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Pain Reports 2022Pain is highly prevalent in patients with cancer-nearly 40% report moderate-severe pain, which is commonly treated with opioids. Increasing cancer survivorship, opioid... (Review)
Review
Pain is highly prevalent in patients with cancer-nearly 40% report moderate-severe pain, which is commonly treated with opioids. Increasing cancer survivorship, opioid epidemics in some regions of the world, and limited opioid access in other regions have focused attention on nonopioid treatments. Given the limitations of monotherapy, combining nonopioids-such as antiepileptics and antidepressants-have shown promise in noncancer pain. This review seeks to evaluate efficacy of nonopioid combinations for cancer-related pain. Systematic searches of PubMed, EMBASE, and Cochrane CENTRAL were conducted for double-blind, randomized, controlled trials comparing a nonopioid combination with at least one of its components and/or placebo. This search yielded 4 randomized controlled trials, published between 1998 and 2019 involving studies of (1) imipramine + diclofenac; (2) mitoxantrone + prednisone + clodronate; (3) pentoxifylline + tocopherol + clodronate; and (4) duloxetine + pregabalin + opioid. In the first 3 of these trials, trends favouring combination efficacy failed to reach statistical significance. However, in the fourth trial, duloxetine + pregabalin + opioid was superior to pregabalin + opioid. This review illustrates recognition for the need to evaluate nonopioid drug combinations in cancer pain, although few trials have been published to date. Given the growing practice of prescribing more than 1 nonopioid for cancer pain and the need to expand the evidence base for rational combination therapy, more high-quality trials in this area are needed.
PubMed: 35261931
DOI: 10.1097/PR9.0000000000000995 -
The Cochrane Database of Systematic... Jun 2023Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015.
OBJECTIVES
To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We also searched the reference lists of identified clinical trials and handsearched conference abstracts. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs assessing the efficacy of PTX with antibiotics (any dose or duration) for treatment of suspected or confirmed sepsis or NEC in neonates. We included three comparisons: (1) PTX with antibiotics compared to placebo or no intervention with antibiotics; (2) PTX with antibiotics compared to PTX with antibiotics and adjunct treatments such as immunoglobulin M-enriched intravenous immunoglobulin (IgM-enriched IVIG); (3) PTX with antibiotics compared to adjunct treatments such as IgM-enriched IVIG with antibiotics.
DATA COLLECTION AND ANALYSIS
We reported typical risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes derived from a fixed-effect model of meta-analysis. We calculated the number needed to treat for an additional beneficial outcome (NNTB) if there was a statistically significant reduction in RD.
MAIN RESULTS
We identified no new studies for this update. We included six RCTs (416 neonates). All of the included studies examined neonates with sepsis; we identified no studies on neonates with NEC. Four of the six trials had high risk of bias for at least one risk of bias domain. Comparison 1: PTX with antibiotics compared to placebo with antibiotics, or antibiotics alone, in neonates with sepsis may reduce all-cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD -0.08, 95% CI -0.14 to -0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low-certainty evidence) and may decrease length of hospital stay (LOS) (MD -7.74, 95% CI -11.72 to -3.76; 2 studies, 157 participants, low-certainty evidence). The evidence is very uncertain that PTX with antibiotics compared to placebo or no intervention results in any change in chronic lung disease (CLD) (RR 1.50, 95% CI 0.45 to 5.05; 1 study, 120 participants, very low-certainty evidence), severe intraventricular haemorrhage (sIVH) (RR 0.75, 95% CI 0.28 to 2.03; 1 study, 120 participants, very low-certainty evidence), periventricular leukomalacia (PVL) (RR 0.50, 95% CI 0.10 to 2.63; 1 study, 120 participants, very low-certainty evidence), NEC (RR 0.56, 95% CI 0.29 to 1.06; 6 studies, 405 participants, very low-certainty evidence), or retinopathy of prematurity (ROP) (RR 0.40, 95% CI 0.08 to 1.98; 1 study, 120 participants, very low-certainty evidence) in neonates with sepsis. Comparison 2: the evidence is very uncertain that PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG has any effect on mortality (RR 0.71, 95% CI 0.24 to 2.10; 102 participants, 1 study, very low-certainty evidence) or development of NEC in neonates with sepsis (RR 1.33, 95% CI 0.31 to 5.66; 1 study, 102 participants, very low-certainty evidence). The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. Comparison 3: the evidence is very uncertain that PTX with antibiotics compared to IgM-enriched IVIG with antibiotics has any effect on mortality (RR 1.25, 95% CI 0.36 to 4.39; 102 participants, 1 study, very low-certainty evidence) or development of NEC (RR 1.33, 95% CI 0.31 to 5.66; 102 participants, 1 study, very low-certainty evidence) in neonates with sepsis. The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. All of the included studies evaluated adverse effects due to PTX, but none were reported in the intervention group in any of the comparisons.
