Tamsulosin use in benign prostatic hyperplasia and risks of Parkinson's disease, Alzheimer's disease and mortality: An observational cohort study of elderly Medicare enrollees.

PURPOSE: To study the effects of benign prostatic hyperplasia treatments, namely: alpha-adrenergic receptor blockers, 5-alpha-reductase inhibitors and phosphodiesterase-5 inhibitors on the risk of Parkinson's disease, Alzheimer's disease and mortality. MATERIALS AND METHODS: All male Medicare enrollees aged 65 or above who were diagnosed with benign prostatic hyperplasia and received one of the study drugs between 2007-2020 were followed-up for the three outcomes. We used Cox regression analysis to assess the relative risk of each of the outcomes for each study drug compared to the most prescribed drug, tamsulosin, while controlling for demographic, socioeconomic and comorbidity factors. RESULTS AND CONCLUSIONS: The study analyzed 1.1 million patients for a mean follow-up period of 3.1 years from being prescribed one of the study drugs. For all outcomes, patients on tamsulosin were used as the reference for comparison. For mortality, alfuzosin was associated with 27% risk reduction (HR 0.73, 95%CI 0.68-0.78), and doxazosin with 6% risk reduction (HR 0.94, 95%CI 0.91-0.97). For Parkinson's disease, terazosin was associated with 26% risk reduction (HR 0.74, 95%CI 0.66-0.83), and doxazosin with 21% risk reduction (HR 0.79, 95%CI 0.72-0.88). For Alzheimer's disease, terazosin was associated with 27% risk reduction (HR 0.73, 95%CI 0.65-0.82), and doxazosin with 16% risk reduction (HR 0.84, 95%CI 0.76-0.92). Tadalafil was associated with risk reduction (27-40%) in all 3 outcomes. More research is needed to elucidate the underlying mechanisms of these observations. Given the availability of safer alternatives for treating benign prostatic hyperplasia, caution should be exercised when using tamsulosin in elderly patients, especially those with an increased risk of developing neurodegenerative diseases.

Autophagy and lysosomal dysfunction in diabetes and its complications.

Autophagy is critical for energy homeostasis and the function of organelles such as endoplasmic reticulum (ER) and mitochondria. Dysregulated autophagy due to aging, environmental factors, or genetic predisposition can be an underlying cause of not only diabetes through ß-cell dysfunction and metabolic inflammation, but also diabetic complications such as diabetic kidney diseases (DKDs). Dysfunction of lysosomes, effector organelles of autophagic degradation, due to metabolic stress or nutrients/metabolites accumulating in metabolic diseases is also emerging as a cause or aggravating element in diabetes and its complications. Here, we discuss the etiological role of dysregulated autophagy and lysosomal dysfunction in diabetes and a potential role of autophagy or lysosomal modulation as a new avenue for treatment of diabetes and its complications.

Use of menopausal hormone therapy beyond age 65 years and its effects on women's health outcomes by types, routes, and doses.

OBJECTIVES: The study aims to assess the use of menopausal hormone therapy beyond age 65 years and its health implications by types of estrogen/progestogen, routes of administration, and dose strengths. METHODS: Using prescription drug and encounter records of 10 million senior Medicare women from 2007-2020 and Cox regression analyses adjusted for time-varying characteristics of the women, we examined the effects of different preparations of menopausal hormone therapy on all-cause mortality, five cancers, six cardiovascular diseases, and dementia. RESULTS: Compared with never use or discontinuation of menopausal hormone therapy after age 65 years, the use of estrogen monotherapy beyond age 65 years was associated with significant risk reductions in mortality (19% or adjusted hazards ratio, 0.81; 95% CI, 0.79-0.82), breast cancer (16%), lung cancer (13%), colorectal cancer (12%), congestive heart failure (CHF) (5%), venous thromboembolism (3%), atrial fibrillation (4%), acute myocardial infarction (11%), and dementia (2%). For the use of estrogen and progestogen combo-therapy, both E+ progestin and E+ progesterone were associated with increased risk of breast cancer by 10%-19%, but such risk can be mitigated using low dose of transdermal or vaginal E+ progestin. Moreover, E+ progestin exhibited significant risk reductions in endometrial cancer (45% or adjusted hazards ratio, 0.55; 95% CI, 0.50-0.60), ovarian cancer (21%), ischemic heart disease (5%), CHF (5%), and venous thromboembolism (5%), whereas E+ progesterone exhibited risk reduction only in CHF (4%). CONCLUSIONS: Among senior Medicare women, the implications of menopausal hormone therapy use beyond age 65 years vary by types, routes, and strengths. In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 rather than conjugated estrogen.

