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Journal of Perinatology : Official... Jun 2024This systematic review and meta-analysis evaluated the evidence for dose and effectiveness of caffeine in preterm infants. MEDLINE, EMBASE, CINHAL Plus, CENTRAL, and... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis evaluated the evidence for dose and effectiveness of caffeine in preterm infants. MEDLINE, EMBASE, CINHAL Plus, CENTRAL, and trial databases were searched to July 2022 for trials randomizing preterm infants to caffeine vs. placebo/no treatment, or low (≤10 mg·kg) vs. high dose (>10 mg·kg caffeine citrate equivalent). Two researchers extracted data and assessed risk of bias using RoB; GRADE evaluation was completed by all authors. Meta-analysis of 15 studies (3530 infants) was performed in REVMAN across four epochs: neonatal/infant (birth-1 year), early childhood (1-5 years), middle childhood (6-11 years) and adolescence (12-19 years). Caffeine reduced apnea (RR 0.59; 95%CI 0.46,0.75; very low certainty) and bronchopulmonary dysplasia (0.77; 0.69,0.86; moderate certainty), with higher doses more effective. Caffeine had no effect on neurocognitive impairment in early childhood but possible benefit on motor function in middle childhood (0.72; 0.57,0.91; moderate certainty). The optimal dose remains unknown; further long-term studies, are needed.
Topics: Humans; Caffeine; Infant, Newborn; Infant, Premature; Apnea; Neurodevelopmental Disorders; Infant; Child; Child, Preschool; Adolescent; Central Nervous System Stimulants; Bronchopulmonary Dysplasia; Infant, Premature, Diseases
PubMed: 38553606
DOI: 10.1038/s41372-024-01939-x -
Frontiers in Pharmacology 2024To systematically compare the efficacy and safety of biologics [tumor necrosis factor inhibitors (TNFi), interleukin (IL) inhibitors, phosphodiesterase-4 inhibitors...
To systematically compare the efficacy and safety of biologics [tumor necrosis factor inhibitors (TNFi), interleukin (IL) inhibitors, phosphodiesterase-4 inhibitors (PDE4i), and Janus kinase inhibitors (JAKi)] for biological-naïve patients with psoriatic arthritis (PsA). PubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched until 12 March 2023. Only head-to-head active comparison studies were included, and placebo-controlled studies without active biologic comparators were excluded. Outcomes included musculoskeletal endpoint [American College of Rheumatology (ACR) 20/50/70, resolution of enthesitis, resolution of dactylitis], function endpoint [Health Assessment Questionnaire-Disability Index (HAQ-DI) change, ∆ HAQ-DI ≥ 0.35], composite index endpoint [ACR 50 + Psoriasis Area Severity Index (PASI) 100], and adverse events. The Jadad scale and Newcastle-Ottawa scale (NOS) were adopted to evaluate the quality of eligible studies. Totally 17 studies with head-to-head comparisons of these biologics were included in this systematic review and network meta-analysis. Compared with IL-17A inhibitors (IL-17Ai), TNFi were associated with a lower rate of achieving ACR 20 response [pooled risk ratios (RR) = 0.92, 95% credibility interval (CrI): 0.86, 0.98]. JAKi had the greatest possibility of achieving ACR 20 (50.25%) and ACR 50 (83.03%). The JAKi group had a higher rate of achieving ACR 70 response than the IL-17Ai group (pooled RR = 1.25, 95%CrI: 1.00, 1.57); TNFi were less effective than JAKi in terms of ACR 70 (pooled RR = 0.77, 95%CrI: 0.64, 0.94). ACR 70 was most likely to be achieved in patients using JAKi (97.48%). The IL-17Ai group had a higher rate of enthesitis resolution than the TNFi group [pooled RR = 1.22, 95% confidence interval (CI): 1.02, 1.47]. Compared with IL-17Ai, TNFi were associated with a lower rate of enthesitis resolution (pooled RR = 0.80, 95%CrI: 0.72, 0.88). Patients receiving IL-17Ai had the highest likelihood of achieving enthesitis resolution (82.76%), dactylitis resolution (58.66%) and the greatest HAQ-DI change (59.74%). IL-17Ai had a similar impact in achieving ∆ HAQ-DI ≥ 0.35 to TNFi (pooled RR = 1.15, 95%CI: 0.93, 1.41). Individuals receiving IL-17Ai had a higher rate of achieving combined ACR 50 and PASI 100 response than those receiving TNFi (pooled RR = 1.56, 95%CI: 1.29, 1.88). Patients receiving PDE4i were least likely to have adverse events (41.59%). In 2023, considering both efficacy and safety, IL-17Ai may be the better treatment option for biological-naïve patients with PsA requiring biological therapy.
