Maternal Marijuana Exposure and Birth Weight: An Observational Study Surrounding Recreational Marijuana Legalization.

OBJECTIVE: This study aimed to study the relationship between prenatal marijuana and infant birth weight using natural cohorts established before, during and after the 20-month lapse between legalization and legal recreational sales in Washington State. STUDY DESIGN: Over 5 years, 5,343 pregnant women with documented urine drug screen (UDS) results delivered at Tacoma General Hospital or Good Samaritan Hospital. Maternal medical data were extracted for three delivery cohorts established based on before (T1), during (T2), and after legalization (T3) of recreational marijuana and legalized availability. Univariate and multivariate models were created to study marijuana exposure on infants' birth weight. RESULTS: Marijuana exposure increased the risk of low birth weight (LBW; odds ratio [OR] = 1.42, 95% confidence interval [CI]: 1.01-2.01). This was more pronounced in full-term babies (OR = 1.72, 95% CI: 1.10-2.69), and was independently associated with a higher risk for small for gestational age (SGA; OR = 1.51, 95% CI: 1.49-1.53). The associations between marijuana exposure and SGA were maintained in cohort-specific models (OR = 1.53, 95% CI: 1.01-2.32 for T2, and OR = 1.43, 95% CI: 1.01-2.02 for T3, respectively). CONCLUSION: Marijuana exposure verified by UDS was associated with LBW and SGA. However, recreational marijuana legalization and availability did not have direct impact on newborns' risk of LBW or SGA.

Demographic Discrepancies in Prenatal Urine Drug Screening in Washington State Surrounding Recreational Marijuana Legalization and Accessibility.

OBJECTIVES: This study evaluated demographic patterns related to prenatal cannabinoid urine drug screening (UDS) over a 5-year period during which recreational marijuana was legalized and became accessible in Washington State. METHODS: Using electronic health record data, we performed a retrospective analysis for deliveries occurring over a 5-year period that encapsulated the transitions to marijuana legalization and legal access. For three cohorts of women delivering prior to legalization, between legalization and accessibility, and following accessibility, the UDS completion rate and screening demographic characteristics were assessed using Chi-squared tests and multivariate logistic regression. RESULTS: 25,514 deliveries occurred between March 2011 and March 2016. A significantly higher percentage of women underwent UDS post-accessibility (24.5%) compared to pre-legalization (20.0%, p < 0.001). A corresponding increase was not observed in the percentage of marijuana-positive UDS in tested patients (22.7% vs. 23.3%, p = 0.86). African American women had 2.8 times higher odds than Latinas of being tested, 2.1 times higher odds than Asian women, 1.7 times higher odds than White women, and 1.4 times higher odds than women of other races (all p < 0.001). Subsidized insurance status was also strongly associated with increased likelihood of testing (aOR = 3.5, p < 0.001). CONCLUSIONS FOR PRACTICE: Prenatal UDS testing patterns changed as recreational marijuana possession and accessibility became legal. Demographic discrepancies in testing reveal biases related to race and insurance status, which may be a proxy for socioeconomic status. As such discrepancies are potential contributors to health outcome disparities, it is important for providers and health care systems to examine their practices and ensure they are being appropriately, equally, and justly applied.

The discriminative power of STOP-Bang as a screening tool for suspected obstructive sleep apnea in clinically referred patients: considering gender differences.

