bluuebunny/crossref_metadata_2025 huggingface dataset:
Health Care Disparity and Pregnancy-Related Mortality in the United States, 2005–2014
Authors: Moaddab Amirhossein , Dildy Gary A. , Brown Haywood L. , Bateni Zhoobin H. , Belfort Michael A. , Sangi-Haghpeykar Haleh , Clark Steven L.
Published: March 2018

OBJECTIVE:

To quantitate the contribution of various demographic factors to the U.S. maternal mortality ratio.

METHODS:

This was a retrospective observational study. We analyzed data from the Centers for Disease Control and Prevention (CDC) National Center for Health Statistics database and the Detailed Mortality Underlying Cause of Death database (CDC WONDER) from 2005 to 2014 that contains mortality and population counts for all U.S. counties. Bivariate correlations between the maternal mortality ratio and all maternal demographic, lifestyle, health, and medical service utilization characteristics were calculated. We performed a maximum likelihood factor analysis with varimax rotation retaining variables that were significant (P<.05) in the univariate analysis to deal with multicollinearity among the existing variables.

RESULTS:

The United States has experienced an increase in maternal mortality ratio since 2005 with rates increasing from 15 per 100,00 live births in 2005 to 21–22 per 100,000 live births in 2013 and 2014. (P<.001) This increase in mortality was most pronounced in non-Hispanic black women, with ratios rising from 39 to 49 per 100,000 live births. A significant correlation between state mortality ranking and the percentage of non-Hispanic black women in the delivery population was demonstrated. Cesarean deliveries, unintended births, unmarried status, percentage of deliveries to non-Hispanic black women, and four or fewer prenatal visits were significantly (P<.05) associated with the increased maternal mortality ratio.

CONCLUSION:

The current U.S. maternal mortality ratio is heavily influenced by a higher rate of death among non-Hispanic black or unmarried patients with unplanned pregnancies. Racial disparities in health care availability and access or utilization by underserved populations are important issues faced by states seeking to decrease maternal mortality.
Prevalence of Depression Among Women of Reproductive Age in the United States
Authors: Guo Nan , Robakis Thalia , Miller Claire , Butwick Alexander
Published: March 2018

OBJECTIVE:

To describe the prevalence, use of antidepressants, and predictors of major and minor depression among nonpregnant women of childbearing age.

METHODS:

Using data from the National Health and Nutrition Examination Surveys 2007–2014, we performed a cross-sectional study of 3,705 nonpregnant women of childbearing age. The primary outcome is the prevalence of major depression, and secondary outcomes are the prevalence of minor depression, rates of antidepressant use, and predictors of major and minor depression. Major and minor depression were classified using the Patient Health Questionnaire 9. Univariate and multivariate associations between major depression and minor depression with potential predictors were estimated using multinomial logistic regression.

RESULTS:

The overall prevalences of major and minor depression were 4.8% (95% CI 4.0–5.7%) and 4.3% (95% CI 3.5–5.2%), respectively. The prevalences of antidepressant use among women with major depression and minor depression were 32.4% (95% CI 25.3–40.4%) and 20.0% (95% CI 12.9–29.7%), respectively. Factors most strongly associated with major depression were government insurance (adjusted relative risk [RR] ratio 2.49, 95% CI 1.56–3.96) and hypertension (adjusted RR 2.09, 95% CI 1.25–3.50); for minor depression, these were education less than high school (adjusted RR 4.34, 95% CI 2.09–9.01) or high school education (adjusted RR 2.92, 95% CI 1.35–6.31).

CONCLUSION:

Our analysis indicates that 1 in 20 nonpregnant women of childbearing age experience major depression. Antidepressants are used by one third of those with major depression and one fifth of those with minor depression.
Simultaneous Compared With Interval Medical Abortion Regimens Where Home Use Is Restricted
Authors: Lohr Patricia A. , Starling Jennifer E. , Scott James G. , Aiken Abigail R. A.
Published: March 2018

OBJECTIVE:

To evaluate outcomes with simultaneous administration of mifepristone and misoprostol for medical abortion at 63 days of gestation or less in the year after its implementation in a British clinic system.

METHODS:

We conducted a retrospective cohort study using deidentified data from the electronic booking and complications databases and medical records of women who underwent medical abortion at British Pregnancy Advisory Service. Our primary outcome was treatment success with simultaneous dosing compared with a regimen with a 24- to 48-hour interval between medications. We defined success as complete abortion without surgical evacuation and without continuing pregnancy. To assess relative regimen effectiveness while accounting for self-assignment to simultaneous or interval dosing, we modeled the probability of treatment success using logistic regression with propensity score adjustment for demographic and clinical characteristics. Secondary outcomes were reasons for abortion failure and clinically significant adverse events (hospital admission, blood transfusion, intravenous antibiotic administration).

RESULTS:

Of 28,901 women treated between May 2015 and April 2016, 85% chose simultaneous dosing. Overall success rates were high with both regimens but lower with simultaneous than with interval dosing (94.5% vs 97.1%, respectively, adjusted relative risk 0.973, 95% CI 0.967–0.979). For both regimens, success rates were lower at higher gestational ages, but the relative effectiveness of simultaneous dosing did not vary significantly with gestational age (P=.268). Surgical intervention rates for continuing pregnancy were lowest at 49 days of gestation or less (1.4% simultaneous vs 0.2% interval, P<.001) and highest at 57–63 days of gestation (5.0% and 2.2%, P<.001). The rate of clinically significant adverse events was 0.2% and did not differ by regimen (P=.972).

