Prospective Monitoring of New Drugs in Older Adults with and without Frailty: Near-Real-Time Assessment of Effectiveness and Safety of Oral Anticoagulants in Medicare Data.

BACKGROUND AND OBJECTIVE: Prospective sequential analyses after a new drug approval allow proactive surveillance of new drugs. In the current study, we demonstrate feasibility of frailty-specific sequential analyses for dabigatran, rivaroxaban, and apixaban versus warfarin. METHODS: We partitioned Medicare data from 2011 to 2020 into datasets based on calendar year following the date of drug approval. Each calendar year of data was added sequentially for analysis. We used a new-user, active comparative design by comparing the initiators of dabigatran versus warfarin, rivaroxaban versus warfarin, and apixaban versus warfarin. Patients aged ≥ 65 years with atrial fibrillation without contraindication to the anticoagulants were included. Claims-based frailty index ≥ 0.25 was used to define frailty. The initiators of each direct oral anticoagulant were propensity-score matched to the initiators of warfarin within each frailty status. The effectiveness outcome was ischemic stroke or systemic thromboembolism, and the safety outcome was major bleeding. For each calendar year, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox proportional hazards models using all data available up to that year. RESULTS: As an example of the results, in the 2020 dataset, compared with warfarin, apixaban was associated with a reduced risk of ischemic stroke or systemic thromboembolism (frail: HR 0.73, 95% CI 0.63-0.85; non-frail: HR 0.65, 95% CI 0.59-0.72) and major bleeding (frail: HR 0.63, 95% CI 0.57-0.69; non-frail: HR 0.59, 95% CI 0.56-0.63) in both frail and non-frail patients. We found evidence for apixaban's effectiveness and safety within 1-2 years after the drug approval in frail older patients. CONCLUSION: Our frailty-specific sequential analyses can be applied to future near-real-time monitoring of newly approved drugs.

Exoticin as a selective agonist of 6TM µ opioid receptors identifies endogenous chaperones essential for its activity.

BACKGROUND: Classical opioids are effective analgesics but carry various side effects, necessitating safer alternatives. Truncated six-transmembrane mu opioid receptors (6TM-µORs) mediate potent analgesia with fewer side effects and are a promising therapeutic target. However, few ligands known selectively target 6TM-µORs. Moreover, endogenous chaperones are believed essential for 6TM-µOR ligand binding and function. PURPOSE: To identify a 6TM-µOR selective agonist and elucidate requisite endogenous chaperones. METHODS: Virtual screening was used to identify promising selective 6TM-µOR agonists from traditional Chinese medicines. The role of 6TM-µOR in Exoticin analgesia was validated in loss- and gain-of-function models. APEX2 proteomics profiled proximal proteins under Exoticin or IBNtxA. Interactions were further characterized in vivo and in vitro. RESULTS: Exoticin was shortlisted for its selective binding to 6TM-µOR and ability to induce 6TM-µOR-dependent signal transduction. Exoticin analgesia was sensitive to ß-FNA and absent in E11 KO mice, but restored in mice infected with AAV-µOR1G. Slc3a2, Lrrc59, and Ppp1cb co-interacted with 6TM-µOR1G and were equally essential for Exoticin binding and 6TM-µOR1G activity. CONCLUSION: Exoticin is a promising selective agonist of 6TM µ opioid receptors with broad-spectrum analgesic efficacy but few side effects. Slc3a2, Lrrc59, Ppp1cb are endogenous chaperones essential for 6TM-µOR ligand binding and function.

A Symmetrical Quasi-Synchronous Step-Transition Folded Waveguide Slow Wave Structure for 650 GHz Traveling Wave Tubes.