AUTHORS' CONCLUSIONS
Low-certainty evidence suggests that adjunct PTX therapy in neonatal sepsis may decrease mortality and length of hospital stay without any adverse effects. The evidence is very uncertain if PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG, or PTX with antibiotics compared to IgM-enriched IVIG with antibiotics, has any effect on mortality or development of NEC. We encourage researchers to undertake well-designed multicentre trials to confirm or refute the effectiveness and safety of pentoxifylline in reducing mortality and morbidity in neonates with sepsis or NEC.
Topics: Humans; Infant, Newborn; Anti-Bacterial Agents; Enterocolitis, Necrotizing; Immunoglobulin M; Immunoglobulins, Intravenous; Infant, Premature; Lung Diseases; Neonatal Sepsis; Pentoxifylline; Retinopathy of Prematurity; Sepsis
PubMed: 37338074
DOI: 10.1002/14651858.CD004205.pub4 -
Drugs in R&D Sep 2023At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical efficacy of a combination of various conventional and adjuvant drugs in treating dilated cardiomyopathy via network meta-analysis.
METHODS
The study was reported according to the PRISMA 2020 statement. From inception through 27 June 2022, the PubMed, Embase, Cochrane library, and Web of Science databases were searched for randomized controlled trials on medicines for treating dilated cardiomyopathy. The quality of the included studies was evaluated according to the Cochrane risk of bias assessment. R4.1.3 and Revman5.3 software were used for analysis.
RESULTS
There were 52 randomized controlled trials in this study, with a total of 25 medications and a sample size of 3048 cases. The network meta-analysis found that carvedilol, verapamil, and trimetazidine were the top three medicines for improving left ventricular ejection fraction (LVEF). Ivabradine, bucindolol, and verapamil were the top 3 drugs for improving left ventricular end-diastolic dimension (LVEDD). Ivabradine, L-thyroxine, and atorvastatin were the top 3 drugs for improving left ventricular end-systolic dimension (LVESD). Trimetazidine, pentoxifylline, and bucindolol were the top 3 drugs for improving the New York Heart Association classification (NYHA) cardiac function score. Ivabradine, carvedilol, and bucindolol were the top 3 drugs for reducing heart rate (HR).
CONCLUSION
A combination of different medications and conventional therapy may increase the clinical effectiveness of treating dilated cardiomyopathy. Beta-blockers, especially carvedilol, can improve ventricular remodeling, cardiac function, and clinical efficacy in patients with dilated cardiomyopathy (DCM). Hence, they can be used if patients tolerate them. If LVEF and HR do not meet the standard, ivabradine can also be used in combination with other treatments. However, since the quality and number of studies in our research were limited, large sample size, multi-center, and high-quality randomized controlled trials are required to corroborate our findings.
Topics: Humans; Cardiomyopathy, Dilated; Carvedilol; Ivabradine; Stroke Volume; Trimetazidine; Network Meta-Analysis; Ventricular Function, Left; Verapamil; Randomized Controlled Trials as Topic
PubMed: 37556093
DOI: 10.1007/s40268-023-00435-5 -
The Cochrane Database of Systematic... May 2020Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The aetiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularisation to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain.This is an update of the review first published in 2016.
OBJECTIVES
To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, AMED, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 15 October 2019. The review authors searched LILACS, ISRCTN, Australian New Zealand Clinical Trials Registry, EU Clinical Trials Register, clincialtrials.gov and the OpenGrey Database to 5 January 2020.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease.