Comparison of clinical outcomes of patients with serial negative surveillance cultures according to a subsequent polymerase chain reaction test for carbapenemase-producing Enterobacterales.

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are of serious concern worldwide due to high morbidity and mortality. AIM: To evaluate the impact of the result of a subsequent polymerase chain reaction (PCR) test for carbapenemase after serial negative surveillance cultures on positive culture conversion in patients with three consecutive negative surveillance cultures for CPE, and to identify risk factors for conversion. METHODS: A retrospective study of patients with positive CPE cultures on CHROMagar KPC medium was performed in a Korean tertiary hospital from October 2018 to December 2022. PCR for blaKPC, blaNDM, blaIMP, blaVIM, blaGES, and blaOXA-48 was performed after three consecutive negative rectal swab cultures. Clinical characteristics and outcomes of patients were compared according to whether follow-up PCR was positive (CNPP) or negative (CNPN). FINDINGS: Of 1075 patients with positive CPE cultures, 150 (14.0%) yielded three consecutive negative rectal swab cultures. Of these, 50 (33.3%) were CNPP, and 100 (66.7%) were CNPN. Risk factors associated with a positive PCR result on multivariate analysis were: age, central venous catheter, and Escherichia coli infection. CNPP patients were more likely to have positive culture conversion for CPE than CNPN patients (39/44 (88.6%) vs 21/50 (42.0%), P<0.001). In multivariate analysis, independent risk factors for culture conversion were: a positive PCR result after surveillance cultures, diabetes mellitus, central venous catheter, and Klebsiella pneumoniae. CONCLUSION: CNPP patients have higher rates of culture conversion than CNPN patients, and a follow-up PCR test after serial negative surveillance cultures is useful in deciding whether or not to discontinue contact precautions.

Trends in Racial Disparities in Healthcare Expenditures Among Senior Medicare Fee-for-service Enrollees in 2007-2020.

Despite the universal healthcare coverages, racial disparities in healthcare expenditures among senior Medicare beneficiaries exist. A few studies explored how racial disparities in healthcare expenditures changed over past decades and how it affected differently across 4 minoritized races, by type of Medicare and poverty levels. We conducted a longitudinal study of 21 healthcare expenditures from senior Medicare fee-for-service enrollees to determine overall and secular trends in racial disparities in healthcare expenditures between 2007 and 2020, during which the Affordable Care Act (ACA) came into full force and the COVID-19 pandemic had begun. We found important disparities in healthcare expenditures across 4 minoritized races compared to Whites, even after adjusting for possible confounders for such disparities. Disparities between Hispanics/Asians and Whites were much greater than disparities between Blacks and Whites, in all Parts A, B, and D expenditures. This reality has not been sufficiently emphasized in the literature. Importantly, Black-White disparities in total Part B expenditure gradually worsened between 2007 and 2020, and Hispanic-White and Asian-White disparities worsened greatly during that time window. Health planners need to focus on these large disparities and develop methods to shrink them.

Nirmatrelvir and Molnupiravir and Post-COVID-19 Condition in Older Patients.