For the purpose of improving performance and reducing the fabrication difficulty of terahertz traveling wave tubes (TWTs), this paper proposes a novel single-section high-gain slow wave structure (SWS), which is named the symmetrical quasi-synchronous step-transition (SQSST) folded waveguide (FW). The SQSST-FW SWS has an artificially designed quasi-synchronous region (QSR) to suppress self-oscillations for sustaining a high gain in an untruncated circuit. Simultaneously, a symmetrical design can improve the efficiency performance to some extent. A prototype of the SQSST-FW SWS for 650 GHz TWTs is designed based on small-signal analysis and numerical simulation. The simulation results indicate that the maximum saturation gain of the designed 650 GHz SQSST-FW TWT is 39.1 dB in a 34.3 mm slow wave circuit, occurring at the 645 GHz point when a 25.4 kV 15 mA electron beam and a 0.43 mW sinusoidal input signal are applied. In addition, a maximum output power exceeding 4 W is observed at the 648 GHz point using the same beam with an increased input power of around 2.8 mW.

Association of both depressive symptoms scores and specific depressive symptoms with all-cause and cardiovascular disease mortality.

BACKGROUND: The presence of depression related to an increased risk of all-cause and cardiovascular disease (CVD) mortality has been reported. However, studies conducted on certain specific depressive symptoms are scarce. Our purpose was to assess the effect of both depressive symptoms scores and certain specific depressive symptoms on all-cause and CVD mortality. METHODS: In the present cohort study, all participants, aged 18 years or older, were enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2014. Depressive symptoms score was assessed using the validated 9-item Patient Health Questionnaire Depression Scale (PHQ-9), which ranges from 0 to 27, with a PHQ-9 score ≥ 10 diagnosed as depression. The outcome events were all-cause and CVD mortality, which were followed up from 2005 to 2014. The associations of both depressive symptoms score and certain specific depressive symptoms with all-cause and CVD mortality were examined by weighted multivariable proportional hazards models. RESULTS: A total of 26,028 participants aged ≥ 18 years were included in the statistical analysis, including 12,813 (49.2%) males and 13,215 (50.8%) females, with a mean (SD) age of 47.34 (18.86) years. During the 9.32 (3.20) years of mean (SD) follow-up, 3261 deaths were recorded, of which 826 were cardiovascular deaths. All-cause mortality was 16.87/1000 person-years in subjects with depression. In terms of CVD mortality, these figures were 4.53/1000 person-years. In the full model (model 3), elevated depressive symptoms scores were independently associated with an increased risk of all-cause mortality (Highest depression symptom score group: adjusted hazard ratio, 1.63; 95% CI 1.44-1.85) and CVD mortality (Highest depression symptom score group: adjusted hazard ratio, 1.73; 95% CI 1.34-2.24). All 9 specific depressive symptoms that make up the PHQ-9 were related to an increased risk of all-cause mortality. However, only 3 symptoms, including trouble sleeping or sleeping too much, poor appetite or overeating, and suicidal ideation, were no significantly associated with an increased risk of CVD mortality. CONCLUSIONS: The elevated depressive symptoms scores were strongly associated with an increased risk of all-cause and CVD mortality in US adults. Furthermore, all 9 specific depressive symptoms were associated with high all-cause mortality. However, trouble sleeping or sleeping too much, poor appetite or overeating, and suicidal ideation might not increase the risk of CVD mortality.

Measuring and Understanding Market Exclusivity Length for New Prescription Drugs in France, Australia, and the USA.

BACKGROUND: Originator drug manufacturers use several strategies to delay generic competition in the USA, but it remains unclear whether this results in longer market exclusivity compared to other countries. OBJECTIVES: We sought to understand how drug market exclusivity lengths vary between the USA and two comparable countries. METHODS: We focused on drugs approved within 2 years of each other in the USA, France, and Australia from 1995 to 2005, and we compared the lengths of exclusivity from marketing approval through first generic competition or June 2023 using Kaplan-Meier analyses. RESULTS: Among 165 drugs in common between the USA and France, the median length of exclusivity was slightly longer in France (15.0 years, interquartile range [IQR]: 13.0-19.6) than the USA (14.5 years, IQR: 11.7-17.6). Among 100 drugs in common between the USA and Australia, the median length of exclusivity was longer in Australia (16.3 years, IQR: 13.9-22.4) than in the USA (14.4 years, IQR: 12.0-17.1). CONCLUSIONS: Market exclusivity lengths in the USA are not longer than in France and Australia. Potential reasons include the larger US market and incentives that offer transient high generic drug prices in the USA for manufacturers that successfully challenge originator market exclusivity.