DATA COLLECTION AND ANALYSIS
Two review authors, independently assessed the studies, extracted data and performed data analysis.
MAIN RESULTS
No new studies were identified for this update. Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid. Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; 1 study; moderate-certainty evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; 1 study; moderate-certainty evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; 1 study; moderate-certainty evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; 2 studies; I² = 0%; very low-certainty evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; 1 study; low-certainty evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; 1 study; moderate-certainty evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; 1 study; moderate-certainty evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; 1 study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; 1 study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low-certainty evidence). Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study. Overall, the certainty of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information (for example regarding baseline tobacco exposure).
AUTHORS' CONCLUSIONS
Moderate-certainty evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Very low and low-certainty evidence suggests there is no clear difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very low-certainty evidence suggests there is no clear difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. Further well designed RCTs assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.
Topics: Adult; Alprostadil; Amputation, Surgical; Aspirin; Epoprostenol; Folic Acid; Hematinics; Humans; Iloprost; Male; Middle Aged; Pain; Placebos; Platelet Aggregation Inhibitors; Prostaglandins; Randomized Controlled Trials as Topic; Thromboangiitis Obliterans; Ulcer
PubMed: 32364620
DOI: 10.1002/14651858.CD011033.pub4 -
World Journal of Gastroenterology Jun 2015To determine whether or not the use of antioxidant supplementation aids in the prevention of post- endoscopic retrograde cholangiopancreatography pancreatitis. (Review)
Review
AIM
To determine whether or not the use of antioxidant supplementation aids in the prevention of post- endoscopic retrograde cholangiopancreatography pancreatitis.
METHODS
A systematic review of randomized controlled trials (RCTs) was made to evaluate the preventive effect of prophylactic antioxidant supplementation in post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The inclusion criteria included: acute post-endoscopic retrograde cholangiopancreatography pancreatitis in adults; randomized clinical trials with the use of any antioxidant as an intervention compared with placebo, to reduce PEP. The outcome measure was the incidence and severity of PEP. Twelve RCTs involving 3110 patients since 1999 were included. The antioxidants used were selenite, β-carotene, and pentoxifylline (each one in one trial), N-acetylcysteine (NAC) in three trials, and allopurinol in six trials. The group of patients treated with NAC received different doses; either oral or intravenous, and allopurinol-treated patients received five different oral doses in two different administration periods. The results are expressed with raw numbers, proportions, as well as mean and standard deviations. The incidence of pancreatitis between groups was analyzed with Pearson's χ(2) test or Fisher's exact test (F). The main outcome is expressed as relative risks and 95%CI.
RESULTS
The incidence of pancreatitis in all antioxidant treatment groups was 8.6%, whereas it was 9.7% in the control group. The antioxidants used were selenite, β-carotene, and pentoxifylline (each one in one trial), NAC in three trials, and allopurinol in six trials. In allopurinol trials, three different dosifications were used; two trials reported a low dosage (of less than 400 mg), two trials reported a moderate dose (600 mg) and the remaining two employed higher doses (more than 900 mg). Supplementation was not associated with a significant reduction in the incidence of PEP [relative risk (RR) = 0.93; 95%CI: 0.82-1.06; P = 0.28]. In addition, the incidences of PEP in patients treated with allopurinol and those treated with other antioxidants were similar to that observed in patients who received the placebo (RR for trials with allopurinol, 0.92; 95%CI: 0.78-1.08; P = 0.31) and, with the use of other antioxidants, the incidence of PEP was 8.9%, whereas it was 9.7% in the control group (RR = 0.95; 95%CI: 0.77-1.18; P = 0.19).
CONCLUSION
Antioxidant supplementation shows no beneficial effect on the incidence of PEP. There is a lack of robust trials to support the use of antioxidants for prevention.
Topics: Antioxidants; Chi-Square Distribution; Cholangiopancreatography, Endoscopic Retrograde; Evidence-Based Medicine; Humans; Incidence; Pancreatitis; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome
PubMed: 26074713
DOI: 10.3748/wjg.v21.i21.6745 -
The World Journal of Men's Health Jan 2024To investigate the efficacy of medical treatment options for Peyronie's disease (PD) including oral drugs, intralesional treatment and mechanical treatment compared with...