This observational cohort study assesses the occurrence of post­COVID-19 condition symptoms in Medicare enrollees prescribed nirmatrelvir and molnupiravir.

Review: Implantation and placentation in ruminants.

Ruminants have a unique placenta in comparison to other mammalian species. Initially, they possess a non-invasive epitheliochorial type of placenta during conceptus elongation. As the conceptus trophectoderm begins to attach to the luminal epithelium (LE) of the endometrium, binucleate cells (BNCs) develop within the trophoblast of the chorion. The BNCs migrate and fuse with the uterine LE to form multinucleate syncytial plaques in sheep and hybrid trinucleate cells in cattle. This area of the ruminant placenta is semi-invasive synepitheliochorial. The BNCs form the foundation of the placental cotyledons and express unique placenta-specific genes including pregnancy-associated glycoproteins and chorionic somatomammotropin hormone 2 or placental lactogen. Attachment and interdigitation of cotyledons into endometrial caruncles form placentomes that are subsequently vascularized to provide essential nutrients for growth of the fetus. This chapter review will discuss historical and current aspects of conceptus implantation and placenta development in ruminant ungulates with a focus on cattle and sheep. Single-cell analysis promises to provide a much more detailed understanding of the different cell populations and insights into pathways mediating trophoblast and placenta. This fundamental is required to understand pregnancy loss and develop strategies to improve pregnancy outcomes in ruminants.

Prevalence and characteristics of long COVID in elderly patients: An observational cohort study of over 2 million adults in the US.

BACKGROUND: Incidence of long COVID in the elderly is difficult to estimate and can be underreported. While long COVID is sometimes considered a novel disease, many viral or bacterial infections have been known to cause prolonged illnesses. We postulate that some influenza patients might develop residual symptoms that would satisfy the diagnostic criteria for long COVID, a condition we call "long Flu." In this study, we estimate the incidence of long COVID and long Flu among Medicare patients using the World Health Organization (WHO) consensus definition. We compare the incidence, symptomatology, and healthcare utilization between long COVID and long Flu patients. METHODS AND FINDINGS: This is a cohort study of Medicare (the US federal health insurance program) beneficiaries over 65. ICD-10-CM codes were used to capture COVID-19, influenza, and residual symptoms. Long COVID was identified by (a) the designated long COVID code B94.8 (code-based definition), or (b) any of 11 symptoms identified in the WHO definition (symptom-based definition), from 1 to 3 months post-infection. A symptom would be excluded if it occurred in the year prior to infection. Long Flu was identified in influenza patients from the combined 2018 and 2019 Flu seasons by the same symptom-based definition for long COVID. Long COVID and long Flu were compared in 4 outcome measures: (a) hospitalization (any cause); (b) hospitalization (for long COVID symptom); (c) emergency department (ED) visit (for long COVID symptom); and (d) number of outpatient encounters (for long COVID symptom), adjusted for age, sex, race, region, Medicare-Medicaid dual eligibility status, prior-year hospitalization, and chronic comorbidities. Among 2,071,532 COVID-19 patients diagnosed between April 2020 and June 2021, symptom-based definition identified long COVID in 16.6% (246,154/1,479,183) and 29.2% (61,631/210,765) of outpatients and inpatients, respectively. The designated code gave much lower estimates (outpatients 0.49% (7,213/1,479,183), inpatients 2.6% (5,521/210,765)). Among 933,877 influenza patients, 17.0% (138,951/817,336) of outpatients and 24.6% (18,824/76,390) of inpatients fit the long Flu definition. Long COVID patients had higher incidence of dyspnea, fatigue, palpitations, loss of taste/smell, and neurocognitive symptoms compared to long Flu. Long COVID outpatients were more likely to have any-cause hospitalization (31.9% (74,854/234,688) versus 26.8% (33,140/123,736), odds ratio 1.06 (95% CI 1.05 to 1.08, p < 0.001)), and more outpatient visits than long Flu outpatients (mean 2.9(SD 3.4) versus 2.5(SD 2.7) visits, incidence rate ratio 1.09 (95% CI 1.08 to 1.10, p < 0.001)). There were less ED visits in long COVID patients, probably because of reduction in ED usage during the pandemic. The main limitation of our study is that the diagnosis of long COVID in is not independently verified. CONCLUSIONS: Relying on specific long COVID diagnostic codes results in significant underreporting. We observed that about 30% of hospitalized COVID-19 patients developed long COVID. In a similar proportion of patients, long COVID-like symptoms (long Flu) can be observed after influenza, but there are notable differences in symptomatology between long COVID and long Flu. The impact of long COVID on healthcare utilization is higher than long Flu.

