Deprescribing Inappropriate Proton Pump Inhibitors in a Family Medicine Residency Practice Office.

INTRODUCTION: Proton pump inhibitors (PPIs) are often prescribed beyond their medically-approved duration of use. Long-term PPI use has been linked with numerous adverse effects and contributes to polypharmacy. This study sought to understand the effect of evidence-based education to resident and faculty physicians on deprescribing inappropriate PPIs. We hypothesized that this educational intervention would result in fewer inappropriate PPI prescriptions. METHODS: We performed a chart review on all adult patients in a family medicine residency program practice, identifying those inappropriately taking PPIs. All physicians in the practice participated in an educational intervention regarding deprescribing inappropriate PPIs and were given frequent reminders to continue their deprescribing efforts. We reviewed charts at the end of the study to identify patients with successful deprescribing attempts. RESULTS: Of the 187 patients prescribed inappropriate PPIs in the study, 100 remained on PPIs at the end of the study (46.6% success rate). There was a significant decrease in the number of patients inappropriately prescribed PPIs by each physician over the course of the study, from a mean of 17.0 (beginning) to 9.1 (end). CONCLUSION: Physician education with reminders is an effective means of reducing the number of inappropriate PPIs prescribed in a family medicine residency practice. Future studies could investigate the effectiveness of educational interventions with other medication classes that are often prescribed inappropriately.

Real-world treatment switching to sacubitril/valsartan in patients with heart failure with reduced ejection fraction: A cohort study.

BACKGROUND: Sacubitril/valsartan is an effective treatment for heart failure with reduced ejection fraction (HFrEF) based on clinical trial data. However, little is known about its use or impact in real-world practice. The aim of this study was to describe our routine clinical experience of switching otherwise optimally treated patients with HFrEF to sacubitril/valsartan with respect to patient outcomes such as quality of life (QoL) and echocardiographic variables. METHODS AND RESULTS: From June 2017 to May 2019, 80 consecutive stable patients with HFrEF on established and maximally tolerated guideline-directed HF therapies were initiated on sacubitril/valsartan with bimonthly uptitration. Clinical assessment, biochemistry, echocardiography and QoL were compared pretreatment and post-treatment switching. We were able to successfully switch 89% of patients from renin-angiotensin axis inhibitors to sacubitril/valsartan (71 of 80 patients). After 3 months of switch therapy, we observed clinically significant and incremental improvements in blood pressure (systolic blood pressure 123 vs 112 mm Hg, p<0.001; diastolic blood pressure 72 vs 68 mm Hg, p=0.004), New York Heart Association functional classification score (2.3 vs 1.9, p<0.001), Minnesota Living with Heart Failure Questionnaire score (46 vs 38, p=0.016), left ventricular ejection fraction (26% vs 33%, p<0.001) and left ventricular end systolic diameter (5.2 vs 4.9 cm, p=0.013) compared with baseline. There were no significant changes in renal function or serum potassium. CONCLUSION: This study provides real-world clinical practice data demonstrating incremental improvements in functional and echocardiographic outcomes in optimally treated patients with HFrEF switched to sacubitril/valsartan. The data provide evidence beyond that observed in clinical trial settings of the potential benefits of sacubitril/valsartan when used as part of a multidisciplinary heart failure programme.

Risk indicators of length of acute hospital stay after traumatic spinal cord injury in South Africa: a prospective, population-based study.

