Measurements and morphometric landmarks of the human spinal cord: A cadaveric study.

The topographical neuroanatomy of the human spinal cord (SC) is currently based on the adjacent vertebrae. This morphometric study sought to develop a dataset allowing for statistical analysis of human SC segment characteristics. Overall, 32 human SCs were dissected (18 female and 14 male donors), and individual SC segments were identified. Anterior and posterior lengths, thicknesses and widths were measured by two examiners. Statistical analyses included t-tests, as well as intraclass and Pearson's correlation coefficients. The SC length was significantly shorter in females than males. The cranial (C4) and caudal (T1/T2) limits of the cervical enlargement, along with its maximal width (C6-C7), were identified by combining widths and thicknesses of the segments. The thoracic region, T2 to T12, could be identified using segments widths and thicknesses values. The length of the lumbosacral region, from segments L2 to S5, was particularly stable, independently of SC length and sex. The lumbar enlargement was characterized by a thickness increase between the segments L2 and S1 which reached its maximum at the level of L3, L4, and L5, whereas the width was not significantly increased. From the S2 to S5 segments, width and thickness were equal, with both decreasing of 1 mm per segment. The morphometrical analysis of 32 human SCs provided a dataset allowing for statistical analysis of segmental measures with significant results. A combined approach mostly using widths and thicknesses provided landmarks of potential interest for the localization of SC segments in a clinical MRI setting.

Retrospective Observational Real-World Outcome Study to Evaluate Safety Among Patients With Erectile Dysfunction (ED) With Co-Possession of Tadalafil and Anti-Hypertensive Medications (anti-HTN).

BACKGROUND: Erectile dysfunction (ED) is a common condition affecting male adults and may be associated with hypertension, diabetes, hyperlipidemia, and obesity. Phosphodiesterase type 5 (PDE5) inhibitors, such as tadalafil, are the first-line drug therapy for ED. Studies and the current prescribing information of these PDE5 inhibitors indicate they are mechanistic mild vasodilators and, as such, concomitant use of a PDE5 inhibitor with anti-hypertensive medication may lead to drops in blood pressure due to possible drug-drug interaction. AIM: Evaluate risks of hypotensive/cardiovascular outcomes in a large cohort of patients with ED that have co-possession of prescriptions for tadalafil and hypertensive medications versus either medication/s alone. METHODS: A cohort study conducted within an electronic health record database (Optum) representing hospitals across the US. Adult male patients prescribed tadalafil and/or anti-hypertensive medications from January 2012 to December 2017 were eligible. Possession periods were defined by the time patients likely had possession of medication, with propensity score-matched groups used for comparison. OUTCOMES: Risk of hypotensive/cardiovascular outcomes were measured using diagnostic codes and NLP algorithms during possession periods of tadalafil + anti-hypertensive versus either medication/s alone. RESULTS: In total there were 127,849 tadalafil + anti-hypertensive medication possession periods, 821,359 anti-hypertensive only medication possession periods, and 98,638 tadalafil only medication possession periods during the study; 126,120 were successfully matched. Adjusted-matched incidence rate ratios (IRRs) for the anti-hypertensive only possession periods compared with tadalafil + anti-hypertensive periods of diagnosed outcomes were all below 1. Two outcomes had a 95% confidence interval (CI) that did not include 1.0: ventricular arrhythmia (IRR 0.79; 95% CI 0.66, 0.94) and diagnosis of hypotension (IRR 0.79; 95% CI 0.71, 0.89). CLINICAL IMPLICATIONS: Provides real world evidence that co-possession of tadalafil and anti-hypertensive medications does not increase risk of hypotensive/cardiovascular outcomes beyond that observed for patients in possession of anti-hypertensive medications only. STRENGTHS AND LIMITATIONS: EHR data are valuable for the evaluation of real world outcomes, however, the data are retrospective and collected for clinical patient management rather than research. Prescription data represent the intent of the prescriber and not use by the patient. Residual bias cannot be ruled out, despite propensity score matching, due to unobserved patient characteristics and severity that are not fully reflected in the EHR database. CONCLUSION: In the studied real world patients, this study did not demonstrate an increased risk of hypotensive or cardiovascular outcomes associated with co-possession of tadalafil and anti-hypertensive medications beyond that observed for patients in possession of anti-hypertensive medications only. Nunes AP, Seeger JD, Stewart A, et al., Retrospective Observational Real-World Outcome Study to Evaluate Safety Among Patients With Erectile Dysfunction (ED) With Co-Possession of Tadalafil and Anti-Hypertensive Medications (anti-HTN). J Sex Med 2022;19:74-82.

