Proton pump inhibitors (PPIs) have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might ...extend to subjects without any prior history of cardiovascular disease. We explore this potential risk in the general population via data-mining approaches.
Using a novel approach for mining clinical data for pharmacovigilance, we queried over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk in the general population.
In multiple data sources, we found gastroesophageal reflux disease (GERD) patients exposed to PPIs to have a 1.16 fold increased association (95% CI 1.09-1.24) with myocardial infarction (MI). Survival analysis in a prospective cohort found a two-fold (HR = 2.00; 95% CI 1.07-3.78; P = 0.031) increase in association with cardiovascular mortality. We found that this association exists regardless of clopidogrel use. We also found that H2 blockers, an alternate treatment for GERD, were not associated with increased cardiovascular risk; had they been in place, such pharmacovigilance algorithms could have flagged this risk as early as the year 2000.
Consistent with our pre-clinical findings that PPIs may adversely impact vascular function, our data-mining study supports the association of PPI exposure with risk for MI in the general population. These data provide an example of how a combination of experimental studies and data-mining approaches can be applied to prioritize drug safety signals for further investigation.
Coping with the current and future burden of cancer requires an in-depth understanding of trends in cancer incidences and deaths. Estimated projections of cancer incidences and deaths will be ...important to guide future research funding allocations, health care planning, and health policy efforts.
To estimate cancer incidences and deaths in the United States to the year 2040.
This cross-sectional study's estimated projection analysis used population growth projections and current population-based cancer incidence and death rates to calculate the changes in incidences and deaths to the year 2040. Cancer-specific incidences and deaths in the US were estimated for the most common cancer types. Demographic cancer-specific delay-adjusted incidence rates from the Surveillance, Epidemiology, and End Results Program were combined with US Census Bureau population growth projections (2016) and average annual percentage changes in incidence and death rates. Statistical analyses were performed from July 2020 to February 2021.
Total cancer incidences and deaths to the year 2040.
This study estimated that the most common cancers in 2040 will be breast (364 000 cases) with melanoma (219 000 cases) becoming the second most common cancer; lung, third (208 000 cases); colorectal remaining fourth (147 000 cases); and prostate cancer dropping to the fourteenth most common cancer (66 000 cases). Lung cancer (63 000 deaths) was estimated to continue as the leading cause of cancer-related death in 2040, with pancreatic cancer (46 000 deaths) and liver and intrahepatic bile duct cancer (41 000 deaths) surpassing colorectal cancer (34 000 deaths) to become the second and third most common causes of cancer-related death, respectively. Breast cancer (30 000 deaths) was estimated to decrease to the fifth most common cause of cancer death.
These findings suggest that there will be marked changes in the landscape of cancer incidence and deaths by 2040.
Objective A key aspect of the precision medicine effort is the development of informatics tools that can analyze and interpret “big data” sets in an automated and adaptive fashion while providing ...accurate and actionable clinical information. The aims of this study were to develop machine learning algorithms for the identification of disease and the prognostication of mortality risk and to determine whether such models perform better than classical statistical analyses. Methods Focusing on peripheral artery disease (PAD), patient data were derived from a prospective, observational study of 1755 patients who presented for elective coronary angiography. We employed multiple supervised machine learning algorithms and used diverse clinical, demographic, imaging, and genomic information in a hypothesis-free manner to build models that could identify patients with PAD and predict future mortality. Comparison was made to standard stepwise linear regression models. Results Our machine-learned models outperformed stepwise logistic regression models both for the identification of patients with PAD (area under the curve, 0.87 vs 0.76, respectively; P = .03) and for the prediction of future mortality (area under the curve, 0.76 vs 0.65, respectively; P = .10). Both machine-learned models were markedly better calibrated than the stepwise logistic regression models, thus providing more accurate disease and mortality risk estimates. Conclusions Machine learning approaches can produce more accurate disease classification and prediction models. These tools may prove clinically useful for the automated identification of patients with highly morbid diseases for which aggressive risk factor management can improve outcomes.
