Comparison of opioid prescribing by dentists in the United States and England

Importance: The United States consumes most of the opioids worldwide despite representing a small portion of the world\u27s population. Dentists are one of the most frequent US prescribers of opioids despite data suggesting that nonopioid analgesics are similarly effective for oral pain. While oral health and dentist use are generally similar between the United States and England, it is unclear how opioid prescribing by dentists varies between the 2 countries. Objective: To compare opioid prescribing by dentists in the United States and England. Design, Setting, and Participants: Cross-sectional study of prescriptions for opioids dispensed from outpatient pharmacies and health care settings between January 1 and December 31, 2016, by dentists in the United States and England. Data were analyzed from October 2018 to January 2019. Exposures: Opioids prescribed by dentists. Main Outcomes and Measures: Proportion and prescribing rates of opioid prescriptions. Results: In 2016, the proportion of prescriptions written by US dentists that were for opioids was 37 times greater than the proportion written by English dentists. In all, 22.3% of US dental prescriptions were opioids (11.4 million prescriptions) compared with 0.6% of English dental prescriptions (28 082 prescriptions) (difference, 21.7%; 95% CI, 13.8%-32.1%; P \u3c .001). Dentists in the United States also had a higher number of opioid prescriptions per 1000 population (35.4 per 1000 US population [95% CI, 25.2-48.7 per 1000 population] vs 0.5 per 1000 England population [95% CI, 0.03-3.7 per 1000 population]) and number of opioid prescriptions per dentist (58.2 prescriptions per dentist [95% CI, 44.9-75.0 prescriptions per dentist] vs 1.2 prescriptions per dentist [95% CI, 0.2-5.6 prescriptions per dentist]). While the codeine derivative dihydrocodeine was the sole opioid prescribed by English dentists, US dentists prescribed a range of opioids containing hydrocodone (62.3%), codeine (23.2%), oxycodone (9.1%), and tramadol (4.8%). Dentists in the United States also prescribed long-acting opioids (0.06% of opioids prescribed by US dentists [6425 prescriptions]). Long-acting opioids were not prescribed by English dentists. Conclusions and Relevance: This study found that in 2016, dentists in the United States prescribed opioids with significantly greater frequency than their English counterparts. Opioids with a high potential for abuse, such as oxycodone, were frequently prescribed by US dentists but not prescribed in England. These results illustrate how 1 source of opioids differs substantially in the United States vs England. To reduce dental opioid prescribing in the United States, dentists could adopt measures similar to those used in England, including national guidelines for treating dental pain that emphasize prescribing opioids conservatively

Differences in Negative Symptom Severity Across Bipolar Disorder With and Without Psychosis

There was no significant difference between BP+ and BP- groups. Significant difference were found in BP+ and SZ groups when tested for Affective Flattening and Alogia.Significant difference were found in HC and BP- when tested for Anhedonia-Asociality.https://digitalscholarship.unlv.edu/durep_posters/1129/thumbnail.jp

First trimester use of artemisinin-based combination therapy and the risk of low birth weight and small for gestational age.

BACKGROUND: While there is increasing evidence on the safety of artemisinin-based combination therapy (ACT) for the case management of malaria in early pregnancy, little is known about the association between exposure to ACT during the first trimester and the effect on fetal growth. METHODS: Data were analysed from prospective studies of pregnant women enrolled in Mozambique, Burkina Faso and Kenya designed to determine the association between anti-malarial drug exposure in the first trimester and pregnancy outcomes, including low birth weight (LBW) and small for gestational age (SGA). Exposure to anti-malarial drugs was ascertained retrospectively by record linkage using a combination of data collected from antenatal and adult outpatient clinic registries, prescription records and self-reported medication usage by the women. Site-level data synthesis (fixed effects and random effects) was conducted as well as individual-level analysis (fixed effects by site). RESULTS: Overall, 1915 newborns were included with 92 and 26 exposed to ACT (artemether-lumefantrine) and quinine, respectively. In Burkina Faso, Mozambique and Kenya at recruitment, the mean age (standard deviation) was 27.1 (6.6), 24.2 (6.2) and 25.7 (6.5) years, and the mean gestational age was 24.0 (6.2), 21.2 (5.7) and 17.9 (10.2) weeks, respectively. The LBW prevalence among newborns born to women exposed to ACT and quinine (QNN) during the first trimester was 10/92 (10.9%) and 7/26 (26.9%), respectively, compared to 9.5% (171/1797) among women unexposed to any anti-malarials during pregnancy. Compared to those unexposed to anti-malarials, ACT and QNN exposed women had the pooled LBW prevalence ratio (PR) of 1.13 (95% confidence interval (CI) 0.62-2.05, p-value 0.700) and 2.03 (95% CI 1.09-3.78, p-value 0.027), respectively. Compared to those unexposed to anti-malarials ACT and QNN-exposed women had the pooled SGA PR of 0.85 (95% CI 0.50-1.44, p-value 0.543) and 1.41 (95% CI 0.71-2.77, p-value 0.322), respectively. Whereas compared to ACT-exposed, the QNN-exposed had a PR of 2.14 (95% CI 0.78-5.89, p-value 0.142) for LBW and 8.60 (95% CI 1.29-57.6, p-value 0.027) for SGA. The level of between sites heterogeneity was moderate to high. CONCLUSION: ACT exposure during the first trimester was not associated with an increased occurrence of LBW or SGA. However, the data suggest a higher prevalence of LBW and SGA for children born to QNN-exposed pregnancies. The findings support the use of ACT (artemether-lumefantrine) for the treatment of uncomplicated malaria during the first trimester of pregnancy