PubMed: 38545545
DOI: 10.3389/fphar.2024.1279525 -
Expert Review of Clinical Immunology Jul 2024The advent of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) have transformed the management of immune-mediated rheumatic diseases,... (Review)
Review
INTRODUCTION
The advent of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) have transformed the management of immune-mediated rheumatic diseases, including spondylarthritis (SpA). However, the data about combining b/ts DMARDs in the treatment of SpA are scarce. The study objectives were to assess the efficacy and safety of combination b/tsDMARD in SpA.
METHODS
We conducted systematic literature review (PubMed and Medline) with two independent reviewers, one adjudicator, exploring the efficacy and safety of combination b/tsDMARDs in the treatment of SpA. Inclusion criteria were studies published in last 20 years, English language, interventions included use of two b/tsDMARDs, and minimal three-month follow-up.
RESULTS
Out of 1936 initial hits, 28 manuscripts fulfilled the inclusion criteria. Two were randomized controlled trials, and the remaining were retrospective cohort studies or case series. Combination of apremilast with bDMARD, or TNF inhibitor plus IL12/23 inhibitor were the commonest and reported good efficacy with no increased safety signal.
CONCLUSIONS
There is not enough data to fully evaluate efficacy and safety of combination b/tsDMARDs in SpA treatment. Limited information shows apremilast plus bDMARD, or TNF inhibitor plus IL12/23 inhibitor combination to be efficacious and safe. Randomized controlled trials and larger cohort with a longer follow-up are required.
Topics: Humans; Antirheumatic Agents; Biological Products; Spondylarthritis; Drug Therapy, Combination; Randomized Controlled Trials as Topic; Thalidomide; Treatment Outcome
PubMed: 38512065
DOI: 10.1080/1744666X.2024.2327589 -
International Journal of Chronic... 2024The clinical efficacy of roflumilast, an oral phosphodiesterase-4 inhibitor, has been demonstrated in patients with severe chronic obstructive pulmonary disease (COPD).... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical efficacy of roflumilast, an oral phosphodiesterase-4 inhibitor, has been demonstrated in patients with severe chronic obstructive pulmonary disease (COPD). However, roflumilast has shown frequent adverse drug reactions (ADRs). This study was performed to investigate the dosing strategy that will improve adherence to roflumilast in COPD.
METHODS
We conducted a systematic review and meta-analysis using PubMed, Embase, and Cochrane Central Register. The dosing strategy for roflumilast was classified into a dose-escalation group and a low-dose group. We investigated clinical outcomes according to dosing strategy.
RESULTS
Five clinical trials involving 2424 patients were included. Both the dose-escalation and the low-dose groups showed a decrease in discontinuation rate compared to the standard dosing group for roflumilast (risk ratio [RR], 0.81; 95% confidence interval [CI], 0.67-0.97; = 0.02 and RR, 0.62; 95% CI, 0.48-0.80; < 0.01, respectively). In the two strategies, the pooled proportions of discontinuation were 27.9% and 11.7%, respectively. Although the pooled proportion of any ADR was not statistically decreased in the two strategies, diarrhea was significantly reduced in the low-dose group compared to the standard group (RR, 0.58; 95% CI, 0.42-0.82; < 0.01). The pooled incidence of acute exacerbations was similar between the low-dose and the standard groups (22.9% and 20.1%, respectively; = 0.27).