Assessment of myocardial microvascular dysfunction in patients with different stages of diabetes mellitus: An adenosine stress perfusion cardiac magnetic resonance study.

PURPOSE: To examine myocardial perfusion and T1 mapping indicesin individuals with type 2 diabetes mellitus (T2DM) at various stages of glycemic control and whether uncontrolled glycemic levels would worsen myocardial microvascular function. METHOD: Cardiac magnetic resonance examinations were performed on 114 T2DM patients without obstructive coronary artery disease and 55 matched controls. Participants were further divided into four subgroups: Q1 (control); Q2 (prediabetes); Q3 (controlled T2DM) and Q4 (uncontrolled T2DM). The correlation between glycosylated hemoglobin (HbA1c) levels and myocardial perfusion parameters was evaluated. RESULTS: Global myocardial perfusion reserve index (MPRI) was significantly reduced in the Q3 and Q4 subgroups compared to the Q1 or Q2 subgroup (all P<0.001). Compared with the Q1 subgroup, global stress T1 reactivity (stress ΔT1) was significantly reduced in the Q3 and Q4 subgroups (P=0.004 and < 0.001, respectively), but elevated in the Q2 subgroup (P=0.018). Global extracellular volume (ECV) was considerably higher in the Q2 subgroup and gradually rose in the Q3 and Q4 subgroups compared to the Q1 subgroup (P=0.011, 0.001, and 0.007, respectively). HbA1c levels correlated negatively with global MPRI and stress ΔT1, but positively with global ECV (ß = -1.993, P<0.001; ß = -0.180, P<0.001; and ß = 0.127, P<0.001, respectively). CONCLUSIONS: Global stress ΔT1 reduced in T2DM patients but rose in prediabetes patients. Compared to MPRI, the ECV parameter can indicate diabetes-induced coronary microvascular dysfunction earlier and persists throughout the disorder. Myocardial perfusion and T1 mapping at stress can be used to detect early signs of microvascular dysfunction and subclinical risk factors in patients with T2DM.

A Staggered Vane-Shaped Slot-Line Slow-Wave Structure for W-Band Dual-Sheet Electron-Beam-Traveling Wave Tubes.

A staggered vane-shaped slot-line slow-wave structure (SV-SL SWS) for application in W-band traveling wave tubes (TWTs) is proposed in this article. In contrast to the conventional slot-line SWSs with dielectric substrates, the proposed SWS consists only of a thin metal sheet inscribed with periodic grooves and two half-metal enclosures, which means it can be easily manufactured and assembled and has the potential for mass production. This SWS not only solves the problem of the dielectric loading effect but also improves the heat dissipation capability of such structures. Meanwhile, the SWS design presented here covers a -15 dB S11 frequency range from 87.5 to 95 GHz. The 3-D simulation for a TWT based on the suggested SWS is also investigated. Under dual-electron injection conditions with a total voltage of 17.2 kV and a total current of 0.3 A, the maximum output power at 90 GHz is 200 W, with a 3 dB bandwidth up to 4 GHz. With a good potential for fabrication using microfabrication techniques, this structure can be a good candidate for millimeter-wave TWT applications.

[Research progress on the role of astrocytes in cerebral ischemia/reperfusion injury].