PURPOSE
To investigate the efficacy of medical treatment options for Peyronie's disease (PD) including oral drugs, intralesional treatment and mechanical treatment compared with placebo treatment using network meta-analysis (NMA).
MATERIALS AND METHODS
We searched the randomized controlled trials (RCTs) of PD in PubMed, Cochrane library, and EMBASE up to October 2022. RCTs included medical treatment options: oral drugs, intralesional treatment and mechanical treatment. Studies reporting at least one of the outcome measures of interest including curvature degree, plaque size, and structured questionnaires (International Index of Erectile Function, IIEF) were included.
RESULTS
Finally, 24 studies including 1,643 participants met our selection criteria for NMA. There was no statistically significant treatment compared to placebo of the curvature degree, plaque size, IIEF in Bayesian analysis. The SUCRA values of ranking probabilities for each treatment performance, which indicated that hyperthermia device ranked first in NMA. However, in frequentist analysis, 7 of mono treatments (coenzyme Q10 [CoQ10] 300 mg, hyperthermia device, interferon alpha 2b, pentoxifylline 400 mg, propionyl-L-carnitine 1 g, penile traction therapy [PTT], vitamin E 300 mg) and 2 of combination treatments ("PTT-extracorporeal shockwave treatment", "vitamin E 300 mg-propionyl-L-carnitine 1 g") were statistically significant for improvement of curvature degree, and 9 of mono treatments (CoQ10 300 mg, hyaluronic acid 16 mg, hyperthermia device, interferon alpha 2b, pentoxifylline 400 mg, propionyl-L-carnitine 1 g, verapamil 10 mg, vitamin E 300 mg, vitamin E 400 U) and 3 of combination treatments ("interferon alpha 2b-vitamin E 400 U", "verapamil 10 mg-antioxidants", "vitamin E 300 mg-propionyl-L-carnitine 1 g") were statistically significant in the improvement of plaque size.
CONCLUSIONS
At present, there is no clinical treatment alternatives that have been demonstrated to be effective compared to placebo. Nonetheless, as the frequentist approach has shown that a number of agents are efficacious, further research is expected to develop more effective treatment options.
PubMed: 37382281
DOI: 10.5534/wjmh.230016 -
The Cochrane Database of Systematic... Nov 2021Acute bacterial meningitis is a bacterial infection of the membranes that surround and protect the brain, known as the meninges. The primary therapy for bacterial... (Review)
Review
BACKGROUND
Acute bacterial meningitis is a bacterial infection of the membranes that surround and protect the brain, known as the meninges. The primary therapy for bacterial meningitis is antibiotics and corticosteroids. Although these therapies significantly improve outcomes, bacterial meningitis still has a high risk of death and a high risk of neurological sequelae in survivors. New adjuvant therapies are needed to further reduce the risk of death and neurological sequelae in bacterial meningitis.
OBJECTIVES
To assess the effects of non-corticosteroid adjuvant pharmacological therapies for mortality, hearing loss, and other neurological sequelae in people with acute bacterial meningitis.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, and LILACS databases and ClinicalTrials.gov and WHO ICTRP trials registers up to 30 September 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of any pharmacological adjuvant therapy for acute bacterial meningitis.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed and extracted data on methods, participants, interventions, and outcomes. We assessed risk of bias of studies with the Cochrane risk of bias tool and the certainty of the evidence using the GRADE approach. We presented results using risk ratios (RR) and 95% confidence intervals (CI) when meta-analysis was possible. All other results are presented in a narrative synthesis.
