Switching patterns of immediate-release forms of generic mixed amphetamine salts products among privately and publicly insured individuals aged 15-64 years in the United States, 2013-2019.

PURPOSE: Immediate-release forms of generic mixed amphetamine salts (MAS) have been the subject of passive surveillance reports signaling lack of effectiveness. We examined switching patterns that might suggest whether long-term users of specific MAS are more likely to switch away or switch back after use of the MAS of interest in the FDA's Sentinel Distributed Database. METHODS: We required at least 60-day continuous supply of selected MAS grouped by Abbreviated New Drug Application (ANDA) to describe patterns of switching away from and to generics approved under the ANDAs of interest among individuals ages 15-64 years with attention deficit hyperactivity disorder or narcolepsy during 2013-2019. RESULTS: We observed the greatest number of treatment episodes for ANDA 040422 (n = 525 771), followed by ANDA 202424 (n = 181 693), ANDA 040439 (n = 62 363), ANDA 040440 (n = 21 143), and ANDA 040480 (n = 8792). Of those with switches away from their original ANDA, episodes initiated on generic products under ANDA 040422 (48.6%) and ANDA 202424 (43.0%) were most likely to switch back, while those initiated on generic product under ANDA 040480 were least likely (24.1%). Of those episodes with switches to a generic under an ANDA of interest, about one-third (range 27.1% to 37.0%) switched back to the same product. These switches back had a median time to switch of about 30 days. CONCLUSIONS: These descriptive analyses, although subject to limitations, did not suggest increased switching away or switching back after use of the generics of interest. Continued post-marketing surveillance is warranted.

Cannabidiol exposures in the United States, National Poison Data System, July 2014-June 2021.

INTRODUCTION: There has been an increase in the interest and availability of products asserting to contain cannabidiol (CBD). OBJECTIVE: To describe demographic and clinical patterns in cases involving CBD exposures documented by the America's Poison Centers (AAPCC). METHODS: We extracted human exposure cases involving CBD from the U.S. National Poison Data System between July 2014 and June 2021. We described monthly case counts and data on demographics, exposure reason, clinical effects, medical outcomes, and co-exposures, overall and by U.S. Food and Drug Administration (FDA) approval status. RESULTS: We identified 6,496 cases, of these, 85.2% involved exposures to non-FDA approved CBD. The monthly number of cases peaked at 336 in March 2021. Cases often occurred in children ages 2-12 years (36.2%). Although in this age group unintentional exposures represented most cases (94.1%), we identified therapeutic errors (3.9%), intentional use (3.0%), and adverse reactions (1.6%) in cases involving exposures to non-FDA approved CBD. Among the 5,248 (80.8%) cases involving exposure to a single product, we identified 44 major medical outcomes, all related to exposures to non-FDA approved CBD. The most frequent clinical effects included neurological, cardiac, and gastrointestinal effects. Among the 1,248 (19.2%) involving exposure to more than one product, the most frequent co-exposures included stimulants and street drugs, sedatives-hypnotics, antipsychotics, and analgesics. CONCLUSIONS: This case series identified an increasing trend in CBD exposure cases managed by AAPCC. It showed serious medical outcomes in temporal association with exposure to non-FDA approved CBD products. Our findings also suggest both unintentional and intentional use of non-FDA approved CBD in children. Consumers should keep these products out of reach of children and exercise caution when purchasing and using non-FDA approved CBD products.

Mortality Among Parkinson's Disease Patients Treated With Pimavanserin or Atypical Antipsychotics: An Observational Study in Medicare Beneficiaries.

