Topical preparations for the treatment of mild-to-moderate acne vulgaris: systematic review and network meta-analysis.

BACKGROUND: Acne is very common and can have a substantial impact on wellbeing. Guidelines suggest first-line management with topical treatments, but there is little evidence regarding which treatments are most effective. OBJECTIVES: To identify the most effective and best tolerated topical treatments for acne using network meta-analysis. METHODS: CENTRAL, MEDLINE, Embase and World Health Organization Trials Registry were searched from inception to June 2020 for randomized trials that included participants with mild/moderate acne. Primary outcomes were self-reported improvement in acne, and trial withdrawal. Secondary outcomes included change in lesion counts, Investigator's Global Assessment, change in quality of life and total number of adverse events. Network meta-analysis was undertaken using a frequentist approach. Risk of bias was assessed using the Cochrane Risk of Bias Tool and confidence in evidence was assessed using CINeMA. RESULTS: A total of 81 papers were included, reporting 40 trials with a total of 18 089 participants. Patient Global Assessment of Improvement was reported in 11 trials. Based on the pooled network estimates, compared with vehicle, benzoyl peroxide (BPO) was effective (35% vs. 26%) for improving self-reported acne. The combinations of BPO with adapalene (54% vs. 35%) or with clindamycin (49% vs. 35%) were ranked more effective than BPO alone. The withdrawal of participants from the trial was reported in 35 trials. The number of patients withdrawing owing to adverse events was low for all treatments. Rates of withdrawal were slightly higher for BPO with adapalene (2·5%) or clindamycin (2·7%) than BPO (1·6%) or adapalene alone (1·0%). Overall confidence in the evidence was low. CONCLUSIONS: Adapalene in combination with BPO may be the most effective treatment for acne but with a slightly higher incidence of withdrawal than monotherapy. Inconsistent reporting of trial results precluded firmer conclusions.

Trends in rifampicin and isoniazid resistance in patients with presumptive TB.

BACKGROUND: Early diagnosis of drug-resistant TB (DR-TB) is crucial in preventing the spread of the disease in the community. Introduction of upfront decentralised drug susceptibility testing to district-level as part of universal drug susceptibility testing (UDST) policy increased the feasibility of rapid and early testing for drug resistance closer to the patient and has resulted in reduced circumstances for transmission. The introduction of the first-line line-probe assay (FL-LPA), GenoType® MTBDRplus v2, has had an extensive impact on the management of multidrug-resistant TB (MDR-TB) in India.MATERIALS and METHODS: Sputum samples of patients with presumptive TB and DR-TB from selected districts of Tamil Nadu received through National TB Elimination Programme (NTEP) were subjected to FL-LPA as per programme guidelines. In this study, we present trends in genotypic resistance to isoniazid (INH) and rifampicin (RIF) during the 4 years (2016-2019) among these patients. Band patterns were analysed as per the updated GLI (Global Laboratory Initiative) LPA interpretation and reporting guidelines.RESULTS: A total of 26,349 samples were received during the study period. Smear-positive samples (n = 20231) were directly subjected to FL-LPA; smear-negative samples were cultured in liquid media and M. tuberculosis-positive cultures were tested using FL-LPA. A total of 18,441 were MTB-positive on FL-LPA. INH monoresistance, RIF monoresistance and MDR-TB was observed in respectively 8.7%, 1.1% and 3.3% of the samples. There was a decreasing trend in all types of resistance observed particularly after 2017 (P < 0.001). MDR-TB showed a steady decrease from 5.6% to 1.8%. S531L (19.5%) and S315T (61.1%) were the most common mutations identified in the rpoB and katG genes, respectively. The percentage of inhA-c-15t promoter mutation, indicating low-level INH resistance, showed a consistent increase (P < 0.001).CONCLUSION: The impact of the UDST policy on the NTEP may have led to this decreasing trend in RIF and INH resistance observed in the study period. The increase in low-level INH resistance mutation inhA-c-15t may be associated with ethionamide/prothionamide resistance, and this should be taken into account when designing DR-TB regimen.

Concomitant pulmonary disease is common among patients with extrapulmonary TB.

