randomized control trial

Comparative Efficacy of Pharmacological Treatments for Acne Vulgaris: A Network Meta-Analysis of 221 Randomized Controlled Trials

Rowan Hutchins — Tue, 26 Sep 2023 05:00:00 +0000

Date Added:

September 26, 2023

Journal/Publication:

Annals of Family Medicine

Publication Date:

July 1, 2023

Issue:

Volume:

Pages:

358-369

URL:

Comparative Efficacy of Pharmacological Treatments for Acne Vulgaris: A Network Meta-Analysis of 221 Randomized Controlled Trials

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

https://doi.org/10.1370/afm.2995

Keywords

randomized control trial

adolescent

acne

PMID (1):

37487721

MeSH

Acne Vulgaris

Duration of Therapy

A useful summary of the relative effectiveness of various acne treatment strategies. James W. Mold, MD, MPH

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PURPOSE Acne is an extremely common skin disease with an estimated global prevalence of 9.4%. We aim to provide comprehensive comparisons of the common pharmacological treatments for acne.

METHODS Randomized controlled trials comparing the efficacy of pharmacological therapies for acne vulgaris in patients of any age and sex and with a treatment duration of >2 weeks were included. PubMed and Embase databases were searched from inception until February 2022. Our prespecified primary end points were mean percentage reduction in total, inflammatory, and noninflammatory lesions. Treatment ranking was determined by P values.

RESULTS There were 210 articles describing 221 trials and 37 interventions included in the analysis. Our primary analysis of percentage reduction in total lesion count had 65,601 patients enrolled. Across all trials, the mean age was 20.4 years. The median duration of treatment was 12 weeks. The median total, inflammatory, and noninflammatory lesion counts were 72, 27, and 44, respectively. The most effective treatment was oral isotretinoin (mean difference [MD] = 48.41; P = 1.00), followed by triple therapy containing a topical antibiotic, a topical retinoid, and benzoyl peroxide (BPO) (MD = 38.15; P = .95) and by triple therapy containing an oral antibiotic, a topical retinoid, and BPO (MD = 34.83; P = .90). For monotherapies, oral or topical antibiotics or topical retinoids have comparable efficacy for inflammatory lesions, while oral or topical antibiotics have less effect on noninflammatory lesions.

CONCLUSION The most effective treatment for acne is oral isotretinoin, followed by triple therapies containing a topical retinoid, BPO, and an antibiotic. We present detailed comparisons of each intervention to serve as a practical database.

Author/s:

Huang, Chung-Yen, Chang, I-Jing, Bolick, Nicole, Hsu, Wan-Ting, Su, Chin-Hua, Hsieh, Tyng-Shiuan, Huang, I-Hsuan, Lee, Chien-Chang

Prune Juice Containing Sorbitol, Pectin, and Polyphenol Ameliorates Subjective Complaints and Hard Feces While Normalizing Stool in Chronic Constipation: A Randomized Placebo-Controlled Trial

Aubrey Delammermore — Sat, 22 Oct 2022 05:00:00 +0000

Date Added:

October 22, 2022

Journal/Publication:

American Journal of Gastroenterology

Publisher:

Wolters Kluwer Health

Publication Date:

August 12, 2022

Issue:

Volume:

117

Pages:

1714-1717

URL:

Prune Juice Containing Sorbitol, Pectin, and Polyphenol Ameliorates Subjective Complaints and Hard Feces While Normalizing Stool in Chronic Constipation: A Randomized Placebo-Controlled Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.14309/ajg.0000000000001931

Keywords

randomized control trial

PMID (1):

35971232

MeSH

Sorbitol*

Constipation / drug therapy

Diarrhea / drug therapy

Defecation

Polyphenols*

Prune juice inexpensively resolves chronic constipation without causing diarrhea or increasing gas. James W. Mold, MD, MPH

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Introduction: The aim of this study was to determine the effectiveness of prune juice on chronic constipation.

Methods: We conducted a double-blind, randomized, placebo-controlled trial in Japanese subjects with chronic constipation.

Results: Prune intake significantly decreased hard and lumpy stools while increasing normal stool and not increasing loose and watery stools. Prune intake also ameliorated subjective complaints of constipation and hard stools, without alteration of flatulence, diarrhea, loose stools, or urgent need for defecation. There were no adverse events or laboratory abnormalities of liver or renal function after prune intake.