CONCLUSION:

Simultaneous administration of mifepristone and misoprostol is 97% as effective as a 24- to 48-hour interval at all gestational ages 63 days or less with no increase in the risk of clinically significant adverse events. Pragmatic use of simultaneous dosing is reasonable given the small difference in effectiveness.
Autoimmune Progesterone Dermatitis Mistaken for Stevens-Johnson Syndrome
Authors: Drayer Sara M. , Laufer Larry R. , Farrell Maureen E.
Published: March 2018

BACKGROUND:

Autoimmune progesterone dermatitis is an uncommon disease presenting with cyclical skin eruptions corresponding with the menstrual cycle luteal phase. Because symptoms are precipitated by rising progesterone levels, treatment relies on hormone suppression.

CASE:

A 22-year-old nulligravid woman presented with symptoms mistaken for Stevens-Johnson syndrome. A cyclic recurrence of symptoms occurred, and the diagnosis of autoimmune progesterone dermatitis was made by an intradermal progesterone challenge. After 48 months, her disease remained refractory to medical management, and definitive surgical treatment with bilateral oophorectomy was performed.

CONCLUSIONS:

Autoimmune progesterone dermatitis is a challenging diagnosis as a result of its rarity and variety of clinical presentations. Treatment centers on suppression of endogenous progesterone and avoidance of exogenous triggers. When these modalities fail, surgical management must be undertaken.
Gottesfeld–Hohler Memorial Foundation Zika Virus Think Tank Summary
Authors: Hobbins John C. , Platt Lawrence D. , Copel Joshua A. , Euser Anna G. , Afshar Yalda , Irani Roxanna A. , Levine Deborah , Sanz Cortes Magda , Abuhamad Alfred , Gaw Stephanie L. , Harris Karen , Herrera Mauricio , Lynch Lauren , Melo Adriana , Noguchi Lisa , Aguiar Renato , Sheffield Jeanne S. , Minton Katherine K.
Published: March 2018

At a think tank bringing together experts on fetal neuroimaging, obstetric infectious diseases, and public health, we discussed trends in all of these areas for Zika virus. There is a wide variety of imaging findings in affected fetuses, influenced by timing of infection and probably host factors. The resources for diagnosis and interventions also vary by location with the hardest hit areas often having the fewest resources. We identified potential areas for both research and clinical collaboration as the Zika virus epidemic continues to evolve.
A 15-Year Study of Trends in Authorship by Gender in Two U.S. Obstetrics and Gynecology Journals
Authors: Metheny William P. , Jagadish Mayuri , Heidel R. Eric
Published: March 2018

OBJECTIVE:

To assess whether there was a significant trend in the number of women as first, last, and coauthors in two U.S. journals of obstetrics and gynecology over the past 15 years and to assess whether this publication rate was commensurate with the percentage of women in the academic specialty.

METHODS:

This retrospective study identified the gender of first and last authors of original research articles for the years 2000, 2005, 2010, and 2015. We determined trends in publication rates of authorship and coauthorship by pairing the gender of the first and last authors. We selected a subset of the data to compare the percentages of women authors with MDs at U.S. academic institutions with the nationally reported percentages of women faculty in the specialty.

RESULTS:

The journals yielded 2,699 articles for analysis. The percentage of articles written by women as first authors increased from 37% in 2000 to 71% in 2015 and, as last authors, increased from 26% in 2000 to 49% in 2015. Paired as coauthors, women published at a rate of 11% in 2000 to 38% in 2015. The analysis of a subset of 1,621 articles showed that as first authors, women published at a rate equal to or above the percentage of women in academics, but as last authors published fewer articles than expected.

CONCLUSION:

Women published more articles over time, kept pace or exceeded their faculty percentages as first authors, lagged behind these percentages as last authors, and as coauthors eventually surpassed the publication rate of male coauthors.
What Is New in Health Disparities?
Authors: Resnik Jamie L.
Published: March 2018

This month we focus on current research in health disparities. Dr. Resnik discusses six recent publications, which are concluded with a “bottom line” that is a take-home message. A complete reference for each can be found in Box 1 on this page along with direct links to abstracts.
Lack of Consensus in Physician Recommendations Regarding Return to Driving After Cervical Spine Surgery
Authors: Moses Michael J. , Tishelman Jared C. , Hasan Saqib , Zhou Peter L. , Zevgaras Ioanna , Smith Justin S. , Buckland Aaron J. , Kim Yong , Razi Afshin , Protopsaltis Themistocles S.
Published: March 2018

Study Design.

A cross-sectional study.

Objective.

The goal of this study is to investigate how surgeons differ in collar and narcotic use, as well as return to driving recommendations following cervical spine surgeries and the associated medico-legal ramifications of these conditions.

Summary of Background Data.

Restoration of quality of life is one of the main goals of cervical spine surgery. Patients frequently inquire when they may safely resume driving after cervical spine surgery. There is no consensus regarding postoperative driving restrictions. This study addresses how surgeons differ in their recommendations concerning cervical immobilization, narcotic analgesia, and suggested timeline of return to driving following cervical spine surgery.

Methods.

Surgeons at the Cervical Spine Research Society annual meeting completed anonymous surveys assessing postoperative patient management following fusion and nonfusion cervical spine surgeries.

Results.