BACKGROUND: Microbiologic screening of extrapulmonary TB (EPTB) patients could inform recommendations for aerosol precautions and close contact prophylaxis. However, this is currently not routinely recommended in India. Therefore, we estimated the proportion of Indian patients with EPTB with microbiologic evidence of pulmonary TB (PTB).METHODS: We characterized baseline clinical, radiological and sputum microbiologic data of 885 adult and pediatric TB patients in Chennai and Pune, India, between March 2014 and November 2018.RESULTS: Of 277 patients with EPTB, enhanced screening led to the identification of 124 (45%) with concomitant PTB, including 53 (19%) who reported a cough >2 weeks; 158 (63%) had an abnormal CXR and 51 (19%) had a positive sputum for TB. Of 70 participants with a normal CXR and without any cough, 14 (20%) had a positive sputum for TB. Overall, the incremental yield of enhanced screening of patients with EPTB to identify concomitant PTB disease was 14% (95% CI 12-16).CONCLUSIONS: A high proportion of patients classified as EPTB in India have concomitant PTB. Our results support the need for improved symptom and CXR screening, and recommends routine sputum TB microbiology screening of all Indian patients with EPTB.

In vitro and in vivo evaluation of hydrophilic and hydrophobic polymers-based nicorandil-loaded peroral tablet compared with its once-daily commercial sustained-release tablet.

CONTEXT: Hydrophilic and hydrophobic polymer-based nicorandil (10 mg)-loaded peroral tablets were prepared using the wet granulation technique. The influence of varying amounts of hydroxypropyl methylcellulose (HPMC) (30-50 mg), ethylcellulose (2-4 mg), microcrystalline cellulose (5-20 mg) and Aerosil® (5-12 mg) in conjunction with the constant amounts (3 mg) of glidant and lubricant (magnesium stearate and talc) on the in vitro performances of the tablets (hardness, friability, weight variation, thickness uniformity, drug content, and drug release behavior) were investigated. OBJECTIVE: The objectives of this study were (i) to select a nicorandil-loaded peroral tablet that matched the in vitro dissolution profile of once-daily commercial sustained-release tablet, and (ii) to compare the in vivo sustaining/controlling efficacy of the selected peroral tablet with that of its commercial counterparts. RESULTS AND DISCUSSION: Because the nicorandil (10 mg)-loaded tablet prepared based on F-IX composition (50 mg HPMC, 4 mg ethylcellulose, 10 mg MCC and 3 mg glidant and lubricant) showed a release profile comparable to that of the Nikoran® OD SR tablet release profile, the tablet with this composition was considered to be the optimized/selected formulation and, therefore, was subjected to stability study and in vivo study in rabbits. Despite of the higher C(max) and AUC values obtained with the optimized tablet, there was no sign of difference between the optimized- and Nikoran® OD SR- tablets following a single-dose crossover oral administration into rabbit. CONCLUSION: The optimized tablet could be used as an alternative to the commercial once-daily tablet.

Interventions for oral lichen planus: A systematic review and network meta-analysis of randomized clinical trials.

BACKGROUND: Corticosteroids, calcineurin inhibitors, vitamin D, photodynamic therapy, herbal drugs are some of the interventions tried in clinical trials for treating oral lichen planus. We carried out the present network meta-analysis to compare the above-mentioned interventions. METHODS: Electronic databases were searched for randomized clinical trials evaluating interventions in patients with symptomatic oral lichen planus. Clinical resolution, clinical score, pain resolution, pain score, and adverse effects were the outcomes evaluated. RESULTS: Fifty-five (2831 patients) trials were included. Corticosteroids (OR: 13.6; 95% CI: 1.2, 155.4), pimecrolimus (OR: 14.7; 95% CI: 1.7, 125), purslane (OR: 18.4; 95% CI: 3.5, 97), and ozonized water/corticosteroids (OR: 52; 95% CI: 1.4, 1882.6) had better rates of clinical resolution compared to placebo. Corticosteroids (OR: 3.18; 95% CI: 1.2, 8.43), ozonized water/corticosteroids (OR: 9.9; 95% CI: 2.7, 36.2), aloe vera (OR: 13; 95%: 1.5, 111.8), pimecrolimus (OR: 18.8; 95% CI: 2, 177.4) and hyaluronic acid (OR: 24.8; 95% CI: 1.3, 457.6) were significantly associated with superior rates of pain resolution compared to placebo. Pimecrolimus and cyclosporine were associated with significantly higher risk of adverse effects than placebo. CONCLUSION: Topical corticosteroids were the most effective drug class for treating oral lichen planus.