OBJECTIVE: Pimavanserin, a serotonin 5-HT2 antagonist, is indicated for treatment of hallucinations and delusions associated with Parkinson's disease psychosis. In premarketing trials in patients with Parkinson's disease psychosis, 11% of patients died during open-label pimavanserin treatment. Antipsychotics, which are used off-label in Parkinson's disease psychosis, increase mortality in dementia patients. The authors compared mortality with pimavanserin and atypical antipsychotics in a large database. METHODS: This was a retrospective new-user cohort study of Medicare beneficiaries with Parkinson's disease initiating pimavanserin (N=3,227) or atypical antipsychotics (N=18,442) from April 2016 to March 2019. All-cause mortality hazard ratios and 95% confidence intervals were estimated for pimavanserin compared with atypical antipsychotics, using segmented proportional hazards regression over 1-180 and 181+ days of treatment. Potential confounding was addressed through inverse probability of treatment weighting (IPTW). RESULTS: Pimavanserin users had a mean age of approximately 78 years, and 45% were female. Before IPTW, some comorbidities were more prevalent in atypical antipsychotic users; after IPTW, comorbidities were well balanced between groups. In the first 180 days of treatment, mortality was approximately 35% lower with pimavanserin than with atypical antipsychotics (hazard ratio=0.65, 95% CI=0.53, 0.79), with approximately one excess death per 30 atypical antipsychotic-treated patients; however, during treatment beyond 180 days, there was no additional mortality advantage with pimavanserin (hazard ratio=1.05, 95% CI=0.82, 1.33). Pimavanserin showed no mortality advantage in nursing home patients. CONCLUSIONS: Pimavanserin use was associated with lower mortality than atypical antipsychotic use during the first 180 days of treatment, but only in community-dwelling patients, not nursing home residents.

Systematic review of risk of SARS-CoV-2 infection and severity of COVID-19 with therapies approved to treat multiple sclerosis.

There is growing concern that multiple sclerosis (MS) patients on certain therapies may be at higher risk for severe coronavirus disease 2019 (COVID-19). We conducted a systematic literature review to examine the available data on U.S. therapies approved to treat MS and the risk of SARS-CoV-2 infection or severe COVID-19 outcomes. We conducted searches in PubMed, Embase, and the WHO COVID-19 database through May 2, 2021, and retrieved articles describing clinical data on therapies approved to treat MS and the risk of infection with SARS-CoV-2 or the effects of such therapies on clinical outcomes of COVID-19. The literature search identified a total of 411 articles: 97 in PubMed, 227 in Embase, and 87 in the WHO database. After excluding duplicates and screening, we identified 15 articles of interest. We identified an additional article through a broader secondary weekly search in PubMed. Thus, ultimately, we reviewed 16 observational studies. Available data, which suggest that MS patients treated with anti-CD20 monoclonal antibodies may be at increased risk for severe COVID-19, are subject to relevant limitations. Generally, studies did not identify increased risk for COVID-19 worsening with other therapies approved to treat MS. Based on observational data, biological plausibility, novelty of the drug-event association, and public health implications in a subpopulation with potential impaired response to the COVID-19 vaccines, this safety signal merits further monitoring.

Validation of an electronic algorithm for Hodgkin and non-Hodgkin lymphoma in ICD-10-CM.

PURPOSE: Lymphoma is a health outcome of interest for drug safety studies. Studies using administrative claims data require the accurate identification of lymphoma cases. We developed and validated an International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM)-based algorithm to identify lymphoma in healthcare claims data. METHODS: We developed a three-component algorithm to identify patients aged ≥15 years who were newly diagnosed with Hodgkin (HL) or non-Hodgkin (NHL) lymphoma from January 2016 through July 2018 among members of four Data Partners within the FDA's Sentinel System. The algorithm identified potential cases as patients with ≥2 ICD-10-CM lymphoma diagnosis codes on different dates within 183 days; ≥1 procedure code for a diagnostic procedure (e.g., biopsy, flow cytometry) and ≥1 procedure code for a relevant imaging study within 90 days of the first lymphoma diagnosis code. Cases identified by the algorithm were adjudicated via chart review and a positive predictive value (PPV) was calculated. RESULTS: We identified 8723 potential lymphoma cases via the algorithm and randomly sampled 213 for validation. We retrieved 138 charts (65%) and adjudicated 134 (63%). The overall PPV was 77% (95% confidence interval: 69%-84%). Most cases also had subtype information available, with 88% of cases identified as NHL and 11% as HL. CONCLUSIONS: Seventy-seven percent of lymphoma cases identified by an algorithm based on ICD-10-CM diagnosis and procedure codes and applied to claims data were true cases. This novel algorithm represents an efficient, cost-effective way to target an important health outcome of interest for large-scale drug safety and public health surveillance studies.

A systematic review of pregnancy exposure registries: examination of protocol-specified pregnancy outcomes, target sample size, and comparator selection.