Cardiovascular Outcome Risks in Patients With Erectile Dysfunction Co-Prescribed a Phosphodiesterase Type 5 Inhibitor (PDE5i) and a Nitrate: A Retrospective Observational Study Using Electronic Health Record Data in the United States.

BACKGROUND: Phosphodiesterase type 5 inhibitors (PDE5i) are first-line therapy for erectile dysfunction (ED). Approximately 1-4% of PDE5i recipients co-possess nitrates, despite this combination potentially producing clinically significant hypotension. Real-world data in these patients and insights into prescriber rationales for co-prescription are limited. AIM: This study investigated whether PDE5i and nitrate co-possession is associated with increased rates of cardiovascular (CV) outcomes. METHODS: Adult males with ED and PDE5i prescription and males with nitrate prescription were identified from a U.S. electronic health record database (2012-2016). Quantitative comparisons were made between patients with ED and co-possession (ED + PDE5i + nitrate), only nitrate possession (ED + nitrate and nitrate only [without ED]), and only PDE5i possession (ED + PDE5i). OUTCOMES: We quantified incidence of CV outcomes in co-possession and comparator periods, calculating incidence rate ratios after propensity score matching. Prescriber rationales were derived by reviewing virtual patient records. RESULTS: Over 168,000 patients had ≥1 PDE5i prescription (∼241,000 possession periods); >480,000 patients had ≥1 nitrate prescription (∼486,000 possession periods); and 3,167 patients had 3,668 co-possession periods. Non-significantly different or lower rates of CV outcomes were observed for co-possession periods vs ED + nitrate and nitrate only periods. Most CV outcome rates were non-significantly different between co-possession and ED + PDE5i periods (myocardial infarction, hospitalized unstable angina and fainting were higher with co-possession). From qualitative assessment of patient records with co-possession, 131 of 252 (52%) documented discussion with a physician regarding co-possession; 69 of 131 (53%) warned or instructed on safely managing these contraindicated medications. CLINICAL IMPLICATIONS: Findings from this real-world study indicate that co-possession of nitrate and PDE5i prescriptions is not associated with increased rates of CV outcomes, relative to possession of nitrates alone. Physicians should and often do discuss the risks of using both medications together with their patients. STRENGTHS & LIMITATIONS: Strengths of this study are the large size of the U.S. real-world patient cohort with data available for analysis, and our ability to utilize natural language processing to explore co-prescription rationales and patient-physician interactions. Limitations are the retrospective nature of the analysis and inability to establish whether recorded prescriptions were filled or the medication was consumed. CONCLUSION: Co-exposure of PDE5i and nitrates should continue to be avoided; however, co-possession of PDE5i and nitrate prescriptions is not necessarily associated with increased CV risk. Co-possession can be successfully managed in suitable circumstances. Nunes AP, Seeger JD, Stewart A, et al. Cardiovascular Outcome Risks in Patients With Erectile Dysfunction Co-Prescribed a Phosphodiesterase Type 5 Inhibitor (PDE5i) and a Nitrate: A Retrospective Observational Study Using Electronic Health Record Data in the United States. J Sex Med 2021;18:1511-1523.

Multiple imputation to quantify misclassification in observational studies of the cognitively impaired: an application for pain assessment in nursing home residents.

BACKGROUND: Despite experimental evidence suggesting that pain sensitivity is not impaired by cognitive impairment, observational studies in nursing home residents have observed an inverse association between cognitive impairment and resident-reported or staff-assessed pain. Under the hypothesis that the inverse association may be partially attributable to differential misclassification due to recall and communication limitations, this study implemented a missing data approach to quantify the absolute magnitude of misclassification of pain, pain frequency, and pain intensity by level of cognitive impairment. METHODS: Using the 2016 Minimum Data Set 3.0, we conducted a cross-sectional study among newly admitted US nursing home residents. Pain presence, severity, and frequency is assessed via resident-reported measures. For residents unable to communicate their pain, nursing home staff document pain based on direct resident observation and record review. We estimate a counterfactual expected level of pain in the absence of cognitive impairment by multiply imputing modified pain indicators for which the values were retained for residents with no/mild cognitive impairment and set to missing for residents with moderate/severe cognitive impairment. Absolute differences (∆) in the presence and magnitude of pain were calculated as the difference between documented pain and the expected level of pain. RESULTS: The difference between observed and expected resident reported pain was greater in residents with severe cognitive impairment (∆ = -10.2%, 95% Confidence Interval (CI): -10.9% to -9.4%) than those with moderate cognitive impairment (∆ = -4.5%, 95% CI: -5.4% to -3.6%). For staff-assessed pain, the magnitude of apparent underreporting was similar between residents with moderate impairment (∆ = -7.2%, 95% CI: -8.3% to -6.0%) and residents with severe impairment (∆ = -7.2%, 95% CI: -8.0% to -6.3%). Pain characterized as "mild" had the highest magnitude of apparent underreporting. CONCLUSIONS: In residents with moderate to severe cognitive impairment, documentation of any pain was lower than expected in the absence of cognitive impairment. This finding supports the hypothesis that an inverse association between pain and cognitive impairment may be explained by differential misclassification. This study highlights the need to develop analytic and/or procedural solutions to correct for recall/reporter bias resulting from cognitive impairment.

