Preliminary side effect profile, safety, and tolerability of hormonal contraception among women receiving opioid-agonist therapy.

OBJECTIVE(S): To characterize for the first time the side effect profile, safety, and tolerability of hormonal contraception among women receiving opioid-agonist therapy. STUDY DESIGN: We conducted a secondary analysis of data collected from participants in a three-arm randomized controlled trial (N = 138) aimed at increasing effective contraceptive use among women receiving opioid-agonist therapy. Participants in the 2 intervention conditions (n = 90) had free access to hormonal contraception at each of the 14 visits scheduled during the 6-month intervention. Contraceptive use and side effects were recorded at each visit; participants could change methods or discontinue use at any time. Verbatim side effects were classified using Medical Dictionary for Regulatory Activities (MedDRA) terminology. RESULTS: Of 67 participants reporting hormonal contraceptive use, 29 (43%) initiated implants, 14 (21%) intrauterine devices, 13 (19%) combined pills, 11 (16%) progestin-only pills, 10 (15%) injectables, 1 (2%) ring, and 1 (2%) patch; the average (±standard deviation) duration of use was 129 ± 55, 129 ± 60, 108 ± 62, 102 ± 61, 111 ± 31, 145, and 18 days, respectively. A total of 321 side effects were reported by 55 (82%) participants. Fifty (75%) participants reported menstrual cycle changes/uterine bleeding, followed by headaches (16, 24%), weight gain (15, 22%), and abdominal pain or nausea/vomiting (11, 16%). No serious side effects were reported. Twelve participants (18%) changed methods and 13 (19%) discontinued all hormonal contraceptive use. CONCLUSION(S): The hormonal contraceptive side effects reported by this small group of women receiving opioid-agonist therapy appear consistent with those reported by the general population, was generally well-tolerated, and did not raise safety concerns. IMPLICATIONS: These results provide important preliminary evidence that hormonal contraceptive use produces a familiar side effect profile and is well-tolerated by women receiving opioid-agonist therapy, although studies with larger samples followed over longer periods of time with appropriate comparison conditions are needed to fully assess tolerability and safety.

Association between antenatal ultrasound findings and neonatal outcomes in rural Uganda: a secondary analysis.

BACKGROUND: Although the use of prenatal ultrasound services has increased in low- income and lower middle-income countries, there has not been a concurrent improvement in perinatal mortality. It remains unknown whether individual ultrasound findings in this setting are associated with neonatal death or the need for resuscitation at delivery. If associations are identified by ultrasound, they could be used to inform the birth attendant and counsel the family regarding risk, potentially altering delivery preparedness in order to reduce neonatal mortality. METHODS: This was a secondary analysis of data collected from a prospective cohort. Data was gathered at Nawanyago Health Centre III in Kamuli District, Uganda. Participants included pregnant women who received second and third trimester prenatal ultrasound scans and delivered at that center between July 2010 and August 2018. All ultrasounds were performed at Nawanyago and deliveries were attended solely by midwives or nurses. Predictor variables included the following ultrasound findings: fetal number, fetal presentation, and amniotic fluid volume. The primary outcome was bag-mask ventilation (BMV) of the neonate at delivery. The secondary outcome was stillbirth or neonatal death in the delivery room. RESULTS: Primary outcome data was available for 1105 infants and secondary outcome data was available for 1098 infants. A total of 33 infants received BMV at delivery. The odds of receiving BMV at delivery was significantly increased if amniotic fluid volume was abnormal (OR 4.2, CI 1.2-14.9) and there were increased odds for multiple gestation (OR 1.9, CI 0.7-5.4) and for non-vertex fetal presentation (OR 1.4, CI 0.6-3.2) that were not statistically significant. Stillbirth or neonatal death in the delivery room was diagnosed for 20 infants. Multiple gestation (OR 4.7, CI 1.6-14.2) and abnormal amniotic fluid volume (OR 4.8, CI 1.0-22.1) increased the odds of stillbirth or neonatal death in the delivery room, though only multiple gestation was statistically significant. CONCLUSION: Common findings that are easily identifiable on ultrasound in low- and lower middle-income countries are associated with adverse perinatal outcomes. Education could lead to improved delivery preparedness, with the potential to reduce perinatal mortality. This was a preliminary study; larger prospective studies are needed to confirm these findings.