PURPOSE: Obstructive sleep apnea (OSA) is the most commonly seen clinical sleep disorder. STOP-Bang, a widely used screening tool, yields a composite score based on eight dichotomized items including male gender. This study was designed to validate STOP-Bang among clinically referred patients and tested alternative scoring designs on tool performance, with a focus on gender differences in OSA. METHOD: STOP-Bang was administered to 403 female and 532 male subjects, followed by comprehensive sleep evaluation that included measurement of apnea-hypopnea indexes. Gender differences in STOP-Bang scores, OSA diagnosis, and severities were explored, and gender-specific alternative score cutoffs evaluated. Optimal operating points (OOP) were tested for female body mass index (BMI) and male neck circumference to inform STOP-Bang threshold refinement. Receiver operating characteristic curves were used to compare conventional and modified STOP-Bang. RESULTS: STOP-Bang performance by gender showed extremely low specificity in males at the recommended cutoff of ≥3. Better utility was presented at a cutoff of 4 or 5 among clinically referred patients irrespective of gender differences. Screening performance was improved by modifying BMI and/or neck circumference thresholds using gender-triaged OOP estimation. Three gender-based model revisions outperformed conventional STOP-Bang. CONCLUSION: Our study suggests that gender-specific consideration needs to be incorporated into the application of STOP-Bang in a clinically referred patient population with a higher risk of OSA. Alternative scoring systems may improve predictive performance of STOP-Bang.

CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk.

BACKGROUND: Menopausal hormone therapy (MHT) use has been consistently associated with a decreased risk of colorectal cancer (CRC) in women. Our aim was to use a genome-wide gene-environment interaction analysis to identify genetic modifiers of CRC risk associated with use of MHT. METHODS: We included 10 835 postmenopausal women (5419 cases and 5416 controls) from 10 studies. We evaluated use of any MHT, oestrogen-only (E-only) and combined oestrogen-progestogen (E+P) hormone preparations. To test for multiplicative interactions, we applied the empirical Bayes (EB) test as well as the Wald test in conventional case-control logistic regression as primary tests. The Cocktail test was used as secondary test. RESULTS: The EB test identified a significant interaction between rs964293 at 20q13.2/CYP24A1 and E+P (interaction OR (95% CIs)=0.61 (0.52-0.72), P=4.8 × 10(-9)). The secondary analysis also identified this interaction (Cocktail test OR=0.64 (0.52-0.78), P=1.2 × 10(-5) (alpha threshold=3.1 × 10(-4)). The ORs for association between E+P and CRC risk by rs964293 genotype were as follows: C/C, 0.96 (0.61-1.50); A/C, 0.61 (0.39-0.95) and A/A, 0.40 (0.22-0.73), respectively. CONCLUSIONS: Our results indicate that rs964293 modifies the association between E+P and CRC risk. The variant is located near CYP24A1, which encodes an enzyme involved in vitamin D metabolism. This novel finding offers additional insight into downstream pathways of CRC etiopathogenesis.

Development of a systematic protocol to identify victims of non-accidental trauma.

PURPOSE: Each year, nearly 1 million children in the USA are victims of non-accidental trauma (NAT). Missed diagnosis or poor case management often leads to repeat/escalation injury. Victims of recurrent NAT are at higher risk for severe morbidity and mortality resulting from abuse. The objective of this review is to describe the evolution and implementation of this tool and evaluate our institutional response to NAT prior to implementation. METHODS: A systematic guideline for the evaluation of pediatric patients in which NAT is suspected or confirmed was developed and implemented at a level II pediatric trauma hospital. To understand the state of our institution prior to implementation of the guideline, a review of 117 confirmed NAT cases at our hospital over the prior 4 years was conducted. RESULTS: In the absence of a systematic management guideline, important and relevant social and family history red flags were often missing in the initial evaluation. Patients with perineal bruising experienced significantly higher mortality than patients without perineal bruising (27.3 vs. 5.7%; p = 0.03) and were significantly more likely to require surgery (45.5 vs. 14.2%; p = 0.02). CONCLUSION: Development and implementation of a standardized tool for the differentiation and diagnosis of NAT and creation of a structured electronic medical record note should improve the description and documentation of child abuse cases in a community hospital setting. A retrospective analysis demonstrated that in the absence of such a tool, management of NAT may be inconsistent or incomplete. Perineal injury is an especially ominous red flag finding.

Association of aspirin and NSAID use with risk of colorectal cancer according to genetic variants.