Outcomes in patients with lung cancer treated with crizotinib and erlotinib in routine clinical practice: A post-authorization safety cohort study conducted in Europe and in the United States.

PURPOSE: We examined safety outcomes of interest (SOI) and overall survival (OS) among lung cancer patients initiating crizotinib and erlotinib in routine clinical practice. METHODS: This descriptive cohort study used routinely collected health data in Denmark, Finland, Sweden, the Netherlands, and the United States (US) during 2011-2017, following crizotinib commercial availability in each country. Among crizotinib or erlotinib initiators, we reported baseline characteristics and incidence rates and cumulative incidences of the SOI - hepatotoxicity, pneumonitis/interstitial lung disease, QT interval prolongation-related events, bradycardia, vision disorders, renal cysts, edema, leukopenia, neuropathy, photosensitivity, malignant melanoma, gastrointestinal perforation, cardiac failure and OS. Results from the European Union (EU) countries were combined using meta-analysis; results from the US were reported separately. RESULTS: There were 456 patients in the crizotinib cohort and 2957 patients in the erlotinib cohort. Rates of the SOI per 1000 person-years in the crizotinib cohort ranged from 0 to 65 in the EU and from 0 to 374 in the US. Rates of the SOI per 1000 person-years in the erlotinib cohort ranged from 0 to 91 in the EU and from 3 to 394 in the US. In the crizotinib cohort, 2-year OS was ~50% in both EU and US. In the erlotinib cohort, 2-year OS was 21% in the EU and 35% in the US. CONCLUSIONS: This study describes clinical outcomes among lung cancer patients initiating crizotinib or erlotinib in routine clinical practice. Differences between SOI rates in EU and US may be partially attributable to differences in the underlying databases.

Pain Behaviors and Pharmacological Pain Management Among Newly Admitted Nursing Home Residents.

BACKGROUND: Clinicians may place more weight on vocal complaints of pain than the other pain behaviors when making decisions about pain management. OBJECTIVES: We examined the association between documented pain behaviors and pharmacological pain management among nursing home residents. METHODS: We included 447,684 residents unable to self-report pain, with staff-documented pain behaviors (vocal, nonverbal, facial expressions, protective behaviors) and pharmacological pain management documented on the 2010-2016 Minimum Data Set 3.0. The outcome was no pharmacological pain medications, as needed only (pro re nata [PRN]), as scheduled only, or as scheduled with PRN medications. We estimated adjusted odds ratios and 95% confidence intervals from multinomial logistic models. RESULTS: Relative to residents with vocal complaints only, those with one pain behavior documented (i.e., nonverbal, facial, or protective behavior) were more likely to lack pain medication versus scheduled and PRN medications. Residents with multiple pain behaviors documented were least likely to have no treatment relative to scheduled with PRN medications, PRN only, or scheduled only pain medication regimens. DISCUSSION: The type and number of pain behaviors observed are associated with pharmacological pain management regimen. Improving staff recognition of pain among residents unable to self-report is warranted in nursing homes.

Prevalence and the factors associated with oral anticoagulant use among nursing home residents.