Validation of a Telemedicine Quality Assurance Method for Point-of-Care Obstetric Ultrasound Used in Low-Resource Settings.

OBJECTIVES: A remote quality assurance and improvement protocol for point-of-care obstetric ultrasound in low-resource areas was validated against the standard of care for obstetric ultrasound in the United States. METHODS: Compressed movie clip ultrasound images (obstetric sweep protocol) obtained by minimally trained personnel were read and interpreted by physicians with training in obstetric ultrasound. Observed findings were compared among readers and between each reader and the gold standard ultrasound scan report. Descriptive statistics were used for the analysis. RESULTS: The agreements among readers and between readers and the gold standard, for the anterior and posterior variables of the placental location were excellent, with Cohen κ values of 0.81 to 0.88 and 0.77 to 0.9, respectively. Cohen κ values were slight or slight/fair for other placental locations (left, right, fundal, and low), and the sensitivity and specificity ranged widely. The agreement among readers and between readers and the gold standard for fetal number comparisons was also excellent, with Cohen κ values ranging from 0.82 to 1, sensitivity from 0.83 to 1, and specificity from 0.99 to 1. The agreement among readers for fetal presentation comparisons, according to the Cohen κ, ranged from 0.79 to 0.85 and between readers and the gold standard had values of 0.43 to 0.49. For biometric parameters and estimated gestational age calculations based on these parameters, inter-reader reliability ranged from 0.79 to 0.85 for all parameters except femur length. Greater than 94% of obstetric sweep protocol ultrasound ages were within 7 days of the corresponding gold standard age. CONCLUSIONS: Movie clip ultrasound images provided adequate information for remote readers to reliably determine the placental location, fetal number, fetal presentation, and pregnancy dating.

Contraceptive Knowledge among Females and Males Receiving Medication Treatment for Opioid Use Disorder Compared to Those Seeking Primary Care.

BACKGROUND: Rates of unintended pregnancy among women receiving medication treatment for opioid use disorder (mOUD) are high, likely due in part to low rates of contraceptive use. Lack of knowledge about contraception may be contributing to inadequate contraceptive use. Objectives: To compare contraceptive knowledge among women and men receiving mOUD relative to a comparison group seeking primary care. Methods: We surveyed 332 reproductive-age women and men receiving mOUD or primary care with the recently validated 25-item Contraceptive Knowledge Assessment. We examined overall differences between patient groups and between females and males using two-way analyses of variance; individual item differences were tested using logistic regression. Results: The mean percent of total correct responses was lower among individuals receiving mOUD (n = 167) relative to the comparison group (n = 165), 47.7% vs. 53.8%, respectively (p < .001), and higher among females (n = 169) relative to males (n = 163), 56.1% vs. 45.2%, respectively (p < .001). Individual item analyses revealed patient group and sex differences primarily in the areas of contraceptive efficacy, attributes of contraceptive methods, and fertility awareness. Conclusion: While there were modest differences between patient groups and sexes, the results suggest a deficit in contraceptive knowledge across all groups. Substance use disorder treatment clinics could be an opportunistic setting in which to provide accurate information about contraception to patients with OUD and other substance use disorders.

