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Randomised trials show that male circumcision reduces the prevalence and incidence of high-risk human papillomavirus (HPV) infection in men. We assessed the efficacy of male circumcision to reduce prevalence and incidence of high-risk HPV in female partners of circumcised men. In two parallel but independent randomised controlled trials of male circumcision, we enrolled HIV-negative men and their female partners between 2003 and 2006, in Rakai, Uganda. With a computer-generated random number sequence in blocks of 20, men were assigned to undergo circumcision immediately (intervention) or after 24 months (control). HIV-uninfected female partners (648 of men from the intervention group, and 597 of men in the control group) were simultaneously enrolled and provided interview information and self-collected vaginal swabs at baseline, 12 months, and 24 months. Vaginal swabs were tested for high-risk HPV by Roche HPV Linear Array. Female HPV infection was a secondary endpoint of the trials, assessed as the prevalence of high-risk HPV infection 24 months after intervention and the incidence of new infections during the trial. Analysis was by intention-to-treat. An as-treated analysis was also done to account for study-group crossovers. The trials were registered, numbers NCT00425984 and NCT00124878. During the trial, 18 men in the control group underwent circumcision elsewhere, and 31 in the intervention group did not undergo circumcision. At 24-month follow-up, data were available for 544 women in the intervention group and 488 in the control group; 151 (27·8%) women in the intervention group and 189 (38·7%) in the control group had high-risk HPV infection (prevalence risk ratio=0·72, 95% CI 0·60–0·85, p=0·001). During the trial, incidence of high-risk HPV infection in women was lower in the intervention group than in the control group (20·7 infections vs 26·9 infections per 100 person-years; incidence rate ratio=0·77, 0·63–0·93, p=0·008). Our findings indicate that male circumcision should now be accepted as an efficacious intervention for reducing the prevalence and incidence of HPV infections in female partners. However, protection is only partial; the promotion of safe sex practices is also important. The Bill & Melinda Gates Foundation, National Institutes of Health, and Fogarty International Center.

In the appropriate clinical setting, the addition of IHC staining for NKX3.1, along with other prostate-restricted markers, may prove to be a valuable adjunct to definitively determine prostatic origin in poorly differentiated metastatic carcinomas. 5 Discussion Barbosa et al 2 indicated that very few paranasal metastases have been reported. Diagnosis is made by local biopsy and histopathological evaluation with immunohistochemical stains.3 Radiotherapy helps alleviate symptoms, such as bleeding and pain, which can diminish quality of life.4 Clinicians must be vigilant that the epistaxis can also be from a metastatic lesion. CS: provided contributions to the acquisition, analysis of data, drafting the work and had final approval of the version published.

Early identification of inpatient discharges to skilled nursing facilities (SNFs) facilitates care transition planning. Predictive information in admission history and physical notes (H&Ps) is dispersed across long documents. Language models adeptly predict clinical outcomes from text but have limitations: token length constraints, noisy inputs, and opaque outputs. Therefore, we developed extraction-based language model classification (ELC): generative language models distill H&Ps into task-relevant categories (“Structured Extracted Data”) before summarizing them into a concise narrative (“AI Risk Snapshot”). We hypothesized that language models utilizing AI Risk Snapshots to predict SNF discharges would perform the best. In this retrospective observational study, nine language models predicted SNF discharges from unstructured predictors (raw H&P text, truncated assessment and plan) and ELC-derived predictors (Structured Extracted Data, AI Risk Snapshots). ELC substantially reduced input length (AI Risk Snapshot median 141 tokens vs raw H&P median 2,120 tokens) and improved average AUROC and AUPRC across models. The best performance was achieved by Bio+Clinical BERT fine-tuned on AI Risk Snapshots (AUROC = .851). AI Risk Snapshots enhanced interpretability by aligning with nurse case managers’ risk assessments and facilitating prompt design. Structuring and summarizing H&Ps via ELC thus mitigates the practical limitations of language models and improves SNF discharge prediction.

Background With almost 20% unnecessary spending on healthcare, there has been increasing interest in high value care defined as the best care for the patient, with the optimal result for the circumstances, delivered at the right price. The American Association of Medical Colleges recommend that medical students are proficient in concepts of cost-effective clinical practice by graduation, thus leading to curricula on high value care. However little is published on the effectiveness of these curricula on medical students’ ability to practice high value care. Methods In addition to the standard curriculum, the intervention group received two classroom sessions and three virtual patients focused on the concepts of high value care. The primary outcome was number of tests and charges for tests on standardized patients. Results 136 students enrolled in the Core Clerkship in Internal Medicine and 70 completed the high value care curriculum. There were no significant differences in ordering of appropriate tests (3.1 vs. 3.2 tests/students, p  = 0.55) and inappropriate tests (1.8 vs. 2.2, p  = 0.13) between the intervention and control. Students in the intervention group had significantly lower median Medicare charges ($287.59 vs. $500.86, p  = 0.04) and felt their education in high value care was appropriate (81% vs. 56%, p  = 0.02). Conclusions This is the first study to describe the impact of a high value care curriculum on medical students’ ordering practices. While number of inappropriate tests was not significantly different, students in the intervention group refrained from ordering expensive tests.