WHAT IS KNOWN AND OBJECTIVE: Anticoagulants are indicated for treatment and prevention of several clinical conditions. Prior studies have examined anticoagulant utilization for specific indications and in community-dwelling populations. Decision-making regarding anticoagulant prescribing in the nursing home setting is particularly challenging because advanced age and clinical complexity places most residents at increased risk for adverse drug events. To estimate the prevalence of oral anticoagulant (OAC) use (overall, warfarin, direct oral anticoagulants (DOACs)) and identify factors associated with oral anticoagulant use among the general population of residents living in nursing homes. METHODS: This point prevalence study was conducted among 506,482 residents in US nursing homes on 31 October 2016 who were enrolled in Medicare fee-for-service. Covariates including demographics, clinical conditions, medications, cognitive impairment and functional status were obtained from Minimum Data Set 3.0 assessments and Medicare Part A and D claims. Oral anticoagulant use was identified using dispensing dates and days supply information from Medicare Part D claims. Robust Poisson models estimated adjusted prevalence ratios (aPR) for associations between covariates and 1) any anticoagulant use, and 2) DOAC versus warfarin use. RESULTS AND DISCUSSION: Overall, 11.8% of residents used oral anticoagulants. Among users, 44.3% used DOACs. Residents with body mass index (BMI) ≥40 kg/m2 (aPR: 1.66; 95% CI: 1.61 -1.71), with functional dependency in activities of daily living, polypharmacy and higher CHA2 DS2 -VASc risk ischaemic stroke scores, had a higher prevalence of oral anticoagulant use. Women (aPR: 0.78; 95% CI: 0.76-0.79), residents with limited life expectancy (aPR 0.80; 95% CI: 0.76-0.83), those with moderate-to-severe cognitive impairment (aPR: 0.67; 95% CI: 0.65-0.68), those using NSAIDs or antiplatelets, and non-white racial/ethnic groups had a lower prevalence of anticoagulant use. Residents with higher levels of polypharmacy, BMI and age had a lower prevalence of DOAC use (versus warfarin). WHAT IS NEW AND CONCLUSION: Approximately one in eight general nursing home residents use oral anticoagulants and among oral anticoagulant users, only slightly more residents used warfarin than DOACs. The lower prevalence of anticoagulation among women and non-white racial/ethnic groups raises concerns of potential inequities in quality of care. Lower oral anticoagulant use among residents with limited life expectancy suggests possible deprescribing at the end of life. Further research is needed to inform resident-centred shared decision-making that explicitly considers treatment goals and individual-specific risks and benefits of anticoagulation at all stages of the medication use continuum.

Using RWE research to extend clinical trials in diabetes: An example with implications for the future.

BACKGROUND: Although randomized, controlled trials (RCTs) are seen as the gold standard for evidence in clinical medicine, a number of considerations are increasing the use of real-world data (RWD) to generate evidence. A series of methodological challenges must be overcome in order for such real-world evidence (RWE) to gain acceptance. In diabetes, RWE faces some particular issues that have limited its development. As the natural history of diabetes progresses, patients' disease changes over time and treatments will be modified as a result. This evolving disease and treatment pattern requires application of methods that account for such changes over time. Research developing RWE in diabetes and other conditions has sometimes been subject to important biases, and researchers should be aware of, and take steps to mitigate potential for bias in order to enhance the evidence produced. RESULTS: We review a RWE study that replicated and extended evidence provided by a RCT regarding the effects of weekly exenatide relative to basal insulin (glargine or detemir) to illustrate a potential application of RWE. This study observed a 0.7% decrease in HbA1C for weekly exenatide relative to a 0.5% decrease in HbA1C for the comparator along with a 2 kg weight loss for weekly exenatide relative to a 0.25 kg weight gain, effects that were close to those from the RCT. Further, the RWE study was able to extend results to patient populations that were not well represented in the RCT. CONCLUSION: Despite numerous challenges, RWE can be used to complement evidence from RCTs.

Differences in Staff-Assessed Pain Behaviors among Newly Admitted Nursing Home Residents by Level of Cognitive Impairment.

OBJECTIVE: Pain is common among nursing home residents with cognitive impairment and dementia. Pain is often underdiagnosed and undertreated, which may lead to adverse health outcomes. Nonverbal behaviors are valid indicators of pain, but the extent to which these behavioral expressions vary across levels of cognitive impairment is unknown. This study sought to examine differences in the prevalence of pain behaviors among nursing home residents with varying levels of cognitive impairment. METHODS: The Minimum Data Set, version 3.0, was used to identify newly admitted nursing home residents with staff-assessed pain (2010-2016, n = 1,036,806). Staff-assessed pain behaviors included nonverbal sounds, vocal complaints, facial expressions, and protective body movements or postures over a 5-day look-back period for residents unable or unwilling to self-report pain. The Cognitive Function Scale was used to categorize residents as having no/mild, moderate, or severe cognitive impairment. Modified Poisson models provided adjusted prevalence ratios (aPR) and 95% CIs. RESULTS: Compared to residents with no/mild cognitive impairments (any pain: 48.1%), residents with moderate cognitive impairment (any pain: 42.4%; aPR: 0.94 [95% CI 0.93-0.95]) and severe cognitive impairment (any pain: 38.4%; aPR: 0.86 [95% CI 0.85-0.88]) were less likely to have any pain behavior documented. Vocal pain behaviors were common (43.5% in residents with no/mild cognitive impairment), but less so in those with severe cognitive impairment (20.1%). Documentation of facial expressions and nonverbal pain behaviors was more frequent for residents with moderate and severe cognitive impairment than those with no/mild cognitive impairment. CONCLUSIONS: The prevalence of behaviors indicative of pain differs by level of cognitive impairment. Pain evaluation and management plays an important role in treatment and care outcomes. Future work should examine how practitioners' perceptions of pain behaviors influence their ratings of pain intensity and treatment choices.