Validation of scoring system predicting permanent pacemaker implantation after transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is being increasingly performed in patients with severe aortic stenosis. Despite newer generation valves, atrioventricular (AV) conduction disturbance is a common complication, necessitating permanent pacemaker (PPM) implantation in about 10% of patients. Hence, it is imperative to improve periprocedural risk stratification to predict PPM implantation after TAVR. The objective of this study was to externally validate a novel risk-stratification model derived from the National Inpatient Sample (NIS) database that predicts risk of PPM from TAVR. METHODS: Components of the score included pre-TAVR left and right bundle branch block, sinus bradycardia, second-degree AV block, and transfemoral approach. The scoring system was applied to 917 patients undergoing TAVR at our institution from November 2011 to February 2017. We assessed its predictive accuracy by looking at two components: discrimination using the C-statistic and calibration using the Hosmer-Lemeshow goodness of fit test. RESULTS: Ninety patients (9.8%) required PPM. The scoring system showed good discrimination with C-statistic score of 0.6743 (95% CI: 0.618-0.729). Higher scores suggested increased PPM risk, that is, 7.3% with score ⩽3, 19.23% with score 4-6, and 37.50% with score ≥7. Patients requiring PPM were older (81.4 versus 78.7 years, P = .002). Length of stay and in-hospital mortality was significantly higher in PPM group. CONCLUSIONS: The NIS database derived PPM risk prediction model was successfully validated in our database with acceptable discriminative and gradation capacity. It is a simple but valuable tool for patient counseling pre-TAVR and in identifying high-risk patients.

Perceptions of long-acting reversible contraception among women receiving medication for opioid use disorder in Vermont.

OBJECTIVES: To evaluate perceptions of long-acting reversible contraceptives (LARC) among women receiving medication for opioid use disorder. STUDY DESIGN: Cross-sectional survey of 200 women receiving medication for opioid use disorder in Vermont. RESULTS: A considerable proportion of women receiving medication for opioid use disorder in Vermont reported previous use of an IUD (40%) and/or a subdermal contraceptive implant (16%); the majority of prior LARC users were satisfied with their IUD (68%) or their implant (74%). Of the 38% of participants who had never considered IUD use, 85% percent (64/75) said that they knew nothing or only a little about IUDs. Of the 61% of participants who had never considered an implant, 81% percent (98/121) said that they knew nothing or only a little about the contraceptive method. The most commonly reported reasons for a lack of interest in the IUD and/or implant were concerns about side effects and preference for a woman-controlled method. CONCLUSIONS: Gaps in LARC knowledge are common among those who have not used LARCs and concerns about side effects and preferences for a woman-controlled method limit some women's interest in these contraceptives. Additionally, reasons for dissatisfaction among past users are generally similar for IUD and implant and include irregular bleeding and having a bad experience with the method. IMPLICATIONS: Efforts to increase awareness of LARC methods among women receiving medication for opioid use disorder should address concerns about side effects and reproductive autonomy and encourage satisfied LARC users to share their experiences with their social networks.

Knowledge and use of family planning among men in rural Uganda.

BACKGROUND: Unmet need for family planning exceeds 33% in Uganda. One approach to decreasing unmet need is promoting male involvement in family planning. Male disapproval of use of family planning by their female partners and misconceptions about side effects are barriers to family planning globally and in Uganda in particular. Researchers have conducted a number of qualitative studies in recent years to examine different aspects of family planning among Ugandan men. The present study aimed to quantify men's knowledge of family planning in rural Uganda to understand how better to involve men in couples' contraceptive decision-making, particularly in low-resource settings. METHODS: Data were derived from in-person, researcher-administered surveys of men in a rural agrarian district in Uganda (N = 178). Participant demographics and knowledge of family planning methods, side effects, and use were queried. Descriptive statistics were used for analysis. RESULTS: Men were 34 years of age on average (range 18-71) and about half (56%) had a primary school education or less. Ninety-eight percent reported any knowledge of family planning, with 73% of men reporting obtaining information via radio and only 43% from health workers. The most common method known by men was the male condom (72%), but more than half also knew of injections (54%) and pills (52%). Relatively few men reported knowing about the most effective reversible contraceptive methods, intrauterine devices and implants (both 16%). Men identified many common contraceptive side-effects, such as vaginal bleeding (31%), and misconceptions about side effects, such as increased risk of infertility and birth defects, were relatively uncommon (both < 10%). About half of all men reported ever using a family planning method (53%), and 40% reported current use. CONCLUSIONS: This study's quantitative results build on those of recent qualitative studies and provide information about the types of family planning information men are lacking and avenues for getting this information to them.