CONCLUSION
Our findings show that the two alternative dosing strategies might have the benefit of improving adherence to roflumilast in COPD. Further large-scale trials are required to support our findings.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Aminopyridines; Benzamides; Cyclopropanes; Phosphodiesterase 4 Inhibitors
PubMed: 38476122
DOI: 10.2147/COPD.S440252 -
Narra J Aug 2023Prostate cancer treatment can significantly impact erectile function, and penile rehabilitation has been proposed to improve the impacts. However, the effectiveness of...
Prostate cancer treatment can significantly impact erectile function, and penile rehabilitation has been proposed to improve the impacts. However, the effectiveness of penile rehabilitations after treatment of prostate cancer is scarce. The aim of this systematic review was to evaluate the effectiveness of different interventions of penile rehabilitation program after prostate cancer treatment. We conducted a comprehensive search of electronic databases, PubMed and Google Scholar, to identify randomized controlled trials that evaluated interventions for penile rehabilitation after prostate cancer treatment. Studies that met our inclusion criteria were systematically reviewed, and data were synthesized and analyzed. We identified 11 randomized controlled trials that evaluated different interventions for penile rehabilitation after prostate cancer treatment. The interventions included the use of phosphodiesterase type 5 inhibitors, intracavernous injections, vacuum erection devices, and penile rehabilitation programs. The data suggest that these phosphodiesterase inhibitors, intracavernous injections, vacuum erection devices, and penile rehabilitation programs are promising in improving erectile function after prostate cancer treatment. However, the optimal timing and duration of these interventions remain unclear, and there is a need for further research to determine their long-term effectiveness and safety. Healthcare providers should consider individualized approaches to penile rehabilitation, taking into account patient characteristics and preferences.
PubMed: 38454969
DOI: 10.52225/narra.v3i2.174 -
Skin Research and Technology : Official... Mar 2024The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine,... (Review)
Review
AIMS AND OBJECTIVES
The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions.
METHOD
Databases including PubMed, Scopus, and Web of Science were meticulously searched for studies spanning from 2010 to August 2023, focusing on systemic oral and injectable therapies for vitiligo, using comprehensive keywords and search syntaxes tailored to each database. Key data extracted included study design, treatment efficacy, patient outcomes, patient satisfaction, and safety profiles.
RESULTS
In a total of 42 included studies, oral mini-pulse corticosteroid therapy (OMP) was the subject of six studies (14.2%). Minocycline was the focus of five studies (11.9%), while methotrexate, apremilast, and tofacitinib each were examined in four studies (9.5%). Antioxidants and Afamelanotide were the subjects of three studies each (7.1%). Cyclosporine, simvastatin, oral zinc, oral corticosteroids (excluding OMP) and injections, and baricitinib were each explored in two studies (4.8%). Azathioprine, mycophenolate mofetil, and Alefacept were the subjects of one study each (2.4%).
CONCLUSION
Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness.
Topics: Humans; Methotrexate; Azathioprine; Vitiligo; Mycophenolic Acid; Minocycline; Alefacept; Cyclosporine; Adrenal Cortex Hormones; Hypopigmentation; Simvastatin; Zinc; Purines; Pyrazoles; Sulfonamides; Azetidines; Thalidomide
PubMed: 38454597
DOI: 10.1111/srt.13642 -
American Journal of Clinical Dermatology May 2024The comparative efficacy of biologics and small-molecule inhibitors in treating palmoplantar psoriasis (PP) and palmoplantar pustulosis (PPP) remains uncertain. (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
The comparative efficacy of biologics and small-molecule inhibitors in treating palmoplantar psoriasis (PP) and palmoplantar pustulosis (PPP) remains uncertain.