Seventy percent of surgeons returned completed surveys (n = 71). About 80.3% were orthopedic surgeons and 94.2% completed a spine fellowship. Experienced surgeons (>15 years in practice) were more likely to let patients return to driving within 2 weeks than less experienced surgeons (47.1% vs. 24.3%, P = 0.013) for multilevel anterior discectomy and fusion (ACDF) and laminectomy with fusion procedures. There were no differences between surgeons practicing inside and outside the USA for prescribing collars or return to driving time. Cervical collars were used more for fusions than nonfusions (57.7% vs. 31.0%, P = 0.001). Surgeons reported 75.3% of patients ask when they may resume driving. For cervical fusions, 31.4% of surgeons allowed their patients to resume driving while restricting them with collars for longer durations. Furthermore, 27.5% of surgeons allowed their patients to resume driving while taking narcotics postoperatively.

Conclusion.

This survey-based study highlights the lack of consensus regarding patient “fitness to drive” following cervical spine surgery. The importance of establishing evidence-based guidelines is critical, as recommendations for driving in the postoperative period may have significant medical, legal, and financial implications.

Level of Evidence: 5
Patient's Subjective Impression of Cervical Range of Motion
Authors: Langenfeld Anke , Bastiaenen Carolien , Sieben Judith , Humphreys B. Kim , Swanenburg Jaap
Published: March 2018

Study Design.

Mixed-method.

Objective.

To evaluate the association between objective and subjective cervical range of motion (ROM) among patients with neck pain, and to assess the awareness of impairments.

Summary of Background Data.

Cervical ROM is frequently used to evaluate neck pain, but it is also important to know what a patient expects from treatment, because this can profoundly affect treatment outcomes and patient satisfaction.

Methods.

We used a cervical ROM instrument, the Neck Disability Index (NDI), and a self-administered ROM questionnaire for the neck (S-ROM-Neck). Ten patients took part in semi-structured interviews. Correlations were analyzed using Spearman rank order correlations (rs). Differences between patient and assessor were evaluated by the Mann-Whitney U test. Qualitative data were analyzed by content analysis.

Results.

Thirty participants (mean age 43.80 years; 21 females) were included. The correlation (rs) for the S-ROM-Neck between patient and assessor was 0.679 [95% confidence interval (95% CI) 0.404–0.884; P = 0.000]. The correlation between the NDI and S-ROM-Neck was 0.178 (95% CI −0.233 to -0.533; P = 346) for the assessor and −0.116 (95% CI −0.475 to −0.219, P = 0.541) for the patient (U = 448, z = −0.030, P = 0.976). Qualitative analysis revealed that patients had general restrictions in daily life and with specific movements, but that they adjusted their behavior to avoid impairment.

Conclusion.

There was a significant correlation between patient and therapist ratings of cervical spine mobility. Although patients experience restriction while moving and are impaired in specific activities, they adjust their lifestyle to accommodate their limitations.

Level of Evidence: 4
Impact of Multilevel Facetectomy and Rod Curvature on Anatomical Spinal Reconstruction in Thoracic Adolescent Idiopathic Scoliosis
Authors: Sudo Hideki , Abe Yuichiro , Kokabu Terufumi , Kuroki Kei , Iwata Akira , Iwasaki Norimasa
Published: March 2018

Study Design.

A prospective, nonrandomized study.

Objective.

The aim of this study was to assess surgical outcomes of multilevel facetectomy and rod curvature with simultaneous double-rod rotation technique for anatomical spinal reconstruction in thoracic adolescent idiopathic scoliosis (AIS).

Summary of Background Data.

Although some surgical techniques maintain or restore thoracic kyphosis (TK), next-generation strategies for thoracic AIS should include corrections in three anatomical planes.

Methods.

The study included 39 consecutive patients with Lenke 1 or Lenke 2 thoracic AIS treated at our institution. After all-level facetectomy at instrumentation level, except for the lowest intervertebral segment, two rods were identically bent to guide postoperative anatomical TK without reference to the intraoperative coronal alignment of the AIS deformity. Outcome measures included patient demographics, radiographic measurements, and Scoliosis Research Society (SRS) questionnaire scores.

Results.

After 2 years of follow-up, the average main thoracic Cobb angle correction rate was 83.5%, and the final correction loss was 2.2°. The average preoperative TK (T5–T12) significantly increased from 13.2° to 24.6° (P < 0.001) at final follow-up. The percentage of patients with a T6–T8 location of the TK apex significantly increased from 51.3% preoperatively to 87.2% at final follow-up. The average preoperative vertebral rotation angle significantly decreased from 18.7° to 12.8° postoperatively (P < 0.001). The average preoperative total SRS questionnaire score significantly increased from 3.5 to 4.5 (P < 0.001) at final follow-up. There was no implant breakage and vascular and neurologic complications, with all patients demonstrating solid fusion at final follow-up.

Conclusion.

Multilevel facetectomy and rod curvature play an important role in anatomical spinal reconstruction in patients with thoracic AIS. From the spatiotemporal point of view, four-dimensional correction could be actively performed by rod curvature under multilevel facetectomy and is expected to obtain an anatomical thoracic spine postoperatively, indicating that an anatomically designed rod could be supplied as a pre-bent rod.

Level of Evidence: 3
Synchrotron Radiation Imaging Reveals the Role of Estrogen in Promoting Angiogenesis After Acute Spinal Cord Injury in Rats
Authors: Ni Shuangfei , Cao Yong , Jiang Liyuan , Luo Zixiang , Lu Hongbin , Hu Jianzhong , Wu Tianding
Published: March 2018

Study Design.