Comparing long-acting reversible contraception insertion rates in women with Medicaid vs. private insurance in a clinic with a two-visit protocol.

OBJECTIVE: This study examined whether women with Medicaid are less likely to receive long-acting reversible contraception (LARC) in a clinic requiring two visits for insertion. STUDY DESIGN: LARC insertion and pregnancy rates were compared among women with Medicaid vs. private insurance, along with other predictors, in a retrospective chart review (N=447). RESULTS: Univariately, fewer women with Medicaid vs. private insurance received LARC (66% vs. 79%, p<.01) and more become pregnant (18% vs. 6%, p<.001). Significant multivariate predictors of not receiving LARC were being unmarried and postpartum, both of which were associated with having Medicaid. CONCLUSION: Women with Medicaid are less likely than women with private insurance to have a requested LARC device inserted when a clinic requires two visits for insertion.

Competency-Based Objectives in Global Underserved Women's Health for Medical Trainees.

The Association of Professors of Gynecology and Obstetrics Committee on Global Health developed an inclusive definition of global women's health and competency-based objectives that reflected work internationally, as well as with U.S. vulnerable and underserved populations, such as refugee and immigrant populations or those who would otherwise have compromised access to health care. The knowledge, skill, and attitude-based competencies required to fulfill each learning objective were mapped to the Accreditation Council for Graduate Medical Education Outcomes Project's educational domains and the Consortium of Universities for Global Health competency domains. The proposed global women's health definition and competency-based learning objective framework is a first step in ensuring quality standards for educating trainees to address global women's health needs. By proposing these objectives, we hope to guide future program development and spark a broader conversation that will improve health for vulnerable women and shape educational, ethical, and equitable global health experiences for medical trainees.

Access, attitudes and training in information technologies and evidence-based medicine among medical students at University of Zimbabwe College of Health Sciences.

BACKGROUND: The Medical Education Partnership Initiative, has helped to mitigate the digital divide in Africa. The aim of the study was to assess the level of access, attitude, and training concerning meaningful use of electronic resources and EBM among medical students at an African medical school. METHODS: The study involved medical students at the University of Zimbabwe College of Health Sciences, Harare. The needs assessment tool consisted of a 21-question, paper-based, voluntary and anonymous survey. RESULTS: A total of 61/67 (91%), responded to the survey. 60% of the medical students were 'third-year medical students'. Among medical students, 85% of responders had access to digital medical resources, but 54% still preferred printed medical textbooks. Although 25% of responders had received training in EBM, but only 7% found it adequate. 98% of the participants did not receive formal training in journal club presentation or analytical reading of medical literature, but 77 % of them showed interest in learning these skills. CONCLUSION: Lack of training in EBM, journal club presentation and analytical reading skills have limited the impact of upgraded technology in enhancing the level of knowledge. This impact can be boosted by developing a curriculum with skills necessary in using EBM.

Bradycardia as a Marker of Chronic Cocaine Use: A Novel Cardiovascular Finding.

Few studies have examined the effects of chronic cocaine use on the resting surface electrocardiogram (ECG) between exposures to cocaine. Researchers compared 12-lead ECGs from 97 treatment-seeking cocaine-dependent patients, with ECG parameters from 8,513 non-cocaine-using control patients from the Atherosclerosis Risk in Communities study. After matching and adjusting for relevant covariates, cocaine use demonstrated large and statistically reliable effects on early repolarization, bradycardia, severe bradycardia, and heart rate. Current cocaine dependence corresponds to an increased odds of demonstrating early repolarization by a factor of 4.92 and increased odds of bradycardia and severe bradycardia by factors 3.02 and 5.11, respectively. This study demonstrates the novel finding that long-lasting effects of cocaine use on both the cardiac conduction and the autonomic nervous system pose a risk of adverse cardiovascular events between episodes of cocaine use, and that bradycardia is a marker of chronic cocaine use.

Radiotherapy-Induced Malfunction in Contemporary Cardiovascular Implantable Electronic Devices: Clinical Incidence and Predictors.