PURPOSE: Our study sought to systematically evaluate protocol-specified study methodology in prospective pregnancy exposure registries including pre-specified pregnancy outcomes, power calculations for sample size, and comparator group selection. METHODS: U.S. pregnancy exposure registries designed to evaluate safety of drugs or biologics were identified from www.clinicaltrials.gov, the FDA's Office of Women's Health website, and the FDA's list of postmarketing studies. Protocols or similar documentation were obtained. RESULTS: We identified 35 U.S. registries for drugs or biologic use during pregnancy. All registries assessed risk for overall major congenital malformations. Pre-specified target enrollment was stated for 18 (51%) registries, and ranged from 150 to 500 exposed pregnancies (median 300). Thirty-two (91%) registries identified at least one comparison group, but only nine (26%) planned to use an internal comparator. The most common external comparator group (n = 24, 69%) was the Metropolitan Atlanta Congenital Defects Program (MACDP). CONCLUSIONS: No registries were designed to have sufficient power to assess specific malformations, despite the plausibility that most teratogens cause specific defects. Only half of the registries included a power analysis. Despite their common use, external comparators, including MACDP, have important limitations. In the absence of randomized controlled trial data in pregnant women, pregnancy registries remain an important tool as part of a comprehensive pregnancy surveillance program; however, pregnancy registries alone may not be sufficient to obtain adequate data regarding risks of specific malformations. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Differences in risk factors for recurrent versus incident preterm delivery.

Risk factors for preterm delivery have been described, but whether risk factors differ in the context of prior preterm delivery history is less understood. We assessed whether known risk factors were different in women with versus without prior preterm delivery using medical records of the first and second singleton deliveries in 25,820 Utah women (2002-2010). Longitudinal transition models with modified Poisson regression calculated adjusted relative risks and 95% confidence intervals, with multiplicative interactions between each preterm risk factor and prior preterm delivery status to explore whether risk factors varied between incident and recurrent preterm delivery at <37 weeks. Fewer second pregnancy factors were associated with recurrent preterm delivery, including alcohol, thyroid disease, and depression. Smoking was associated with increased risk for incident (relative risk (RR) = 1.95, 95% confidence interval (CI): 1.53, 2.49) but not recurrent (RR = 1.09, 95% CI: 0.71, 1.19) preterm delivery, whereas alcohol was associated with an increased risk for recurrent (RR = 2.38, 95% CI: 1.53, 3.71) but not incident (RR = 0.98, 95% CI: 0.67, 1.43; Pinteraction = 0.02 and <0.01) preterm delivery, respectively. Prior term delivery did not necessarily confer protection from known second pregnancy preterm delivery risk factors. In the setting of a prior preterm delivery, many risk factors did not persist. Prior preterm delivery history is important when assessing subsequent preterm delivery risk factors.

Acute and recent air pollution exposure and cardiovascular events at labour and delivery.

OBJECTIVE: To study the relationship between acute air pollution exposure and cardiovascular events during labour/delivery. METHODS: The Consortium on Safe Labor (2002-2008), an observational US cohort with 223,502 singleton deliveries provided electronic medical records. Air pollution exposure was estimated by modified Community Multiscale Air Quality models. Cardiovascular events (cardiac failure/arrest, stroke, myocardial infarcts and other events) were recorded in the hospital discharge records for 687 pregnancies (0.3%). Logistic regression with generalised estimating equations estimated the relationship between cardiovascular events and daily air pollutant levels for delivery day and the 7 days preceding delivery. RESULTS: Increased odds of cardiovascular events were observed for each IQR increase in exposure to nitric oxides at 5 and 6 days prior to delivery (OR=1.17, 99% CI 1.04 to 1.30 and OR=1.15, 1.03 to 1.28, respectively). High exposure to toxic air pollution species such as ethylbenzene (OR=1.50, 1.08 to 2.09), m-xylene (OR=1.54, 1.11 to 2.13), o-xylene (OR=1.51, 1.09 to 2.09), p-xylene (OR=1.43, 1.03 to 1.99) and toluene (OR=1.42, 1.02 to 1.97) at 5 days prior to delivery were also associated with cardiovascular events. Decreased odds of events were observed with exposure to ozone. CONCLUSIONS: Air pollution in the days prior to delivery, especially nitrogen oxides and some toxic air pollution species, was associated with increased risk of cardiovascular events during the labour/delivery admission.