STUDY DESIGN: Population-based cohort study. OBJECTIVES: To determine non-modifiable and modifiable risk indicators of acute length of hospital stay (LOHS) after traumatic spinal cord injury (TSCI). SETTING: Government-funded hospitals within the City of Cape Town, South Africa. METHODS: Newly injured survivors of TSCI during a 1 year period were prospectively included. Non-modifiable (e.g., demographic factors and clinical characteristics) and modifiable risk indicators (e.g., clinical processes, timing of surgery, secondary complications) of prolonged LOHS (31 days) were determined using univariate and multivariable logistic regression analyses. RESULTS: Of the total population-based cohort of 145 individuals, 139 (96%) had valid LOHS data and were included in the analyses. Significant univariate non-modifiable risk indicators of LOHS were age, complete injury and vertebral injury, whereas modifiable risk indicators were delayed spinal surgery (>72 h) and the occurrence of any secondary complications, as well as specifically pressure ulcers, pneumonia and urinary tract infection. In the final multivariable model showing good fit and acceptable discrimination (AUC = 0.86), older age (OR: 1.04, 95% CI: 1.00-1.07), vertebral injury (OR: 3.18, 95% CI: 1.07-9.44), pneumonia (OR: 8.40, 95% CI: 2.76-25.55) and pressure ulcers (OR: 7.16, 95% CI: 2.54-20.22) remained significant independent factors. Only injury completeness was insignificant in the final model. CONCLUSIONS: Our findings shed light on the need of developing prevention programs for secondary complications to improve the quality and efficiency of acute SCI care in South Africa. SPONSORSHIP: The National Research Foundation of South Africa.

Magnetic resonance imaging of the time course of hyperpolarized 129Xe gas exchange in the human lungs and heart.

PURPOSE: To perform magnetic resonance imaging (MRI), human lung imaging, and quantification of the gas-transfer dynamics of hyperpolarized xenon-129 (HPX) from the alveoli into the blood plasma. MATERIALS AND METHODS: HPX MRI with iterative decomposition of water and fat with echo asymmetry and least-square estimation (IDEAL) approach were used with multi-interleaved spiral k-space sampling to obtain HPX gas and dissolved phase images. IDEAL time-series images were then obtained from ten subjects including six normal subjects and four patients with pulmonary emphysema to test the feasibility of the proposed technique for capturing xenon-129 gas-transfer dynamics (XGTD). The dynamics of xenon gas diffusion over the entire lung was also investigated by measuring the signal intensity variations between three regions of interest, including the left and right lungs and the heart using Welch's t test. RESULTS: The technique enabled the acquisition of HPX gas and dissolved phase compartment images in a single breath-hold interval of 8 s. The y-intersect of the XGTD curves were also found to be statistically lower in the patients with lung emphysema than in the healthy group (p < 0.05). CONCLUSION: This time-series IDEAL technique enables the visualization and quantification of inhaled xenon from the alveoli to the left ventricle with a clinical gradient strength magnet during a single breath-hold, in healthy and diseased lungs. KEY POINTS: • The proposed hyperpolarized xenon-129 gas and dissolved magnetic resonance imaging technique can provide regional and temporal measurements of xenon-129 gas-transfer dynamics. • Quantitative measurement of xenon-129 gas-transfer dynamics from the alveolar to the heart was demonstrated in normal subjects and pulmonary emphysema. • Comparison of gas-transfer dynamics in normal subjects and pulmonary emphysema showed that the proposed technique appears sensitive to changes affecting the alveoli, pulmonary interstitium, and capillaries.

Patterns of Single and Multiple Tobacco Product Use Among US Women of Reproductive Age.

Introduction: Understanding patterns of single and multiple tobacco product use among reproductive-aged women is critical given the potential for adverse health effects on mother and infant should a woman become pregnant. Methods: Patterns of tobacco use over a 2-year period were examined among all women (18-44 years) who completed wave 1 (W1) and wave 2 (W2) of the US Population Assessment of Tobacco and Health (PATH, 2013-2014, 2014-2015) Study. We examined the most common patterns of single and multiple tobacco product use in W1, and longitudinal trajectories of women engaged in each of these patterns of use from W1 to W2, among women not pregnant in either wave (n = 7480), not pregnant in W1 and pregnant in W2 (n = 332), and pregnant in W1 and not pregnant in W2 (n = 325). Results: The most prevalent patterns of tobacco use in W1 among all three subgroups were using cigarettes alone followed by using cigarettes plus e-cigarettes. In all three subgroups, women using multiple products in W1 were more likely to adopt new use patterns in W2 relative to single-product users, with the new patterns generally involving dropping rather than adding products. The majority of multiple product use included cigarettes, and transitions to single product use typically involved dropping the noncigarette product. The most common trajectory among tobacco users transitioning to or from pregnancy was to use cigarettes alone in W2. Discussion: This study contributes new knowledge characterizing tobacco use patterns across time and reproductive events among reproductive-aged women.