Male circumcision reduces the transmission of high-risk human papillomavirus (HPV) in HIV-uninfected men and their female partners. We assessed whether circumcision of HIV-infected men would reduce the transmission of high-risk HPV to their female partners. Female partners of HIV-infected men (aged 15–49 years) in Rakai, Uganda, with CD4 counts of greater than 350 cells per mL who were randomly assigned to undergo circumcision immediately (intervention group) and after 24 months (control group) were assessed for infection with high-risk HPV. Randomisation was done in blocks of 20, stratified by community, with computer-generated random numbers. Laboratory technicians and female fieldworkers were masked to the circumcision status of male participants. The main outcome assessed in this study was the effects of circumcision of HIV-infected men on transmission of HPV to their female partners. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00124878. 474 men were assigned to the intervention group, 448 to the control group. 211 women were in consensual relationships with 193 men in the intervention group, and 171 women were in consensual unions with 155 men in the control group. High-risk HPV at the 2-year follow-up was prevalent in 88 female partners (55%) of 159 men in the intervention group and 68 (52%) of 131 female partners of men in the control group (prevalence risk ratio 1·07, 95% CI 0·86–1·32, p=0·64). Incidence of high-risk HPV over 2 years was 32·0 per 100 person-years in the female partners of men in the intervention group and 30·6 per 100 person-years in the female partners of men in the control group (incidence rate ratio 1·05, 0·77–1·43, p=0·78). No difference was noted in the clearance of genotype-specific high-risk HPV between the intervention group (196 [46%] of 424) and control group (167 [48%] of 347; rate ratio 0·96, 0·83–1·12; p=0·61). Because circumcision of HIV-infected men did not affect transmission of high-risk HPV to their female partners, promotion of consistent safe sexual practices for HIV-infected men remains important. Bill & Melinda Gates Foundation and National Institutes of Health.

Background. The association between human papillomavirus (HPV) infection and the risk of human immunodeficiency virus (HIV) seroconversion is unclear, and the genital cellular immunology has not been evaluated. Methods. A case-control analysis nested within a male circumcision trial was conducted. Cases consisted of 44 male HIV seroconverters, and controls were 787 males who were persistently negative for HIV. The Roche HPV Linear Array Genotype Test detected high-risk HPV (HR-HPV) and low-risk HPV (LR-HPV) genotypes. Generalized estimating equations logistic regression was used to estimate adjusted odds ratios (aORs) of HIV seroconversion. In addition, densities of CD1a + dendritic cells, CD4 + T cells, and CD8 + T cells were measured using immunohistochemistry analysis in foreskins of 79 males randomly selected from participants in the circumcision trial. Results. HR-HPV or LR-HPV acquisition was not significantly associated with HIV seroconversion, after adjustment for sexual behaviors. However, HR-HPV and LR-HPV clearance was significantly associated with HIV seroconversion (aOR, 3.25 [95% confidence interval {CI}, 1.11—9.55] and 3.18 [95% CI, 1.14—8.90], respectively). The odds of HIV seroconversion increased with increasing number of HPV genotypes cleared (P < .001, by the test for trend). The median CD1a + dendritic cell density in the foreskin epidermis was significantly higher among males who cleared HPV (72.0 cells/mm 2 [interquartile range {IQR}, 29.4—138.3 cells/mm 2 ]), compared with males who were persistently negative for HPV (32.1 cells/mm 2 [IQR, 3.1—96.2 cells/mm 2 ]; P = .047), and increased progressively with the number of HPV genotypes cleared (P = .05). Conclusions. HPV clearance was associated with subsequent HIV seroconversion and also with increased epidermal dendritic cell density, which potentially mediates HIV seroconversion.