Discussion: Prune juice exerted an effective and safe natural food therapy for chronic constipation.

Author/s:

Koyama, T., Nagata, N., Nishiura, K., Miura, N., Kawai, T., Yamamota, H.

Pharmacologic and Nonpharmacologic Therapies in Adult Patients With Exacerbation of COPD: A Systematic Review

John Bayhi — Fri, 18 Oct 2019 13:01:46 +0000

Date Added:

October 18, 2019

Journal/Publication:

AHRQ Website

Publisher:

Agency for Healthcare Research and Quality

Publication Date:

October 11, 2019

URL:

Pharmacologic and Nonpharmacologic Therapies in Adult Patients With Exacerbation of COPD

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.23970/AHRQEPCCER221

Keywords

copd

chronic obstructive pulmonary disease

therapy

randomized control trial

systematic review

Key points are on page ii. Antibiotics and corticosteroids and some non-pharmacologic strategies are effective. We still don’t know the best corticosteroid dose or route. James W. Mold, MD, MPH

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Objectives. To synthesize existing knowledge about the effectiveness and harms of pharmacologic and nonpharmacologic treatments for exacerbations of chronic obstructive pulmonary disease (ECOPD).

Data sources. Embase®, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, MEDLINE® Daily, MEDLINE, Cochrane Central Registrar of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from database inception to January 2, 2019.

Review methods. We included randomized controlled trials (RCTs) that evaluated pharmacologic intervention or nonpharmacologic interventions for ECOPD. The strength of evidence (SOE) was graded for critical final health outcomes.

Results. We included 98 RCTs (13,401 patients, mean treatment duration 9.9 days, mean followup 3.7 months). Final health outcomes, including mortality, resolution of exacerbation, hospital readmissions, repeat exacerbations, and need for intubation, were infrequently evaluated and often showed no statistically significant differences between groups. Antibiotic therapy increases the clinical cure rate and reduces the clinical failure rate regardless of the severity of ECOPD (moderate SOE). There is insufficient evidence to support a particular antibiotic regimen. Oral and intravenous corticosteroids improve dyspnea and reduce the clinical failure rate (low SOE). Despite the ubiquitous use of inhaled bronchodilators in ECOPD, we found only a small number of trials that assessed lung function tests, and not final health outcomes. The evidence is insufficient to support the effect of aminophyllines, magnesium sulfate, mucolytics, inhaled corticosteroids, inhaled antibiotics, 5-lipoxygenase inhibitor, and statins on final health outcomes. Titrated oxygen reduces mortality compared with high flow oxygen (low SOE). Low SOE suggested benefit from some nonpharmacologic interventions such as chest physiotherapy using vibration/percussion/massage or breathing technique (on dyspnea), resistance training (on dyspnea and quality of life), early pulmonary rehabilitation commenced before hospital discharge during the initial most acute phase of exacerbation rather than the convalescence period (on dyspnea) and whole body vibration training (on quality of life). Vitamin D supplementation may improve quality of life (low SOE).

Conclusions. Although chronic obstructive pulmonary disease is a common condition, the evidence base for most interventions in ECOPD remains limited. Systemic antibiotics and corticosteroids are associated with improved outcomes in mild and moderate to severe ECOPD. Titrated oxygen reduces mortality. Future research is required to assess the effectiveness of several emerging nonpharmacologic and dietary treatments.

Author/s:

Dobler, CC, Morrow, AS, Farah, MH, Beuschel, B, Majzoub, AM, Wilson, ME, Hasan, B, Seisa, MO, Daraz, L, Prokop, LJ, Murad, MH, Wang, Z

Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma

John Bayhi — Thu, 26 Sep 2019 14:21:17 +0000

Date Added:

September 26, 2019

Journal/Publication:

The New England Journal of Medicine

Publisher:

Massachusetts Medical Society

Publication Date:

September 26, 2019

Issue:

Volume:

381

Pages:

1227-1239

URL:

Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa1905560

Keywords

asthma

African Americans

glucocorticoids

randomized control trial

PMID (1):

31553835

MeSH

fluticasone-salmeterol drug combination

Some patients with poorly controlled asthma need significantly increased doses of inhaled corticosteroids. James W. Mold, MD, MPH

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BACKGROUND:

Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients.