IMPORTANCE: Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with lower risk of colorectal cancer. OBJECTIVE: To identify common genetic markers that may confer differential benefit from aspirin or NSAID chemoprevention, we tested gene × environment interactions between regular use of aspirin and/or NSAIDs and single-nucleotide polymorphisms (SNPs) in relation to risk of colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS: Case-control study using data from 5 case-control and 5 cohort studies initiated between 1976 and 2003 across the United States, Canada, Australia, and Germany and including colorectal cancer cases (n=8634) and matched controls (n=8553) ascertained between 1976 and 2011. Participants were all of European descent. EXPOSURES: Genome-wide SNP data and information on regular use of aspirin and/or NSAIDs and other risk factors. MAIN OUTCOMES AND MEASURES: Colorectal cancer. RESULTS: Regular use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer (prevalence, 28% vs 38%; odds ratio [OR], 0.69 [95% CI, 0.64-0.74]; P = 6.2 × 10(-28)) compared with nonregular use. In the conventional logistic regression analysis, the SNP rs2965667 at chromosome 12p12.3 near the MGST1 gene showed a genome-wide significant interaction with aspirin and/or NSAID use (P = 4.6 × 10(-9) for interaction). Aspirin and/or NSAID use was associated with a lower risk of colorectal cancer among individuals with rs2965667-TT genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.61-0.70]; P = 7.7 × 10(-33)) but with a higher risk among those with rare (4%) TA or AA genotypes (prevalence, 35% vs 29%; OR, 1.89 [95% CI, 1.27-2.81]; P = .002). In case-only interaction analysis, the SNP rs16973225 at chromosome 15q25.2 near the IL16 gene showed a genome-wide significant interaction with use of aspirin and/or NSAIDs (P = 8.2 × 10(-9) for interaction). Regular use was associated with a lower risk of colorectal cancer among individuals with rs16973225-AA genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.62-0.71]; P = 1.9 × 10(-30)) but was not associated with risk of colorectal cancer among those with less common (9%) AC or CC genotypes (prevalence, 36% vs 39%; OR, 0.97 [95% CI, 0.78-1.20]; P = .76). CONCLUSIONS AND RELEVANCE: In this genome-wide investigation of gene × environment interactions, use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer, and this association differed according to genetic variation at 2 SNPs at chromosomes 12 and 15. Validation of these findings in additional populations may facilitate targeted colorectal cancer prevention strategies.

Fructose intolerance/malabsorption and recurrent abdominal pain in children.

OBJECTIVES: The purpose of the present study was to ascertain whether pediatric patients with chronic abdominal pain had concurrent fructose intolerance as determined by a standardized dose breath hydrogen test (BHT), and whether symptoms would improve with a low-fructose diet. METHODS: The fructose BHT test was administered to patients evaluated in clinic with unexplained chronic abdominal pain alone or associated with constipation, gas or bloating, and/or diarrhea. The patients were given a standard dose of 1 g/kg fructose to maximum of 25 g. Hydrogen and methane were measured at 8 time points. The test was presumed positive if breath hydrogen exceeded 20 ppm above baseline. If positive, patients were given a dietitian-prescribed low-fructose diet. RESULTS: A total of 222 patients were part of the study. Ages ranged from 2 to 19 years with a mean of 10.5. BHT for fructose was performed in all of the patients and it was positive for fructose intolerance in 121 of 222 patients (54.5%). A total of 101 of 222 (45.5%) patients had negative BHT for fructose intolerance. All BHT-positive patients had a nutrition consult with a registered dietitian and were placed on a low-fructose diet. Using a standard pain scale for children, 93 of 121 patients (76.9%) reported resolution of symptoms on a low-fructose diet (P < 0.0001). Furthermore, 55 of 101 patients (54.4%) with negative BHT for fructose reported resolution of symptoms without a low-fructose diet (P = 0.37). CONCLUSIONS: Fructose intolerance/malabsorption is common in children with recurrent/functional abdominal pain and a low-fructose diet is an effective treatment.

Putting Adolescents and Young Adults in a Room Together: Launching an Adolescent and Young Adult Oncology Council.

