Male circumcision and prostate cancer: a meta-analysis revisited.

INTRODUCTION The relationship between circumcision and prostate cancer has been controversial. A recently published meta-analysis contradicted previous meta-analyses of male circumcision and prostate cancer risk. Our aim was to conduct a de novo meta-analysis and critically evaluate this recent paper published by Van Howe. MATERIALS AND METHODS: We retrieved data from each of the 12 source studies Van Howe used, then performed a random effects meta-analysis of those data. We critically examined the data and other information in Van Howe's study. RESULTS: Using the same values as Van Howe, we confirmed his finding of a positive association of circumcision with prostate cancer (random effects summary OR = 1.14; 95% CI 0.99, 1.31). However, our independent meta-analysis found a negative association of circumcision with prostate cancer (random effects summary OR= 0.87; 95% CI 0.76, 1.00; p = 0.05). The reason for this critical discrepancy was Van Howe's erroneous transposition of values for circumcised and uncircumcised men in his Table columns, leading to inversion of the result. We further critically evaluated a geographical analysis and cost analysis of circumcision and prostate cancer, as well as claims denying a role for sexually transmitted infections in prostate cancer etiology, finding these too to be misleading. CONCLUSIONS: Van Howe's 2020 meta-analysis was based on erroneous data transposition leading to an inverted outcome. The journal concerned recently corrected his Table. Van Howe's claim of a positive association of circumcision with country-level-age standardized prostate cancer prevalence and his cost analysis were found to be questionable. Our meta-analysis showed that circumcision is associated with lower prostate cancer risk.

Interferon-ß Is Less Effective Than Other Drugs in Controlling the Rate of Retinal Ganglion Cell Loss in MS.

OBJECTIVE: To investigate the association between disease-modifying therapies (DMTs) and the rate of progressive retinal ganglion cell (RGC) and nerve fiber loss in MS. METHODS: One hundred five relapsing-remitting patients with MS were followed annually for a median of 4.0 years using optical coherence tomography. Twenty-five healthy subjects were also included as normal controls. The rates of global peripapillary retinal nerve fiber layer (pRNFL), temporal RNFL (tRNFL), and ganglion cell inner plexiform layer (GCIPL) thinning were analyzed according to DMT type using a linear mixed-effects model. Optic radiation lesion volume was measured on brain MRI and included as a covariate to minimize the effects of retrograde transsynaptic degeneration. RESULTS: The annual rates of RNFL and GCIPL thinning were higher in patients treated with "platform" therapies (interferon-ß and glatiramer acetate) compared with DMTs of higher clinical efficacy (including fingolimod, dimethyl fumarate, natalizumab, alemtuzumab, rituximab, and ocrelizumab) (difference = -0.22 µm/y, p = 0.02 for pRNFL; difference = -0.34 µm/y, p = 0.009 for tRNFL; and difference = -0.16 µm/y, p = 0.005 for GCIPL). Based on an analysis of individual treatments (interferon-ß, glatiramer acetate, fingolimod, and natalizumab), interferon-ß was associated with inferior RGC preservation, relative to the other drugs. No effect difference was found between glatiramer acetate, fingolimod, and natalizumab. CONCLUSIONS: Progressive loss of RGCs in patients with MS is more pronounced in patients treated with interferon-ß than other DMTs. This finding may have implications for DMT selection in MS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with MS, treatment with interferon-ß compared with other DMTs leads to a more pronounced rate of retinal ganglion cell loss.

Prevalence of Phimosis in Males of All Ages: Systematic Review.

CONTEXT: Phimosis is considered virtually universal in newborn males and likely to resolve within a few years. Persistent phimosis can result in pain, sexual dysfunctions, increased risk of penile inflammatory conditions and penile cancer. There are two forms - primary phimosis and secondary phimosis - the latter often representing a consequence of lichen sclerosis, diabetes and obesity. OBJECTIVES: To conduct a systematic review to determine the prevalence of phimosis at different ages. DATA SOURCES: PubMed, Google Scholar, the Cochrane Library, and bibliographies of original studies were searched using the keyword phimosis. STUDY SELECTION: Studies containing original data on phimosis at any age. DATA EXTRACTION: Two reviewers independently verified study design, extracted data and rated studies for quality. RESULTS: Forty-three eligible studies were included: 27 from PubMed, 4 from Google Scholar, and 12 from bibliography searches. Phimosis was reported in most newborns, then gradually decreased in prevalence. Most studies did not differentiate primary from secondary phimosis, so values reported were net phimosis prevalence. There were 13 studies with data for males age ≥18 years. In all, 962 of 17,136 men had been diagnosed with phimosis (range 0.5%-13%). A random effects model found risk of phimosis in men was 3.4% (95% CI 1.8-6.6). CONCLUSION: Phimosis takes many years to resolve. Apart from spontaneous resolution, clinical interventions also contribute to the gradual reduction in prevalence among uncircumcised boys. The wide range of phimosis prevalence reported in adulthood may reflect variability in the extent of foreskin-preserving treatment of phimosis in different study cohorts.