bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abortion and fertility control in Pakistan: the role of misoprostol
Authors: Chahal Harneet , Mumtaz Zubia 
Published: February 2017

ObjectiveTo examine how availability of misoprostol has impacted women's abortion-seeking behaviour in Pakistan.DesignFocused ethnography.SettingA facility providing reproductive health services, including induced abortions in Chakwal, a small town in Northern Punjab, Pakistan.PopulationWomen who came to the clinic seeking an abortion or who had had one in the last 6 months (n=23) and all healthcare providers working in the facility (n=14).MethodsSemi-structured interviews (n=37), a focus group discussion (n=1) and participant observation (n=41). Latent content analysis was conducted drawing on principles of constant comparison to generate key themes in reported experiences.ResultsAll the respondents had sought an abortion to limit their fertility. Although some reported contraceptive use, improper use, undesirable side effects and restrictions on use had led to the unwanted pregnancy. All the women specifically requested misoprostol within days of their pregnancy, suggesting that they not only had knowledge of misoprostol as a backup in case of contraceptive failure, but may have pre-planned its use ofin place ofusing contraception. Women reconciled their decision to undergo an abortion by describing it as a mistake, miscarriage or menstrual cycle issue.ConclusionsMisoprostol's availability, ease of use and effectiveness have increased the role of abortion in fertility control.
Presentation of SLE in UK primary care using the Clinical Practice Research Datalink
Authors: Nightingale Alison L , Davidson Julie E , Molta Charles T , Kan Hong J , McHugh Neil J 
Published: February 2017

ObjectivesTo describe the presenting symptoms of SLE in primary care using the Clinical Practice Research Database (CPRD) and to calculate the time from symptom presentation to SLE diagnosis.MethodsIncident cases of SLE were identified from the CPRD between 2000 and 2012. Presenting symptoms were identified from the medical records of cases in the 5 years before diagnosis and grouped using the British Isles Lupus Activity Group (BILAG) symptom domains. The time from the accumulation of one, two and three BILAG domains to SLE diagnosis was investigated, stratified by age at diagnosis (<30, 30–49 and ≥50 years).ResultsWe identified 1426 incident cases (170 males and 1256 females) of SLE. The most frequently recorded symptoms and signs prior to diagnosis were musculoskeletal, mucocutaneous and neurological. The median time from first musculoskeletal symptom to SLE diagnosis was 26.4 months (IQR 9.3–43.6). There was a significant difference in the time to diagnosis (log rank p<0.01) when stratified by age and disease severity at baseline, with younger patients <30 years and those with severe disease having the shortest times and patients aged ≥50 years and those with mild disease having the longest (6.4 years (IQR 5.8–6.8)).ConclusionsThe time from symptom onset to SLE diagnosis is long, especially in older patients. SLE should be considered in patients presenting with flaring or chronic musculoskeletal, mucocutaneous and neurological symptoms.
Sildenafil improves clinical signs and radiographic features in dogs with congenital idiopathic megaoesophagus: a randomised controlled trial
Authors: Quintavalla F. , Menozzi A. , Pozzoli C. , Poli E. , Donati P. , Wyler D. K. , Serventi P. , Bertini S. 
Published: February 2017

We evaluated the efficacy of oral sildenafil citrate in dogs with congenital idiopathic megaoesophagus (CIM). Twenty‐one puppies were randomly assigned to two groups (treatment and control). The dogs were given sildenafil oral suspension 1 mg/kg every 12 hours for 14 days or placebo in a masked fashion. Clinical signs (frequency of regurgitation and weight gain) and oesophagrams (relative oesophageal diameter, ROD) were evaluated in order to assess the efficacy of drug treatment, by examiners who were unaware of the study protocol. In addition, a set of in vitro experiments on isolated samples of canine lower oesophageal sphincter (LOS) was performed, and the effects of increasing concentrations of sildenafil on basal tone and electrically‐stimulated motility were assessed. Sildenafil administration significantly reduced the number of regurgitation episodes (0.88±1.40 v 2.65±1.56, P<0.0001) and significantly increased weight gain in the treated dogs compared to controls (79.76±28.30 per cent v 53.40±19.30 per cent, P=0.034). ROD values, at the end of the treatment period, were significantly decreased in the sildenafil group, compared to pre‐treatment values (0.97±0.19 v 0.24±0.14, P<0.0001), in contrast to control subjects (0.98±0.17 v 1.10±0.25, P=0.480). In accordance with the in vivo findings, sildenafil dose‐dependently reduced basal tone and increased electrically‐induced relaxation of dog LOS samples. These results suggest that sildenafil citrate helps ameliorate clinical and radiographic signs in dogs with CIM by reducing LOS tone, and could represent a novel therapeutic tool for the treatment of this disease.
Transcranial Doppler-determined change in posterior cerebral artery blood flow velocity does not reflect vertebral artery blood flow during exercise
Authors: Washio Takuro , Sasaki Hiroyuki , Ogoh Shigehiko 
Published: February 2017