Weekly miscarriage rates in a community-based prospective cohort study in rural western Kenya

Objective Information on adverse pregnancy outcomes is important to monitor the impact of public health interventions. Miscarriage is a challenging end point to ascertain and there is scarce information on its rate in low-income countries. The objective was to estimate the background rate and cumulative probability of miscarriage in rural western Kenya. Design This was a population-based prospective cohort. Participants and setting Women of childbearing age were followed prospectively to identify pregnancies and ascertain their outcomes in Siaya County, western Kenya. The cohort study was carried out in 33 adjacent villages under health and demographic surveillance. Outcome measure Miscarriage. Results Between 2011 and 2013, among 5536 women of childbearing age, 1453 pregnancies were detected and 1134 were included in the analysis. The cumulative probability was 18.9%. The weekly miscarriage rate declined steadily with increasing gestation until approximately 20 weeks. Known risk factors for miscarriage such as maternal age, gravidity, occupation, household wealth and HIV infection were confirmed. Conclusions This is the first report of weekly miscarriage rates in a rural African setting in the context of high HIV and malaria prevalence. Future studies should consider the involvement of community health workers to identify the pregnancy cohort of early gestation for better data on the actual number of pregnancies and the assessment of miscarriage

Assessment of the safety of antimalarial drug use during early pregnancy (ASAP): protocol for a multicenter prospective cohort study in Burkina Faso, Kenya and Mozambique.

BACKGROUND: A major unresolved safety concern for malaria case management is the use of artemisinin combination therapies (ACTs) in the first trimester of pregnancy. There is a need for human data to inform policy makers and treatment guidelines on the safety of artemisinin combination therapies (ACT) when used during early pregnancy. METHODS: The overall goal of this paper is to describe the methods and implementation of a study aimed at developing surveillance systems for identifying exposures to antimalarials during early pregnancy and for monitoring pregnancy outcomes using health and demographic surveillance platforms. This was a multi-center prospective observational cohort study involving women at health and demographic surveillance sites in three countries in Africa: Burkina Faso, Kenya and Mozambique [(ClinicalTrials.gov Identifier: NCT01232530)]. The study was designed to identify pregnant women with artemisinin exposure in the first trimester and compare them to: 1) pregnant women without malaria, 2) pregnant women treated for malaria, but exposed to other antimalarials, and 3) pregnant women with malaria and treated with artemisinins in the 2nd or 3rd trimesters from the same settings. Pregnant women were recruited through community-based surveys and attendance at health facilities, including antenatal care clinics and followed until delivery. Data from the three sites will be pooled for analysis at the end of the study. Results are forthcoming. DISCUSSION: Despite few limitations, the methods described here are relevant to the development of sustainable pharmacovigilance systems for drugs used by pregnant women in the tropics using health and demographic surveillance sites to prospectively ascertain drug safety in early pregnancy. TRIAL REGISTRATION: NCT01232530

First-trimester artemisinin derivatives and quinine treatments and the risk of adverse pregnancy outcomes in Africa and Asia: A meta-analysis of observational studies.