Effectiveness and tolerability of therapy with exenatide once weekly vs basal insulin among injectable-drug-naïve elderly or renal impaired patients with type 2 diabetes in the United States.

AIM: To evaluate the effectiveness and tolerability of exenatide once weekly (EQW) compared with basal insulin (BI) among injectable-drug-naïve patients with type 2 diabetes mellitus (T2DM) who are elderly or have renal impairment (RI). MATERIALS AND METHODS: Initiators of EQW and BI with T2DM were identified for the period 2012 to 2015 within a US electronic health record database and matched by propensity score. Matched EQW and BI initiators aged ≥65 years or who had RI were compared. Data on weight, glycated haemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), blood pressure and lipids were obtained at baseline and quarterly (Q1-Q4) or semi-annually for 1 year after drug initiation. Hypoglycaemia and gastrointestinal symptoms were identified using diagnosis codes and data abstracted from clinical notes. RESULTS: Among patients aged ≥65 years, HbA1c changed by -0.50 and -0.31 percentage points from baseline to Q4 for EQW and BI initiators, respectively. Weight changed by -1.6 kg among EQW initiators compared with 0.2 kg among BI initiators. Compared with BI initiators, EQW initiators had a 1.45-fold increased risk of nausea and vomiting. Among patients with RI, HbA1c changed by -0.58 and -0.33 percentage points from baseline to Q4 for EQW and BI initiators, respectively. Weight changed by -1.9 kg for EQW initiators while BI initiators had no change in weight. EQW initiators had a 1.28-fold increased risk of constipation and diarrhoea compared with BI initiators. CONCLUSION: Regardless of age or renal function, the benefits of EQW relative to BI treatment are improved glycaemic control and increased weight loss, which should be weighed against the increased risk of gastrointestinal symptoms.

Effectiveness and Tolerability of Therapy With Once-Weekly Exenatide Versus Basal Insulin Among Injectable-Naive Patients With Type 2 Diabetes in a Real-World Setting in the United States.

A propensity-matched cohort study compared injectable-naive patients with type 2 diabetes initiating exenatide once weekly (EQW) or basal insulin (BI), from 2012 through 2015, within a U.S. electronic health record database. A1C and weight were obtained as observed or multiply imputed values at baseline and quarterly for 1 year (Q1-Q4). Hypoglycemia and gastrointestinal symptoms were identified using diagnostic codes and clinical notes. EQW (n = 2,008) and BI (n = 4,016) cohorts were comparable at baseline (mean A1C and weight: EQW, 8.3% and 107.5 kg, respectively; BI, 8.5% and 107.9 kg, respectively). A1C declined in Q2: -0.69 and -0.50 percentage points for EQW and BI, respectively, with little further change in year 1. The EQW cohort lost 0.9 kg in Q1 and 1.9 kg by the end of the year; no weight change was observed in the BI cohort. Among EQW and BI cohorts, 25.9% and 14.3% achieved both glycemic control and weight loss, respectively. In the EQW and BI cohorts, the incidence of hypoglycemia per 1,000 person-years was 52.5 and 65.7, respectively. The incidence of nausea was greater among EQW relative to BI initiators (relative rate 1.18). EQW offers an advantage compared to BI in achieving glycemic control and weight loss and a lower incidence of hypoglycemia, but is associated with greater risk of gastrointestinal symptoms.

Hypoglycaemia seriousness and weight gain as determinants of cardiovascular disease outcomes among sulfonylurea users.