Powered toothbrushes for plaque control in fixed orthodontic patients: a network meta-analysis.

BACKGROUND: Orthodontic patients are at greater risk due to the inability to clean around the components directly bonded to teeth. Hence, the aim of the present network meta-analysis is to compare the utility of powered toothbrushes in plaque control in patients with orthodontic brackets compared with manual tooth brushing. METHODOLOGY: Necessary data were extracted and analysed for Risk of Bias. Heterogeneity was assessed using Chi-square and I2 tests. Random effects model was used for both direct and mixed treatment comparisons. Standardized mean difference with 95% confidence interval was the effect estimate for plaque and bleeding scores and mean difference for pocket depth. Inconsistencies between the direct and indirect estimates were evaluated by H-statistics. GRADE approach was used to assess the quality of evidence. RESULTS: Pooled results from 14 studies showed significantly higher plaque scores in patients using manual toothbrushes. Pooled results from 13 studies showed significant higher bleeding scores as well with manual brushes. There was a significant reduction in pocket depth with electric toothbrushes. CONCLUSION: Powered toothbrushes are a promising alternative for plaque control in patients with fixed orthodontic brackets. Stronger evidence can be established with addition of long-term clinical trials based on the recommendations.

Patient preference and operating time for digital versus conventional impressions: a network meta-analysis.

BACKGROUND: Digital impression techniques have seen many advancements, with new hardware and software being developed each year. The technical advantages of these systems are real-time visualization, evaluation and archive, segmental capture, ease of recapture if necessary, economical in terms of no use of impression material or trays or disinfection, easy file transfer and communication with the laboratory. However patient satisfaction is one major factor that might influence the choice of impression technique. The aim of this network meta-analysis was to identify statistically the evidence on overall patient preferences relative to digital versus conventional impression techniques, in addition to the time taken in making these impressions. METHODOLOGY: Randomized or prospective clinical studies were identified based on the inclusion criteria in PUBMED, DARE and COCHRANE databases; subsequently pertinent data were extracted. Risk of bias of the included studies was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa scale. Heterogeneity amongst the studies in direct comparison was assessed by Chi-square and I2 tests using the Inverse variance heterogeneity model. Direct comparison estimates were derived by pooling the data from studies that compared the same intervention. Indirect comparison pooled estimates were derived by using the data amongst the studies, through a common comparator, using MetaXL software. Mean differences and Odds ratio at 95% confidence interval were used as the effect estimates, while inconsistencies were evaluated by H-statistics. GRADE working group approach was used to assess the quality of available evidence. RESULTS: Fourteen studies were included. Results from 11 studies  on 471 patients (236-Digital; 235-conventional) were pooled for patient preference with 95% confidence interval. The Forest plot showed a pooled estimate of 31.23 [5.95, 163.87], showing a statistically significant number of patients favouring digital impressions. Results from 11 studies reported the time taken in 589 patients (278-digital; 311 conventional). The pooled estimate (2.72 [0.08, 5.32]) (95% confidence interval) showed a statistically significant increase in the time required to make digital impressions. The overall time taken in minutes for the interventions in the digital group in decreasing order were: LAVA Cos (8.14[3.64,12,26] (statistically significant); I tero (4.11[-1.02,9.24]; CEREC (0.34[-4.14,4.82]). CONCLUSION: There was an overall preference for digital impressions, although the time required is longer. The factors related to the digital system, the operator and the patient were studied, with recommendations forming a basis for possible hardware and software upgrades of the digital systems that can produce significant improvement in the acceptance rate for both the patient and the clinician.

Diabetes and pre-diabetes among household contacts of tuberculosis patients in India: is it time to screen them all?