Purpose: This article describes the formation and first meeting of a community adolescent and young adult oncology council (AYAOC), which was created to promote patient and stakeholder involvement in research and programmatic initiatives within community-based cancer centers. Methods: The AYAOC (comprising patients/survivors, family members, researchers and clinicians) convened at a one-day workshop moderated by an Australian not-for-profit AYA cancer organization. The council shared and compared health care experiences and then identified and prioritized unmet health care needs. Workshop notes were analyzed using inductive content analysis. Results: AYAOC members identified similarities in their experiences of cancer care and priorities for improvement of the health care system. Peer connection and the creation of adolescent and young adult (AYA)-specific care facilities were identified as the most pressing needs for AYAs with cancer, closely followed by integration of complementary medicine into medical practice and government advocacy to improve the quality and consistency of AYA cancer care delivery. Themes identified from AYAOC discussion included emotional isolation, naivety with and sometimes distrust of the medical system, the lasting impact of cancer on identity, the need for emotionally safe interactions with both individual clinicians and groups of peers, and the desire to take personal action to improve care for future patients. Conclusion: AYAOC members expressed a drive to share their experiences, advocate for others, and improve health care services for the "next generation" of AYAs diagnosed with cancer. Sharing stories and connecting with peers may have personal value for individuals. Channeling the altruistic energy of AYAs and stakeholders into group advisory and advocacy efforts also has value for health care systems, allowing stakeholder insights to inform clinical service delivery and research priorities.

Delay in Treatment After Cancer Diagnosis in Adolescents and Young Adults: Does Facility Transfer Matter?

Background: Timeliness is one of the fundamental yet understudied quality metrics of cancer care. Little is known about cancer treatment delay among adolescent and young adult (AYA) cancer patients. This study assessed cancer treatment delay, with a specific focus on facility transfer and diagnosis/treatment interval. Methods: Based on MultiCare Health System's (MHS's) institutional cancer registry data of AYA patients diagnosed during 2006-2015, this study analyzed patient demographics, insurance, clinical characteristics, and time of diagnosis and treatment initiation. Chi-squared tests, cumulative hazard estimates, and Cox proportional regression were used for univariable analysis. Multivariate regression models were used to test the association between care transfer and days of interval or prolonged delay, controlling for baseline parameters. Results: Of 840 analytic AYA cases identified, 457 (54.5%) were both diagnosed and treated within MHS. A total of 45.5% were either diagnosed or treated elsewhere. Mean and median intervals for treatment initiation were 27.03 (95% CI = 21.94-33.14) and 8.00 days (95% CI = 5.00-11.00), respectively, with significant differences between patients with and without facility transfer. Transfer was significantly correlated with longer length of diagnosis-to-treatment interval. Treatment delay, ≥1 week, was associated with transfer, female sex, older age, no surgery involvement, and more treatment modalities. Treatment delay, ≥4 weeks, was associated with transfer, female sex, no insurance, and no surgery involvement. Conclusion: In a community care setting, the diagnosis-to-treatment interval is significantly longer for transferred AYA cancer patients than for patients without a transfer. Future studies are warranted to explore the prognostic implications and the reasons for delays within specific cancer types.

Impact on Hospital Resources of Systematic Evaluation and Management of Suspected Nonaccidental Trauma in Patients Less Than 4 Years of Age.