The pathophysiological mechanism of cerebral ischemia/reperfusion injury (CIRI) is complex, and the current treatment methods are limited and the efficacy is not good. Previous therapeutic strategies of CIRI mostly target neurons, but no significant progress has been made. At present, astrocytes are expected to be promising effector cells for the treatment of CIRI. Astrocytes are a "double-edged sword" in the pathological process of CIRI, with both neurotoxic and neuroprotective effects on the central nervous system. How to effectively use astrocytes to treat CIRI has become a research hotspot. In this review, the dual roles of astrocytes in CIRI mechanism were reviewed, and the related mechanisms of astrocytes in relieving oxidative stress induced by CIRI were emphasized, in order to provide new ideas for the treatment of CIRI.

Trust in the Food and Drug Administration: A National Survey Study.

Building trust in public health agencies like the US Food and Drug Administration (FDA) has become a key government priority. Understanding the roots of FDA mistrust is important if the agency is to develop targeted messaging and reforms aimed at building confidence in the agency. We conducted a survey of 2,021 respondents in the US probing attitudes toward the FDA. The primary outcome was FDA trust, defined as the mean score that each respondent assigned to the FDA across four prespecified axes: (1) competence and effectiveness; (2) commitment to acting in the best interests of the American public; (3) abiding by the rules and regulations set forth by policy or law; and (4) expertise in health, science, and medicine. On multivariable ordinal logistic regression, FDA mistrust was associated with female gender (odds ratio [OR] = 0.74, 95% confidence interval [CI] 0.62-0.88), rural community (OR 0.85, 95% CI 0.75-0.96), conservative political views (OR 0.77, 95% CI 0.74-0.81), worse self-reported health (OR 0.89, 95% CI 0.80-0.98), lower satisfaction with health care received (OR 0.63, 95% CI 0.56-0.71), less attention to health and science news (OR 0.72, 95% CI 0.64-0.80), and not having children under the age of 18 (OR 0.72, 95% CI 0.60-0.86). These findings underscore the challenges faced by US political leaders in convincing a heterogeneous American public to trust the FDA. The FDA should develop and deploy targeted outreach strategies to populations with lower levels of trust and strengthen internal processes that minimize biases and ensure sound decision-making.

Associations between static and dynamic changes of platelet counts and in-hospital mortality in critical patients with acute heart failure.

To investigate the predictive value of baseline platelet count and its short-term dynamic changes in the prognosis of patients with acute heart failure (AHF) in the intensive care unit. Patients diagnosed with AHF in the medical information mart for intensive care III and their clinical data were retrospectively filtered. Patients were divided into survivor and non-survivor groups based on their prognosis during hospitalization, and differences in baseline data between groups were compared. Logistic regression models and restricted cubic spline (RCS) plots were performed to evaluate the relationship between baseline platelet counts and in-hospital mortality. Changes and trends in platelet counts were compared between the survivor and non-survivor groups after adjusting for confounders with the generalized additive mixing model (GAMM). A total of 2930 critical patients with acute heart failure were included, of which 2720 were survivors and 210 were non-survivors. Multiple logistic regression models revealed that baseline platelet count was an independent factor in hospital mortality (OR 0.997, 95% CI 0.994-0.999, P-value = 0.018). The RCS plot demonstrated a U-shaped dose-response relationship between baseline platelet count and in-hospital mortality. GAMM analysis suggested that the platelet counts decreased and then increased in the survivor group and gradually decreased in the non-survivor group, with a gradual increase of difference between two groups. After adjusting for confounders, the mean daily increase was -6.014 (95% CI -7.076-4.953, P-value < 0.001). Baseline platelet demonstrated a U-shaped dose-response relationship with adverse outcomes in critical patients with AHF. Early elevation of platelet was correlated with higher in-hospital mortality, indicating that tracking early changes in platelet might help determine the short-term prognosis of critical patients with AHF.

The causal association between artificial sweeteners and the risk of cancer: a Mendelian randomization study.