Mis-mappings between a producer's quantitative test codes and LOINC codes and an algorithm for correcting them.

OBJECTIVES: To access the accuracy of the Logical Observation Identifiers Names and Codes (LOINC) mapping to local laboratory test codes that is crucial to data integration across time and healthcare systems. MATERIALS AND METHODS: We used software tools and manual reviews to estimate the rate of LOINC mapping errors among 179 million mapped test results from 2 DataMarts in PCORnet. We separately reported unweighted and weighted mapping error rates, overall and by parts of the LOINC term. RESULTS: Of included 179 537 986 mapped results for 3029 quantitative tests, 95.4% were mapped correctly implying an 4.6% mapping error rate. Error rates were less than 5% for the more common tests with at least 100 000 mapped test results. Mapping errors varied across different LOINC classes. Error rates in chemistry and hematology classes, which together accounted for 92.0% of the mapped test results, were 0.4% and 7.5%, respectively. About 50% of mapping errors were due to errors in the property part of the LOINC name. DISCUSSIONS: Mapping errors could be detected automatically through inconsistencies in (1) qualifiers of the analyte, (2) specimen type, (3) property, and (4) method. Among quantitative test results, which are the large majority of reported tests, application of automatic error detection and correction algorithm could reduce the mapping errors further. CONCLUSIONS: Overall, the mapping error rate within the PCORnet data was 4.6%. This is nontrivial but less than other published error rates of 20%-40%. Such error rate decreased substantially to 0.1% after the application of automatic detection and correction algorithm.

Cluster Analysis of DSC MRI, Dynamic Contrast-Enhanced MRI, and DWI Parameters Associated with Prognosis in Patients with Glioblastoma after Removal of the Contrast-Enhancing Component: A Preliminary Study.

BACKGROUND AND PURPOSE: No report has been published on the use of DSC MR imaging, DCE MR imaging, and DWI parameters in combination to create a prognostic prediction model in glioblastoma patients. The aim of this study was to develop a machine learning-based model to find preoperative multiparametric MR imaging parameters associated with prognosis in patients with glioblastoma. Normalized CBV, volume transfer constant, and ADC of the nonenhancing T2 high-signal-intensity lesions were evaluated using K-means clustering. MATERIALS AND METHODS: A total of 142 patients with glioblastoma who underwent preoperative MR imaging and total resection were included in this retrospective study. From the normalized CBV, volume transfer constant, and ADC maps, the parametric data were sorted using the K-means clustering method. Patients were divided into training and test sets (ratio, 1:1), and the optimal number of clusters was determined using receiver operating characteristic analysis. Kaplan-Meier survival analysis and log-rank tests were performed to identify potential parametric predictors. A multivariate Cox proportional hazard model was conducted to adjust for clinical predictors. RESULTS: The nonenhancing T2 high-signal-intensity lesions were divided into 6 clusters. The cluster (class 4) with the relatively low normalized CBV and volume transfer constant value and the lowest ADC values was most associated with predicting glioblastoma prognosis. The optimal cutoff of the class 4 volume fraction of nonenhancing T2 high-signal-intensity lesions predicting 1-year progression-free survival was 9.70%, below which the cutoff was associated with longer progression-free survival. Two Kaplan-Meier curves based on the cutoff value showed a statistically significant difference (P = .037). When we adjusted for all clinical predictors, the cluster with the relatively low normalized CBV and volume transfer constant values and the lowest ADC value was an independent prognostic marker (hazard ratio, 3.04; P = .048). The multivariate Cox proportional hazard model showed a concordance index of 0.699 for progression-free survival. CONCLUSIONS: Our model showed that nonenhancing T2 high-signal-intensity lesions with the relatively low normalized CBV, low volume transfer constant values, and the lowest ADC values could serve as useful prognostic imaging markers for predicting survival outcomes in patients with glioblastoma.

Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients.

BACKGROUND: Maintenance drugs are used to treat chronic conditions. Several classes of maintenance drugs have attracted attention because of their potential to affect susceptibility to and severity of COVID-19. METHODS: Using claims data on 20% random sample of Part D Medicare enrollees from April to December 2020, we identified patients diagnosed with COVID-19. Using a nested case-control design, non-COVID-19 controls were identified by 1:5 matching on age, race, sex, dual-eligibility status, and geographical region. We identified usage of angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), statins, warfarin, direct factor Xa inhibitors, P2Y12 inhibitors, famotidine and hydroxychloroquine based on Medicare prescription claims data. Using extended Cox regression models with time-varying propensity score adjustment we examined the independent effect of each study drug on contracting COVID-19. For severity of COVID-19, we performed extended Cox regressions on all COVID-19 patients, using COVID-19-related hospitalization and all-cause mortality as outcomes. Covariates included gender, age, race, geographic region, low-income indicator, and co-morbidities. To compensate for indication bias related to the use of hydroxychloroquine for the prophylaxis or treatment of COVID-19, we censored patients who only started on hydroxychloroquine in 2020. RESULTS: Up to December 2020, our sample contained 374,229 Medicare patients over 65 who were diagnosed with COVID-19. Among the COVID-19 patients, 278,912 (74.6%) were on at least one study drug. The three most common study drugs among COVID-19 patients were statins 187,374 (50.1%), ACEI 97,843 (26.2%) and ARB 83,290 (22.3%). For all three outcomes (diagnosis, hospitalization and death), current users of ACEI, ARB, statins, warfarin, direct factor Xa inhibitors and P2Y12 inhibitors were associated with reduced risks, compared to never users. Famotidine did not show consistent significant effects. Hydroxychloroquine did not show significant effects after censoring of recent starters. CONCLUSION: Maintenance use of ACEI, ARB, warfarin, statins, direct factor Xa inhibitors and P2Y12 inhibitors was associated with reduction in risk of acquiring COVID-19 and dying from it.

The Mortality Risk of Proton Pump Inhibitors in 1.9 Million US Seniors: An Extended Cox Survival Analysis.

BACKGROUND & AIMS: Observational studies have linked proton pump inhibitors (PPIs) with increased risk of mortality and other safety outcomes, in contradiction with a recent PPI randomized controlled trial (RCT). Observational studies may be prone to reverse causality, where deaths are attributed to the treatment rather than the conditions that are treated (protopathic bias). METHODS: We analyzed an incident drug user cohort of 1,930,728 elderly Medicare fee-for-service beneficiaries to evaluate the PPI-associated risk of death with a Cox regression analysis with time-varying covariates and propensity score adjustments. To correct for protopathic bias which occurs when a given drug is associated with prodromal signs of death, we implemented a lag-time approach by which any study drug taken during a 90-day look-back window before each death was disregarded. RESULTS: Among 1,930,728 study individuals, 80,972 (4.2%) died during a median 3.8 years of follow-up, yielding an overall unadjusted death rate/1000 person-years of 9.85; 14.31 for PPI users and 7.93 for non- users. With no lag-time, PPI use (vs no use) was associated with 10% increased mortality risk (adjusted HR=1.10; 95% CI 1.08-1.12). However, with a lag-time of 90 days, mortality risk associated with PPI use was near zero (adjusted HR=1.01; 95% CI 0.99-1.02). CONCLUSION: Given the usage patterns of PPIs in patients with conditions that may presage death, protopathic bias may explain the association of PPIs with increased risk of death reported in observational studies.