Examining the relationship between pregnancy and quitting use of tobacco products in a U.S. national sample of women of reproductive age.

This study examined quit rates longitudinally for cigarettes, e-cigarettes, hookah, cigars, and all tobacco products in a U.S. national sample of women aged 18-44 who completed both Wave 1 (W1) and Wave 2 (W2) of the Population Assessment of Tobacco and Health (PATH, 2013-2014, 2014-2015) study (N = 7814). Quit rates were examined among women who transitioned into pregnancy across survey waves, and among a comparable sample of non-pregnant women to provide contextual information about quitting among the broader population of reproductive-aged women. Multiple logistic regression modeling was used to estimate the associations of pregnancy and quitting adjusting for other demographic and psychosocial characteristics. Quit rates among women who were pregnant in W2 were highest for hookah (98.3%), followed by cigars (88.0%), e-cigarettes (81.3%), and lowest for tobacco cigarettes (53.4%). Slightly more than half (58.7%) of women reported quitting use all tobacco products while pregnant. Pregnancy was independently associated with increased odds of quitting hookah (AOR = 52.9, 95%CI = 3.4, 830.2), e-cigarettes (AOR = 21.0, 95%CI = 2.6, 170.3), all tobacco products (AOR = 9.6, 95%CI = 6.4, 14.5), and cigarettes (AOR = 6.5, 95%CI = 4.2, 10.1), although not cigars. Relative to other demographic and psychosocial characteristics, pregnancy was the strongest predictor of quitting use of each tobacco product. While these data indicate that pregnancy has strong, independent associations with quitting a variety of commercially available tobacco products, the comparatively lower quit rates for cigarettes versus other tobacco products underscores the long-standing need for more intensive, multipronged clinical and regulatory interventions to reduce cigarette use among reproductive-aged women.

The Suspected CANcer (SCAN) pathway: protocol for evaluating a new standard of care for patients with non-specific symptoms of cancer.

INTRODUCTION: Cancer survival in England lags behind most European countries, due partly to lower rates of early stage diagnosis. We report the protocol for the evaluation of a multidisciplinary diagnostic centre-based pathway for the investigation of 'low-risk but not no-risk' cancer symptoms called the Suspected CANcer (SCAN) pathway. SCAN is a new standard of care being implemented in Oxfordshire; one of a number of pathways implemented during the second wave of the Accelerate, Coordinate, Evaluate (ACE) programme, an initiative which aims to improve England's cancer survival rates through establishing effective routes to early diagnosis. METHODS AND ANALYSIS: To evaluate SCAN, we are collating a prospective database of patients referred onto the pathway by their general practitioner (GP). Patients aged over 40 years, with non-specific symptoms such as weight loss or fatigue, who do not meet urgent cancer referral criteria or for whom symptom causation remains unclear after investigation via other existing pathways, can be referred to SCAN. SCAN provides rapid CT scanning, laboratory testing and clinic review within 2 weeks. We will follow all patients in the primary and secondary care record for at least 2 years. The data will be used to understand the diagnostic yield of the SCAN pathway in the short term (28 days) and the long term (2 years). Routinely collected primary and secondary care data from patients not referred to SCAN but with similar symptoms will also be used to evaluate SCAN. We will map the routes to diagnosis for patients referred to SCAN to assess cost-effectiveness. Acceptability will be evaluated using patient and GP surveys. ETHICS AND DISSEMINATION: The Oxford Joint Research Office Study Classification Group has judged this to be a service evaluation and so outside of research governance. The results of this project will be disseminated by peer-reviewed publication and presentation at conferences.

Associations of maternal obesity and smoking status with perinatal outcomes.