Artificial sweeteners (ASs) have been widely added to food and beverages because of their properties of low calories and sweet taste. However, whether the consumption of ASs is causally associated with cancer risk is not clear. Here, we utilized the two-sample Mendelian randomization (MR) method to study the potential causal association. Genetic variants like single-nucleotide polymorphisms (SNPs) associated with exposure (AS consumption) were extracted from a genome-wide association study (GWAS) database including 64 949 Europeans and the influence of confounding was removed. The outcome was from 98 GWAS data and included several types of cancers like lung cancer, colorectal cancer, stomach cancer, breast cancer, and so on. The exposure-outcome SNPs were harmonized and then MR analysis was performed. The inverse-variance weighted (IVW) with random effects was used as the main analytical method accompanied by four complementary methods: MR Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses consisted of heterogeneity, pleiotropy, and leave-one-out analysis. Our results demonstrated that ASs added to coffee had a positive association with high-grade and low-grade serous ovarian cancer; ASs added to tea had a positive association with oral cavity and pharyngeal cancers, but a negative association with malignant neoplasm of the bronchus and lungs. No other cancers had a genetic causal association with AS consumption. Our MR study revealed that AS consumption had no genetic causal association with major cancers. Larger MR studies or RCTs are needed to investigate small effects and support this conclusion.

Low-frequency electroacupuncture exerts antinociceptive effects through activation of POMC neural circuit induced endorphinergic input to the periaqueductal gray from the arcuate nucleus.

It has been widely recognized that electroacupuncture (EA) inducing the release of ß-endorphin represents a crucial mechanism of EA analgesia. The arcuate nucleus (ARC) in the hypothalamus is a vital component of the endogenous opioid peptide system. Serving as an integration center, the periaqueductal gray (PAG) receives neural fiber projections from the frontal cortex, insular cortex, and ARC. However, the specific mechanisms how EA facilitates the release of ß-endorphin within the ARC, eliciting analgesic effects are yet to be elucidated. In this study, we conducted in vivo and in vitro experiments by transcriptomics, microdialysis, photogenetics, chemical genetics, and calcium imaging, combined with transgenic animals. Firstly, we detected 2 Hz EA at the Zusanli (ST36) increased the level of ß-endorphin and transcriptional level of proopiomelanocortin (POMC). Our transcriptomics profiling demonstrated that 2 Hz EA at the ST36 modulates the expression of c-Fos and Jun B in ARC brain nuclear cluster, and the transcriptional regulation of 2 Hz EA mainly occur in POMC neurons by Immunofluorescence staining verification. Meaning while, 2 Hz EA specifically activated the cAMP-PKA-CREB signaling pathway in ARC which mediating the c-Fos and Jun B transcription, and 2 Hz EA analgesia is dependent on the activation of cAMP-PKA-CREB signaling pathway in ARC. In order to investigate how the ß-endorphin produced in ARC transfer to integration center PAG, transneuronal tracing technology was used to observe the 2 Hz EA promoted the neural projection from ARC to PAG compared to 100 Hz EA and sham mice. Inhibited PAGGABA neurons, the transfer of ß-endorphin from the ARC nucleus to the PAG nucleus through the ARCPOMC-PAGGABA neural circuit. Furthermore, by manipulating the excitability of POMC neurons from ARCPOMC to PAGGABA using inhibitory chemogenetics and optogenetics, we found that this inhibition significantly reduced transfer of ß-endorphin from the ARC nucleus to the PAG nucleus and the effectiveness of 2 Hz EA analgesia in neurological POMC cyclization recombination enzyme (Cre) mice and C57BL/6J mice, which indicates that the transfer of ß-endorphin depends on the activation of POMC neurons prefect from ARCPOMC to PAGGABA. These findings contribute to our understanding of the neural circuitry underlying the EA pain-relieving effects and maybe provide valuable insights for optimizing EA stimulation parameters in clinical pain treatment using the in vivo dynamic visual investigating the central analgesic mechanism.

Single-cell transcriptomics of the human parasite Schistosoma mansoni first intra-molluscan stage reveals tentative tegumental and stem-cell regulators.