We examined whether a change in posterior cerebral artery flow velocity (PCAv) reflected the posterior cerebral blood flow in healthy subjects during both static and dynamic exercise. PCAv and vertebral artery (VA) blood flow, as an index of posterior cerebral blood flow, were continuously measured during an exercise trial using transcranial Doppler (TCD) ultrasonography and Doppler ultrasound, respectively. Static handgrip exercise significantly increased both PCAv and VA blood flow. Increasing intensity of dynamic exercise further increased VA blood flow from moderate exercise, while PCAv decreased to almost resting level. During both static and dynamic exercise, the PCA cerebrovascular conductance (CVC) index significantly decreased from rest (static and high-intensity dynamic exercise, −11.5 ± 12.2% and −18.0 ± 16.8%, means ± SD, respectively) despite no change in the CVC of VA. These results indicate that vasoconstriction occurred at PCA but not VA during exercise-induced hypertension. This discrepancy in vascular response to exercise between PCA and VA may be due to different cerebral arterial characteristics. Therefore, to determine the effect of exercise on posterior cerebral circulation, at least, we need to carefully consider which cerebral artery to measure, regardless of exercise mode. NEW & NOTEWORTHY We examined whether transcranial Doppler-determined flow velocity in the posterior cerebral artery can be used as an index of cerebral blood flow during exercise. However, the changes in posterior cerebral artery flow velocity during exercise do not reflect vertebral artery blood flow.
Interaction Landscape of Inherited Polymorphisms with Somatic Events in Cancer
Authors: Carter Hannah , Marty Rachel , Hofree Matan , Gross Andrew M. , Jensen James , Fisch Kathleen M. , Wu Xingyu , DeBoever Christopher , Van Nostrand Eric L. , Song Yan , Wheeler Emily , Kreisberg Jason F. , Lippman Scott M. , Yeo Gene W. , Gutkind J. Silvio , Ideker Trey 
Published: February 2017

Abstract
Recent studies have characterized the extensive somatic alterations that arise during cancer. However, the somatic evolution of a tumor may be significantly affected by inherited polymorphisms carried in the germline. Here, we analyze genomic data for 5,954 tumors to reveal and systematically validate 412 genetic interactions between germline polymorphisms and major somatic events, including tumor formation in specific tissues and alteration of specific cancer genes. Among germline–somatic interactions, we found germline variants in RBFOX1 that increased incidence of SF3B1 somatic mutation by 8-fold via functional alterations in RNA splicing. Similarly, 19p13.3 variants were associated with a 4-fold increased likelihood of somatic mutations in PTEN. In support of this association, we found that PTEN knockdown sensitizes the MTOR pathway to high expression of the 19p13.3 gene GNA11. Finally, we observed that stratifying patients by germline polymorphisms exposed distinct somatic mutation landscapes, implicating new cancer genes. This study creates a validated resource of inherited variants that govern where and how cancer develops, opening avenues for prevention research.
Significance: This study systematically identifies germline variants that directly affect tumor evolution, either by dramatically increasing alteration frequency of specific cancer genes or by influencing the site where a tumor develops. Cancer Discovery; 7(4); 410–23. ©2017 AACR.
See related commentary by Geeleher and Huang, p. 354.
This article is highlighted in the In This Issue feature, p. 339
Population Impact & Efficiency of Benefit‐Targeted Versus Risk‐Targeted Statin Prescribing for Primary Prevention of Cardiovascular Disease
Authors: Pletcher Mark J. , Pignone Michael , Jarmul Jamie A. , Moran Andrew E. , Vittinghoff Eric , Newman Thomas 
Published: February 2017

Background
Benefit‐targeted statin prescribing may be superior to risk‐targeted statin prescribing (the current standard), but the impact and efficiency of this approach are unclear.