The efficacy of estrogen on vessel angiogenesis in acute spinal cord injury (SCI) in a rat model was evaluated by synchrotron radiation.

Objective.

Here, we investigate the change in injured spinal cord vessels and used the synchrotron radiation to investigate the effect of estrogen on vessel angiogenesis and functional recovery in a rat model of SCI.

Summary of Background Data.

The promotion of angiogenesis after SCI may be a therapeutic target in the treatment of SCI. Estrogen has been reported to improve locomotor recovery after SCI. However, how estrogen regulates angiogenesis in acute SCI and enhances neurological functional recovery has not been fully characterized.

Methods.

Synchrotron radiation imaging combined with histological methods was used to image angiogenesis in acute spinal cord treatment with estrogen in rats.

Results.

Synchrotron radiation imaging vividly demonstrated three-dimensional vessel changes in the spinal cord after injury. The imaging showed that vessel number, vessel volume fraction, and vessel connectivity value in the groups treated with estrogen after SCI were significantly increased compared to control groups (P < 0.05). Vessel angiogenesis increased in groups treated with estrogen compared with control rats, which was confirmed with histological staining. Estrogen treatment also attenuated the injury-induced lesion area compared with control groups and improved locomotor functional recovery after SCI.

Conclusion.

The results indicated that synchrotron radiation is a powerful imaging tool for visualizing angiogenesis after acute SCI. Estrogen treatment exerted a neuroprotective effect on acute SCI treatment by promoting angiogenesis and reducing the injury-induced lesion area could be recommended as a potential preclinical treatment approach for acute SCI.

Level of Evidence: N/A
Selective Anterior Lumbar Interbody Fusion for Low Back Pain Associated With Degenerative Disc Disease Versus Nonsurgical Management
Authors: Kleimeyer John P. , Cheng Ivan , Alamin Todd F. , Hu Serena S. , Cha Thomas , Yanamadala Vijay , Wood Kirkham B.
Published: March 2018

Study Design.

This is a retrospective cohort study.

Objective.

To evaluate the long-term outcomes of selective one- to two-level anterior lumbar interbody fusions (ALIFs) in the lower lumbar spine versus continued nonsurgical management.

Summary of Background Data.

Low back pain associated with lumbar intervertebral disc degeneration is common with substantial economic impact, yet treatment remains controversial. Surgical fusion has previously provided mixed results with limited durable improvement of pain and function.

Methods.

Seventy-five patients with one or two levels of symptomatic Pfirrmann grades 3 to 5 disc degeneration from L3-S1 were identified. All patients had failed at least 6 months of nonsurgical treatment. Forty-two patients underwent one- or two-level ALIFs; 33 continued multimodal nonsurgical care. Patients were evaluated radiographically and the visual analog pain scale (VAS), Oswestry Disability Index (ODI), EuroQol five dimensions (EQ-5D), and Patient-Reported Outcomes Measurement Information System scores for pain interference, pain intensity, and anxiety. As-treated analysis was performed to evaluate outcomes at a mean follow-up of 7.4 years (range: 2.5–12).

Results.

There were no differences in pretreatment demographics or nonsurgical therapy utilization between study arms. At final follow-up, the surgical arm demonstrated lower VAS, ODI, EQ-5D, and Patient-Reported Outcomes Measurement Information System pain intensity scores versus the nonsurgical arm. VAS and ODI scores improved 52.3% and 51.1% in the surgical arm, respectively, versus 15.8% and −0.8% in the nonsurgical arm. Single-level fusions demonstrated improved outcomes versus two-level fusions. The pseudarthrosis rate was 6.5%, with one patient undergoing reoperation. Asymptomatic adjacent segment degeneration was identified in 11.9% of patients.

Conclusion.

Selective ALIF limited to one or two levels in the lower lumbar spine provided improved pain and function when compared with continued nonsurgical care. ALIF may be a safe and effective treatment for low back pain associated with disc degeneration in select patients who fail nonsurgical management.

Level of Evidence: 3
NRS20: Combined Back and Leg Pain Score
Authors: Cawley Derek T. , Larrieu Daniel , Fujishiro Takashi , Kieser David , Boissiere Louis , Acaroglu Emre , Alanay Ahmet , Kleinstück Frank , Pellisé Ferran , Pérez-Grueso Francisco Sánchez , Vital Jean-Marc , Gille Olivier , Obeid Ibrahim
Published: March 2018

Study Design.

Multicenter, prospective study of consecutive adult spinal deformity (ASD) patients.

Objective.

To evaluate back and leg pain as a combined score in ASD and compare their relative and cumulative correlations with health-related quality of life (HRQOL) and sagittal parameters.

Summary of Background Data.

Pain and disability are commonly reported in patients with ASD. This can affect their back, their legs or both. ASD-associated pain has been correlated with numerous HRQOL scores and radiological parameters.

Methods.

Preoperative pain intensity was assessed with a Numerical Rating Scale (NRS) for individual back and leg pain as well as a combined score, NRS20 (0–20, back plus leg pain).

This yielded a range of static measures in all patients with ASD with differing burdens of disease. Linear regression analysis was performed to calculate the correlation between pain and HRQOL scores (Scoliosis Research Society 22, 36-Item Short Form Health Survey Physical Component Summary, 36-Item Short Form Health Survey Mental Component Summary, Core Outcome Measures Index, and Oswestry Disability Index), and radiological spinopelvic parameters (sagittal and coronal planes).

Results.