AIMS: Certain treatments for type 2 diabetes mellitus cause hypoglycaemia and weight gain, and thus might counteract the benefits of intensive glucose control. We quantify the association of cardiovascular disease (CVD) outcomes with hypoglycaemia and weight gain among patients with type 2 diabetes treated with sulfonylureas. MATERIALS AND METHODS: This cohort study included patients from January 2009 through December 2014 who were selected from within a deidentified nationwide electronic health records repository, including multiple provider networks and electronic medical records systems. Hypoglycaemia measures from structured data fields and free text clinical notes were categorized as serious or non-serious. Covariate adjusted Poisson regression analysis was used to assess the association between frequency of hypoglycaemia (by severity), or magnitude of weight change, and incidence of acute myocardial infarction (AMI), congestive heart failure (CHF) and stroke. RESULTS: Among 143 635 eligible patients, we observed 5669 cases of AMI, 14 109 incident cases of CHF and 7017 cases of stroke. Overall incidence rates were 1.53, 4.26 and 1.92 per 100 person-years for AMI, CHF and stroke, respectively. The associations between overall hypoglycaemia and each of the CVD outcomes were positive, with stronger associations observed for serious hypoglycaemia and attenuated or null associations observed for non-serious hypoglycaemia. Weight change exhibited a U-shaped association with increased risks associated with both weight loss and weight gain relative to stable weight. CONCLUSIONS: This study provides evidence of increased CVD risk associated with hypoglycaemia, especially with serious hypoglycaemia events. While associations were attenuated with non-serious hypoglycaemia, the results were suggestive of a potential increased risk.

Unexpected complications of low-risk pregnancies in the United States.

OBJECTIVE: Determining appropriate sites of care for any type of medical issue assumes successful matching of patient risks to facility capabilities and resources. In obstetrics, predicting patients who will have a need for additional resources beyond routine obstetric and neonatal care is difficult. Women without prenatal risk factors and their newborns may experience unexpected complications during delivery or postpartum. In this study, we report the risk of unexpected maternal and newborn complications among pregnancies without identified prenatal risk factors. STUDY DESIGN: We conducted a cross-sectional investigation utilizing US natality data to analyze 10 million birth certificate records from 2011 through 2013. We categorized pregnancies as low risk (no prenatal risk factors) or high risk (at least 1 prenatal risk factor) according to 19 demographic, medical, and pregnancy characteristics. We evaluated 21 individual unexpected or adverse intrapartum and postpartum outcomes in addition to a composite indicator of any adverse outcome. RESULTS: Among 10,458,616 pregnancies, 38% were identified as low risk and 62% were identified as high risk for unexpected complications. At least 1 unexpected complication was indicated on the birth certificate for 46% of all pregnancies, 29% of low-risk pregnancies, and 57% of high-risk pregnancies. While the risk for unexpected or adverse outcomes was greatly reduced for the low-risk group compared to the high-risk group overall and for several of the individual outcomes, low-risk pregnancies had higher risks of vacuum delivery, forceps delivery, meconium staining, and chorioamnionitis compared to high-risk pregnancies. CONCLUSION: Of births, 29% identified to be low risk had an unexpected complication that would require nonroutine obstetric or neonatal care. Additionally, for select outcomes, risks were higher in the low-risk group compared to the group with identified risk factors. This information is important for planning location of birth and evaluating birthing centers and hospitals for necessary resources to ensure quality care and patient safety.

Effectiveness of Short-Acting Opioid Escalation vs Initiation of a Long-Acting Opioid in Nursing Home Residents.

OBJECTIVES: Modifications to opioid regimens for persistent pain are typically made after an initial period of short-acting opioid (SAO) use. Regimen changes may include an escalation of the SAO dosage or an initiation of a long-acting opioid (LAO) as a switch or add-on therapy. This study evaluates the comparative effectiveness between these alternative regimens in nursing home residents. DESIGN: A retrospective observational cohort analysis of US long-stay nursing home residents. SETTING AND PARTICIPANTS: Nursing home resident data were obtained from the national Minimum Dataset (MDS) version 3.0 and linked Medicare data, 2011-2016. METHODS: Opioid regimen changes were identified using Part D dispensing claims to identify dosage escalation of SAOs, initiation of an LAO, or a switch to an LAO. Outcomes included indices of pain occurrence, frequency, and severity reported on the earliest MDS assessment within 3 months following the opioid regimen change. Resident attributes were described by opioid regimen cohort. Prevalence ratios of pain and depression indices were quantified using doubly robust inverse probability of treatment (IPT)-weighted log-binomial regression. RESULTS: The study cohorts included 2072 SAO dose escalations, 575 LAO add-on initiations, and 247 LAO switch initiations. After IPT weighting, we observed comparable effects on pain and mood across the opioid regimen cohorts. A substantial number of residents continued to report frequent/constant pain (36% in SAO Escalation Cohort, 42% in LAO Add-on Cohort, 42% in the LAO Switch Cohort). The distribution of depressive symptoms was similar regardless of the opioid regimen change. CONCLUSIONS AND IMPLICATIONS: Initiation of an LAO as an add-on to SAO or a switch from SAO had comparable effects on pain and mood to SAO dose escalation without initiation of an LAO. Although fewer residents reported any pain after the regimen change, persistent pain was reported by most residents.

