined with economic/cost terms where appropriate. Using inclusion and exclusion criteria, two reviewers independently assessed the citations and abstracts, and full-text articles were retrieved. A review of study characteristics and methodological quality was assessed.
RESULTS
Sixteen citations met the inclusion criteria and were model-based cost-utility studies evaluating: Botox (n = 6); Erenumab (n = 8); Fremanezumab (n = 2); and Galcanezumab (n = 1) as the main treatment. They varied in their use of comparators, perspective, and model type. Botox was cost-effective compared to placebo with an incremental cost-effectiveness ratio (ICER) ranging between £15,028 (€17,720) and £16,598 (€19,572). Erenumab, Fremanezumab and Galcanezumab when compared to Botox, was associated with ICERs ranging between £59,712 ($81,080) and £182,128 (€218,870), with the ICERs above the most common willingness-to-pay thresholds (WTPs). But they were cost-effective within the commonly used WTPs among the population for whom the previous treatments including Botox were failed. Three studies compared the cost-effectiveness of Erenumab against the placebo and found that Erenumab was dominant. All studies performed sensitivity analyses to check the robustness of their results. None of the findings from the included articles were generalisable and none of the included studies fulfilled all the criteria mentioned in the CHEERS 2022 reporting checklist and Phillips's checklist for economic models.
CONCLUSIONS
Evidence to support the cost-effectiveness of pharmacological treatments of chronic migraine in the adult population using Botox and Erenumab were identified. Our findings suggest that both Botox and Erenumab, are cost-effective compared to placebo; although Erenumab had more incremental economic benefits compared to Botox, the ICERs were above the most common willingness-to-pay thresholds. Hence, Erenumab might be an acceptable treatment for chronic migraine for patients whom other treatments such as Botox do not work. Further research is needed to help characterise the data to adequately structure and parameterise an economic model to support decision-making for chronic migraine therapies.
Topics: Adult; Botulinum Toxins, Type A; Cost-Benefit Analysis; Humans; Migraine Disorders
PubMed: 36114468
DOI: 10.1186/s10194-022-01492-y -
Cephalalgia : An International Journal... Dec 2022This meta-analysis evaluated the real-world effectiveness of onabotulinumtoxinA (BOTOX®), the first preventive treatment FDA-approved specifically for chronic migraine... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This meta-analysis evaluated the real-world effectiveness of onabotulinumtoxinA (BOTOX®), the first preventive treatment FDA-approved specifically for chronic migraine in 2010.
METHODS
We systematically reviewed onabotulinumtoxinA observational data in chronic migraine published between 1 January 2010 and 31 March 2021. Random-effects models evaluated available data for primary and secondary endpoints defined in onabotulinumtoxinA pivotal trials at approximately 24 weeks and 52 weeks.
RESULTS
Of the 44 full-text eligible studies (29 prospective; 13 retrospective; 2 other), seven evaluated change from baseline (mean[confidence interval]) at ∼24 weeks and ∼52 weeks, respectively, for onabotulinumtoxinA in: : (-10.64 [-12.31, -8.97]; -10.32 [-14.92, -5.73]); (-7.40 [-13.04, -1.77]; overlapping CIs at 52 weeks); (-11.70 [-13.86, -9.54]); -11.80 [14.70, -8.90]); and (MSQ; 23.60 [CI: 21.56, 25.64]; 30.90 [CI: 28.29, 33.51]). At ∼24 weeks onabotulinumtoxinA showed of 44.74 [28.50, 60.99] and of 46.57% [29.50%, 63.65%]. A sensitivity analysis at study-end suggested durability of onabotulinumtoxinA effectiveness on MSQ.
CONCLUSION
The meta-analysis reflecting real-world practice broadly corroborated with evidence from pivotal and long-term open-label studies of onabotulinumtoxinA in chronic migraine preventive treatment.
Topics: Humans; Botulinum Toxins, Type A; Retrospective Studies; Prospective Studies; Treatment Outcome; Chronic Disease; Migraine Disorders; Headache; Acute Pain
PubMed: 36081276
DOI: 10.1177/03331024221123058 -
Thrombosis Research Oct 2022Endotheliopathy and coagulopathy appear to be the main causes for critical illness and death in patients with coronavirus disease 2019 (COVID-19). The adhesive ligand... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Endotheliopathy and coagulopathy appear to be the main causes for critical illness and death in patients with coronavirus disease 2019 (COVID-19). The adhesive ligand von Willebrand factor (VWF) has been involved in immunothrombosis responding to endothelial injury. Here, we reviewed the current literature and performed meta-analyses on the relationship between both VWF and its cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) with the prognosis of COVID-19.
