Randomized Controlled Trials as Topic

In patients with prediabetes, Vitamin D supplementation appears to improve blood glucose levels and reduce progression to diabetes. James W. Mold, MD, MPH

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Background: The role of vitamin D in people who are at risk for type 2 diabetes remains unclear.

Purpose: To evaluate whether administration of vitamin D decreases risk for diabetes among people with prediabetes.

Data sources: PubMed, Embase, and ClinicalTrials.gov from database inception through 9 December 2022.

Study selection: Eligible trials that were specifically designed and conducted to test the effects of oral vitamin D versus placebo on new-onset diabetes in adults with prediabetes.

Data extraction: The primary outcome was time to event for new-onset diabetes. Secondary outcomes were regression to normal glucose regulation and adverse events. Prespecified analyses (both unadjusted and adjusted for key baseline variables) were conducted according to the intention-to-treat principle.

Data synthesis: Three randomized trials were included, which tested cholecalciferol, 20 000 IU (500 mcg) weekly; cholecalciferol, 4000 IU (100 mcg) daily; or eldecalcitol, 0.75 mcg daily, versus matching placebos. Trials were at low risk of bias. Vitamin D reduced risk for diabetes by 15% (hazard ratio, 0.85 [95% CI, 0.75 to 0.96]) in adjusted analyses, with a 3-year absolute risk reduction of 3.3% (CI, 0.6% to 6.0%). The effect of vitamin D did not differ in prespecified subgroups. Among participants assigned to the vitamin D group who maintained an intratrial mean serum 25-hydroxyvitamin D level of at least 125 nmol/L (≥50 ng/mL) compared with 50 to 74 nmol/L (20 to 29 ng/mL) during follow-up, cholecalciferol reduced risk for diabetes by 76% (hazard ratio, 0.24 [CI, 0.16 to 0.36]), with a 3-year absolute risk reduction of 18.1% (CI, 11.7% to 24.6%). Vitamin D increased the likelihood of regression to normal glucose regulation by 30% (rate ratio, 1.30 [CI, 1.16 to 1.46]). There was no evidence of difference in the rate ratios for adverse events (kidney stones: 1.17 [CI, 0.69 to 1.99]; hypercalcemia: 2.34 [CI, 0.83 to 6.66]; hypercalciuria: 1.65 [CI, 0.83 to 3.28]; death: 0.85 [CI, 0.31 to 2.36]).

Limitations: Studies of people with prediabetes do not apply to the general population. Trials may not have been powered for safety outcomes.

Conclusion: In adults with prediabetes, vitamin D was effective in decreasing risk for diabetes.

Primary funding source: None. (PROSPERO: CRD42020163522).

Author/s:

Pittas, A. G., Kawahara, T., Jorde, R., Dawson-Hughes, B., Vickery, E. M., Angellotti, E., Nelson, J., Trikalinos, T. A., Balk, E. M.

Comparative efficacy, tolerability, and acceptability of pharmacological interventions for the treatment of children, adolescents, and young adults with Tourette's syndrome: a systematic review and network meta-analysis

Aubrey Delammermore — Sat, 28 Jan 2023 06:00:00 +0000

Date Added:

January 28, 2023

Journal/Publication:

The Lancet

Publisher:

Elsevier

Publication Date:

December 14, 2022

Issue:

Volume:

Pages:

112-126

URL:

Comparative efficacy, tolerability, and acceptability of pharmacological interventions for the treatment of children, adolescents, and young adults with Tourette's syndrome: a systematic review and network meta-analysis

Type:

Meta-analyses, Reviews, and Guidelines

DOI (1):

10.1016/S2352-4642(22)00316-9

Keywords

Antipsychotic Agents

Obsessive-Compulsive Disorder

Systematic Reviews as Topic

Randomized Controlled Trials as Topic

MeSH

A review of the effectiveness of medications for treatment of the signs and symptoms of Tourette's Syndrome. James W. Mold, MD, MPH