Sex Differences in Time to Initiate Nonsteroidal Anti-Inflammatory Drugs or Biologic Disease-Modifying Antirheumatic Drugs Among Patients With Axial Spondyloarthritis.

OBJECTIVE: We evaluated sex differences in time to initiation of receiving nonsteroidal anti-inflammatory drugs (NSAIDs) or biologic disease-modifying antirheumatic drugs (bDMARDs) among patients with axial spondyloarthritis (axSpA). METHODS: Using the 2013 to 2018 IBM MarketScan Database, we identified 174,632 patients with axSpA aged ≥18 years. We evaluated the time between axSpA diagnosis and the first prescription NSAID dispensing (among those with no baseline NSAIDs reception) or bDMARDs infusion/procedure claim (among those who were dispensed two or more different prescription NSAIDs in the baseline period). Adjusted hazard ratios (aHRs) for time to initiation of patients receiving NSAIDs or bDMARDs were computed using survival analyses. Cox proportional hazard models estimated associations between sex and predictors of treatment initiation. RESULTS: Average age at diagnosis was 48.2 years, 65.7% were female, and 37.8% were dispensed one or more NSAIDs before axSpA diagnosis. Of those who did not receive two or more different prescription NSAIDs before diagnosis, NSAID reception was initiated earlier in female patients than in male patients (NSAID reception initiators: female patients (32.9%), male patients (29.3%); aHR 1.14, 95% confidence interval [CI] 1.11-1.16). Among those who received two or more different prescription NSAIDs in the baseline period, 4.2% received a bDMARD, whereas 77.9% continued receiving NSAIDs after diagnosis. Time to bDMARD reception initiation was longer for female patients than for male patients (aHR 0.61, 95% CI 0.52-0.72), but bDMARDs were received sooner among those who received NSAIDs in the baseline period. CONCLUSION: Prescription NSAID reception was more common than initiation of receiving bDMARDs among patients newly diagnosed with axSpA. Female patients appeared more likely to continue receiving NSAIDs after diagnosis, and the time to initiation of receiving bDMARDs was longer for female patients than for male patients.

Postpartum depression in adolescent and adult mothers: comparing prenatal risk factors and predictive models.

Our objective was to assess whether postpartum depression risk factors differ between adolescent and adult mothers and to evaluate the need for adolescent specific screening instruments. We performed a retrospective cohort study using data from the Rhode Island Pregnancy Risk Assessment Monitoring System, 2004-2008. We identified maternal age specific risk factors using weighted logistic regression and developed predictive models using a forward selected weighted logistic regression. Notable differences in odds ratios were observed for risk factors such as maternal race (OR Hispanic vs. White: 0.99, 95 % CI 0.49-1.99 among adolescents; 3.32, 95 % CI 2.01-5.49 among adults), pre-pregnancy alcohol use (OR use vs. non-use: 2.04, 95 % CI 1.08-3.86 among adolescents; 0.49, 95 % CI 0.33-0.73 among adults), and pregnancy intention (OR unintended vs. intended: 1.05, 95 % CI 0.37-2.97 among adolescents; 2.67, 95 % CI 1.51-4.74 among adults). In predictive models, adolescent postpartum depressive symptoms were most influenced by prior depression and social support while adult postpartum depressive symptoms were associated with risk factors including maternal race, pregnancy intention, SES, prior depression, mental health during pregnancy, stressors, and social support. We were able to identify similarities and dissimilarities in risk factors for postpartum depressive symptoms among adolescents and adults. Predictive models developed in the general population of pregnant women performed poorly among adolescents relative to age specific predictive models, suggesting that current screening tools may not adequately identify high risk adolescents.

Unhealed pressure ulcers among nursing home residents with diabetes.