Maternal obesity and smoking are associated with adverse perinatal outcomes. These prevalent conditions contribute to health disparities. In this study, we examine whether maternal BMI moderates the impact of smoking cessation on short-term perinatal outcomes. This is a secondary analysis of assessments conducted from several prospective clinical trials examining the efficacy of incentives to promote smoking cessation during pregnancy. Participants were randomly assigned to receive financial incentives contingent upon smoking abstinence or a control condition. Pregnancy outcomes were abstracted from the medical record. ANCOVA and multiple logistic regression were used for statistical analysis. Among 388 women, there was a significant interaction between maternal pre-pregnancy BMI and smoking status on gestational age at delivery (p = .03) and admission to the NICU (p = .04). Among underweight/normal weight gravidas, smoking resulted in earlier deliveries and a greater likelihood of NICU admission than in those who abstained. Among overweight/obese gravidas, there was no effect of smoking on gestational age at delivery and infants of smokers were less likely to be admitted to the NICU. Maternal obesity and smoking have significant individual effects on perinatal outcome. Maternal overweight/obesity appears to moderate the effect of smoking on gestational age at delivery and on NICU admissions.

Tobacco and nicotine delivery product use in a national sample of pregnant women.

Monitoring use of tobacco products among pregnant women is a public health priority, yet few studies in U.S. national samples have been reported on this topic. We examined prevalence and correlates of using cigarettes, e-cigarettes, and other tobacco/nicotine delivery products in a U.S. national sample of pregnant women. Data were obtained from all pregnant women (≥18 years) in the first wave of the Population Assessment of Tobacco and Health (PATH, 2013-2014) Study (N=388). Prevalence of current and prior use of tobacco/nicotine products was examined overall and among current cigarette smokers. Multiple logistic regression was used to examine correlates of use of cigarettes, e-cigarettes, hookah and cigars. Overall prevalence was highest for cigarettes (13.8%), followed by e-cigarettes (4.9%), hookah (2.5%) and cigars (2.3%), and below 1% for all other products. Prevalence of using other tobacco products is much higher among current smokers than the general population, with e-cigarettes (28.5%) most prevalent followed by cigars (14.0%), hookah (12.4%), smokeless (4.7%), snus (4.6%), and pipes (2.1%). Sociodemographic characteristics (poverty, low educational attainment, White race) and past-year externalizing psychiatric symptoms were correlated with current cigarette smoking. In turn, current cigarette smoking and past year illicit drug use were correlated with using e-cigarettes, hookah, and cigars. These results underscore that tobacco/nicotine use during pregnancy extends beyond cigarettes. The results also suggest that use of these other products should be included in routine clinical screening on tobacco use, and the need for more intensive tobacco control and regulatory strategies targeting pregnant women.

Co-occurring obesity and smoking among U.S. women of reproductive age: Associations with educational attainment and health biomarkers and outcomes.

INTRODUCTION: Obesity and smoking are independently associated with socioeconomic disadvantage and adverse health effects in women of reproductive age and their children, but little is known about co-occurring obesity and smoking. The purpose of this study was to investigate relationships between co-occurring obesity and smoking, socioeconomic status, and health biomarkers and outcomes in a nationally representative sample. METHODS: Data from non-pregnant women of reproductive age were obtained from the U.S. National Health and Nutrition Examination Surveys reported between 2007 and 2010. Linear and logistic regressions were used to examine associations between obesity and smoking alone and in combination with educational attainment and a range of health biomarkers and outcomes. RESULTS: Prevalence of co-occurring obesity and smoking was 8.1% (~4.1 million U.S. women of reproductive age) and increased as an inverse function of educational attainment, with the least educated women being 11.6 times more likely to be obese smokers than the most educated. Compared to women with neither condition, obese smokers had significantly poorer cardiovascular and glycemic biomarker profiles, and higher rates of menstrual irregularity, hysterectomy, oophorectomy, physical limitations, and depression. Obese smokers also had significantly worse high-density lipoprotein (HDL) cholesterol levels, physical mobility, and depression scores than those with obesity or smoking alone. CONCLUSIONS: Co-occurring obesity and smoking is highly associated with low educational attainment, a marker of socioeconomic disadvantage, and a broad range of adverse health biomarkers and outcomes. Interventions specifically targeting co-occurring obesity and smoking are likely necessary in efforts to reduce health disparities among disadvantaged women and their children.

Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis.

BACKGROUND: High-density lipoprotein (HDL) may provide cardiovascular protection by promoting reverse cholesterol transport from macrophages. We hypothesized that the capacity of HDL to accept cholesterol from macrophages would serve as a predictor of atherosclerotic burden. METHODS: We measured cholesterol efflux capacity in 203 healthy volunteers who underwent assessment of carotid artery intima-media thickness, 442 patients with angiographically confirmed coronary artery disease, and 351 patients without such angiographically confirmed disease. We quantified efflux capacity by using a validated ex vivo system that involved incubation of macrophages with apolipoprotein B-depleted serum from the study participants. RESULTS: The levels of HDL cholesterol and apolipoprotein A-I were significant determinants of cholesterol efflux capacity but accounted for less than 40% of the observed variation. An inverse relationship was noted between efflux capacity and carotid intima-media thickness both before and after adjustment for the HDL cholesterol level. Furthermore, efflux capacity was a strong inverse predictor of coronary disease status (adjusted odds ratio for coronary disease per 1-SD increase in efflux capacity, 0.70; 95% confidence interval [CI], 0.59 to 0.83; P<0.001). This relationship was attenuated, but remained significant, after additional adjustment for the HDL cholesterol level (odds ratio per 1-SD increase, 0.75; 95% CI, 0.63 to 0.90; P=0.002) or apolipoprotein A-I level (odds ratio per 1-SD increase, 0.74; 95% CI, 0.61 to 0.89; P=0.002). Additional studies showed enhanced efflux capacity in patients with the metabolic syndrome and low HDL cholesterol levels who were treated with pioglitazone, but not in patients with hypercholesterolemia who were treated with statins. CONCLUSIONS: Cholesterol efflux capacity from macrophages, a metric of HDL function, has a strong inverse association with both carotid intima-media thickness and the likelihood of angiographic coronary artery disease, independently of the HDL cholesterol level. (Funded by the National Heart, Lung, and Blood Institute and others.).

Evidence for distinct preterm and term phenotypes of preeclampsia.

OBJECTIVE: To determine differences in maternal and fetal characteristics in pregnancies complicated by preterm versus term preeclampsia. METHODS: Using our electronic database we identified 143 women who met the American College of Obstetricians and Gynecologists criteria for preeclampsia between January 1995 and August 2003. We collected data on age, smoking status, maternal serum markers, and newborns. We compared the group delivering preterm (<37 weeks) with those delivering at term (> or =37 weeks). Analyses were based on ANOVA, Wilcoxon Rank Sum test, and chi-square test. Statistical significance was determined based on alpha = 0.05. Data are expressed as mean +/- SD unless otherwise indicated. RESULTS: Eighty women delivered preterm and 63 delivered at term. Women who delivered preterm with preeclampsia were younger, lighter, and were more likely to smoke cigarettes than those delivering at term with preeclampsia. Maternal liver enzyme concentrations were significantly greater in the preterm group. Newborn birthweight percentile (gestational age specific) was significantly lower for preterm preeclampsia. We found no significant differences in maternal platelet count, uric acid concentration, or newborn gender between groups. CONCLUSIONS: Differences exist in maternal and fetal characteristics between women who develop preterm preeclampsia and those who develop preeclampsia at term. These data support the hypothesis that multiple preeclamptic phenotypes exist.

Glomeruloid hemangioma leading to a diagnosis of POEMS syndrome.

POEMS is an acronym for polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes. It is a poorly understood paraneoplastic syndrome that stems from an underlying plasma cell dyscrasia. Of the skin changes, the glomeruloid hemangioma is considered to be a specific marker of POEMS syndrome. We describe a 68-year-old man who presented to his dermatologist with multiple hemangiomas, whose biopsy diagnosis of glomeruloid hemangioma resulted in further evaluation and an eventual diagnosis of POEMS.