OBJECTIVE
The aim was to perform a systematic review and network meta-analysis (NMA) to compare the efficacy of biologics and small-molecule inhibitors for the treatment of PP and PPP.
METHODS
MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched for eligible studies from inception to May 13, 2023. This NMA was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension Statement for Network Meta-Analyses guidelines. Frequentist random-effects models NMA was performed with the surface under the cumulative ranking curve calculated for ranking. Our primary outcome was the proportion of patients achieving a clear/minimal Palmoplantar Psoriasis/Pustulosis Physician Global Assessment score (PPPGA 0/1 or PPPPGA 0/1) response at 12-16 weeks. Secondary outcomes consisted of the percentage of overall improvement in palmoplantar score and of improvement ≥ 75%, at 12-16 weeks.
RESULTS
The study comprised a total of 29 randomized controlled trials (RCTs), involving 4798 psoriasis patients with palmoplantar diseases. For PP, 16 RCTs with nine different treatments, including adalimumab, apremilast, bimekizumab, etanercept, guselkumab, infliximab, ixekizumab, secukinumab, and ustekinumab were included for the analysis. In the NMA of PP, secukinumab 300 mg ranked highest (odds ratio [OR] 33.50, 95% confidence interval [CI] 4.37-256.86) in achieving PPPGA 0/1, followed by guselkumab 100 mg (OR 18.68, 95% CI 10.07-34.65). In the case of PPP, seven RCTs with six treatments, including apremilast, etanercept, guselkumab, imsidolimab, spesolimab, and ustekinumab, were included for the analysis. In the NMA of PPP, although no treatment demonstrated a significant difference compared to placebo in achieving PPPPGA 0/1, guselkumab 100 mg showed the greatest statistically significant improvement in the palmoplantar score (weighted mean difference 31.73, 95% CI 19.89-43.57) as a secondary outcome.
CONCLUSION
Among all available biologics and small-molecule inhibitors, secukinumab 300 mg and guselkumab 100 mg had the most favorable efficacy in treating PP and PPP, respectively.
Topics: Psoriasis; Humans; Biological Products; Network Meta-Analysis; Treatment Outcome; Dermatologic Agents; Randomized Controlled Trials as Topic; Severity of Illness Index; Antibodies, Monoclonal, Humanized; Thalidomide
PubMed: 38438782
DOI: 10.1007/s40257-024-00849-0 -
Minerva Urology and Nephrology Feb 2024Patients' treatment preferences (PTP) depend on the complex interaction of numerous patient- and treatment-related factors; their assessment can guide therapy and...
INTRODUCTION
Patients' treatment preferences (PTP) depend on the complex interaction of numerous patient- and treatment-related factors; their assessment can guide therapy and promote compliance of patients with erectile dysfunction (ED). We aimed to systematically describe the literature evaluating the treatment preferences of patients with ED, published in the last 25 years.
EVIDENCE ACQUISITION
A comprehensive bibliographic search of multiple databases was conducted in June, 2023. The literature search was limited to the articles published since 1998. Articles were deemed eligible if they described male patients with ED (P) undergoing treatment for this condition (I) compared with other treatments, placebo or sham therapy (C), and reported PTP (O). Only randomized controlled trials (RCTs) and post-hoc analyses of RCTs were selected (S). The data were presented in a narrative fashion. The risk of bias (RoB) was evaluated using the RoB 2 tool and the Mulhall-Montorsi model.
EVIDENCE SYNTHESIS
A total 14 RCTs evaluating 6,841 patients and 4 post-hoc analyses of RCTs were included. All RCTs were considered to be at high RoB. No validated tool was used to investigate PTP. Sildenafil was the most frequently evaluated ED treatment (9 RCTs). Sildenafil was chosen over placebo by 78-100% of subjects and over ICI in 70% of patients due to its easier route of administration. No significant difference in patient preference was recorded between Sildenafil tablets and orodispersible (53% vs. 47%, P>0.05). Tadalafil was preferred over Sildenafil by 66-73% of patients (P<0.05), mainly because it allowed an erection long after taking the drug (55-67%). Tadalafil as-needed was chosen over Tadalafil 3 times/week by 57-59% of the patients (P<0.05).