A total of 1309 patients were included in this study. A combined score (NRS20) was better correlated with HRQOL (P < 0.01 for all) and sagittal parameters (P < 0.01 for all) than individual back or leg pain scores. Evaluation of the relative contributions of back and leg pain demonstrate a higher correlation with HRQOL scores for back pain and a higher correlation with sagittal parameters for leg pain. The distribution of NRS20 pain scores demonstrated three clear patterns of pain: back pain only, moderate back pain with varying mild-moderate leg pain, and severe equivalent back and leg pain. Similar values were noted for nonoperative and operative patients.

Conclusion.

The distribution and intensity of pain and its correlations with clinical and radiological parameters provide insight into the pathogenesis of ASD. A combined score has a simple yet valuable contribution to the assessment of symptoms in ASD.

Level of Evidence: 3
Does Regional Lung Strain Correlate With Regional Inflammation in Acute Respiratory Distress Syndrome During Nonprotective Ventilation? An Experimental Porcine Study*
Authors: Retamal Jaime , Hurtado Daniel , Villarroel Nicolás , Bruhn Alejandro , Bugedo Guillermo , Amato Marcelo Britto Passos , Costa Eduardo Leite Vieira , Hedenstierna Göran , Larsson Anders , Borges João Batista
Published: March 2018

Objective:

It is known that ventilator-induced lung injury causes increased pulmonary inflammation. It has been suggested that one of the underlying mechanisms may be strain. The aim of this study was to investigate whether lung regional strain correlates with regional inflammation in a porcine model of acute respiratory distress syndrome.

Design:

Retrospective analysis of CT images and positron emission tomography images using [18F]fluoro-2-deoxy-D-glucose.

Setting:

University animal research laboratory.

Subjects:

Seven piglets subjected to experimental acute respiratory distress syndrome and five ventilated controls.

Interventions:

Acute respiratory distress syndrome was induced by repeated lung lavages, followed by 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressures (mean, 4 cm H2O) and high inspiratory pressures (mean plateau pressure, 45 cm H2O). All animals were subsequently studied with CT scans acquired at end-expiration and end-inspiration, to obtain maps of volumetric strain (inspiratory volume – expiratory volume)/expiratory volume, and dynamic positron emission tomography imaging. Strain maps and positron emission tomography images were divided into 10 isogravitational horizontal regions-of-interest, from which spatial correlation was calculated for each animal.

Measurements and Main Results:

The acute respiratory distress syndrome model resulted in a decrease in respiratory system compliance (20.3 ± 3.4 to 14.0 ± 4.9 mL/cm H2O; p < 0.05) and oxygenation (Pao
2/Fio
2, 489 ± 80 to 92 ± 59; p < 0.05), whereas the control animals did not exhibit changes. In the acute respiratory distress syndrome group, strain maps showed a heterogeneous distribution with a greater concentration in the intermediate gravitational regions, which was similar to the distribution of [18F]fluoro-2-deoxy-D-glucose uptake observed in the positron emission tomography images, resulting in a positive spatial correlation between both variables (median R
2 = 0.71 [0.02–0.84]; p < 0.05 in five of seven animals), which was not observed in the control animals.

Conclusion:

In this porcine acute respiratory distress syndrome model, regional lung strain was spatially correlated with regional inflammation, supporting that strain is a relevant and prominent determinant of ventilator-induced lung injury.
Impact of Preadmission Opioid Treatment on 1-Year Mortality Following Nonsurgical Intensive Care*
Authors: Munch Troels , Christiansen Christian Fynbo , Pedersen Lars , Sørensen Henrik Toft
Published: March 2018

Objectives:

Compare all-cause mortality following nonsurgical ICU admission for opioid users with nonusers.

Design:

Nationwide register-based cohort study.

Setting:

All 43 ICUs in Denmark (7,028,668 citizens cumulatively during the study period). The Danish National Health Service provides universal healthcare, guaranteeing equal access to healthcare along with partial reimbursement for prescribed drugs.

Patients:

All 118,388 nonsurgical patients admitted to an ICU from 2005 to 2014.

Intervention:

Patients were categorized according to timing of last redeemed opioid prescription before admission: current user (prior 0–30 d), recent user (prior 31–365 d), former user (prior 365+ d), or nonuser (no prescription since 1994).

Measurements:

All-cause mortality 0–30 days and 31–365 days following ICU admission was calculated using the Kaplan-Meier method. Crude and adjusted hazard ratios with 95% CIs were computed using Cox regression, comparing users with nonusers. Adjusted models included age, gender, socioeconomic factors, comedications, and comorbidity.

Main Results:

Fifteen percent of the patients were current opioid users, 15% recent users, 30% former users, and 40% nonusers. Zero- to 30-day mortality was 35% for current users, 29% for recent users, 24% for former users, and 21% for nonusers. After confounder adjustment, current users remained at elevated risk during the first 30 days following ICU admission (hazard ratio, 1.20; 95% CI, 1.15–1.24). No association remained for recent or former users. A similar pattern was evident for 31–365-day all-cause mortality: 24% for current users, 19% for recent users, 13% for former users, and 10% for nonusers. During 31–365 days of follow-up, both current users and recent users remained at elevated risk of mortality after adjustment (hazard ratio, 1.47; 95% CI, 1.39–1.55 and hazard ratio, 1.20; 95% CI, 1.13–1.27, respectively).