Methods and Results

We analyzed the National Health and Nutrition Examination Survey (
NHANES
) using an open‐source model (the Prevention Impact and Efficiency Model) to compare targeting of statin therapy according to expected benefit (benefit‐targeted) versus baseline risk (risk‐targeted) in terms of projected population‐level impact and efficiency. Impact was defined as relative % reduction in atherosclerotic cardiovascular disease in the
US
population for the given strategy compared to current statin treatment patterns; and efficiency as the number needed to treat over 10 years (
NNT
10
, average and maximum) to prevent each atherosclerotic cardiovascular disease event. Benefit‐targeted moderate‐intensity statin therapy at a treatment threshold of 2.3% expected 10‐year absolute risk reduction could produce a 5.7% impact (95% confidence interval, 4.8–6.7). This is approximately equivalent to the potential impact of risk‐targeted therapy at a treatment threshold of 5% 10‐year atherosclerotic cardiovascular disease risk (5.6% impact [4.7–6.6]). Whereas the estimated maximum
NNT
10
is much improved for benefit‐targeted versus risk‐targeted therapy at these equivalent‐impact thresholds (43.5 vs 180), the average
NNT
10
is nearly equivalent (24.2 vs 24.6). Reaching 10% impact (half the Healthy People 2020 impact objective, loosely defined) is theoretically possible with benefit‐targeted moderate‐intensity statins of persons with expected absolute risk reduction >2.3% if we expand age eligibility and account for treatment of all persons with diabetes mellitus or with low‐density lipoprotein >190 mg/dL (impact=12.4%; average
NNT
10
=23.0).

Conclusions
Benefit‐based targeting of statin therapy provides modest gains in efficiency over risk‐based prescribing and could theoretically help attain approximately half of the Healthy People 2020 impact goal with reasonable efficiency.
Long‐Term Risk of Cardiovascular Events in Patients With Chronic Kidney Disease Who Have Survived Sepsis: A Nationwide Cohort Study
Authors: Shih Chia‐Jen , Chao Pei‐Wen , Ou Shuo‐Ming , Chen Yung‐Tai 
Published: February 2017

Background
Long‐term cardiovascular outcomes after sepsis in patients with chronic kidney disease are not well known. We aimed to examine the risk of subsequent cardiovascular events in patients with chronic kidney disease discharged after hospitalization for sepsis in Taiwan.

Methods and Results

Using complete claims data for patients with chronic kidney disease from Taiwan's National Health Insurance Research Database, we identified patients with sepsis who survived hospitalization between 2000 and 2010. Each sepsis survivor was propensity score–matched to one nonsepsis hospitalized control patient. Cox regression models were used to estimate the hazard ratios (
HR
s) of clinical outcomes, including major adverse cardiovascular events (myocardial infarction and ischemic stroke), hospitalization for heart failure, and all‐cause death. Among 66 961 sepsis survivors, the incidence rates of all‐cause mortality and major adverse cardiovascular events during the study period were 288.51 and 47.05 per 1000 person‐years, respectively. In comparison with matched hospitalized nonsepsis control patients, sepsis survivors had greater risks of major adverse cardiovascular events (
HR
, 1.42; 95%
CI
, 1.37–1.47), myocardial infarction (
HR
, 1.39; 95%
CI
, 1.32–1.47), ischemic stroke (
HR
, 1.46; 95%
CI
, 1.40–1.52), hospitalization for heart failure (
HR
, 1.55; 95%
CI
, 1.51–1.59), and all‐cause mortality (
HR
, 1.56; 95%
CI
, 1.54–1.58). The results remained unchanged in analyses of several subgroups of patients, and were similar in analyses accounting for the competing risk of death.

Conclusions
Our findings highlight the association of sepsis with a significantly increased long‐term risk of cardiovascular events among survivors in the chronic kidney disease population.
Role of Genetic Variation in Collateral Circulation in the Evolution of Acute Stroke
Authors: Kao Yu-Chieh Jill , Oyarzabal Esteban A. , Zhang Hua , Faber James E. , Shih Yen-Yu Ian 
Published: February 2017

Background and Purpose—

No studies have determined the effect of differences in pial collateral extent (number and diameter), independent of differences in environmental factors and unknown genetic factors, on severity of stroke. We examined ischemic tissue evolution during acute stroke, as measured by magnetic resonance imaging and histology, by comparing 2 congenic mouse strains with otherwise identical genetic backgrounds but with different alleles of the
Determinant of collateral extent-1
(
Dce1
) genetic locus. We also optimized magnetic resonance perfusion and diffusion–deficit thresholds by using histological measures of ischemic tissue.