IMPORTANCE: Risk stratification and management paradigms for patients with cardiovascular implantable electronic devices (CIEDs) requiring radiotherapy (RT) vary widely and are based on limited clinical data. OBJECTIVE: To identify the incidence and predictors of CIED malfunction and describe associated clinical consequences in a large cohort of patients treated with photon- and electron-based RT. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of all patients with a functioning CIED who underwent RT between August 2005 and January 2014 with CIED interrogation data following RT at an academic cancer center. We identified 249 courses of photon- and electron-based RT in 215 patients (123 pacemakers [57%]; 92 implantable cardioverter-defibrillators [43%]). Substantial neutron production was generated in 71 courses (29%). EXPOSURE: Implantation of CIED with subsequent therapeutic radiation treatment (neutron producing with 15- or 18-MV photons and non-neutron producing with electrons, GammaKnife, or 6-MV photons). MAIN OUTCOMES AND MEASURES: Malfunction of CIED, characterized as single-event upset (data loss, parameter resets, unrecoverable resets), and delayed effects including signal interference, pacing threshold changes, and premature battery depletion. RESULTS: Malfunction of CIED attributable to RT occurred during 18 courses (7%), with 15 CIEDs experiencing single-event upsets, and 3, transient signal interference. All single-event upsets occurred during neutron-producing RT, at a rate of 21%, 10%, and 34% per neutron-producing course for CIEDs, pacemakers, and implantable cardioverter-defibrillators, respectively. No single-event upsets were found among 178 courses of non-neutron-producing RT. Incident CIED dose did not correlate with device malfunction. Patients treated to the abdomen and pelvis region were more likely to undergo a single-event upset (hazard ratio, 5.2 [95% CI, 1.2-22.6]; P = .03). Six patients with a CIED parameter reset developed clinical symptoms: 3 experienced hypotension and/or bradycardia, 2 experienced abnormal chest ticking consistent with pacemaker syndrome, and 1 developed congestive heart failure. The 3 episodes of signal interference did not result in clinical effects. No delayed malfunctions were directly attributed to RT. CONCLUSIONS AND RELEVANCE: In a cohort of contemporary CIEDs, all cases of single-event upset malfunction occurred in the setting of notable neutron production, at a rate of 21% for neutron-producing RT and 0% for non-neutron-producing RT. Where clinically feasible, the use of non-neutron-producing RT is recommended. Given the lack of correlation between CIED malfunction and incident dose observed up to 5.4 Gy, invasive CIED relocation procedures in these settings can be minimized.

Biomarkers for the development of new medications for cocaine dependence.

There has been significant progress in personalized drug development. In large part, this has taken place in the oncology field and been due to the ability of researchers/clinicians to discover and develop novel drug development tools (DDTs), such as biomarkers. In cancer treatment research, biomarkers have permitted a more accurate pathophysiological characterization of an individual patient, and have enabled practitioners to target mechanistically the right drug, to the right patient, at the right time. Similar to cancer, patients with substance use disorders (SUDs) present clinically with heterogeneous symptomatology and respond variably to therapeutic interventions. If comparable biomarkers could be identified and developed for SUDs, significant diagnostic and therapeutic advances could be made. In this review, we highlight current opportunities and difficulties pertaining to the identification and development of biomarkers for SUDs. We focus on cocaine dependence as an example. Putative diagnostic, pharmacodynamic (PD), and predictive biomarkers for cocaine dependence are discussed across a range of methodological approaches. A possible cocaine-dependent clinical outcome assessment (COA)--another type of defined DDT--is also discussed. At present, biomarkers for cocaine dependence are in their infancy. Much additional research will be needed to identify, validate, and qualify these putative tools prior to their potential use for medications development and/or application to clinical practice. However, with a large unmet medical need and an estimated market size of several hundred million dollars per year, if developed, biomarkers for cocaine dependence will hold tremendous value to both industry and public health.

Malfunctions of implantable cardiac devices in patients receiving proton beam therapy: incidence and predictors.