Conclusions:

Current opioid users experience increased mortality during the first year following ICU admission.
Emerging Implications of Genetic Testing in Inherited Primary Arrhythmia Syndromes
Authors: Asatryan Babken , Medeiros-Domingo Argelia
Published: March 2018

Inherited primary arrhythmia syndromes are genetically determined disorders of cardiac ion channels or ion channel macromolecular complexes usually associated with a higher risk of sudden cardiac death. These conditions have a very broad spectrum of clinical manifestations, ranging from an asymptomatic course to syncope, atrial and ventricular arrhythmias, and conduction disturbances, but may produce sudden infant death syndrome and unexplained sudden cardiac death in apparently healthy individuals. During the last 20 years, the evolving knowledge on the genetic basis of inherited arrhythmia syndromes has dramatically reshaped our understanding of these conditions and, consequently, had a great impact on patient care. Based on the knowledge of the genetic substrates, specific risk factors for individual genotypes have been identified, and various investigations have been launched with the intention of developing a gene- and even mutation-specific therapy. Preliminary results from animal studies suggest that gene therapy rescues the normal ion channel function and thereby prevents cardiac events in some primary arrhythmia syndromes, which suggests that upon appropriate validation in a clinical setting, it may become available for affected patients. The purpose of this review is to provide clinicians with a contemporary insight into the role of genetic testing in the diagnosis, therapy, and prognosis of patients with primary arrhythmia syndromes, and the clinical implications of screening family members who are at risk of sudden cardiac death.
Increased Postoperative Morbidity Associated With Prolonged Laparoscopic Colorectal Resections Is Not Increased by Resident Involvement
Authors: Kulaylat Audrey S. , Hollenbeak Christopher S. , Stewart David B.
Published: March 2018

BACKGROUND:

Although longer operative times are associated with increased postoperative morbidity, the influence of surgical residents on this association is unclear.

OBJECTIVE:

The purpose of this study was to evaluate whether morbidity associated with operative times in laparoscopic colorectal surgery is increased by resident training.

DESIGN:

This was a retrospective cohort study.

SETTINGS:

The study was conducted using a national database.

PATIENTS:

Laparoscopic ileocolectomies, partial colectomies, and low anterior resections were identified in the National Surgical Quality Improvement Project (2005–2012). This cohort was stratified by the presence of resident involvement (postgraduate clinical year ≤5) and then divided into tertiles of operative time (low, medium, and high), allowing comparisons of cases by duration with resident involvement with cases of similar length without resident involvement.

MAIN OUTCOME MEASURES:

Postoperative morbidity (infectious and noninfectious), length of hospital stay, and unplanned reoperations were the primary study outcomes.

RESULTS:

A total of 20,785 procedures were identified. In aggregate, prolonged operative time was associated with both infectious (OR = 1.49, p < 0.001 with residents; OR = 1.38, p < 0.001 without residents) and noninfectious complications (OR = 1.51, p < 0.001 with residents; OR = 1.48, p < 0.001 without residents) when compared with short cases without residents. Longer hospital stay was observed both within the highest (additional 1.2 days (p < 0.001) with residents; 1.1 days (p < 0.001) without residents) and middle (additional 0.4 days (p < 0.001) with residents; 0.4 days (p = 0.001) without residents) tertiles of operative time. Within the highest tertile of operative length, there was no statistically significant difference in complication rates between cases with and without resident participation.

LIMITATIONS:

The study was limited by its retrospective design and inability to define the complexity of case and extent of resident involvement.

CONCLUSIONS:

Although longer operative times confer increased postoperative morbidity, there was no significant difference in complication rates within the highest tertile between cases with and without resident participation. Resident involvement does not appear to add to the risk of morbidity associated with longer and more complicated surgeries. See Video Abstract at http://links.lww.com/DCR/A440.
Recurrence of Rectal Prolapse After Surgical Repair in Women With Pelvic Organ Prolapse
Authors: Catanzarite Tatiana , Klaristenfeld Daniel D. , Tomassi Marco J. , Zazueta-Damian Gisselle , Alperin Marianna
Published: March 2018

BACKGROUND:

Pelvic organ prolapse is prevalent among women with rectal prolapse.

OBJECTIVE:

This study aimed to determine whether clinically significant pelvic organ prolapse impacts rectal prolapse recurrence after surgical repair.

DESIGN:

A retrospective cohort.

SETTING:

This study was performed at a single managed-care institution.

PATIENTS:

Consecutive women undergoing rectal prolapse repair between 2008 and 2016 were included.

INTERVENTIONS:

There were no interventions.

MAIN OUTCOME MEASURES:

Full-thickness rectal prolapse recurrence was compared between 4 groups: abdominal repair without pelvic organ prolapse (AR−POP); abdominal repair with pelvic organ prolapse (AR+POP); perineal repair without pelvic organ prolapse PR−POP; and perineal repair with pelvic organ prolapse (PR+POP). Recurrence-free period and hazard of recurrence were compared using Kaplan-Meier and Cox proportional hazards methods. To identify potential confounding risk factors for rectal prolapse recurrence, the characteristics of subjects with/without recurrence were compared with univariable and multivariable analyses.