METHODS
We searched MEDLINE, Cochrane Library, Web of Science, and EMBASE databases from inception to 4 March 2022 for studies analyzing the relationship between VWF-related variables and composite clinical outcomes of patients with COVID-19. The VWF-related variables analyzed included VWF antigen (VWF:Ag), VWF ristocetin cofactor (VWF:Rco), ADAMTS13 activity (ADAMTS13:Ac), the ratio of VWF:Ag to ADAMTS13:Ac, and coagulation factor VIII (FVIII). The unfavorable outcomes were defined as mortality, intensive care unit (ICU) admission, and severe disease course. We used random or fixed effects models to create summary estimates of risk. Risk of bias was assessed based on the principle of the Newcastle-Ottawa Scale.
RESULTS
A total of 3764 patients from 40 studies were included. The estimated pooled means indicated increased plasma levels of VWF:Ag, VWF:Rco, and VWF:Ag/ADAMTS13:Ac ratio, and decreased plasma levels of ADAMTS13:Ac in COVID-19 patients with unfavorable outcomes when compared to those with favorable outcomes (composite outcomes or subgroup analyses of non-survivor versus survivor, ICU versus non-ICU, and severe versus non-severe). In addition, FVIII were higher in COVID-19 patients with unfavorable outcomes. Subgroup analyses indicated that FVIII was higher in patients admitting to ICU, while there was no significant difference between non-survivors and survivors.
CONCLUSIONS
The imbalance of the VWF-ADAMTS13 axis (massive quantitative and qualitative increases of VWF with relative deficiency of ADAMTS13) is associated with poor prognosis of patients with COVID-19.
Topics: ADAMTS13 Protein; COVID-19; Disintegrins; Factor VIII; Humans; Ligands; Prognosis; Thrombospondins; von Willebrand Factor
PubMed: 36027630
DOI: 10.1016/j.thromres.2022.08.017 -
Toxins Aug 2022OnabotulinumtoxinA, targeting the CGRP machinery, has been approved for the last two decades for chronic migraine prevention. The recently approved monoclonal antibodies... (Meta-Analysis)
Meta-Analysis
OnabotulinumtoxinA, targeting the CGRP machinery, has been approved for the last two decades for chronic migraine prevention. The recently approved monoclonal antibodies (mAbs) directed towards the calcitonin gene-related peptide (CGRP) pathway open a new age for chronic migraine control. However, some 40% patients suffering from chronic migraine is still resistant to treatment. The aim of this work is to answer the following PICOS (participants intervention comparator outcome study design) question: Is there evidence of efficacy and safety of the combined administration of anti-CGRP mAbs and onabotulinumtoxinA in chronic migraine? A systematic review and meta-analysis [Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations] was made up to 19 April 2022. The results are encouraging: the combined treatment proved to afford ≥50% monthly headache days (MHDs)/frequency reduction respect to baseline in up to 58.8% of patients; in comparison, anti-CGRP mAbs reduce MHDs of 1.94 days from baseline and botulinum toxin of 1.86 days. Our study demonstrates for the first time that the combination therapy of onabotulinumtoxinA with anti-CGRP mAbs affords a reduction of 2.67 MHDs with respect to onabotulinumtoxinA alone, with moderate certainty of evidence. Adequately powered, good-quality studies are needed to confirm the response to combination therapy in terms of efficacy and safety. PROSPERO registration: CRD42022313640.
Topics: Antibodies, Monoclonal; Botulinum Toxins, Type A; Calcitonin Gene-Related Peptide; Drug Therapy, Combination; Humans; Migraine Disorders; Treatment Outcome
PubMed: 36006191
DOI: 10.3390/toxins14080529 -
International Journal of Surgery... Aug 2022There are no consensus guidelines on the optimal dose or injection site of botulinum toxin (BT) for chronic anal fissure (CAF). The objective of this study was to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are no consensus guidelines on the optimal dose or injection site of botulinum toxin (BT) for chronic anal fissure (CAF). The objective of this study was to determine the appropriate dose and injection site of BT for CAF by comparing healing rate and adverse effects (incontinence and recurrence).