Physicians make critical time-constrained decisions every day. Clinical predictive models can help physicians and administrators make decisions by forecasting clinical and operational events. Existing structured data-based clinical predictive models have limited use in everyday practice owing to complexity in data processing, as well as model development and deployment 1 – 3 . Here we show that unstructured clinical notes from the electronic health record can enable the training of clinical language models, which can be used as all-purpose clinical predictive engines with low-resistance development and deployment. Our approach leverages recent advances in natural language processing 4 , 5 to train a large language model for medical language (NYUTron) and subsequently fine-tune it across a wide range of clinical and operational predictive tasks. We evaluated our approach within our health system for five such tasks: 30-day all-cause readmission prediction, in-hospital mortality prediction, comorbidity index prediction, length of stay prediction, and insurance denial prediction. We show that NYUTron has an area under the curve (AUC) of 78.7–94.9%, with an improvement of 5.36–14.7% in the AUC compared with traditional models. We additionally demonstrate the benefits of pretraining with clinical text, the potential for increasing generalizability to different sites through fine-tuning and the full deployment of our system in a prospective, single-arm trial. These results show the potential for using clinical language models in medicine to read alongside physicians and provide guidance at the point of care. A clinical language model trained on unstructured clinical notes from the electronic health record enhances prediction of clinical and operational events.

Objectives Human papillomavirus (HPV) infection causes genital warts, penile cancer and cervical cancer. Africa has one of the highest rates of penile and cervical cancers, but there are little data on high-risk human papillomavirus (HR-HPV) prevalence in heterosexual men. Knowledge of HR-HPV prevalence, risk factors and genotype distribution among heterosexual men is important to establish risk-reduction prevention strategies. Methods 1578 uncircumcised men aged 15–49 years who enrolled in male circumcision trials in Rakai, Uganda, were evaluated for HR-HPV from swabs of the coronal sulcus/glans using Roche HPV Linear Array. Adjusted prevalence risk ratios (adjPRRs) were estimated using modified Poisson multivariable regression. Results HPV prevalence (either high risk or low risk) was 90.7% (382/421) among HIV-positive men and 60.9% (596/978) among HIV-negative men (PRR 1.49, 95% CI 1.40 to 1.58). HIV-positive men had a significantly higher risk of infection with three or more HR-HPV genotypes (PRR=5.76, 95% CI 4.27 to 7.79). Among HIV-positive men, high-risk sexual behaviours were not associated with increased HR-HPV prevalence. Among HIV-negative men, HR-HPV prevalence was associated with self-reported genital warts (adjPRR 1.57, 95% CI 1.07 to 2.31). Among all men (both HIV negative and HIV positive), HR-HPV prevalence was associated with more than 10 lifetime sexual partners (adjPRR 1.30, 95% CI 1.01 to 1.66), consistent condom use (adjPRR 1.31, 95% CI 1.08 to 1.60) and HIV infection (adjPRR 1.80, 95% CI 1.60 to 2.02). HR-HPV prevalence was lower among men who reported no sexual partners during the past year (adjPRR 0.47, 95% CI 0.23 to 0.94). Conclusion The burden of HR-HPV infection is high among heterosexual men in sub-Saharan Africa and most pronounced among the HIV-infected individuals.

A large portion of buildings total energy use is caused by chilled water systems (CHW). As a result, it can drastically affect the energy cost. Usually there is no holistic approach to optimize the whole CHW as most of the efforts that have been made are limited to optimization of different components of CHW. It's crucial to find optimal methods to design a more efficient CWS and develop holistic optimization tools to reduce the energy consumption by incorporating system models and genetic algorithm technics, using real time data from the chilled water system. The proposed optimization technique can reduce the energy consumption by analyzing the data, generated by the building automation system (BAS) and developing a model that can predict the behavior of the system. It can also assess the performance of the system and tune the model if necessary to increase the efficiency of the system by using optimization algorithms. This paper proposes an integrated optimization method to determine controller's set points and the sequence of control of different components for different chilled water system configurations. It also develops a data driven system model by using machine learning techniques to predict the energy consumption of the system. An optimization algorithm is also created that can be incorporated with the system model to produce the integrated optimization method and find the optimal solution. The objective function for this algorithm is the total energy consumption for different components of chilled water systems, using the two main variables of: controller's set points and sequence of operation. The integration of the optimization algorithm with the system model is the other objective of the proposed model. The result of using different machine learning testing methods to predict the chiller power shows that the model can capture and predict the performance of the chiller with a high level of accuracy. The initial result of the optimization shows that optimization technique can reduce the energy consumption of the chilled water system.

Dapsone is a common medication that is utilized in the treatment of dermatological conditions, pneumocystis pneumonia, and toxoplasmosis. Methemoglobinemia is a known but rare complication of dapsone therapy that can result in cyanosis. We present a case of a patient on dapsone therapy who developed hypoxia due to methemoglobinemia. This case emphasizes the importance of knowledge of drugs likely to cause methemoglobinemia which requires clinicians to have a high degree of suspicion especially when the patient's oxygen saturation does not improve with treatment.