The association between experience of hospital accreditation and nurses' perception of patient safety culture in South Korean general hospitals: a cross-sectional study.

BACKGROUND: Hospital accreditation programs can positively affect nurses' perceptions of patient safety culture. However, no previous research has identified the association between experience of hospital accreditation and nurses' perception of patient safety culture in general hospitals. This study aims to examine 1) the level of perception of each area of patient safety culture in nurses working in general hospitals and 2) the relationship between experience of hospital accreditation and nurses' overall perceptions of safety in Korean general hospitals. METHODS: A cross-sectional survey design was used, with a convenience sample of 310 nurses from six general hospitals. Nurses were asked to complete the self-reported Korean version of the Hospital Survey on Patient Safety Culture and the experience of hospital accreditation. A hierarchical multiple regression analysis was used to examine the associations between hospital accreditation experience and perception of patient safety culture. RESULTS: The patient safety composites with the highest positive response were the frequency of events reported (90.6) and supervisor/manager expectations promoting patient safety (69.4%). The composites with the lowest scores were non-punitive responses to errors (22.9%) and organizational learning/continuous improvement (35.5%). Hierarchical multiple regression analysis showed that the experience of hospital accreditation had a very small increase on overall perceptions of safety (ß = 0.097, p = 0.023). CONCLUSIONS: This study found that general hospital nurses' experience of hospital accreditation had very weak relationship with their overall perceptions of patient safety. Therefore, a longitudinal study is needed to confirm the influence of hospital accreditation on nurses' patient safety culture in general hospitals.

Search for Sub-eV Sterile Neutrinos at RENO.

We report a search result for a light sterile neutrino oscillation with roughly 2200 live days of data in the RENO experiment. The search is performed by electron antineutrino (ν[over ¯]_{e}) disappearance taking place between six 2.8 GW_{th} reactors and two identical detectors located at 294 m (near) and 1383 m (far) from the center of the reactor array. A spectral comparison between near and far detectors can explore reactor ν[over ¯]_{e} oscillations to a light sterile neutrino. An observed spectral difference is found to be consistent with that of the three-flavor oscillation model. This yields limits on sin^{2}2θ_{14} in the 10^{-4}≲|Δm_{41}^{2}|≲0.5 eV^{2} region, free from reactor ν[over ¯]_{e} flux and spectrum uncertainties. The RENO result provides the most stringent limits on sterile neutrino mixing at |Δm_{41}^{2}|≲0.002 eV^{2} using the ν[over ¯]_{e} disappearance channel.

Changes of Neurotransmitters in Youth with Internet and Smartphone Addiction: A Comparison with Healthy Controls and Changes after Cognitive Behavioral Therapy.