METHODS:

We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry.

RESULTS:

When quintupling the dose of fluticasone (to 250 μg twice a day) was compared with adding salmeterol (50 μg twice a day) and doubling the fluticasone (to 100 μg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P = 0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol-low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P = 0.003]; salmeterol-medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P = 0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age.

CONCLUSIONS:

In contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA. (Funded by the National Heart, Lung, and Blood Institute; BARD ClinicalTrials.gov number, NCT01967173.).

Author/s:

Wechsler, ME, Szefler, SJ, Ortega, VE, Pongracic, JA, Chinchili, V, Lima, JJ, Krishnan, JA, Kunselman, SJ, Mauger, D, Bleecker, ER, Bacharier, LB, Beigelman, A, Benson, M, Blake, KV, Cabana, MD, Cardet, JC, Castro, M, Chmiel, JF, Covar, R, Denlinger, L, DiMango, E, Fitzpatrick, AM, Gentile, D, Grossman, N, Holguin, F, Jackson, DJ, Kumar, H, Kraft, M, LaForce, CF, Lang, J, Lazarus, SC, Lemanske, RF Jr, Long, D, Lugogo, N, Martinez, F, Meyers, DA, Moore, WC, Moy, J, Naureckas, E, Olin, JT, Peters, SP, Phipatanakul, W, Que, L, Raissy, H, Robison, RG, Ross, K, Sheehan, W, Smith, LJ, Solway, J, Sorkness, CA, Sullivan-Vedder, L, Wenzel, S, Israel, E, NHLBI AsthmaNet

Glucocorticoids for croup in children

John Bayhi — Tue, 24 Sep 2019 22:49:32 +0000

Date Added:

September 24, 2019

Journal/Publication:

Cochrane Database of Systematic Reviews

Publisher:

The Cochrane Collaboration / John Wiley & Sons, Ltd.

Publication Date:

August 22, 2018

URL:

Glucocorticoids for croup in children

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1002/14651858.CD001955.pub4

Keywords

croup

children

randomized control trial

adolescent

PMID (1):

30133690

MeSH

Randomized Controlled Trials as Topic

Corticosteroids reduce symptoms of croup in children for at least 24 hours. The optimal dose and route have not been established. James W. Mold, MD, MPH

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BACKGROUND:

Glucocorticoids are commonly used for croup in children. This is an update of a Cochrane Review published in 1999 and previously updated in 2004 and 2011.

OBJECTIVES:

To examine the effects of glucocorticoids for the treatment of croup in children aged 0 to 18 years.

SEARCH METHODS:

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 2, 2018), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE (1946 to 3 April 2018), and Embase (Ovid) (1996 to 3 April 2018, week 14), and the trials registers ClinicalTrials.gov (3 April 2018) and the World Health Organization International Clinical Trials Registry Platform (ICTRP, 3 April 2018). We scanned the reference lists of relevant systematic reviews and of the included studies.

SELECTION CRITERIA:

We included randomised controlled trials (RCTs) that investigated children aged 0 to 18 years with croup and measured the effects of glucocorticoids, alone or in combination, compared to placebo or another pharmacologic treatment. The studies needed to report at least one of our primary or secondary outcomes: change in croup score; return visits, (re)admissions or both; length of stay; patient improvement; use of additional treatments; and adverse events.

DATA COLLECTION AND ANALYSIS:

One author extracted data from each study and another verified the extraction. We entered the data into Review Manager 5 for meta-analysis. Two review authors independently assessed risk of bias for each study using the Cochrane 'Risk of bias' tool and the certainty of the body of evidence for the primary outcomes using the GRADE approach.

MAIN RESULTS:

We added five new RCTs with 330 children. This review now includes 43 RCTs with a total of 4565 children. We assessed most (98%) studies as at high or unclear risk of bias. Compared to placebo, glucocorticoids improved symptoms of croup at two hours (standardised mean difference (SMD) -0.65, 95% confidence interval (CI) -1.13 to -0.18; 7 RCTs; 426 children; moderate-certainty evidence), and the effect lasted for at least 24 hours (SMD -0.86, 95% CI -1.40 to -0.31; 8 RCTs; 351 children; low-certainty evidence). Compared to placebo, glucocorticoids reduced the rate of return visits or (re)admissions or both (risk ratio 0.52, 95% CI 0.36 to 0.75; 10 RCTs; 1679 children; moderate-certainty evidence). Glucocorticoid treatment reduced the length of stay in hospital by about 15 hours (mean difference -14.90, 95% CI -23.58 to -6.22; 8 RCTs; 476 children). Serious adverse events were infrequent. Publication bias was not evident. Uncertainty remains with regard to the optimal type, dose, and mode of administration of glucocorticoids for reducing croup symptoms in children.