A phase 1 trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation.

Donor lymphocyte infusions (DLIs) induce potent graft versus tumor (GVT) effects for relapsed chronic myelogenous leukemia (CML) after allogeneic stem cell transplantation (SCT) but are disappointing for other diseases. Disease resistance can occur if donor T cells are not appropriately activated in vivo. Ex vivo T-cell activation might overcome disease-induced anergy and augment GVT activity. We performed a phase 1 trial of ex vivo-activated DLI (aDLI) for 18 patients with relapse after SCT. Activated donor T cells are produced through costimulation with anti-CD3- and anti-CD28-coated beads. Patients with aggressive malignancies received induction chemotherapy, and all patients received conventional DLI (median, 1.5 x 10(8) mononuclear cells/kg) followed 12 days later by aDLI. Activated DLI was dose escalated from 1 x 10(6) to 1 x 10(8) CD3+ cells per kilogram in 5 levels. Seven patients developed acute graft versus host disease (GVHD) (5 grade I-II, 2 grade III), and 4 developed chronic GVHD. Eight patients achieved complete remission, including 4 of 7 with acute lymphocytic leukemia (ALL), 2 of 4 with acute myelogenous leukemia (AML), 1 with chronic lymphocytic leukemia (CLL), and 1 of 2 with non-Hodgkin lymphoma (NHL). Four complete responders relapsed while 4 remain alive in remission a median 23 months after aDLI. Overall, 10 of 18 remain alive 11 to 53 months after aDLI. Adoptive transfer of costimulated activated allogeneic T cells is feasible, does not result in excessive GVHD, and may contribute to durable remissions in diseases where conventional DLI has been disappointing.

Bacterial colonization of the donor lower airways is a predictor of poor outcome in lung transplantation.

OBJECTIVE: At the time of lung transplant, we routinely perform bronchoalveolar lavage (BAL) of the donor lungs on the recipient operating table immediately before implantation, for bacterial and fungal cultures. We sought to determine whether the results correlate with the outcome. METHODS: We retrospectively analysed 115 consecutive cadaveric lung transplants (single lung: 42; bilateral lung: 63; heart-lung: 10) performed over 4 years. RESULTS: Fifty-three (46%) grafts had positive BAL (bacteria: 33; fungus: 10; mixed: 10) and 62 (54%) were negative. Recipients with donor BAL culture positive for bacteria had lower mean oxygenation index in the first 6 h compared with those with negative bacterial culture (36.5+/-14.73 vs. 44.1+/-16.79 kPa) (P=0.019). They also had longer median intensive treatment unit stay (2.5 vs. 1.5 days) (P=0.035), and median time of mechanical ventilation (37.5 vs. 23.0 h) (P=0.008), as well as inferior 6-month, 1-year, 2-year and 4-year cumulative survival (79, 77, 74, 60% vs. 93, 92, 88, 79% respectively) (P=0.04). There was no difference in the above parameters between recipients with Gram-negative (n=18) and recipients with Gram-positive bacteria (n=19) in the donor BAL. Incidence of acute rejection within the first 2 weeks and time of onset of bronchiolitis obliterans syndrome (BOS) were similar in the bacteria-positive and bacteria-negative groups. Recipients with donor BAL positive for fungi alone had similar outcome with the negatives. There was no difference in the donor oxygenation index and age, recipient age, transplant type and ischaemic time between compared groups. There was a significant difference in the median length of donor mechanical ventilation between donors with Gram-positive and donors with Gram-negative bacteria in the BAL (24 vs. 48 h) (P=0.01), as well as between donors with fungi alone in the BAL and donors with negative BAL (67 vs. 48 h) (P=0.04). CONCLUSIONS: Donor lungs with lower airways colonized with bacteria result in inferior recipient outcome. Bacterial colonization of the donor lower airways could therefore be used as a marker of donor lung injury, but evidence from a prospective study is necessary.