INTRODUCTION: Nearly a third of US nursing home residents have diabetes mellitus. These residents have an increased risk of pressure ulcer (PU) development and progression; however, little is known about the characteristics of their PUs or the role of other risk factors. This study estimates the prevalence of PUs, describes characteristics of PUs, and quantifies associations between risk factors and PUs in nursing home residents with diabetes. METHODS: We conducted a cross-sectional study of nursing home residents aged ≥50 years with diabetes mellitus using national 2016 Minimum Data Set 3.0 data. Pressure ulcers were defined as the presence of any stage PU and by subgroups of stage and tissue type. Prevalence estimates of PUs were calculated overall and by covariate subgroups. Unadjusted and adjusted odds ratios were calculated using logistic regression. RESULTS: The prevalence of any unhealed PU was 8.1%. Of those with a PU, 19.4% had at least two ulcers and the most common subtypes were identified as unstageable and stage 2 ulcers. These were most often treated by pressure reducing devices. In our fully adjusted model, risk factors that were strongly associated with PUs were related to mobility, nutrition, incontinence, and infections. CONCLUSION: We observed that the prevalence of PUs remains high in nursing home residents with diabetes and that higher stage ulcers were common in this population. Our adjusted model highlights the importance of suspected risk factors in the development of PUs. Further research is needed to understand the unique needs of nursing home residents with diabetes.

Trends in Screening for Diabetes in Early Pregnancy in the United States.

Objective: The aim of this study was to characterize current diabetes screening practices in the first trimester of pregnancy in the United States, evaluate patient characteristics and risk factors associated with early diabetes screening, and compare perinatal outcomes by early diabetes screening. Methods: This was a retrospective cohort study of US medical claims data of persons diagnosed with a viable intrauterine pregnancy and who presented for care with private insurance before 14 weeks of gestation, without pre-existing pregestational diabetes, from the IBM MarketScan® database for the period January 1, 2016, to December 31, 2018. Univariate and multivariate analyses were used to evaluate perinatal outcomes. Results: A total of 400,588 pregnancies were identified as eligible for inclusion, with 18.0% of persons receiving early screening for diabetes. Of those with laboratory order claims, 53.1% underwent hemoglobin A1c testing, 30.0% underwent fasting glucose testing, and 16.9% underwent oral glucose tolerance testing. Compared with those who did not undergo early diabetes screening, those who did were more likely to be older; obese; having a history of gestational diabetes, chronic hypertension, polycystic ovarian syndrome, or hyperlipidemia; and having a family history of diabetes. In adjusted logistic regression, history of gestational diabetes (adjusted odds ratio 3.99; 95% confidence interval 3.73-4.26) had the strongest association with early diabetes screening. Adverse perinatal outcomes, including a higher rate of cesarean delivery, preterm delivery, preeclampsia, and gestational diabetes, occurred more frequently among women who underwent early diabetes screening. Conclusions: First-trimester early diabetes screening was mostly commonly performed by hemoglobin A1c evaluation, and persons who underwent early diabetes screening were more likely to experience adverse perinatal outcomes.

Understanding Perinatal Depression Care Gaps by Examining Care Access and Barriers in Perinatal Individuals With and Without Psychiatric History.

Background: Depression affects one in seven perinatal individuals and remains underdiagnosed and undertreated. Individuals with a psychiatric history are at an even greater risk of perinatal depression, but it is unclear how their experiences with the depression care pathway may differ from individuals without a psychiatric history. Methods: We conducted a secondary analysis evaluating care access and barriers to care in perinatal individuals who screened positive for depression using the Edinburgh Postnatal Depression Scale (N = 280). Data were analyzed from the PRogram in Support of Moms (PRISM) study, a cluster randomized controlled trial of two interventions for perinatal depression. Results: Individuals with no prepregnancy psychiatric history (N = 113), compared with those with a history (N = 167), were less likely to be screened for perinatal depression, and less likely to be offered a therapy referral, although equally likely to attend if referred. When examining how these differences affected outcomes, those without a psychiatric history had 46% lower odds of attending therapy (95% confidence interval [CI]: 0.19-1.55), 79% lower odds of taking medication (95% CI: 0.08-0.54), and 80% lower odds of receiving any depression care (95% CI: 0.08-0.47). Barriers were similar across groups, except for concerns regarding available treatments and beliefs about self-resolution of symptoms, which were more prevalent in individuals without a psychiatric history. Conclusions: Perinatal individuals without a prepregnancy psychiatric history were less likely to be screened, referred, and treated for depression. Differences in screening and referrals resulted in missed opportunities for care, reinforcing the urgent need for universal mental health screening and psychoeducation during the perinatal period. Clinical Trial Registration No.: NCT02935504.