AUTHORS' CONCLUSIONS:

Glucocorticoids reduced symptoms of croup at two hours, shortened hospital stays, and reduced the rate of return visits to care. Our conclusions have changed, as the previous version of this review reported that glucocorticoids reduced symptoms of croup within six hours.

Author/s:

Gates, A, Gates, M, Vandermeer, B, Johnson, C, Hartling, L, Johnson, DW, Klassen, TP

C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations

John Bayhi — Thu, 11 Jul 2019 19:47:05 +0000

Date Added:

July 11, 2019

Journal/Publication:

New England Journal of Medicine

Publisher:

Massachusetts Medical Society

Publication Date:

July 11, 2019

Issue:

Volume:

381

Pages:

111-120

URL:

C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa1803185

Keywords

C-reactive protein

primary care

chronic obstructive pulmonary disease

copd

CRP

randomized control trial

antibiotics

PMID (1):

31291514

MeSH

Point-Of-Care Testing

anti-bacterial agents

technology assessment, biomedical

Wales

follow-up studies

random allocation

pulmonary disease, chronic obstructive

health status

Surveys and Questionnaires

primary health care

referral and consultation

England

In adults with acute COPD exacerbations, serum CRP-based decision-making led to fewer antibiotic prescriptions with no adverse consequences. Physicians and patients in the intervention group were advised to consider all clinically relevant information. However, they were advised to consider that CRP levels < 4omg/L indicated that antibiotics were probably not needed, levels between 20 and 40 mg/L were indeterminant, and levels above 40 mg/L suggested that antibiotics were probably necessary. Note: In this study, physicians were able to obtain CRP levels at the point of care. James W. Mold, MD, MPH

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BACKGROUND

Point-of-care testing of C-reactive protein (CRP) may be a way to reduce unnecessary use of antibiotics without harming patients who have acute exacerbations of chronic obstructive pulmonary disease (COPD).

METHODS

We performed a multicenter, open-label, randomized, controlled trial involving patients with a diagnosis of COPD in their primary care clinical record who consulted a clinician at 1 of 86 general medical practices in England and Wales for an acute exacerbation of COPD. The patients were assigned to receive usual care guided by CRP point-of-care testing (CRP-guided group) or usual care alone (usual-care group). The primary outcomes were patient-reported use of antibiotics for acute exacerbations of COPD within 4 weeks after randomization (to show superiority) and COPD-related health status at 2 weeks after randomization, as measured by the Clinical COPD Questionnaire, a 10-item scale with scores ranging from 0 (very good COPD health status) to 6 (extremely poor COPD health status) (to show noninferiority).

RESULTS

A total of 653 patients underwent randomization. Fewer patients in the CRP-guided group reported antibiotic use than in the usual-care group (57.0% vs. 77.4%; adjusted odds ratio, 0.31; 95% confidence interval [CI], 0.20 to 0.47). The adjusted mean difference in the total score on the Clinical COPD Questionnaire at 2 weeks was −0.19 points (two-sided 90% CI, −0.33 to −0.05) in favor of the CRP-guided group. The antibiotic prescribing decisions made by clinicians at the initial consultation were ascertained for all but 1 patient, and antibiotic prescriptions issued over the first 4 weeks of follow-up were ascertained for 96.9% of the patients. A lower percentage of patients in the CRP-guided group than in the usual-care group received an antibiotic prescription at the initial consultation (47.7% vs. 69.7%, for a difference of 22.0 percentage points; adjusted odds ratio, 0.31; 95% CI, 0.21 to 0.45) and during the first 4 weeks of follow-up (59.1% vs. 79.7%, for a difference of 20.6 percentage points; adjusted odds ratio, 0.30; 95% CI, 0.20 to 0.46). Two patients in the usual-care group died within 4 weeks after randomization from causes considered by the investigators to be unrelated to trial participation.