BACKGROUND AND PURPOSE: Neurotransmitter changes in youth addicted to the Internet and smartphone were compared with normal controls and in subjects after cognitive behavioral therapy. In addition, the correlations between neurotransmitters and affective factors were investigated. MATERIALS AND METHODS: Nineteen young people with Internet and smartphone addiction and 19 sex- and age-matched healthy controls (male/female ratio, 9:10; mean age, 15.47 ± 3.06 years) were included. Twelve teenagers with Internet and smartphone addiction (male/female ratio, 8:4; mean age, 14.99 ± 1.95 years) participated in 9 weeks of cognitive behavioral therapy. Meshcher-Garwood point-resolved spectroscopy was used to measure γ-aminobutyric acid and Glx levels in the anterior cingulate cortex. The γ-aminobutyric acid and Glx levels in the addicted group were compared with those in controls and after cognitive behavioral therapy. The γ-aminobutyric acid and Glx levels correlated with clinical scales of Internet and smartphone addiction, impulsiveness, depression, anxiety, insomnia, and sleep quality. RESULTS: Brain parenchymal and gray matter volume-adjusted γ-aminobutyric acid-to-creatine ratios were higher in subjects with Internet and smartphone addiction (P = .028 and .016). After therapy, brain parenchymal- and gray matter volume-adjusted γ-aminobutyric acid-to-creatine ratios were decreased (P = .034 and .026). The Glx level was not statistically significant in subjects with Internet and smartphone addiction compared with controls and posttherapy status. Brain parenchymal- and gray matter volume-adjusted γ-aminobutyric acid-to-creatine ratios correlated with clinical scales of Internet and smartphone addictions, depression, and anxiety. Glx/Cr was negatively correlated with insomnia and sleep quality scales. CONCLUSIONS: The high γ-aminobutyric acid levels and disrupted balance of γ-aminobutyric acid-to-Glx including glutamate in the anterior cingulate cortex may contribute to understanding the pathophysiology and treatment of Internet and smartphone addiction and associated comorbidities.

Midkine Promotes Odontoblast-like Differentiation and Tertiary Dentin Formation.

Autophagy is an intracellular self-degradation process that is essential for tissue development, cell differentiation, and survival. Nevertheless, the role of autophagy in tooth development has not been definitively identified. The goal of this study was to investigate how autophagy is involved in midkine (MK)-mediated odontoblast-like differentiation, mineralization, and tertiary dentin formation in a mouse tooth pulp exposure model. In vitro studies show that MK and LC3 have similar expression patterns during odontoblast-like cell differentiation. Odontoblast-like cell differentiation is promoted through MK-mediated autophagy, which leads to increased mineralized nodule formation. Subcutaneous transplantation of hydroxyapatite/tricalcium phosphate with rMK-treated human dental pulp cells led to dentin pulp-like tissue formation through MK-mediated autophagy. Furthermore, MK-mediated autophagy induces differentiation of dental pulp cells into odontoblast-like cells that form DSP-positive tertiary dentin in vivo. Our findings may provide 1) novel insight into the role of MK in regulating odontoblast-like differentiation and dentin formation in particular via autophagy and 2) potential application of MK in vital pulp therapy.

Independent effects of 15 commonly prescribed drugs on all-cause mortality among US elderly patients with type 2 diabetes mellitus.

OBJECTIVE: Most patients with type 2 diabetes mellitus (T2DM) also have hypertension and hyperlipidemia. Consequently, they are taking medications for all three conditions concurrently and the effect of one drug could be confounded with that of another. This study aimed to determine the independent effects of 15 commonly prescribed medications for three conditions on the risk of all-cause mortality among elderly patients with T2DM. RESEARCH DESIGN AND METHODS: A cohort of 360 437 elderly patients with T2DM from 2007 to 2016 US Medicare data was traced along with cumulative uses of 8 diabetes, 6 hypertension and 1 hyperlipidemia drugs. The relative risk of all-cause mortality for each study drug was estimated using an extended Cox regression analysis adjusting for the concurrent use of other study drugs. RESULTS: Compared with the no use of each study medication, mortality risk declined with use of 3 diabetes drugs, sodium-glucose cotransporter-2 inhibitors (HR=0.73; 95% CI 0.64 to 0.84), glucagon-like peptide-1 receptor agonists (HR=0.75; 95% CI 0.70 to 0.80) and dipeptidyl peptidase-4 inhibitors (HR=0.94; 95% CI 0.91 to 0.98), the use of 3 blood pressure medications, diuretics (HR=0.89; 95% CI 0.87 to 0.92), angiotensin receptor blockers (HR=0.86; 95% CI 0.84 to 0.89), ACE inhibitors (HR=0.98; 95% CI 0.95 to 1.01) as well as statins (HR=0.83; 95% CI 0.80 to 0.85). It increased moderately with insulin (HR=1.55; 95% CI 1.51 to 1.59), sulfonylureas (HR=1.16; 95% CI 1.13 to 1.20), a small inconsistent amount with metformin (HR=1.05), beta-blockers (HR=1.07), dihydropyridine calcium-channel blockers (HR=0.99) and non-dihydropyridine calcium-channel blockers (HR=1.05). The use of thiazolidinedione had no effect. CONCLUSION: Among older patients with diabetes, mortality risk decreased importantly with three new diabetes drugs, 3 blood pressure drugs and statins. It increased moderately with sulfonylurea and insulin. Studies of aggressive use of new T2DM drugs instead of sulfonylureas and insulin are needed. Our statin results empirically validate two national guidelines for using statins in older patients with diabetes. However, 23% of study patients never took a statin, suggesting missed opportunities for prevention.