CONCLUSIONS
The available RCTs support the preference of ED patients for Sildenafil over ICI, Tadalafil over Sildenafil, and Tadalafil as-needed over Tadalafil 3 times/week. However, these findings should be considered at high RoB.
Topics: Humans; Male; Erectile Dysfunction; Randomized Controlled Trials as Topic; Sildenafil Citrate; Tadalafil; Patient Preference
PubMed: 38426421
DOI: 10.23736/S2724-6051.23.05552-0 -
Reproductive Toxicology (Elmsford, N.Y.) Apr 2024Studies have suggested associations between gestational exposure to caffeine and adverse outcomes, however the evidence is still limited. Therefore, a systematic review... (Review)
Review
Studies have suggested associations between gestational exposure to caffeine and adverse outcomes, however the evidence is still limited. Therefore, a systematic review was conducted to investigate the association between prenatal caffeine exposure and neurobehavioral disorders. The MEDLINE (PubMed), EMBASE, Scopus, Web of Science, and LILACS databases were searched. Observational studies involving women with documented caffeine consumption during pregnancy were eligible for inclusion. The outcomes evaluated were behavioral and intellectual development, Attention Deficit Hyperactivity Disorder, and related behaviors. The data were analyzed by qualitative synthesis. The ROBINS-I tool was employed to assess the risk of bias, and the certainty of evidence was evaluated using GRADE (PROSPERO: CRD42023421164). The search yielded fourteen studies that met the inclusion/exclusion criteria. The sample size among pregnant women ranged from 173 to 64,189, and among children ranged from 88 to 49,190. Maternal caffeine consumption during pregnancy ranged from 0 to 1000 mg/day, with the highest levels observed during mid-pregnancy. Seven studies indicated a potential association between prenatal caffeine exposure and neurobehavioral/neurodevelopment deficits, one study showed that prenatal caffeine exposure improved peer problems, and six studies did not show a significant effect of prenatal caffeine consumption on neurobehavioral disorders. The included studies were classified as moderate for the risk of bias and with very low certainty of evidence. Thus, the evidence is insufficient to confirm with certainty that the prenatal caffeine exposure leads to neurobehavioral disorders. Studies heterogenicity, as well as their variable quality and the presence of several confounding factors, generate uncertainty.
Topics: Child; Humans; Pregnancy; Female; Caffeine; Attention Deficit Disorder with Hyperactivity
PubMed: 38417581
DOI: 10.1016/j.reprotox.2024.108563 -
The Cochrane Database of Systematic... Feb 2024Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity that causes progressive constriction of the cheeks and mouth accompanied by severe pain and reduced... (Review)
Review
BACKGROUND
Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity that causes progressive constriction of the cheeks and mouth accompanied by severe pain and reduced mouth opening. OSF has a significant impact on eating and swallowing, affecting quality of life. There is an increased risk of oral malignancy in people with OSF. The main risk factor for OSF is areca nut chewing, and the mainstay of treatment has been behavioural interventions to support habit cessation. This review is an update of a version last published in 2008.
OBJECTIVES
To evaluate the benefits and harms of interventions for the management of oral submucous fibrosis.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 5 September 2022.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) of adults with a biopsy-confirmed diagnosis of OSF treated with systemic, locally delivered or topical drugs at any dosage, duration or delivery method compared against placebo or each other. We considered surgical procedures compared against other treatments or no active intervention. We also considered other interventions such as physiotherapy, ultrasound or alternative therapies.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. participant-reported resumption of normal eating, chewing and speech; 2. change or improvement in maximal mouth opening (interincisal distance); 3. improvement in range of jaw movement; 4. change in severity of oral/mucosal burning pain/sensation; 5.