To test the association of androgen deprivation therapy (ADT) in the treatment of prostate cancer with subsequent Alzheimer's disease risk.
We used a previously validated and implemented ...text-processing pipeline to analyze electronic medical record data in a retrospective cohort of patients at Stanford University and Mt. Sinai hospitals. Specifically, we extracted International Classification of Diseases-9th revision diagnosis and Current Procedural Terminology codes, medication lists, and positive-present mentions of drug and disease concepts from all clinical notes. We then tested the effect of ADT on risk of Alzheimer's disease using 1:5 propensity score-matched and traditional multivariable-adjusted Cox proportional hazards models. The duration of ADT use was also tested for association with Alzheimer's disease risk.
There were 16,888 individuals with prostate cancer meeting all inclusion and exclusion criteria, with 2,397 (14.2%) receiving ADT during a median follow-up period of 2.7 years (interquartile range, 1.0-5.4 years). Propensity score-matched analysis (hazard ratio, 1.88; 95% CI, 1.10 to 3.20; P = .021) and traditional multivariable-adjusted Cox regression analysis (hazard ratio, 1.66; 95% CI, 1.05 to 2.64; P = .031) both supported a statistically significant association between ADT use and Alzheimer's disease risk. We also observed a statistically significant increased risk of Alzheimer's disease with increasing duration of ADT (P = .016).
Our results support an association between the use of ADT in the treatment of prostate cancer and an increased risk of Alzheimer's disease in a general population cohort. This study demonstrates the utility of novel methods to analyze electronic medical record data to generate practice-based evidence.
Background:
Previous studies have shown improvement in patellar tendinopathy symptoms after platelet-rich plasma (PRP) injections, but no randomized controlled trial has compared PRP with dry ...needling (DN) for this condition.
Purpose:
To compare clinical outcomes in patellar tendinopathy after a single ultrasound-guided, leukocyte-rich PRP injection versus DN.
Study Design:
Randomized controlled trial; Level of evidence, 1.
Methods:
A total of 23 patients with patellar tendinopathy on examination and MRI who had failed nonoperative treatment were enrolled and randomized to receive ultrasound-guided DN alone (DN group; n = 13) or with injection of leukocyte-rich PRP (PRP group; n = 10), along with standardized eccentric exercises. Patients and the physician providing follow-up care were blinded. Participants completed patient-reported outcome surveys before and at 3, 6, 9, 12, and ≥26 weeks after treatment during follow-up visits. The primary outcome measure was the Victorian Institute of Sports Assessment (VISA) score for patellar tendinopathy at 12 weeks, and secondary measures included the visual analog scale (VAS) for pain, Tegner activity scale, Lysholm knee scale, and Short Form (SF-12) questionnaire at 12 and ≥26 weeks. Results were analyzed using 2-tailed paired and unpaired t tests. Patients who were dissatisfied at 12 weeks were allowed to cross over into a separate unblinded arm.
Results:
At 12 weeks after treatment, VISA scores improved by a mean ± standard deviation of 5.2 ± 12.5 points (P = .20) in the DN group (n = 12) and by 25.4 ± 23.2 points (P = .01) in the PRP group (n = 9); at ≥26 weeks, the scores improved by 33.2 ± 14.0 points (P = .001) in the DN group (n = 9) and by 28.9 ± 25.2 points (P = .01) in the PRP group (n = 7). The PRP group had improved significantly more than the DN group at 12 weeks (P = .02), but the difference between groups was not significant at ≥26 weeks (P = .66). Lysholm scores were not significantly different between groups at 12 weeks (P = .81), but the DN group had improved significantly more than the PRP group at ≥26 weeks (P = .006). At 12 weeks, 3 patients in the DN group failed treatment and subsequently crossed over into the PRP group. These patients were excluded from the primary ≥26-week analysis. There were no treatment failures in the PRP group. No adverse events were reported. Recruitment was stopped because interim analysis demonstrated statistically significant and clinically important results.