MAIN RESULTS
We found that five different adjuvant therapies have been tested in RCTs for bacterial meningitis. These include paracetamol (3 studies, 1274 participants who were children); immunoglobulins (2 studies, 49 participants; one study included children, and the other adults); heparin (1 study, 15 participants who were adults); pentoxifylline (1 study, 57 participants who were children); and a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide (1 study, 30 participants who were children). Paracetamol may make little or no difference to mortality (paracetamol 35.2% versus placebo 37.4%, 95% CI 30.3% to 40.8%; RR 0.94, 95% CI 0.81 to 1.09; 3 studies, 1274 participants; I² = 0%; low certainty evidence); hearing loss (RR 1.04, 95% CI 0.80 to 1.34; 2 studies, 901 participants; I² = 0%; low certainty evidence); neurological sequelae other than hearing loss (RR 1.56, 95% CI 0.98 to 2.50; 3 studies, 1274 participants; I² = 60%; low certainty evidence); and severe hearing loss (RR 0.96, 95% CI 0.67 to 1.36; 2 studies, 901 participants; I² = 0%; low certainty evidence). Paracetamol may lead to slightly more short-term neurological sequelae other than hearing loss (RR 1.99, 95% CI 1.40 to 2.81; 2 studies, 1096 participants; I² = 0%; low certainty evidence) and slightly more long-term neurological sequelae other than hearing loss (RR 2.32, 95% CI 1.34 to 4.04; 2 studies, 901 participants; I² = 0%; low certainty evidence). No adverse events were reported in either group in any of the paracetamol studies (very low certainty evidence). Two paracetamol studies had a low risk of bias in most domains, and one had low or unclear risk of bias in all domains. We judged the certainty of evidence to be low for mortality due to limitations in study design (unclear risk of bias in at least one domain and imprecision (high level of uncertainty in absolute effects), and low for all other outcomes due to limitations in study design (unclear risk of bias in at least one domain), and imprecision (low sample size and few events) or inconsistency in effect estimates (heterogeneity). We were not able to perform meta-analysis for any of the other adjuvant therapies due to the limited number of included studies. It is uncertain whether immunoglobulins, heparin, or pentoxifylline improves mortality outcomes due to the very low certainty of the evidence. Zero adverse events were reported for immunoglobulins (very low certainty evidence), and allergic reactions occurred at a rate of 3.3% in participants receiving a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide (intervention group) (very low certainty evidence). None of our other outcomes (hearing loss, neurological sequelae other than hearing loss, severe hearing loss, and short-term or long-term neurological sequelae other than hearing loss) were reported in these studies, and all of these studies were judged to have a high risk of bias. All reported outcomes for all included adjuvant therapies, other than paracetamol, were graded as very low certainty of evidence due to limitations in study design (unclear or high risk of bias in at least four domains) and imprecision (extremely low sample size and few events).
AUTHORS' CONCLUSIONS
Few adjuvant therapies for bacterial meningitis have been tested in RCTs. Paracetamol may make little or no difference to mortality, with a high level of uncertainty in the absolute effects (low certainty evidence). Paracetamol may make little or no difference to hearing loss, neurological sequelae other than hearing loss, and severe hearing loss (all low certainty evidence). Paracetamol may lead to slightly more short-term and long-term neurological sequelae other than hearing loss (both outcomes low certainty evidence). There is insufficient evidence to determine whether any of the adjuvant therapies included in this review (paracetamol, immunoglobulins, heparin, pentoxifylline, or a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide) are beneficial or detrimental in acute bacterial meningitis.
Topics: Acetaminophen; Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Child; Hearing Loss; Humans; Meningitis, Bacterial
PubMed: 34813078
DOI: 10.1002/14651858.CD013437.pub2 -
The Cochrane Database of Systematic... Oct 2014Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age-matched controls, people with intermittent claudication have a three- to six-fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007.
OBJECTIVES
To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication.
SEARCH METHODS
For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9).
SELECTION CRITERIA
Double-blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta-analysis as a fixed-effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data.
MAIN RESULTS
We included fifteen double-blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta-analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta-analysis, for initial claudication distance (ICD - the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD - the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI -43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI.There was no association between treatment type and all-cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups.
AUTHORS' CONCLUSIONS
Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all-cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study.