Methods—

Perfusion, diffusion, and T
2
-weighted magnetic resonance imaging were performed on collateral-poor (congenic-Bc) and collateral-rich (congenic-B6) mice at 1, 5, and 24 hours after permanent middle cerebral artery occlusion. Magnetic resonance imaging–derived penumbra and ischemic core volumes were confirmed by histology in a subset of mice at 5 and 24 hours after permanent middle cerebral artery occlusion.

Results—

Although perfusion-deficit volumes were similar between strains 1 hour after permanent middle cerebral artery occlusion, diffusion-deficit volumes were 32% smaller in collateral-rich mice. At 5 hours, collateral-rich mice had markedly restored perfusion patterns showing reduced perfusion-deficit volumes, smaller infarct volumes, and smaller perfusion–diffusion mismatch volumes compared with the collateral-poor mice (
P
<0.05). At 24 hours, collateral-rich mice had 45% smaller T
2
-weighted lesion volumes (
P
<0.005) than collateral-poor mice, with no difference in perfusion–diffusion mismatch volumes because of penumbral death occurring 5 to 24 hours after permanent middle cerebral artery occlusion in collateral-poor mice.

Conclusions—
Variation in collateral extent significantly alters infarct volume expansion, transiently affects perfusion and diffusion magnetic resonance imaging signatures, and impacts salvage of ischemic penumbra after stroke onset.
Novel Pump Control Technology Accelerates Drug Delivery Onset in a Model of Pediatric Drug Infusion
Authors: Parker Michael J. , Lovich Mark A. , Tsao Amy C. , Deng Hao , Houle Timothy , Peterfreund Robert A. 
Published: February 2017

BACKGROUND:
Laboratory data suggest that newly initiated drug infusions reach steady-state delivery after a significant time lag. Depending on drug and carrier flow rates and the infusion system’s common volume, lag times may exceed 20 or more minutes, especially in the neonatal/pediatric critical care environment. This study tested the hypothesis that a computer-executed algorithm controlling infusion pumps in a coordinated fashion predictably hastens the achievement of the intended steady-state drug delivery in a model of neonatal/pediatric drug infusion.

METHODS:
We constructed an in vitro model of neonatal/pediatric drug infusions through a pediatric 4-Fr central venous catheter at total system flows of 2 mL/h or 12 mL/h, representing a clinically relevant infusion range. Methylene blue served as the model infused drug for quantitative analysis. A novel algorithm, based on Taylor Dispersion Theory of fluid flow through tubes and executed by a computer, generated flow patterns that controlled and coordinated drug and carrier delivery by syringe pumps. We measured the time to achieve the intended steady-state drug delivery by conventional initiation of the drug infusion (“turning on the drug pump”) and by algorithm-controlled infusion initiation.

RESULTS:
At 2 mL/h total system flow, application of the algorithm reduced the time to achieve half of the intended drug delivery rate (T50) from 17 minutes [17, 18] to 3 minutes [3, 3] (median, interquartile range). At 12 mL/h total system flow, application of the algorithm reduced T50 from 6 minutes [6, 7] to 3 minutes [3, 3] The bootstrapped median difference is −14 (95% confidence interval [CI], −16 to −12, adjusted P=.00192) for 2 mL/h flow and −3 (95% CI, −4 to −3, adjusted P=.02061) for 12 mL/h flow. Compared with conventional initiation, the additional fluid required by the algorithm-directed infusion was 0.43 and 1.03 mL for the low- and high-infusion rates, respectively.