Schistosomiasis is a major Neglected Tropical Disease, caused by the infection with blood flukes in the genus Schistosoma. To complete the life cycle, the parasite undergoes asexual and sexual reproduction within an intermediate snail host and a definitive mammalian host, respectively. The intra-molluscan phase provides a critical amplification step that ensures a successful transmission. However, the cellular and molecular mechanisms underlying the development of the intra-molluscan stages remain poorly understood. Here, single cell suspensions from S. mansoni mother sporocysts were produced and sequenced using the droplet-based 10X Genomics Chromium platform. Six cell clusters comprising two tegument, muscle, neuron, parenchyma and stem/germinal cell clusters were identified and validated by in situ hybridisation. Gene Ontology term analysis predicted key biological processes for each of the clusters, including three stem/germinal sub-clusters. Furthermore, putative transcription factors predicted for stem/germinal and tegument clusters may play key roles during parasite development and interaction with the intermediate host.

How Do Risk Evaluation and Mitigation Strategies Impact Clinical Practice? A National Survey of Physicians.

The US Food and Drug Administration can require risk evaluation and mitigation strategy (REMS) programs for prescription drugs to ensure the benefits of use outweigh the risks. We conducted a national survey of physicians' experiences prescribing eight REMS-covered drugs: (1) ambrisentan; (2) bosentan; (3) clozapine; (4) isotretinoin; (5-7) the multiple myeloma (MM) drugs lenalidomide, pomalidomide, thalidomide; and (8) sodium oxybate. Between May 2022 and January 2023, we surveyed 5,331 physician prescribers of these drugs, and 1,295 (24%) returned surveys (range: 149 for bosentan to 226 for MM drugs). Although 765 (68%) respondents thought the certification process provided useful drug information, 757 (67%) wanted materials to include benefit data and 944 (84%) non-REMS-related risk data. A majority (704, 63%) thought the safe use requirements facilitated discussion with patients, but a similar number (637, 57%) attributed delayed medication access to these requirements. In multivariable modeling, MM drug and isotretinoin respondents were less likely than sodium oxybate respondents to agree that the certification process provided useful drug information (MM drug: odds ratio (OR) = 0.37, 95% confidence interval (CI) = 0.25-0.55; isotretinoin: OR = 0.39, 95% CI = 0.25-0.61), and isotretinoin, clozapine, and bosetan respondents were more likely than sodium oxybate respondents to agree that the safe use requirements often delayed medication access (isotretinoin: OR = 5.83, 95% CI = 3.70-9.19; clozapine: OR = 1.65, 95% CI = 1.08-2.54; bosentan: OR = 1.78, 95% CI = 1.12-2.85). Most physicians believe REMS programs convey useful drug safety information and facilitate discussion with patients but also seek information on benefits and non-REMS-related risks and better integration of REMS processes into clinical workflows.

Water Leaching Kinetics of Boron from the Alkali-Activated Ludwigite Ore.

The primary aim of this study was to investigate the boron leaching process from alkali-activated ludwigite ore. Initially, the ore underwent activation through roasting at 1050 °C for 60 min with 20% sodium carbonate. Subsequently, the study examined the influence of leaching parameters, including temperature, time, liquid-to-solid ratio, and particle size, using the activated ore as the raw material. Additionally, water leaching characteristics of the residues and boron kinetics were analyzed. The results demonstrated that boron leaching efficiency reached 93.71% from the reduced ludwigite ore under specific conditions: leaching temperature of 180 °C, leaching time of 6 h, liquid-to-solid ratio of 8:1, and feed particle size of 52.31 µm (average particle size). Leach residue characteristics indicated the dissolution of minerals during the process. The boron behavior during water leaching followed the Avrami Equation, and the kinetics equation was derived by fitting the leaching data. Moreover, the activation energy (Ea) value for boron leaching was determined to be 8.812 kJ·mol-1 using the Arrhenius Equation, indicating that the leaching process is controlled by diffusion.