Does maternal asthma contribute to racial/ethnic disparities in obstetrical and neonatal complications?

PURPOSE: To examine whether maternal asthma contributes to racial/ethnic differences in obstetrical and neonatal complications. METHODS: Data on white (n = 110,603), black (n = 50,284), and Hispanic (n = 38,831) singleton deliveries came from the Consortium on Safe Labor. Multilevel logistic regression models, with an interaction term for asthma and race/ethnicity, estimated within-group adjusted odds ratios (aORs) for gestational diabetes, gestational hypertension, pre-eclampsia, placental abruption, premature rupture of membranes, preterm delivery, maternal hemorrhage, neonatal intensive care unit admissions, small for gestational age, apnea, respiratory distress syndrome, transient tachypnea of the newborn, anemia, and hyperbilirubinemia after adjustment for clinical and demographic confounders. Nonasthmatics of the same racial/ethnic group were the reference group. RESULTS: Compared with nonasthmatics, white asthmatics had increased odds of pre-eclampsia (aOR, 1.28; 95% confidence interval [CI], 1.15-1.43) and maternal hemorrhage (aOR, 1.14; 95% CI, 1.04-1.23). White and Hispanic infants were more likely to have neonatal intensive care unit admissions (aOR, 1.19; 95% CI, 1.11-1.28; aOR, 1.16; 95% CI, 1.02-1.32, respectively) and be small for gestational age (aOR, 1.11; 95% CI, 1.02-1.20; aOR, 1.26; 95% CI, 1.10-1.44, respectively), and Hispanic infants were more likely to have apnea (aOR, 1.32; 95% CI, 1.02-1.69). CONCLUSIONS: Maternal asthma did not affect most obstetrical and neonatal complication risks within racial/ethnic groups. Despite their increased risk for both asthma and many complications, our findings for black women were null. Asthma did not contribute to racial/ethnic disparities in complications.

Acute air pollution exposure and blood pressure at delivery among women with and without hypertension.

BACKGROUND: Chronic air pollution exposure increases risk for hypertensive disorders of pregnancy, but the effect of acute air pollution exposure on blood pressure during pregnancy is less well known. METHODS: We studied 151,276 singleton term deliveries from the Consortium on Safe Labor (2002-2008) with clinical blood pressure measured at admission to labor/delivery and diagnoses of hypertensive disorders collected from electronic medical records and hospital discharge summaries. Air pollution exposures were estimated for the admission hour and the 4 hours preceding admission using a modified version of the Community Multiscale Air Quality models and observed air monitoring data. Blood pressure was categorized as normal; high normal; and mild, moderate, or severe hypertension based on pregnancy cut points. Adjusted ordinal logistic regression estimated the odds of women having a higher admission blood pressure category as a function of air pollutant, hypertensive disorders, and their interaction effect. RESULTS: Odds of high blood pressure at admission to labor/delivery were increased in normotensive women after exposure to nitrogen oxides (by 0.2%/5 units), sulfur dioxide (by 0.3%/1 unit), carbon monoxide and several air toxics (by 3%-4%/high exposure). The effects were often similar or stronger among women with gestational hypertension and preeclampsia. Exposure to particulate matter <10 µm increased odds of high blood pressure in women with preeclampsia by 3%/5 units. CONCLUSIONS: Air pollution can influence admission blood pressure in term deliveries and may increase likelihood of preeclampsia screening at delivery admission.

High vitamin B12 levels are not associated with increased mortality risk for ICU patients after adjusting for liver function: a cohort study.

BACKGROUND AND AIMS: Recent research has suggested that high vitamin B12 levels may be associated with increased mortality after ICU admission. However, it is known that impaired liver function may lead to elevated B12 since B12 is metabolized through the liver, and therefore high B12 levels may serve as a proxy for poor liver function. The aim of this study is to assess the impact that liver function and liver disease have on the relationship between high vitamin B12 levels and mortality in the ICU. METHODS: We performed an observational cohort study using ICU data that were collected from patients admitted to four ICU types (medical, surgical, cardiac care and cardiac surgery recovery) in one large urban hospital from 2001 to 2008. We analyzed the medical records of 1,684 adult patients (age ≥ 18 years) who had vitamin B12 and liver function measurements up to 14 days prior to ICU admission or within 24 hours after admission. RESULTS: While we found an association between high B12 and mortality when we did not control for any potential confounders, after we adjusted for liver function and liver disease, no significant association existed between B12 and mortality using multivariable logistic regression (30-day mortality: OR=1.18, 95% CI 0.81 to 1.72, p=0.3890; 90-day mortality: OR=1.20, 95% CI 0.84 to 1.71, p=0.3077). CONCLUSIONS: Elevated B12 levels are not a significant predictor of mortality after ICU admission when liver function is controlled for, and may instead be a proxy for poor liver function.