ADVERSE EFFECTS
Our secondary outcomes were 6. quality of life; 7. postoperative discomfort or pain as a result of the intervention; 8. participant satisfaction; 9. hospital admission; 10. direct costs of medication, hospital bed days and any associated inpatient costs for the surgical interventions. We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We included 30 RCTs (2176 participants) in this updated review. We assessed one study at low risk of bias, five studies at unclear risk of bias and 24 studies at high risk of bias. We found diverse interventions, which we categorised according to putative mechanism of action. We present below our main findings for the comparison 'any intervention compared with placebo or no active treatment' (though most trials included habit cessation for all participants). Results for head-to-head comparisons of active interventions are presented in full in the main review. Any intervention versus placebo or no active treatment Participant-reported resumption of normal eating, chewing and speech No studies reported this outcome. Interincisal distance Antioxidants may increase mouth opening (indicated by interincisal distance (mm)) when measured at less than three months (mean difference (MD) 3.11 mm, 95% confidence interval (CI) 0.46 to 5.77; 2 studies, 520 participants; low-certainty evidence), and probably increase mouth opening slightly at three to six months (MD 8.83 mm, 95% CI 8.22 to 9.45; 3 studies, 620 participants; moderate-certainty evidence). Antioxidants may make no difference to interincisal distance at six-month follow-up or greater (MD -1.41 mm, 95% CI -5.74 to 2.92; 1 study, 90 participants; low-certainty evidence). Pentoxifylline may increase mouth opening slightly (MD 1.80 mm, 95% CI 1.02 to 2.58; 1 study, 106 participants; low-certainty evidence). However, it should be noted that these results are all less than 10 mm, which could be considered the minimal change that is meaningful to someone with oral submucous fibrosis. The evidence was very uncertain for all other interventions compared to placebo or no active treatment (intralesional dexamethasone injections, pentoxifylline, hydrocortisone plus hyaluronidase, physiotherapy). Burning sensation Antioxidants probably reduce burning sensation visual analogue scale (VAS) scores at less than three months (MD -30.92 mm, 95% CI -31.57 to -30.27; 1 study, 400 participants; moderate-certainty evidence), at three to six months (MD -70.82 mm, 95% CI -94.39 to -47.25; 2 studies, 500 participants; moderate-certainty evidence) and at more than six months (MD -27.60 mm, 95% CI -36.21 to -18.99; 1 study, 90 participants; moderate-certainty evidence). The evidence was very uncertain for the other interventions that were compared to placebo and measured burning sensation (intralesional dexamethasone, vasodilators). Adverse effects Fifteen studies reported adverse effects as an outcome. Six of these studies found no adverse effects. One study evaluating abdominal dermal fat graft reported serious adverse effects resulting in prolonged hospital stay for 3/30 participants. There were mild and transient general adverse effects to systemic drugs, such as dyspepsia, abdominal pain and bloating, gastritis and nausea, in studies evaluating vasodilators and antioxidants in particular.
AUTHORS' CONCLUSIONS
We found moderate-certainty evidence that antioxidants administered systemically probably improve mouth opening slightly at three to six months and improve burning sensation VAS scores up to and beyond six months. We found only low/very low-certainty evidence for all other comparisons and outcomes. There was insufficient evidence to make an informed judgement about potential adverse effects associated with any of these treatments. There was insufficient evidence to support or refute the effectiveness of the other interventions tested. High-quality, adequately powered intervention trials with a low risk of bias that compare biologically plausible treatments for OSF are needed. It is important that relevant participant-reported outcomes are evaluated.
Topics: Adult; Humans; Oral Submucous Fibrosis; Pentoxifylline; Drug-Related Side Effects and Adverse Reactions; Vasodilator Agents; Abdominal Pain; Antioxidants; Dexamethasone
PubMed: 38415846
DOI: 10.1002/14651858.CD007156.pub3