METHODS
MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Scopus were searched from inception through May 31, 2021. Randomized controlled trials evaluating healing and adverse effects of BT injection for CAF published in any language were selected. Multiple treatment comparisons and ranking were performed using a two-stage network meta-analysis, and results were graded by Confidence in Network Meta-Analysis tool.
RESULTS
Twenty-seven trials involving 1880 patients were included. The results demonstrated that high-dose-BT had significantly higher short-term healing when injected out of the fissure (OF) site than each side of the fissure (SF) site, with a risk ratio (RR) of 2.12 (1.08, 4.15); low-dose-BT did not show any difference across OF and SF site with RR of 1.20 (0.85, 1.68). High-dose-BT at the OF site showed similar healing to low-dose-BT at the same site (RR of 1.02 (0.79, 1.31)) but with a higher risk of incontinence with RR of 3.54 (0.85, 14.76). In contrast, high-dose-BT at the SF site showed lower healing compared to low-dose-BT at the same site with RR of 0.57 (0.29, 1.14). Both high-dose-BT and low-dose-BT at the OF site had higher recurrence than high-dose-BT or low-dose-BT at the SF site with RR of 2.08 (0.33, 13.11) and 1.89 (0.60, 5.94), respectively.
CONCLUSIONS
Given moderate level of evidence, low-dose BT is optimal; injection out of the fissure site improves short-term outcomes while injection each side of the fissure site tends to reduce recurrence in the longer term.
Topics: Anal Canal; Botulinum Toxins, Type A; Chronic Disease; Fissure in Ano; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35934283
DOI: 10.1016/j.ijsu.2022.106798 -
Pain Physician Aug 2022Piriformis syndrome (PS) is a painful condition caused by entrapment of the sciatic nerve within the piriformis muscle. PS is typically unilateral and mainly occurs... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Piriformis syndrome (PS) is a painful condition caused by entrapment of the sciatic nerve within the piriformis muscle. PS is typically unilateral and mainly occurs related to entrapment of the sciatic nerve. Treatments include physiotherapy, analgesics, anti-inflammatory drugs, behavioral modifications, injection therapy with local anesthetics (LAs) and steroids, epidural injection, botulinum toxin (BT) injection, and surgery.
OBJECTIVES
To investigate the efficacy of BT, LA, and corticosteroid (CS) injections in relieving pain in patients affected by PS.
STUDY DESIGN
This systematic review and meta-analysis was conducted according to the "Cochrane Handbook for Systematic Reviews of Interventions" and the "Preferred Reporting Items for Systematic Reviews and Metaanalyses (PRISMA)" guidelines.
METHODS
A systematic search was conducted through PubMed, Cochrane, Web of Science, and Scopus through April 2021 for studies investigating the efficacy of BT, LA, or CS injection in improving pain in patients with PS. After screening retrieved studies, data were extracted from included studies and pooled. Overall results were reported as standardized mean difference (SMD) and 95% confidence interval (CI). Analysis was performed using RevMan software version 5.4.
RESULTS
Sixteen studies were included in this systematic review, and 12 of them were included in the quantitative synthesis. The pain scores decreased significantly after treatment with BT (SMD = -2.00; 95% CI [-2.84, -1.16], P < 0.001), LA and CS (SMD = -4.34; 95% CI [-5.77, 2.90], P < 0.001), LA (SMD = -3.73; 95% CI [-6.47, -0.99], P = 0.008), CS (SMD = -2.78; 95% CI [-3.56, -2.00], P < 0.001), and placebo injection (SMD = -0.04; 95% CI [-0.07, -0.01], P = 0.002). BT injection was less effective than LA and CS together (P = 0.006), more effective than placebo (P = 0.001), and similar to LA (P = 0.24) and CS (P = 0.18), when injected alone.
LIMITATIONS
A wide variety of study designs were utilized to obtain the largest sample size available. Many of the included studies lack randomization, and some are retrospective in nature. These limitations may introduce bias into the analyzed data and affect the results. Many studies had a low sample size and are of moderate quality, limiting the generalizability of the results. Also, we could not conduct a direct meta-analysis due to the lack of sufficient double-arm studies comparing different types of injection therapies.
CONCLUSIONS
In patients with PS, satisfactory pain improvement can be obtained by BT, LA plus CS, LA, or CS injection therapy. Injection of LA plus CS showed the best efficacy.
Topics: Adrenal Cortex Hormones; Anesthetics, Local; Botulinum Toxins; Humans; Piriformis Muscle Syndrome; Retrospective Studies
PubMed: 35901473
DOI: No ID Found