Conclusion:
A therapeutic regimen of standardized eccentric exercise and ultrasound-guided leukocyte-rich PRP injection with DN accelerates the recovery from patellar tendinopathy relative to exercise and ultrasound-guided DN alone, but the apparent benefit of PRP dissipates over time.
The aim of this study is to summarize recently published literature examining androgens and depression.
The impact of androgen levels, androgen replacement therapy and pharmacologic androgen ...deprivation on depression and depressive symptoms remain active areas of investigation. Recent publications support the finding that testosterone replacement therapy in men with low testosterone may improve depression, and that androgen deprivation therapy in men with prostate cancer may contribute to depression.
We review the recent literature on androgens and depression and highlight key developments.
Objectives To draw attention to sex related disparities in academic medical leadership by investigating the representation of female leaders compared with leaders with moustaches.Design Cross ...sectional analysis.Setting Academic medical departments in the United States.Participants Clinical department leaders (n=1018) at the top 50 US medical schools funded by the National Institutes of Health (NIH).Main outcome measures The proportions of female leaders and moustachioed leaders across institutions and specialties (n=20). Additionally, the moustache index: the proportion of women compared with the proportion of moustaches, analyzed with multinomial logistic regression models.Results Women accounted for 13% (137/1018) of department leaders at the top 50 NIH funded medical schools in the US. Moustachioed leaders accounted for 19% (190/1018). The proportion of female department leaders ranged from 0% (0/20) to 26% (5/19) across institutions and 0% (0/53) to 36% (19/53) across specialties. Only seven institutions and five specialties had more than 20% of female department leaders. The overall moustache index of all academic medical departments studied was 0.72 (95% confidence interval 0.58 to 0.90; P=0.004). Only six of 20 specialties had more women than moustaches (moustache index >1).Conclusions Moustachioed individuals significantly outnumber women as leaders of medical departments in the US. We believe that every department and institution should strive for a moustache index ≥1. Known, effective, and evidence based policies to increase the number of women in leadership positions should be prioritized.
IMPORTANCE: Population-level disease metrics are critical to guide the distribution of resources and implementation of public health initiatives. Internet search data reflect population interest in ...health topics and may be an alternative metric of disease characteristics when traditional sources are lacking, such as in basal and squamous cell carcinomas, which are not included in national cancer registries. However, these data are not yet well validated or understood. OBJECTIVE: To evaluate whether state-specific normalized internet search volume correlates with incidence and mortality rates of common cancers in the United States, including melanoma. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional analysis of Google search volume index data and US cancer incidences and mortalities of 8 of the most incident cancers in the United States in 2009 to 2013, at the state level, per the National Program of Cancer Registries. Participants were people performing Google searches and patients diagnosed as having cancers reported to cancer registries. MAIN OUTCOMES AND MEASURES: Correlation between Google search volumes, normalized to total Google search volume, and National Program of Cancer Registries recorded cancer incidence and mortality rates. RESULTS: By state, relative Google search volume statistically significantly correlated with cancer incidence rates in 5 of 8 commonly diagnosed cancers in the United States (colon cancer: R = 0.61; P < .001; lung cancer: R = 0.73; P < .001; lymphoma: R = 0.51; P < .001; melanoma: R = 0.36; P = .01; and thyroid cancer: R = 0.30; P = .03). For 4 of those 5 cancers (colon cancer: R = 0.61; P < .001; lung cancer: R = 0.62; P < .001; lymphoma: R = 0.38; P = .006; and melanoma: R = 0.31; P = .03), relative Google search volume also correlated with mortality rates. CONCLUSIONS AND RELEVANCE: Population-level internet search behavior may be a valuable real-time tool to estimate cancer incidence and mortality rates, especially for cancers not included in national registries, such as basal and squamous cell carcinomas.
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