CONCLUSIONS

CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm. (Funded by the National Institute for Health Research Health Technology Assessment Program; PACE Current Controlled Trials number, ISRCTN24346473.)

Author/s:

Butler, Christopher C., Gillespie, David, White, Patrick, Bates, Janine, Lowe, Rachel, Thomas-Jones, Emma, Wootton, Mandy, Hood, Kerenza, Phillips, Rhiannon, Melbye, M., Llor, Carl, Cals, Jochen W.L.

Controlled Trial of Budesonide–Formoterol as Needed for Mild Asthma

Tracy Ashby — Thu, 23 May 2019 05:00:00 +0000

Date Added:

May 23, 2019

Journal/Publication:

The New England Journal of Medicine

Publisher:

Massachusetts Medical Society

Publication Date:

May 23, 2019

Issue:

Volume:

380

Pages:

2020-2030

URL:

Controlled Trial of Budesonide-Formoterol as Needed for Mild Asthma.

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa1901963

Keywords

asthma

randomized control trial

PMID (1):

31112386

MeSH

nebulizers and vaporizers

metered dose inhalers

In this randomized clinical trial, budesonide–formoterol (e.g. Symbacort) used on an as-needed basis resulted in a lower risk of severe exacerbation of asthma than as-needed use of a short-acting SABA; the risk was similar to that of budesonide maintenance therapy plus as-needed SABA. James W. Mold, MD, MPH

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BACKGROUND:

In double-blind, placebo-controlled trials, budesonide-formoterol used on an as-needed basis resulted in a lower risk of severe exacerbation of asthma than as-needed use of a short-acting β2-agonist (SABA); the risk was similar to that of budesonide maintenance therapy plus as-needed SABA. The availability of data from clinical trials designed to better reflect clinical practice would be beneficial.

METHODS:

We conducted a 52-week, randomized, open-label, parallel-group, controlled trial involving adults with mild asthma. Patients were randomly assigned to one of three treatment groups: albuterol (100 μg, two inhalations from a pressurized metered-dose inhaler as needed for asthma symptoms) (albuterol group); budesonide (200 μg, one inhalation through a Turbuhaler twice daily) plus as-needed albuterol (budesonide maintenance group); or budesonide-formoterol (200 μg of budesonide and 6 μg of formoterol, one inhalation through a Turbuhaler as needed) (budesonide-formoterol group). Electronic monitoring of inhalers was used to measure medication use. The primary outcome was the annualized rate of asthma exacerbations.

RESULTS:

The analysis included 668 of 675 patients who underwent randomization. The annualized exacerbation rate in the budesonide-formoterol group was lower than that in the albuterol group (absolute rate, 0.195 vs. 0.400; relative rate, 0.49; 95% confidence interval [CI], 0.33 to 0.72; P<0.001) and did not differ significantly from the rate in the budesonide maintenance group (absolute rate, 0.195 in the budesonide-formoterol group vs. 0.175 in the budesonide maintenance group; relative rate, 1.12; 95% CI, 0.70 to 1.79; P = 0.65). The number of severe exacerbations was lower in the budesonide-formoterol group than in both the albuterol group (9 vs. 23; relative risk, 0.40; 95% CI, 0.18 to 0.86) and the budesonide maintenance group (9 vs. 21; relative risk, 0.44; 95% CI, 0.20 to 0.96). The mean (±SD) dose of inhaled budesonide was 107±109 μg per day in the budesonide-formoterol group and 222±113 μg per day in the budesonide maintenance group. The incidence and type of adverse events reported were consistent with those in previous trials and with reports in clinical use.

CONCLUSIONS:

In an open-label trial involving adults with mild asthma, budesonide-formoterol used as needed was superior to albuterol used as needed for the prevention of asthma exacerbations. (Funded by AstraZeneca and the Health Research Council of New Zealand; Novel START Australian New Zealand Clinical Trials Registry number, ACTRN12615000999538.).

Author/s:

Beasley, Richard, Holliday, Mark, Reddel, Helen K., Braithwaite, Irene, Ebmeier, Stefan, Hancox, Robert J., Harrison, Tim, Houghton, Claire, Oldfield, Karen, Papi, Alberto, Pavord, Ian D., Williams, Mathew, Weatherall, Mark