Background Familial Hypercholesterolemia (FH) is an autosomal-dominant disorder caused by mutations in one of three genes. In the 60% of patients who are mutation-negative we have recently shown that the clinical phenotype can be associated with an accumulation of common small-effect LDL-C-raising alleles using a 12-SNP score. The aims of the study were to improve the selection of SNPs, and to replicate the results in additional samples. Methods Receiver-operating characteristic curves were used to determine the optimum number of LDL-C SNPs. For replication analysis, we genotyped patients with a clinical diagnosis of FH from six countries for six LDL-C-associated alleles. We compared the weighted SNP score among patients with no confirmed mutation (FH/M-), those with a mutation (FH/M+), and controls from an UK population sample (WHII). Results Increasing the number of SNPs to 33 did not improve the ability of the score to discriminate between FH/M- and controls, while sequential removal of SNPs with smaller effects/lower frequency showed a weighted score of six SNPs performed as well as the 12-SNP score. Meta-analysis of the weighted 6-SNP score, based on polymorphisms in CELSR2, APOB, ABCG5/8, LDLR and APOE loci, in the independent FH/M- cohorts showed a consistently higher score in comparison to the WHII population (P<2.2×10-16). Modeling in individuals with a 6-SNP score in the top three quarters of the score distribution, indicated a >95% likelihood of a polygenic explanation of their increased LDL-C. Conclusion A 6-SNP LDL-C score consistently distinguishes FH/M- patients from healthy subjects. The hypercholesterolemia in 88% of mutation-negative patients is likely to have a polygenic basis.

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IMPORTANCEThere are knowledge gaps regarding the relative efficacy of 3 commonly used drugs for androgenetic alopecia (AGA), namely, minoxidil and the two 5-α reductase inhibitors dutasteride and finasteride.OBJECTIVE To examine the relative efficacy of any dose and administration route of minoxidil, dutasteride, and finasteride for the treatment of male AGA. DATA SOURCES Systematic searches were performed in PubMed on March 5, 2021, without date restrictions.STUDY SELECTION Eligible studies included those that investigated monotherapy with any dose and administration route of minoxidil, dutasteride, and finasteride.DATA EXTRACTION AND SYNTHESIS Data on the mean (SD) difference and sample size were used for the bayesian network meta-analyses. League tables and surface under the cumulative ranking curve values were used to examine the relative efficacy of the interventions. MAIN OUTCOMES AND MEASURESStudy end points were change in total and terminal hair count after 24 and 48 weeks of therapy. The 4 end points were quantified in hairs per square centimeters. RESULTSThe PubMed search yielded 848 records; after the 2 stages of screening, 23 studies were eligible for quantitative analyses. Mean (SD) age of patients ranged from 22.8 (3.3) years to 41.8 (12.3) years. The greatest increase in total hair count at 24 weeks (ie, first end point) was with 0.5 mg/d of dutasteride, which was significantly more efficacious than 1 mg/d of finasteride (mean difference, 7.1 hairs/cm 2 ; 95% CI, 5.1-9.3 hairs/cm 2 ) and minoxidil (0.25 mg/d [mean difference, 23.7 hairs/cm 2 ; 95% CI, 9.5-38.0 hairs/cm 2 ], 5 mg/d [mean difference, 15.0 hairs/cm 2 ; 95% CI, 3.9-26.1 hairs/cm 2 ], and 2% solution [mean difference, 8.5 hairs/cm 2 ; 95% CI, 4.8-12.3 hairs/cm 2 ]). The greatest increase in terminal hair count at 24 weeks (ie, second end point) was with 5 mg/d of minoxidil, which was significantly more efficacious than the 0.25-mg/d dose (mean difference, 43.6 hairs/cm 2 ; 95% CI, 29.7-57.7 hairs/cm 2 ) and its topical forms (in 2% [mean difference, 29.3 hairs/cm 2 ; 95% CI, 21.1-37.5 hairs/cm 2 ] and 5% [mean difference, 29.8 hairs/cm 2 ; 95% CI, 19.7-39.8 hairs/cm 2 ]); 5 mg/d of minoxidil was significantly more efficacious than 1 mg/d of finasteride (mean difference, 10.4 hairs/cm 2 ; 95% CI, 2.2-18.6 hairs/cm 2 ). The greatest increase in total hair count at 48 weeks (ie, third end point) was with 5 mg/d of finasteride, which was significantly more efficacious than 2% topical minoxidil (mean difference, 20.7 hairs/cm 2 ; 95% CI, 9.5-31.9 hairs/cm 2 ). The greatest increase in terminal hair count at 48 weeks (ie, fourth end point) was with 1 mg/d of finasteride, which was significantly more effective than topical minoxidil (in 2% [mean difference, 32.1 hairs/cm 2 ; 95% CI, 23.9-40.3 hairs/cm 2 ] and 5% [mean difference, 26.2 hairs/cm 2 ; 95% CI, 16.2-36.2 hairs/cm 2 ]). CONCLUSIONS AND RELEVANCEAs efficacy data from head-to-head trials accumulate, there could be a better sense of the relative efficacy of the different doses of the 5-...

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Griseofulvin was the treatment of choice for tinea capitis in the 1950s; however, newer treatments have emerged, ketoconazole, terbinafine, itraconazole, and fluconazole. 1-3 The efficacy and safety of many monotherapies used for tinea capitis have not been simultaneously compared in a randomized controlled trial (RCT) study design; information on relative efficacy and safety is relevant to medical practice and health policy. We conducted a systematic review and network meta-analyses (NMAs) to determine the relative efficacy

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