SETTING: Pre-diabetes mellitus (pre-DM) and DM increase the risk of developing tuberculosis (TB). Screening contacts of TB patients for pre-DM/DM and linking them to care may mitigate the risk of developing TB and improve DM management. OBJECTIVE: To measure the prevalence of pre-DM/DM and associated factors among the adult household contacts (HHCs) of pulmonary TB patients. METHODS: Between August 2014 and May 2017, adult HHCs of newly diagnosed adult PTB patients in Pune and Chennai, India, had single blood samples tested for glycosylated haemoglobin (HbA1c) at enrolment. DM was defined as previously diagnosed, self-reported DM or HbA1c 6.5%, and pre-DM as HbA1c between 5.7% and 6.4%. Latent tuberculous infection (LTBI) was defined as a positive tuberculin skin test (5 mm induration) or QuantiFERON® Gold In-Tube (0.35 international units/ml). RESULTS: Of 652 adult HHCs, 175 (27%) had pre-DM and 64 (10%) had DM. Forty (64%) HHCs were newly diagnosed with DM and 48 (75%) had poor glycaemic control (HbA1c 7.0%). Sixty-eight (22%) pre-DM cases were aged 18-34 years. Age 35 years, body mass index 25 kg/m2, chronic disease and current tobacco smoking were significantly associated with DM among HHCs. CONCLUSIONS: Adult HHCs of TB patients in India have a high prevalence of undiagnosed DM, pre-DM and LTBI, putting them at high risk for developing TB. Routine DM screening should be considered among all adult HHCs of TB.

Comparison of implant supported mandibular overdentures and conventional dentures on quality of life: a systematic review and meta-analysis of randomized controlled studies.

BACKGROUND: Conventional complete dentures and implant supported overdentures are commonly used by dentists to treat completely edentulous mandibular arches. There have been problems associated with retention and stability while treating completely edentulous mandibular arches compared to maxillary arches. Many factors have been attributed to this, primarily focusing on the decreased area available for support and increased resorption. Implant supported overdentures have increased the treatment options for resorbed ridges, especially the mandible. However, no reports have proved the superiority of one treatment option over the other, especially in terms of patient-centric outcome measures such as the Oral Health Impact Profile (OHIP). Hence, this meta-analysis was conducted. METHODS: A literature search of Medline (via PubMed), the Cochrane Central Register of Clinical Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) was performed. The reviewers screened titles, abstracts and performed full-text screening of eligible studies. The references from these studies were further screened for additional relevant studies. A random effects model was applied to measure the significance of the per cent mean difference in OHIP scale improvement between implant and conventional dentures. The Cochrane Risk of Bias Tool was applied to assess the selection, ascertainment and selective reporting biases. RESULTS: Five studies were reviewed and identified. Results of 441 patients (228 implant and 213 conventional) were pooled for analysis of primary outcome and other secondary outcomes. A forest plot of total OHIP scores and for secondary outcomes were obtained between the interventions. Results of 441 patients (228 implant and 213 conventional) were pooled for analysis of primary outcome with a mean difference [95% confidence interval] in the score of -30.72[-48.39, -13.05]; mean difference [95% confidence interval] in the score of -26.45[-43.56, -9.35] for functional limitation; -29.16[-60.89, 2.56] for physical pain; -77.61[-154.63, -0.60] for psychological discomfort; -33.70[-47.96, -19.44] for physical disability; -41.17[-55.93, -26.40] for psychological disability; -17.27[-29.44, 5.10] for social disability; and -28.45[-33.97, -22.92] for handicap. A statistically significant difference favouring the implant group was obtained except for physical pain. CONCLUSIONS: The implant overdenture group performed better in regard to patient satisfaction as measured using the OHIP questionnaire. Further studies are required to identify superiority between the two treatment options.

Phage lysin as a substitute for antibiotics to detect Mycobacterium tuberculosis from sputum samples with the BACTEC MGIT 960 system.

Phage lysin was evaluated as a substitute for antibiotics in sputum samples processed by a modified Petroff's method for the detection of Mycobacterium tuberculosis with the MGIT 960 system. One hundred and fifty sputum samples were processed, inoculated onto two slopes of Lowenstein-Jensen medium, and divided in to two aliquots of 0.5 mL each. One aliquot was added to 7 mL of MGIT medium containing polymyxin B, amphotericin B, nalidixic acid, trimethoprim and azlocillin (PANTA) (MGIT-PANTA) and the other was added to 7 mL of MGIT medium containing 0.8 mL of lysin (MGIT-Lysin). The samples were randomized and incubated at 37°C in the MGIT 960 system. The sensitivity and specificity of MGIT-Lysin were 97% and 88%, respectively, as compared with MGIT-PANTA. The average times to detection with MGIT-Lysin and MGIT-PANTA were 9.3 and 8.6 days, respectively. The rate of contamination with MGIT-PANTA and MGIT-Lysin were 16% and 7.3%, respectively. Phage lysin can be substituted for antibiotics in processed sputum samples for the detection of M. tuberculosis.