RESULTS:

Overall, pelvic organ prolapse was present in 33% of 112 women and was more prevalent among subjects with rectal prolapse recurrence (52.4% vs 28.6%, p = 0.04). Median follow-up was 42.5 months; rectal prolapse recurrence occurred in 18.8% at a median of 9 months. The rate of recurrence and the recurrence-free period differed significantly between groups: AR−POP 3.8%, 95.7 months; AR+POP 13.0%, 86.9 months; PR−POP 34.8%, 42.1 months; PR+POP 57.1%, 23.7 months (p < 0.001). Compared with AR−POP the HR (95% CI) of rectal prolapse recurrence was 3.1 (0.5–18.5) for AR+POP; 14.7 (3.0–72.9) for PR−POP and 31.1 (6.2–154.5) for PR+POP. Compared with AR+POP, PR+POP had a shorter recurrence-free period (p < 0.001) and a higher hazard of recurrence (HR, 10.2; 95% CI, 2.1–49.3).

LIMITATIONS:

The retrospective design was a limitation of this study.

CONCLUSIONS:

Pelvic organ prolapse was associated with a higher rectal prolapse recurrence rate and earlier recurrence in women undergoing perineal, but not abdominal, repairs. Multidisciplinary evaluation can facilitate individualized management of women with rectal prolapse. Abdominal repair should be considered in women with concomitant rectal and pelvic organ prolapse. See Video Abstract at http://links.lww.com/DCR/A513.
Closing Perianal Fistulas Using a Laser: Long-Term Results in 103 Patients
Authors: Terzi Mustafa Cem , Agalar Cihan , Habip Sari , Canda Aras Emre , Arslan Naciye Cigdem , Obuz Funda
Published: March 2018

BACKGROUND:

Primary closure of the fistula tract using energy emitted by a radial fiber connected to a diode laser is a novel procedure for treating perianal fistulas.

OBJECTIVE:

The aim of this study was to determine the long-term effectiveness of this new technique.

DESIGN:

The surgical objective was to seal the fistula tract using laser energy.

SETTINGS:

The study was conducted at a single day-case surgery center.

PATIENTS:

Between April 2012 and June 2016, 103 consecutive patients with primary or recurrent perianal fistula underwent a laser closure procedure using a 12-watt laser emitting at a wavelength of 1470 nm.

MAIN OUTCOME MEASURES:

Patients were classified according to the Park classification, and healing was evaluated based on the perianal fistula disease severity score.

RESULTS:

Among the 103 patients treated using the laser closure procedure, 82 (80%) were men and 21 (20%) were women. The median age of the patients was 43 years (range, 18–78 y). Fifty-three patients (52%) had previous perianal fistula repair surgery. Based on the Park classification, 56 patients (54%) had intersphincteric fistula, 29 (28%) had transsphincteric fistula, 11 (11%) had suprasphincteric or extrasphincteric fistula, and 7 (7%) had superficial perianal fistula. Based on the perianal disease severity score, 41 patients (40%) obtained overall complete healing, 38 (37%) had persistent symptomatic drainage, 20 (19%) had slight drainage with minimal symptoms, and 4 (4%) had painful symptomatic drainage.

LIMITATIONS:

This was a retrospective analysis of noncomparative data with a lack of formal prospective continence assessment.

CONCLUSIONS:

Closure of perianal fistulas using a laser should be considered as a treatment option but with modest expectations. Although our complete healing rate was not as high as in earlier studies, this technique is a reasonable option with nearly no risk of sphincter damage when treating perianal fistulas. See Video Abstract at http://links.lww.com/DCR/A545.
Relationship of Anticoagulant Therapy With Cognitive Impairment Among Patients With Atrial Fibrillation: A Meta‐Analysis and Systematic Review
Authors: Cheng Wenke , Liu Weijun , Li Bin , Li Dongfang
Published: March 2018

Background:

At present, it is considered that atrial fibrillation (AF) is a risk factor for cognitive impairment and dementia. It is independent of stroke, but the relationship between anticoagulant drugs and cognitive function in patients with AF is unknown.

Objective:

The purpose of this study was to complete a meta-analysis of studies and investigate the association between anticoagulant therapy and cognitive impairment in patients with AF.

Methods and Results:

Two investigators systematically searched the Cochrane Library, PubMed, EMBASE databases, and Web of Science for all studies that present associations. Hazard ratios (HRs) were extracted and pooled. Finally, the 8 studies included 471,057 participants; time in therapeutic range (TTR) <25% versus TTR >75%; (HR 3.02, 95% CI 1.12–8.91; P = 0.03); TTR 25%–50% versus TTR >75% (HR 2.44, 95% CI 0.95–6.22; P = 0.06); TTR 50%–75% versus TTR >75% (HR 1.75, 95% CI 0.90–3.99; P = 0.1); oral anticoagulants (OAC) versus No OAC (HR 0.71, 95% CI 69–0.74; P < 0.00001); and new oral anticoagulants versus warfarin (HR 0.51, 95% CI 0.37–0.71; P < 0.00001).

Conclusions:

OACs significantly reduce the occurrence of cognitive impairment in patients with AF. Compared with warfarin, new oral anticoagulants have an efficiently protective effect on cognition. In the range of INR 2–3, with the increase of TTR, the incidence of cognitive impairment is lower.
Quantification of Idelalisib in Human Plasma by Ultra-Performance Liquid Chromatography Coupled to Mass Spectrometry in Negative Ionization Mode
Authors: Huynh Huu H. , Roessle Clara , Sauvageon Hélène , Plé Alain , Madelaine Isabelle , Thieblemont Catherine , Mourah Samia , Goldwirt Lauriane
Published: March 2018

Background:

Idelalisib is the first orally active selective phosphatidylinositol 3-kinase delta inhibitor approved by Food and Drug Administration and European Medicines Agency in 2014 for the treatment of several types of blood cancer. Idelalisib is widely used as a monotherapy or in combination with rituximab, bendamustine, or ofatumumab with a significant efficacy. However, idelalisib has shown increased risk of infection and a higher frequency of serious adverse events. It may be useful to determine idelalisib concentration in human plasma to adjust dose and to manage adverse effects in clinical practice.