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In clinical practice guidelines there is no consensus about the medications that should be initially offered to children and young people with Tourette's syndrome. To provide a rigorous evidence base that could help guide decision making and guideline development, we aimed to compare the efficacy, tolerability, and acceptability of pharmacological interventions for Tourette's syndrome.
Methods
For this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, Embase, PsycINFO, PubMed, Web of Science, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov, for published and unpublished studies from database inception to Nov 19, 2021. We included double-blind randomised controlled trials of any medication administered as a monotherapy for at least 1 week against another medication or placebo in children and adolescents (aged ≥4 years and ≤18 years), adults (>18 years), or both, diagnosed with Tourette's syndrome according to standardised criteria. We excluded studies that exclusively recruited participants with comorbid attention-deficit hyperactivity disorder or obsessive-compulsive disorder. The primary outcome was change in severity of tic symptoms (efficacy). Secondary outcomes were treatment discontinuations due to adverse events (tolerability) and for any reason (acceptability). Pharmacological interventions were examined considering medication categories and medications individually in separate analyses. Summary data were extracted and pooled with a random-effects network meta-analysis to calculate standardised mean differences for efficacy and odds ratios for tolerability and acceptability, with 95% CIs. The Confidence in Network Meta-Analysis (CINeMA) framework was used to assess the certainty of evidence. The protocol was pre-registered in PROSPERO (CRD42022296975).
Findings
Of the 12 088 records identified through the database search, 88 records representing 39 randomised controlled trials were included in the network meta-analysis; these 39 randomised controlled trials comprised 4578 participants (mean age 11·8 [SD 4·5] years; 3676 [80·8%] male participants) and evaluated 23 individual medications distributed across six medication categories. When considering medication categories, first-generation (standardised mean difference [SMD] –0·65 [95% CI –0·79 to –0·51]; low certainty of evidence) and second-generation (–0·71 [–0·88 to –0·54]; moderate certainty of evidence) antipsychotic drugs, as well as α-2 agonists (–0·21 [–0·39 to –0·03]; moderate certainty of evidence), were more efficacious than placebo. First-generation and second-generation antipsychotic drugs did not differ from each other (SMD 0·06 [95% CI –0·14 to 0·25]; low certainty of evidence). However, both first-generation (SMD 0·44 [95% CI 0·21 to 0·66]) and second-generation (0·49 [0·25 to 0·74]) antipsychotic drugs outperformed α-2 agonists, with moderate certainty of evidence. Similar findings were observed when individual medications were considered: aripiprazole (SMD –0·60 [95% CI –0·83 to –0·38]), haloperidol (–0·51 [–0·88 to –0·14]), olanzapine (–0·83 [–1·49 to –0·18]), pimozide (–0·48 [–0·84 to –0·12]), risperidone (–0·66 [–0·98 to –0·34]), and clonidine (–0·20 [–0·37 to –0·02]) all outperformed placebo, with moderate certainty of evidence. Antipsychotic medications did not differ from each other, but there was low to very low certainty of evidence for these comparisons. However, aripiprazole (SMD –0·40 [95% CI –0·69 to –0·12]) and risperidone (–0·46 [–0·82 to –0·11]) outperformed clonidine, with moderate certainty of evidence. Heterogeneity or inconsistency only emerged for a few comparisons. In terms of tolerability and acceptability, there were no relevant findings for any of the efficacious medication categories or individual medications against each other or placebo, but there was low to very low certainty of evidence associated with these comparisons.
Interpretation
Our analyses show that antipsychotic drugs are the most efficacious intervention for Tourette's syndrome, while α-2 agonists are also more efficacious than placebo and could be chosen by those who elect not to take antipsychotic drugs. Shared decision making about the degree of tic-related severity and distress or impairment, the trade-offs of efficacy and safety between antipsychotic drugs and α-2 agonists, and other highly relevant individual factors that could not be addressed in the present analysis, should guide the choice of medication for children and young people with Tourette's syndrome.

Author/s:

Farhat, L. C., Behling, E., Landeros-Weisenberger, A., Levine, J. L. S., Ferreira de Barros, P. M., Wang, Z., Bloch, M. H.

Sacral Neuromodulation for Neurogenic Lower Urinary Tract Dysfunction

Aubrey Delammermore — Tue, 25 Oct 2022 05:00:00 +0000

Date Added:

October 25, 2022

Journal/Publication:

New England Journal of Medicine Evidence

Publisher:

Massachusetts Medical Society

Publication Date:

July 7, 2022

Issue:

Volume:

URL:

Sacral Neuromodulation for Neurogenic Lower Urinary Tract Dysfunction

Type:

Clinical Research Results

Format:

Article

Keywords

Sacral Neuromodulation

Lower Urinary Tract Dysfunction

referral and consultation

Odds Ratio

Randomized Controlled Trials as Topic

MeSH

Electric Stimulation Therapy

Many patients with various forms of neurogenic bladder (neurogenic lower urinary tract dysfunction) appear to benefit significantly from sacral neuromodulation, a fairly simple, reversible surgical procedure. James W. Mold, MD, MPH

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BACKGROUND
Neurogenic lower urinary tract dysfunction (NLUTD) is a highly prevalent and disabling condition; nevertheless, standard treatments often remain unsatisfactory. Sacral neuromodulation (SNM) is a well-established therapy for non-NLUTD, but there is a lack of randomized controlled trials to show benefit in patients with NLUTD.

METHODS
For this sham-controlled, double-blind, multicenter trial, patients with refractory NLUTD (and intended SNM) were recruited at four Swiss SNM referral centers. After lead placement into the sacral foramina S3 (rarely, S4), all participants underwent SNM testing. If successful (≥50% improvement in key bladder diary variables), the neurostimulator was implanted for permanent stimulation. For 2 months, neuromodulation was optimized using subsensory stimulation with individually adjusted parameters. Thereafter, the neurostimulator remained on or was switched off (1:1 random allocation to group SNM ON or SNM OFF, respectively) for 2 months, followed by a neurourologic reevaluation. The primary outcome was success, as defined above, of SNM compared with baseline.

RESULTS
Of 124 patients undergoing SNM testing, 65 (52%) had successfully improved lower urinary tract function. Of these, 60 patients (median age, 49.5 years; 43 women) were randomly assigned to the intervention. After 2 months of intervention, the SNM ON group demonstrated a success rate of 76%. In the SNM OFF group, 42% of patients showed sustained SNM effects despite their neurostimulator being switched off during the last 2 months (odds ratio, 4.35; 95% confidence interval, 1.43 to 13.21; P=0.009). During the entire study period, there were 11 adverse events (6 dropouts; no dropouts during the intervention phase).

CONCLUSIONS
SNM effectively corrected refractory NLUTD in the short term in well-selected neurologic patients. (Funded by the Swiss National Science Foundation, Vontobel–Stiftung, Gottfried und Julia Bangerter–Rhyner Stiftung, Dr. Urs Mühlebach, and the Swiss Continence Foundation; ClinicalTrials.gov number, NCT02165774.)

Author/s:

Liechti, M. D., van der Lely, S., Knüpfer, S. C., Abt, D., Kiss, B., Lietner, L., Mordasini, L., Tornic, J., Wöllner, J., Mehnert, U., Bachmann, L. M., Burkhard, F. C., Engeler, D. S., Pannek, J., Kessler, T. M.