A method for prioritizing risk groups for early SARS-CoV-2 Vaccination, By the Numbers.

Background: Given the limited supply of two COVID-19 vaccines, it will be important to choose which risk groups to prioritize for vaccination in order to get the most health benefits from that supply. Method: In order to help decide how to get the maximum health yield from this limited supply, we implemented a logistic regression model to predict COVID-19 death risk by age, race, and sex and did the same to predict COVID-19 case risk. Results: Our predictive model ranked all demographic groups by COVID-19 death risk. It was highly concentrated in some demographic groups, e.g. 85+ year old Black, Non-Hispanic patients suffered 1,953 deaths per 100,000. If we vaccinated the 17 demographic groups at highest COVID-19 death ranked by our logistic model, it would require only 3.7% of the vaccine supply needed to vaccinate all the United States, and yet prevent 47% of COVID-19 deaths. Nursing home residents had a higher COVID-19 death risk at 5,200 deaths/100,000, more than our highest demographic risk group. Risk of prison residents and health care workers (HCW) were lower than that of our demographic groups with the highest risks.We saw much less concentration of COVID-19 case risk in any demographic groups compared to the high concentration of COVID-19 death in some such groups. We should prioritize vaccinations with the goal of reducing deaths, not cases, while the vaccine supply is low. Conclusion: SARS-CoV-2 vaccines protect against severe COVID-19 infection and thus against COVID-19 death per vaccine studies. Allocating at least some of the early vaccine supplies to high risk demographic groups could maximize lives saved. Our model, and the risk estimate it produced, could help states define their vaccine allocation rules.

Association between use of proton pump inhibitors and tuberculosis risk: a systematic review.

SETTING: A comprehensive systematic review on whether proton pump inhibitors (PPIs) are associated with tuberculosis (TB) incidence is lacking.OBJECTIVE: To conduct a systematic review to elucidate if there is an association between PPI use and TB risk.DESIGN: We searched the MEDLINE, EMBASE, and Cochrane Library databases from their inception through 14 February 2018. Risk of Bias Assessment tool for Non-randomised Studies (ROBANS) was used to estimate the quality of each study. We could not undertake a meta-analysis because of the small number of studies and the diversity of outcome measures. All results of included studies are described narratively.RESULTS: Five studies were identified. In three case-control studies, compared with non-PPI use, PPI use was associated significantly with TB incidence, a 1.2-to-1.7-fold increased risk (adjusted OR 1.29; 95%CI 1.29-1.30, OR 1.31; 95%CI 1.22-1.41, adjusted hazard ratio 1.71; 95%CI 1.17-2.50). A cohort study reported that ≥3 months of PPI treatment was not associated significantly with TB incidence compared PPI treatment of <3 months. One cohort study reported that lansoprazole use decreased TB development significantly when compared with omeprazole/pantoprazole use.CONCLUSION: Compared with non-PPI use, PPI use was associated significantly with TB risk but the studies were heterogeneous.