Topics: Aged; Cilostazol; Humans; Intermittent Claudication; Middle Aged; Myocardial Infarction; Pentoxifylline; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Tetrazoles; Walking
PubMed: 25358850
DOI: 10.1002/14651858.CD003748.pub4 -
European Review For Medical and... May 2022This systematic review and meta-analysis aimed to synthesize the latest evidence on pentoxifylline effect on the contrast-induced nephropathy (CIN) and whether the... (Meta-Analysis)
Meta-Analysis
The role of pentoxifylline in preventing contrast-induced nephropathy in coronary angiography/intervention - systematic review, meta-analysis, and meta-regression of randomized controlled trials.
OBJECTIVE
This systematic review and meta-analysis aimed to synthesize the latest evidence on pentoxifylline effect on the contrast-induced nephropathy (CIN) and whether the quality evidence is sufficient to make a definite conclusion MATERIALS AND METHODS: We performed a systematic literature search on topics that assesses pentoxifylline and CIN in coronary angiography/intervention up until 01 April 2021 using PubMed, Scopus, Embase, and hand-sampling. Primary outcome was CIN defined as ≥0.5 mg/dL or 25% rise in the SCr 48 h after procedure.
RESULTS
There were a total of 1142 subjects from 6 studies. There was no difference between pentoxifylline and control group in terms of serum creatinine at baseline (p=0.46) and after the procedure (p=0.33). The incidence of CIN was 51/571 (8.9%) in the pentoxifylline group and 61/571 (10.7%) in the control group. Pentoxifylline was not significantly associated with increase or decrease in the risk of CIN (RR 0.84 [0.59, 1.19], p=0.32; I2: 0%, p=0.89). Subgroup analysis for elective studies showed a non-significant result (RR 0.77 [0.47, 1.27], p=0.31; I2: 0%). Meta-regression analysis showed that the association between pentoxifylline and mortality was not affected by age (p=0.994), gender (reference: male, p=0.562), hypertension (p=0.336), diabetes (p=0.536), baseline serum creatinine (p=0.344), contrast used (p=0.431), and CIN incidence (p=0.521). GRADE Approach showed a low certainty of evidence for the effect estimate of pentoxifylline on CIN.
CONCLUSIONS
Our meta-analysis showed that pentoxifylline was not associated with the risk of CIN with low certainty of evidence. Hence, larger, multicentre, double-blind randomized controlled trials are required.
Topics: Contrast Media; Coronary Angiography; Creatinine; Humans; Kidney Diseases; Male; Pentoxifylline; Randomized Controlled Trials as Topic
PubMed: 35587083
DOI: 10.26355/eurrev_202205_28750 -
Dermatology Reports Nov 2022Febrile Ulceronecrotic Mucha- Habermann Disease (FUMHD) is a variant of Pityriasis Lichenoides Et Varioliformis Acuta (PLEVA). Although rare, the condition may progress...
Febrile Ulceronecrotic Mucha- Habermann Disease (FUMHD) is a variant of Pityriasis Lichenoides Et Varioliformis Acuta (PLEVA). Although rare, the condition may progress to involve serious complications and even lead to fatal outcomes if diagnosis and appropriate treatment is delayed. A PubMed search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRIMSA) guidelines was performed to find cases of FUMHD from the earliest records to October 2021. Treatments, complications, and patient outcomes were extracted from the literature and summarized, while a review of quality was also performed. A total of 63 publications with 68 patients were found. Successful treatment modalities for FUMHD included antibiotics, antivirals, systemic steroids, Methotrexate (MTX), cyclophosphamide, Cyclosporine (CYA), Intravenous Immunoglobulins (IVIG), pentoxifylline, and ultraviolet B phototherapy. Out of 68 patients, 55 patients had their condition fully resolved and 13 cases were fatal. Increased age, systemic involvement, and monoclonal T-cell receptor rearrangement were associated with worst prognosis, but mucosal involvement did not affect mortality risk. Overall, the publications had low risk of bias, but most lacked adequate follow-up periods. FUMHD is a diagnostic and therapeutic challenge due to the lack of clearly defined diagnostic criteria and optimum treatment. Further studies with larger patient populations and longer follow-up periods may lead to refinement of diagnostic criteria, establish an optimum treatment regimen, and better estimate the likelihood of recurrence.
PubMed: 36483219
DOI: 10.4081/dr.2022.9492