PURPOSE: Photon therapy has been reported to induce resets of implanted cardiac devices, but the clinical sequelae of treating patients with such devices with proton beam therapy (PBT) are not well known. We reviewed the incidence of device malfunctions among patients undergoing PBT. METHODS AND MATERIALS: From March 2009 through July 2012, 42 patients with implanted cardiac implantable electronic devices (CIED; 28 pacemakers and 14 cardioverter-defibrillators) underwent 42 courses of PBT for thoracic (23, 55%), prostate (15, 36%), liver (3, 7%), or base of skull (1, 2%) tumors at a single institution. The median prescribed dose was 74 Gy (relative biological effectiveness; range 46.8-87.5 Gy), and the median distance from the treatment field to the CIED was 10 cm (range 0.8-40 cm). Maximum proton and neutron doses were estimated for each treatment course. All CIEDs were checked before radiation delivery and monitored throughout treatment. RESULTS: Median estimated peak proton and neutron doses to the CIED in all patients were 0.8 Gy (range 0.13-21 Gy) and 346 Sv (range 11-1100 mSv). Six CIED malfunctions occurred in 5 patients (2 pacemakers and 3 defibrillators). Five of these malfunctions were CIED resets, and 1 patient with a defibrillator (in a patient with a liver tumor) had an elective replacement indicator after therapy that was not influenced by radiation. The mean distance from the proton beam to the CIED among devices that reset was 7.0 cm (range 0.9-8 cm), and the mean maximum neutron dose was 655 mSv (range 330-1100 mSv). All resets occurred in patients receiving thoracic PBT and were corrected without clinical incident. The generator for the defibrillator with the elective replacement indicator message was replaced uneventfully after treatment. CONCLUSIONS: The incidence of CIED resets was about 20% among patients receiving PBT to the thorax. We recommend that PBT be avoided in pacing-dependent patients and that patients with any type of CIED receiving thoracic PBT be followed closely.

Combination of Modafinil and d-amphetamine for the Treatment of Cocaine Dependence: A Preliminary Investigation.

BACKGROUND: Two stimulant medications, modafinil and d-amphetamine, when tested individually, have shown safety and efficacy for treatment of cocaine addiction. We hypothesized that the combination of modafinil and d-amphetamine, at low doses, would show equivalent or greater benefit in reducing cocaine use compared to higher doses of each individual medication or placebo. METHODS: Sixteen week, randomized, parallel-group design with four treatment arms comparing placebo to modafinil 400 mg; d-amphetamine 60 mg; modafinil 200 mg plus d-amphetamine 30 mg. Primary outcome variables, retention and cocaine use, were analyzed on the sample of 73 participants who received the first dose of the study medication. RESULTS: Retention rates did not differ between groups and were generally low, with 40% remaining in treatment at week 12 and 20% at week 16. Participants receiving the combination of modafinil and d-amphetamine showed a trend of increased cocaine use over time with a corresponding low Bayesian probability of benefit (33%). Relatively better cocaine outcomes were observed in the placebo and d-amphetamine only groups. The study medications were generally well-tolerated with few adverse effects, yet rates of adherence were suboptimal (≤80%). CONCLUSION: Data from this preliminary investigation fail to provide evidential support for conducting a larger study of this dual-agonist medication combination for treatment of cocaine dependence.

Recurrent syncope in a cancer patient: a case report and review of the literature.

A 59-year-old male with invasive squamous cell carcinoma of the left preauricular region, treated with several chemotherapy regimens and radiation therapy, was admitted for recurrent syncopal episodes. He was found to be suffering from neurocardiogenic reflex-mediated syncope secondary to mechanical compression of the carotid baroreceptors and glossopharyngeal nerve by the tumor. We discuss the pathophysiology of this case and the available treatment options.

Noncompacted ventricular myocardium: is syncope the only warning sign?

We present a case of a 14-year-old young boy with ventricular noncompaction and coexistent Wolff-Parkinson-White syndrome who presented with syncope. Detailed testing was performed, and an ablation was successful for Wolff-Parkinson-White syndrome; however, because of patient/family desires, an implantable cardiodefibrillator was placed. A careful review of the literature highlights the complex decision making involved with this condition.