The NICHD Consecutive Pregnancies Study: recurrent preterm delivery by subtype.

OBJECTIVE: Attention for recurrent preterm delivery has primarily focused on spontaneous subtypes with less known about indicated preterm delivery. STUDY DESIGN: In a retrospective cohort of consecutive pregnancies among 51,086 women in Utah (2002-2010), binary relative risk regression was performed to examine the risk of preterm delivery (PTD; <37 weeks) in the second observed delivery by PTD in the first, adjusting for maternal age, race/ethnicity, prepregnancy body mass index, insurance, smoking, alcohol and/or drug use, and chronic disease. Analyses were also performed stratified by prior preterm delivery subtype: spontaneous, indicated, or no recorded indication. RESULTS: There were 3836 women who delivered preterm in the first observed pregnancy (7.6%), of which 1160 repeated in the second (30.7%). Rate of recurrent PTD was 31.6% for prior spontaneous, 23.0% for prior indicated delivery, and 27.4% for prior elective delivery. Prior spontaneous PTD was associated with a relative risk (RR) of 5.64 (95% confidence interval [CI], 5.27-6.05) of subsequent spontaneous and RR of 1.61 (95% CI, 0.98-2.67) of subsequent indicated PTD. Prior indicated PTD was associated with an RR of 9.10 (95% CI, 4.68-17.71) of subsequent indicated and RR of 2.70 (95% CI, 2.00-3.65) of subsequent spontaneous PTD. CONCLUSION: Prior indicated PTD was strongly associated with subsequent indicated PTD and with increased risk for subsequent spontaneous PTD. Spontaneous PTD had the highest rate of recurrence. Some common pathways for different etiologies of preterm delivery are likely, and indicated PTD merits additional attention for recurrence risk.

Neonatal health of infants born to mothers with asthma.

BACKGROUND: Maternal asthma is associated with serious pregnancy complications, but newborn morbidity is understudied. OBJECTIVE: We wanted to determine whether infants of asthmatic mothers have more neonatal complications. METHODS: The Consortium on Safe Labor (2002-2008), a retrospective cohort, included 223,512 singleton deliveries at ≥ 23 weeks' gestation. Newborns of mothers with asthma (n = 17,044) were compared with newborns of women without asthma by using logistic regression models with generalized estimating equations to calculate adjusted odds ratios (ORs) and 95% CIs. Electronic medical record data included gestational week at delivery, birth weight, resuscitation, neonatal intensive care unit (NICU) admission, NICU length of stay, hyperbilirubinemia, respiratory distress syndrome, apnea, sepsis, anemia, transient tachypnea of the newborn, infective pneumonia, asphyxia, intracerebral hemorrhage, seizure, cardiomyopathy, periventricular or intraventricular hemorrhage, necrotizing enterocolitis, aspiration, retinopathy of prematurity, and perinatal mortality. RESULTS: Preterm delivery was associated with maternal asthma for each week after 33 completed weeks of gestation and not earlier. Maternal asthma also increased the adjusted odds of small for gestational age (OR = 1.10; 95% CI, 1.05-1.16), NICU admission (OR = 1.12; 95% CI, 1.07-1.17), hyperbilirubinemia (OR = 1.09; 95% CI, 1.04-1.14), respiratory distress syndrome (OR = 1.09; 95% CI, 1.01-1.19), transient tachypnea of the newborn (OR = 1.10; 95% CI, 1.02-1.19), and asphyxia (OR = 1.34; 95% CI, 1.03-1.75). Findings persisted for term infants (≥ 37 weeks) who had additional increased odds of intracerebral hemorrhage (OR = 1.84; 95% CI, 1.11-3.03) and anemia (OR = 1.30; 95% CI, 1.04-1.62). CONCLUSIONS: Maternal asthma was associated with prematurity and small for gestational age. Adverse neonatal outcomes, including respiratory complications, hyperbilirubinemia, and NICU admission, were increased in association with maternal asthma even among term deliveries.