OBJECTIVE: There has been an increasing movement worldwide to create systematic screening and management procedures for atypical injury patterns in children with the hope of better detecting and evaluating nonaccidental trauma (NAT). A legitimate concern for any hospital considering implementation of a systematic evaluation process is the impact on already burdened hospital resources. We hypothesized that implementation of a guideline that uses red flags related to history, physical, or radiologic findings to trigger a standardized NAT evaluation of patients <4 years would not negatively affect resource utilization at our level II pediatric trauma center. METHODS: NAT cases were evaluated retrospectively before and prospectively after implementation of the NAT guideline (n = 117 cases before implementation, n = 72 cases postimplementation). Multiple linear and logistic regression, χ2, and Wilcoxon rank-sum tests were used to evaluate human, laboratory, technology, and hospital resource usage between cohorts. RESULTS: Human (child abuse intervention department, ophthalmology, and evaluation by a pediatric surgeon for admitted patients), laboratory (urine toxicology and liver function tests), and imaging (skeletal survey and head or abdominal computed tomography) resource use did not differ significantly between cohorts (all P > .05). Emergency department and hospital lengths of stays also did not differ between cohorts. A significant 13% decrease in the percentage of patients admitted to the hospital was observed (P = .01). CONCLUSIONS: Structured evaluation and management of pediatric patients with injuries atypical for their age does not confer an added burden on hospital resources and may reduce the percentage of such patients who are hospitalized.

Functional electrical stimulation improves quality of life by reducing intermittent claudication.

OBJECTIVE: To determine if Functional Electrical Stimulation (FES) would improve ischemic pain, walking distance, and quality of life of patients with intermittent claudication. DESIGN: Single blind, randomized block, two factorial design. PATIENTS: Patients diagnosed with Peripheral Artery Disease (PAD) and intermittent claudication (IC). Ankle Brachial Index ranged 0.4-0.9 on at least one leg. Patients were randomly assigned to experimental (FES+Walk, N=13) or control (WALK, N=14) groups. INTERVENTION: Experimental group patients received FES to the dorsiflexor and plantarflexor muscles while walking for 1h/day, six days/week for eight weeks. Control group patients received similar intervention without FES. A Follow-up period of both groups lasted eight weeks. OUTCOME MEASURES: Outcome measures were taken at baseline (T0), after intervention (T1), and after follow-up (T2). Primary measures included Perceived Pain Intensity (PPI), Six minute walk (6MW), and Peripheral Arterial Disease Quality of Life (PADQOL). Secondary measures included Intermittent Claudication Questionnaire (ICQ) and Timed Up and Go (TUG). RESULTS: Group by time interactions in PPI were significant (P<0.001) with differences of 27.9 points at T1 and 36.9 points at T2 favoring the FES+Walk group. Groups difference in Symptoms and Limitations in Physical Function of the PADQOL reached significance (T1=8.9, and T2=8.3 improvements; P=0.007). ICQ was significant (T1=9.3 and T2=13.1 improvements; P=0.003). Improvement in 6MW and TUG tests were similar between groups. CONCLUSIONS AND RELEVANCE: Walking with FES markedly reduced ischemic pain and enhanced QOL compared to just walking. FES while walking may offer an effective treatment option for the elderly with PAD and Intermittent Claudication. TRIAL REGISTRATION: NIH-NIA 1R21AG048001 https://projectreporter.nih.gov/project_info_description.cfm?aid=8748641&icde=30695377&ddparam=&ddvalue=&ddsub=&cr=1&csb=default&cs=ASC. https://clinicaltrials.gov/ct2/show/NCT02384980?term=David+Embrey&rank=1.

Virtual Visits: Managing prenatal care with modern technology.

PURPOSE: To implement and evaluate a novel model of prenatal care for low-risk pregnant women that intersperses in-person physician visits with nurse practitioner visits conducted via videoconference. METHODS: This Quality Improvement initiative gave low-risk pregnant women the option of enrolling in a Traditional (N = 941) or Virtual Visit (N = 117) track for their prenatal care. Traditional patients had 14 physician visits and a postpartum visit. Virtual Visit patients had nine physician visits, five prenatal videoconference visits, and a 2-week postpartum videoconference visit. Measured outcomes include demographic variables, pregnancy and birth outcomes, and use of the health system. Logistic regression was used to assess demographic factors affecting track enrollment decisions. Multivariate logistic regression and ANCOVA methods were used to evaluate pregnancy and birth outcomes, adjusting for relevant confounding variables. RESULTS: Women enrolling in the Virtual Visit track were twice as likely to be partnered (p = 0.03) and not enrolled in government supplemental nutrition assistance (p = 0.01). They were seven times as likely to have been pregnant at least once before this enrollment (p < 0.001). Although a significantly higher percentage of Virtual Visit patients had a preeclampsia diagnosis (p = 0.02, N = 10 Virtual Visit patients), no other differences were observed between the groups in pregnancy/birth outcomes or health system use. CLINICAL IMPLICATIONS: The Virtual Visit program provides low-risk pregnant women with a new model of prenatal care that does not appear to demonstrate increased risk for mother or baby compared to a traditional model. This program may be especially appealing to middle-/high-income mothers who are partnered and already have children.