CONCLUSIONS:
The output of infusion pumps can be predictably controlled and coordinated by a computer-executed algorithm in a model of neonatal/pediatric drug infusions. Application of an algorithm can reduce the time to achieve the intended rate of infused drug delivery with minimal incremental volume administration.
Decision Support for the Capacity Management of Bronchoscopy Devices: Optimizing the Cost-Efficient Mix of Reusable and Single-Use Devices Through Mathematical Modeling
Authors: Edenharter Günther M. , Gartner Daniel , Pförringer Dominik 
Published: February 2017

BACKGROUND:
Increasing costs of material resources challenge hospitals to stay profitable. Particularly in anesthesia departments and intensive care units, bronchoscopes are used for various indications. Inefficient management of single- and multiple-use systems can influence the hospitals’ material costs substantially. Using mathematical modeling, we developed a strategic decision support tool to determine the optimum mix of disposable and reusable bronchoscopy devices in the setting of an intensive care unit.

METHODS:
A mathematical model with the objective to minimize costs in relation to demand constraints for bronchoscopy devices was formulated. The stochastic model decides whether single-use, multi-use, or a strategically chosen mix of both device types should be used. A decision support tool was developed in which parameters for uncertain demand such as mean, standard deviation, and a reliability parameter can be inserted. Furthermore, reprocessing costs per procedure, procurement, and maintenance costs for devices can be parameterized.

RESULTS:
Our experiments show for which demand pattern and reliability measure, it is efficient to only use reusable or disposable devices and under which circumstances the combination of both device types is beneficial.

CONCLUSIONS:
To determine the optimum mix of single-use and reusable bronchoscopy devices effectively and efficiently, managers can enter their hospital-specific parameters such as demand and prices into the decision support tool.
The software can be downloaded at: https://github.com/drdanielgartner/bronchomix/.
Associations Between Impaired Cerebral Blood Flow Autoregulation, Cerebral Oxygenation, and Biomarkers of Brain Injury and Postoperative Cognitive Dysfunction in Elderly Patients After Major Noncardiac Surgery
Authors: Goettel Nicolai , Burkhart Christoph S. , Rossi Ariane , Cabella Brenno C.T. , Berres Manfred , Monsch Andreas U. , Czosnyka Marek , Steiner Luzius A. 
Published: February 2017

BACKGROUND:
Increasing evidence links postoperative cognitive dysfunction (POCD) to surgery and anesthesia. POCD is recognized as an important neuropsychological adverse outcome in surgical patients, particularly the elderly. This prospective cohort study aimed to investigate whether POCD is associated with impaired intraoperative cerebral autoregulation and oxygenation, and increased levels of biomarkers of brain injury.

METHODS:
Study subjects were patients ≥65 years of age scheduled for major noncardiac surgery. Cognitive function was assessed before and 1 week after surgery. POCD was diagnosed if a decline of >1 standard deviation of z-scores was present in ≥2 variables of the test battery. The incidence of POCD 1 week after surgery was modeled as a multivariable function of the index of autoregulation (MxA) and tissue oxygenation index (TOI), adjusting for baseline neuropsychological assessment battery (Consortium to Establish a Registry for Alzheimer’s Disease-Neuropsychological Assessment Battery [CERAD-NAB]) total score and the maximum C-reactive protein (CRP) concentration. The biomarkers of brain injury neuron-specific enolase and S100β protein, age, and level of education were included in secondary multivariable logistic regression analyses.

RESULTS:
Of the 82 patients who completed the study, 38 (46%) presented with POCD 1 week after surgery. In the multivariable regression analysis, higher intraoperative MxA (odds ratio [OR; 95% confidence interval (CI)], 1.39 [1.01–1.90] for an increase of 0.1 units, P = .08 after Bonferroni adjustment), signifying less effective autoregulation, was not associated with higher odds of POCD. The univariable logistic regression model for MxA yielded an association with POCD (OR [95% CI], 1.44 [1.06–1.95], P = .020). Tissue oxygenation index (1.12 [0.41–3.01] for an increase of 10%, P = 1.0 after Bonferroni adjustment) and baseline CERAD-NAB total score (0.80 [0.45–1.42] for an increase of 10 points, P = .45) did not affect the odds of POCD. POCD was associated with elevated CRP on postoperative day 2 (median [interquartile range]; 175 [81–294] vs 112 [62–142] mg/L, P = .033); however, the maximum CRP value (OR [95% CI], 1.35 [0.97–1.87] for a 2-fold increase, P = .07) had no distinct effect on POCD.

CONCLUSIONS:
Impairment of intraoperative cerebral blood flow autoregulation is not predictive of early POCD in elderly patients, although secondary analyses indicate that an association probably exists.