Obstetric complications among US women with asthma.

OBJECTIVE: We sought to characterize complications of pregnancy, labor, and delivery associated with maternal asthma in a contemporary US cohort. STUDY DESIGN: We studied a retrospective cohort based on electronic medical record data from 223,512 singleton deliveries from 12 clinical centers across the United States from 2002 through 2008. RESULTS: Women with asthma had higher odds of preeclampsia (adjusted odds ratio [aOR], 1.14; 95% confidence interval [CI], 1.06-1.22), superimposed preeclampsia (aOR, 1.34; 95% CI, 1.15-1.56), gestational diabetes (aOR, 1.11; 95% CI, 1.03-1.19), placental abruption (aOR, 1.22; 95% CI, 1.09-1.36), and placenta previa (aOR, 1.30; 95% CI, 1.08-1.56). Asthmatic women had a higher odds of preterm birth overall (aOR, 1.17; 95% CI, 1.12-1.23) and of medically indicated preterm delivery (aOR, 1.14; 95% CI, 1.01-1.29). Asthmatics were less likely to have spontaneous labor (aOR, 0.87; 95% CI, 0.84-0.90) and vaginal delivery (aOR, 0.84; 95% CI, 0.80-0.87). Risks were higher for breech presentation (aOR, 1.13; 95% CI, 1.05-1.22), hemorrhage (aOR, 1.09; 95% CI, 1.03-1.16), pulmonary embolism (aOR, 1.71; 95% CI, 1.05-2.79), and maternal intensive care unit admission (aOR, 1.34; 95% CI, 1.04-1.72). CONCLUSION: Maternal asthma increased risk for nearly all outcomes studied in a general obstetric population.

Lower short- and long-term mortality associated with overweight and obesity in a large cohort study of adult intensive care unit patients.

INTRODUCTION: Two thirds of United States adults are overweight or obese, which puts them at higher risk of developing chronic diseases and of death compared with normal-weight individuals. However, recent studies have found that overweight and obesity by themselves may be protective in some contexts, such as hospitalization in an intensive care unit (ICU). Our objective was to determine the relation between body mass index (BMI) and mortality at 30 days and 1 year after ICU admission. METHODS: We performed a cohort analysis of 16,812 adult patients from MIMIC-II, a large database of ICU patients at a tertiary care hospital in Boston, Massachusetts. The data were originally collected during the course of clinical care, and we subsequently extracted our dataset independent of the study outcome. RESULTS: Compared with normal-weight patients, obese patients had 26% and 43% lower mortality risk at 30 days and 1 year after ICU admission, respectively (odds ratio (OR), 0.74; 95% confidence interval (CI), 0.64 to 0.86) and 0.57 (95% CI, 0.49 to 0.67)); overweight patients had nearly 20% and 30% lower mortality risk (OR, 0.81; 95% CI, 0.70 to 0.93) and OR, 0.68 (95% CI, 0.59 to 0.79)). Severely obese patients (BMI ≥ 40 kg/m2) did not have a significant survival advantage at 30 days (OR, 0.94; 95% CI, 0.74 to 1.20), but did have 30% lower mortality risk at 1 year (OR, 0.70 (95% CI, 0.54 to 0.90)). No significant difference in admission acuity or ICU and hospital length of stay was found across BMI categories. CONCLUSION: Our study supports the hypothesis that patients who are overweight or obese have improved survival both 30 days and 1 year after ICU admission.

Relationship between vitamin B12 and sensory and motor peripheral nerve function in older adults.