Gene-environment interaction involving recently identified colorectal cancer susceptibility Loci.

BACKGROUND: Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) that are associated with risk of colorectal cancer. Prior research has evaluated the presence of gene-environment interaction involving the first 10 identified susceptibility loci, but little work has been conducted on interaction involving SNPs at recently identified susceptibility loci, including: rs10911251, rs6691170, rs6687758, rs11903757, rs10936599, rs647161, rs1321311, rs719725, rs1665650, rs3824999, rs7136702, rs11169552, rs59336, rs3217810, rs4925386, and rs2423279. METHODS: Data on 9,160 cases and 9,280 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR) were used to evaluate the presence of interaction involving the above-listed SNPs and sex, body mass index (BMI), alcohol consumption, smoking, aspirin use, postmenopausal hormone (PMH) use, as well as intake of dietary calcium, dietary fiber, dietary folate, red meat, processed meat, fruit, and vegetables. Interaction was evaluated using a fixed effects meta-analysis of an efficient Empirical Bayes estimator, and permutation was used to account for multiple comparisons. RESULTS: None of the permutation-adjusted P values reached statistical significance. CONCLUSIONS: The associations between recently identified genetic susceptibility loci and colorectal cancer are not strongly modified by sex, BMI, alcohol, smoking, aspirin, PMH use, and various dietary factors. IMPACT: Results suggest no evidence of strong gene-environment interactions involving the recently identified 16 susceptibility loci for colorectal cancer taken one at a time.

Characterization of gene-environment interactions for colorectal cancer susceptibility loci.

Genome-wide association studies (GWAS) have identified more than a dozen loci associated with colorectal cancer (CRC) risk. Here, we examined potential effect-modification between single-nucleotide polymorphisms (SNP) at 10 of these loci and probable or established environmental risk factors for CRC in 7,016 CRC cases and 9,723 controls from nine cohort and case-control studies. We used meta-analysis of an efficient empirical-Bayes estimator to detect potential multiplicative interactions between each of the SNPs [rs16892766 at 8q23.3 (EIF3H/UTP23), rs6983267 at 8q24 (MYC), rs10795668 at 10p14 (FLJ3802842), rs3802842 at 11q23 (LOC120376), rs4444235 at 14q22.2 (BMP4), rs4779584 at 15q13 (GREM1), rs9929218 at 16q22.1 (CDH1), rs4939827 at 18q21 (SMAD7), rs10411210 at 19q13.1 (RHPN2), and rs961253 at 20p12.3 (BMP2)] and select major CRC risk factors (sex, body mass index, height, smoking status, aspirin/nonsteroidal anti-inflammatory drug use, alcohol use, and dietary intake of calcium, folate, red meat, processed meat, vegetables, fruit, and fiber). The strongest statistical evidence for a gene-environment interaction across studies was for vegetable consumption and rs16892766, located on chromosome 8q23.3, near the EIF3H and UTP23 genes (nominal P(interaction) = 1.3 × 10(-4); adjusted P = 0.02). The magnitude of the main effect of the SNP increased with increasing levels of vegetable consumption. No other interactions were statistically significant after adjusting for multiple comparisons. Overall, the association of most CRC susceptibility loci identified in initial GWAS seems to be invariant to the other risk factors considered; however, our results suggest potential modification of the rs16892766 effect by vegetable consumption.