Sophoricoside ameliorates cerebral ischemia-reperfusion injury dependent on activating AMPK.

AIMS: Ischemic stroke accounts for 87% of all strokes, and its death and disability bring a huge burden to society. Brain injury caused by ischemia-reperfusion (I/R) is also a major difficulty in clinical treatment and prognosis. Sophoricoside (SOP) is an isoflavone glycoside isolated from the seed of medical herb Sophora japonica L. Previously, SOP was found to be effective in anti-inflammation and glucose-lipid metabolism-related diseases. In order to investigate whether SOP has a regulatory effect on cerebral I/R injury, we conducted this study. METHODS: Here, by application of SOP into MCAO (transient middle cerebral artery occlusion)-induced mice and OGD/R (oxygen glucose deprivation/reperfusion)-induced primary neurons, the regulation effects of SOP was analyzed by detecting neurological score of post-stroke mice, phenotypes of brains and brain sections, cell viabilities, and apoptosis- and inflammation-regulation. RNA sequencing and molecular biology experiments were performed to explore the mechanism of SOP regulating cerebral I/R injury. RESULTS: SOP administration decreased the infarct size, neurological deficit score, neuronal cell injury, inflammation and apoptosis. Mechanistically, SOP exerted its protective effect by activating the AMP-activated protein kinase (AMPK) signaling pathway. CONCLUSION: SOP inhibits cerebral I/R injury by promoting the phosphorylation of AMPK.

Physicians' Perspectives On FDA Regulation Of Drugs And Medical Devices: A National Survey.

Physicians' knowledge of Food and Drug Administration (FDA) approval processes is important in informing clinical decisions and patient discussions. Among a randomly selected national sample of 509 internists, cardiologists, and oncologists, 41 percent reported moderate or better understanding of the FDA's drug approval process, and 17 percent reported moderate or better understanding of the FDA's medical device approval process. Nearly all physicians thought that randomized, blinded trials that met primary endpoints should be very important factors required to secure regulatory approval. Also, nearly all physicians thought that the FDA should revoke approval for accelerated-approval drugs or breakthrough devices that did not show benefit in postapproval studies. Our findings suggest that physicians commonly lack familiarity with drug and medical device regulatory practices and are under the impression that the data supporting FDA drug and high-risk device approvals are more rigorous than they often are. Physicians would value more rigorous premarket evidence, as well as regulatory action for drugs and devices that do not demonstrate safety and effectiveness in the postmarket setting.

Development and Validation of a Claims-Based Model to Predict Categories of Obesity.

We developed and validated a claims-based algorithm that classifies patients into obesity categories. Using Medicare (2007-2017) and Medicaid (2000-2014) claims data linked to 2 electronic health record (EHR) systems in Boston, Massachusetts, we identified a cohort of patients with an EHR-based body mass index (BMI) measurement (calculated as weight (kg)/height (m)2). We used regularized regression to select from 137 variables and built generalized linear models to classify patients with BMIs of ≥25, ≥30, and ≥40. We developed the prediction model using EHR system 1 (training set) and validated it in EHR system 2 (validation set). The cohort contained 123,432 patients in the Medicare population and 40,736 patients in the Medicaid population. The model comprised 97 variables in the Medicare set and 95 in the Medicaid set, including BMI-related diagnosis codes, cardiovascular and antidiabetic drugs, and obesity-related comorbidities. The areas under the receiver-operating-characteristic curve in the validation set were 0.72, 0.75, and 0.83 (Medicare) and 0.66, 0.66, and 0.70 (Medicaid) for BMIs of ≥25, ≥30, and ≥40, respectively. The positive predictive values were 81.5%, 80.6%, and 64.7% (Medicare) and 81.6%, 77.5%, and 62.5% (Medicaid), for BMIs of ≥25, ≥30, and ≥40, respectively. The proposed model can identify obesity categories in claims databases when BMI measurements are missing and can be used for confounding adjustment, defining subgroups, or probabilistic bias analysis.