OBJECTIVES: To examine whether deficient B12 status or low serum B12 levels are associated with worse sensory and motor peripheral nerve function in older adults. DESIGN: Cross-sectional. SETTING: Health, Aging and Body Composition Study. PARTICIPANTS: Two thousand two hundred and eighty-seven adults aged 72 to 83 (mean 76.5 ± 2.9; 51.4% female; 38.3% black). MEASUREMENTS: Low serum B12 was defined as serum B12 less than 260 pmol/L, and deficient B12 status was defined as B12 less than 260 pmol/L, methylmalonic acid (MMA) greater than 271 nmol/L, and MMA greater than 2-methylcitrate. Peripheral nerve function was assessed according to peroneal nerve conduction amplitude and velocity (NCV) (motor), 1.4 g/10 g monofilament detection, average vibration threshold detection, and peripheral neuropathy symptoms (numbness, aching or burning pain, or both) (sensory). RESULTS: B12-deficient status was found in 7.0% of participants, and an additional 10.1% had low serum B12 levels. B12 deficient status was associated with greater insensitivity to light (1.4 g) touch (odds ratio = 1.50, 95% confidence interval = 1.06-2.13) and worse NCV (42.3 vs 43.5 m/s) (ß = -1.16, P = .01) after multivariable adjustment for demographics, lifestyle factors, and health conditions. Associations were consistent for the alternative definition using low serum B12 only. No significant associations were found for deficient B12 status or the alternative low serum B12 definition and vibration detection, nerve conduction amplitude, or peripheral neuropathy symptoms. CONCLUSION: Poor B12 (deficient B12 status and low serum B12) is associated with worse sensory and motor peripheral nerve function. Nerve function impairments may lead to physical function declines and disability in older adults, suggesting that prevention and treatment of low B12 levels may be important to evaluate.

Vitamin B12 and homocysteine levels and 6-year change in peripheral nerve function and neurological signs.

BACKGROUND: Low vitamin B12 and high homocysteine (Hcy) levels are common in older adults and may be associated with worse neurological function. The aim of this study is to determine whether changes in B12 or Hcy levels are associated with longitudinal changes in peripheral nerve function and clinical neurological signs and symptoms. METHODS: Participants aged 60 years and older at baseline (n = 678; 72.2 ± 6.2 years; 43.5% male) were from the InCHIANTI Study. Low B12 (<260 pmol/L) and high Hcy (≥13 µmol/L) were measured at baseline and 3-year follow-up. Neurological function was assessed by peroneal nerve conduction amplitude (compound motor action potential) and velocity, neurological examination, and peripheral neuropathy symptoms at baseline, 3-year, and 6-year follow-up. RESULTS: At baseline, 43.8% had low B12 levels and 58.6% had high Hcy levels. Over 6 years, 12.4% declined to poor compound motor action potential (<1 mV) and 42.1% declined to poor nerve conduction velocity (<40 m/s). In mixed models analyses, sustained high Hcy was associated with worse compound motor action potential compared with sustained normal Hcy (p = .04), adjusting for demographics, diabetes, and folate level. Participants whose Hcy level became high at follow-up were more likely to become unable to detect monofilament at 6-year follow-up compared with those with sustained normal Hcy (odds ratio: 5.4; 95% CI: 1.5-19.0), adjusting for demographics, diabetes, body mass index, and peripheral arterial disease. There was no association with vitamin B12 level or with symptoms. CONCLUSIONS: High Hcy may be associated with worse sensory and motor peripheral nerve function. Because poor nerve function has been associated with lower strength and physical performance, these results have important implications for disability in older adults.

Determining activity monitor wear time: an influential decision rule.

BACKGROUND: Accurately measuring physical activity (PA) with activity monitors requires sufficient monitor wear time which can be difficult to assess. Monitor sensitivity to movement and population characteristics (eg, children vs. adults) may dictate the duration of monitor inactivity indicative of nonwear. A standardized method for determining appropriate decision rules to identify wear time is needed. METHODS: Several decision rules based on minimum durations of monitor inactivity (ie, 60, 90, 120, 150 minutes) to identify nonwear were applied to Stepwatch Activity Monitor data from 1064 adult bariatric surgical candidates. The frequency, pattern, and duration of resulting nonwear and wear periods were examined. Generalized Estimating Equations tested the effect of these decision rules on PA measures. RESULTS: A 60-minute duration resulted in unreasonably large percentages of subjects with unlikely wear patterns [eg, ≥3 nonwear periods in a day (29.9%); ≥2 wear periods of less than an hour in a day (28.7%)]; 120 minutes appeared most reasonable. Wear time decision rules impacted PA measures. CONCLUSIONS: The methods described in this paper can be used to determine appropriate instrument and population specific wear time decision rules. Recognizing monitor wear time is estimated, PA measures least affected by wear time are preferable.