BACKGROUND: Animal embryotoxicity data, and the scarcity of safety data in human pregnancies, have prevented artemisinin derivatives from being recommended for malaria treatment in the first trimester except in lifesaving circumstances. We conducted a meta-analysis of prospective observational studies comparing the risk of miscarriage, stillbirth, and major congenital anomaly (primary outcomes) among first-trimester pregnancies treated with artemisinin derivatives versus quinine or no antimalarial treatment. METHODS AND FINDINGS: Electronic databases including Medline, Embase, and Malaria in Pregnancy Library were searched, and investigators contacted. Five studies involving 30,618 pregnancies were included; four from sub-Saharan Africa (n = 6,666 pregnancies, six sites) and one from Thailand (n = 23,952). Antimalarial exposures were ascertained by self-report or active detection and confirmed by prescriptions, clinic cards, and outpatient registers. Cox proportional hazards models, accounting for time under observation and gestational age at enrollment, were used to calculate hazard ratios. Individual participant data (IPD) meta-analysis was used to combine the African studies, and the results were then combined with those from Thailand using aggregated data meta-analysis with a random effects model. There was no difference in the risk of miscarriage associated with the use of artemisinins anytime during the first trimester (n = 37/671) compared with quinine (n = 96/945; adjusted hazard ratio [aHR] = 0.73 [95% CI 0.44, 1.21], I2 = 0%, p = 0.228), in the risk of stillbirth (artemisinins, n = 10/654; quinine, n = 11/615; aHR = 0.29 [95% CI 0.08-1.02], p = 0.053), or in the risk of miscarriage and stillbirth combined (pregnancy loss) (aHR = 0.58 [95% CI 0.36-1.02], p = 0.099). The corresponding risks of miscarriage, stillbirth, and pregnancy loss in a sensitivity analysis restricted to artemisinin exposures during the embryo sensitive period (6-12 wk gestation) were as follows: aHR = 1.04 (95% CI 0.54-2.01), I2 = 0%, p = 0.910; aHR = 0.73 (95% CI 0.26-2.06), p = 0.551; and aHR = 0.98 (95% CI 0.52-2.04), p = 0.603. The prevalence of major congenital anomalies was similar for first-trimester artemisinin (1.5% [95% CI 0.6%-3.5%]) and quinine exposures (1.2% [95% CI 0.6%-2.4%]). Key limitations of the study include the inability to control for confounding by indication in the African studies, the paucity of data on potential confounders, the limited statistical power to detect differences in congenital anomalies, and the lack of assessment of cardiovascular defects in newborns. CONCLUSIONS: Compared to quinine, artemisinin treatment in the first trimester was not associated with an increased risk of miscarriage or stillbirth. While the data are limited, they indicate no difference in the prevalence of major congenital anomalies between treatment groups. The benefits of 3-d artemisinin combination therapy regimens to treat malaria in early pregnancy are likely to outweigh the adverse outcomes of partially treated malaria, which can occur with oral quinine because of the known poor adherence to 7-d regimens. REVIEW REGISTRATION: PROSPERO CRD42015032371

The association between cardiometabolic risk factors and breast cancer outcomes

Thesis (Ph.D.)--University of Washington, 2014Background: Prevalence of cardiometabolic risk factors contributing to metabolic syndrome is common, and numerous metabolic syndrome components are associated with increased primary breast cancer risk. However, less is known about their relation to breast cancer outcomes. In addition, adherence to chronic medications for metabolic syndrome risk factors such as diabetes is generally low and associated with adverse health outcomes. The growing population of breast cancer survivors and increasingly high prevalence of comorbidity warrants better understanding of medication adherence and clinical management. We sought to evaluate whether metabolic syndrome risk factors increase risk of second breast cancer events (SBCE) and breast cancer-specific mortality and describe whether adherence to oral diabetes medications and clinical control of diabetes vary prior to and following breast cancer treatment. Methods: We conducted a retrospective cohort study among female health plan enrollees ages ≥18 years diagnosed with stage I or II breast cancer between 1990-2008 via the Surveillance, Epidemiology, and End Results registry. Data sources included automated health plan data and medical records. We used Cox regression models to estimate the relation between metabolic syndrome components and SBCE (first of recurrence or second primary) and breast cancer-specific mortality while adjusting for potential confounders. We measured adherence and discontinuation of oral diabetes medications, biguanides (i.e., metformin) and sulfonylureas using medication possession ratios (MPR) and discontinuation rates (DR) in the year prior to incident cancer diagnosis, during treatment and the subsequent three years. We evaluated medication adherence (MPR ≥0.80), persistence (1-DR) and glycemic control (HbA1c ≤7.0%) in corresponding periods. Results: Among the 4,216 women in the cohort, 26% had ≥3 metabolic syndrome components and 13% developed SBCE during follow-up. Presence of metabolic syndrome (≥3 components) was associated with increased risk of SBCE (HR 1.50, 95% CI 1.08-2.07) and increased risk of breast cancer-specific mortality (HR 1.65, 95% CI 1.02-2.69). Among the 509 oral diabetes medication users, the proportion of adherent users declined during breast cancer treatment (75.3% versus 24.6%, P7.0%) was increased in the year following treatment (34.9% versus 51.1%, P<0.001) compared with baseline. Conclusion: Risk of SBCE and breast cancer-specific mortality may be altered by cardiometabolic risk factors contributing to metabolic syndrome. Adherence to oral medications for diabetes and glycemic control declines during and following breast cancer diagnosis. Further research in larger more diverse populations as well as other site-specific cancers and comorbidities is warranted