Methods:

After a single-step protein precipitation of plasma samples, the chromatographic separation was performed using an ultra-high performance liquid chromatography system coupled with mass tandem spectrometry in a negative ionization mode using isotope-labeled internal standard. This method was validated by studies of its linearity, accuracy, imprecision, limit of quantification, recovery, matrix effect, selectivity, and stability.

Results:

The quantification method was linear from 10 to 2500 ng/mL with a 5 ng/mL lower limit of quantification that encompasses the clinical range of drug concentration. The intraday and interday imprecisions were below 8.1% and 11.4%, respectively. The recoveries and matrix effect of idelalisib were 85.6% ± 1.2% and 95.7% ± 3.0%, respectively, which are consistent, precise, and reproducible (coefficient of variation % < 15%). Peak plasma concentration and trough plasma concentration ranges of idelalisib reached 1591–1937 ng/mL and 256.3–303.3 ng/mL, respectively, in 3 follicular lymphoma patients treated with idelalisib 150 mg twice a day.

Conclusions:

A robust and sensitive liquid chromatography–tandem mass spectrometry method was developed and validated to quantify idelalisib concentration in human plasma. This method was effectively applied to 3 follicular lymphoma patients.
Potential of Oral Fluid as a Clinical Specimen for Compliance Monitoring of Psychopharmacotherapy
Authors: Neumann Jasna , Beck Olof , Dahmen Norbert , Böttcher Michael
Published: March 2018

Background:

Oral fluid (OF) is being developed as a specimen for the determination of drug intake as an alternative to serum and plasma. It is generally considered as an attractive specimen due to the noninvasive nature of the sampling procedure and the relation to the free fraction of drug in the blood. These features are of particular value in drug treatment of psychiatric disorders. To establish OF for the purpose of monitoring drug therapy, the relationship between concentrations in OF and serum/plasma must be documented. This study explored one promising sampling device and comprised the following 10 drugs: aripiprazole, citalopram, duloxetine, escitalopram, mirtazapine, pipamperone, pregabalin, promethazine, quetiapine, and venlafaxine.

Methods:

For this purpose, 100 paired serum and OF samples were collected from patients undergoing pharmacotherapy and analyzed using a liquid chromatography–tandem mass spectrometry method. A commercial method from Chromsystems for the determination of these drugs in plasma was used and was adapted for OF and ultrafiltrated (Centrifree device) serum.

Results:

The ratio of each individual pair of samples was used to calculate a mean and SD value between OF and serum free and total concentrations. The OF concentration ratios to serum total fraction differed markedly between substances and differed from 10-fold lower to 8-fold higher. The ratios to serum free fractions were always higher. The relation between the OF and serum concentrations was also evaluated by regression analysis and determination of slopes and correlation coefficients. For all measured relations, there was a statistically significant relation between the OF and serum concentrations. The degree of drug protein binding was in agreement with literature. The aripiprazole, duloxetine, pipamperone, pregabalin, and promethazine concentrations in ultrafiltrated serum were not possible to measure because of low concentrations and nonspecific binding.

Conclusions:

Despite a strong statistical correlation between OF and serum concentrations observed for most of the studied substances, it is still evident that OF concentrations cannot simply substitute serum/plasma as therapeutic drug monitoring specimen, but rather be considered as a unique specimen. We believe that OF is a promising matrix especially for compliance testing in psychiatry settings. The Greiner Bio-One device used in this study provides a sampling procedure that offers advantages over the available alternatives.
Explaining Interpatient Variability in Adalimumab Pharmacokinetics in Patients With Crohn's Disease
Authors: Berends Sophie E. , Strik Anne S. , Van Selm Juliet C. , Löwenberg Mark , Ponsioen Cyriel Y. , D'Haens Geert R. , Mathôt Ron A.
Published: March 2018

Background:

A significant proportion of patients with Crohn's disease (CD) require dose escalation or fail adalimumab (ADL) therapy over time. ADL, a monoclonal antibody directed against tumor necrosis factor, is approved for treatment of CD. Understanding pharmacokinetics (PK) of ADL is essential to optimize individual dosing in daily practice. The aim of this study was to evaluate PK of ADL in patients with CD and to identify factors that influence PK of ADL.

Methods:

In a retrospective cohort study, the authors reviewed the charts of 96 patients with CD receiving ADL induction and maintenance treatment. This patient cohort was used for external validation of population pharmacokinetic models of ADL available from literature. In addition, a novel population PK model was developed using nonlinear mixed-effects modeling.

Results:

None of the literature models properly described the PK of ADL in our cohort. Therefore, a novel population pharmacokinetic model was developed. Clearance of ADL increased 4-fold in the presence of anti-ADL antibodies. Patients who received ADL every week had a 40% higher clearance compared with patients receiving ADL every other week.

Conclusions:

Clearance of ADL increased in the presence of anti-ADL antibodies and was associated with weekly ADL administrations. In clinical practice, the decision to intensify ADL treatment to weekly administrations is primarily based on disease activity. Increased disease activity may be the result of lower drug concentrations due to higher clearance. However, increased disease activity may also increase clearance due to increased target engagement. The causal relationship between these factors remains to be elucidated.