bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Analysis Supports an Early, Type 17 Cell-Associated Divergence of Blunt Trauma Survival and Mortality*
Authors: Abboud Andrew , Namas Rami A. , Ramadan Mostafa , Mi Qi , Almahmoud Khalid , Abdul-Malak Othman , Azhar Nabil , Zaaqoq Akram , Namas Rajaie , Barclay Derek A. , Yin Jinling , Sperry Jason , Peitzman Andrew , Zamora Ruben , Simmons Richard L. , Billiar Timothy R. , Vodovotz Yoram
Published: August 2016

Objective:

Blunt trauma patients may present with similar demographics and injury severity yet differ with regard to survival. We hypothesized that this divergence was due to different trajectories of systemic inflammation and utilized computational analyses to define these differences.

Design:

Retrospective clinical study and experimental study in mice.

Setting:

Level 1 trauma center and experimental laboratory.

Patients:

From a cohort of 493 victims of blunt trauma, we conducted a pairwise, retrospective, case-control study of patients who survived over 24 hours but ultimately died (nonsurvivors; n = 19) and patients who, after ICU admission, went on to be discharged(survivors; n = 19).

Interventions:

None in patients. Neutralizing anti-interleukin-17A antibody in mice.

Measurements and Main Results:

Data on systemic inflammatory mediators assessed within the first 24 hours and over 7 days were analyzed with computational modeling to infer dynamic networks of inflammation. Network density among inflammatory mediators in nonsurvivors increased in parallel with organ dysfunction scores over 7 days, suggesting the presence of early, self-sustaining, pathologic inflammation involving high-mobility group protein B1, interleukin-23, and the Th17 pathway. Survivors demonstrated a pattern commensurate with a self-resolving, predominantly lymphoid response, including higher levels of the reparative cytokine interleukin-22. Mice subjected to trauma/hemorrhage exhibited reduced organ damage when treated with anti-interleukin-17A.

Conclusions:

Variable type 17 immune responses are hallmarks of organ damage, survival, and mortality after blunt trauma and suggest a lymphoid cell–based switch from self-resolving to self-sustaining inflammation.
Association of Freestanding Children’s Hospitals With Outcomes in Children With Critical Illness*
Authors: Gupta Punkaj , Rettiganti Mallikarjuna , Fisher Paige L. , Chang Anthony C. , Rice Tom B. , Wetzel Randall C.
Published: August 2016

Objectives:

Little is known about the relationship between freestanding children’s hospitals and outcomes in children with critical illness. The purpose of this study was to evaluate the association of freestanding children’s hospitals with outcomes in children with critical illness.

Design:

Propensity score matching was performed to adjust for potential confounding variables between patients cared for in freestanding or nonfreestanding children’s hospitals. We tested the sensitivity of our findings by repeating the primary analyses using inverse probability of treatment weighting method and regression adjustment using the propensity score.

Setting:

Retrospective study from an existing national database, Virtual PICU Systems (LLC) database.

Patients:

Patients less than 18 years old admitted to one of the participating PICUs in the Virtual PICU Systems, LLC database were included (2009–2014).

Interventions:

None.

Measurements and Main Results:

A total of 538,967 patients from 140 centers were included. Of these, 323,319 patients were treated in 60 freestanding hospitals. In contrast, 215,648 patients were cared for in 80 nonfreestanding hospitals. By propensity matching, 134,656 patients were matched 1:1 in the two groups (67,328 in each group). Prior to matching, patients in the freestanding hospitals were younger, had greater comorbidities, had higher severity of illness scores, had higher incidence of cardiac arrest, had higher resource utilization, and had higher proportion of patients undergoing complex procedures such as cardiac surgery. Before matching, the outcomes including mortality were worse among the patients cared for in the freestanding hospitals (freestanding vs nonfreestanding, 2.5% vs 2.3%; p < 0.001). After matching, the majority of the study outcomes were better in freestanding hospitals (freestanding vs nonfreestanding, mortality: 2.1% vs 2.8%, p < 0.001; standardized mortality ratio: 0.77 [0.73–0.82] vs 0.99 [0.87–0.96], p < 0.001; reintubation: 3.4% vs 3.8%, p < 0.001; good neurologic outcome: 97.7% vs 97.1%, p = 0.001).

Conclusions:

In this large observational study, we demonstrated that ICU care provided in freestanding children’s hospitals is associated with improved risk-adjusted survival chances compared to nonfreestanding children’s hospitals. However, the clinical significance of this change in mortality should be interpreted with caution. It is also possible that the hospital structure may be a surrogate of other factors that may bias the results.
Academic Productivity of Accreditation Council for Graduate Medical Education–Accredited Critical Care Fellowship Program Directors*
Authors: Fahy Brenda G. , Vasilopoulos Terrie , White Peggy , Culley Deborah J.
Published: August 2016

Objectives:

Academic productivity is an expectation for program directors of Accreditation Council for Graduate Medical Education–accredited subspecialty programs in critical care medicine. Within the adult critical care Accreditation Council for Graduate Medical Education–accredited programs, we hypothesized that program director length of time from subspecialty critical care certification would correlate positively with academic productivity, and primary field would impact academic productivity.

Design:

This study received Institutional Review Board exemption from the University of Florida. Data were obtained from public websites on program directors from all institutions that had surgery, anesthesiology, and pulmonary Accreditation Council for Graduate Medical Education–accredited subspecialty critical care training programs during calendar year 2012. Information gathered included year of board certification and appointment to program director, academic rank, National Institutes of Health funding history, and PubMed citations.

Results:

Specialty area was significantly associated with total (all types of publications) (p = 0.0002), recent (p < 0.0001), last author (p = 0.008), and original research publications (p < 0.0001), even after accounting for academic rank, years certified, and as a program director. These differences were most prominent in full professors, with surgery full professors having more total, recent, last author, and original research publications than full professors in the other critical care specialties.

Conclusions:

This study demonstrates that one’s specialty area in critical care is an independent predictor of academic productivity, with surgery having the highest productivity. For some metrics, such as total and last author publications, surgery had more publications than both anesthesiology and pulmonary, whereas there was no difference between the latter groups. This suggests that observed differences in academic productivity vary by specialty.
An In Vitro Model That Predicts the Therapeutic Efficacy of Immunomodulatory Antibodies
Authors: Dai Min , Yip Yuen Yee , Hellstrom Ingegerd , Hellstrom Karl Erik
Published: August 2016

Immunomodulatory monoclonal antibodies (mAbs) have efficacy in patients with advanced cancer and are the focus of intensive research. However, cures are infrequent and responses vary among tumor types and among subjects with the same tumor. An in vitro test would be valuable to determine the most effective mAb combination for a given case and to evaluate novel agents. Toward this goal, we investigated the ability of various mAb combinations to generate a tumor-destructive immune response in vitro in the presence of lymphoid cells from mice with established TC1 lung carcinoma, B16 melanoma, or SW1 melanoma. The data strongly correlate (r=0.9, 0.89, and 0.91, respectively) with the therapeutic efficacy of the respective mAb combinations. Both in vivo and in vitro, tumor destruction was associated with a shift from a Th2 to a Th1 response and included a dramatic increase of long-term memory cells. A combination of mAbs to CD137/PD-1/CTLA4/CD19 was most efficacious.
Central antinociceptive effect of tapentadol is increased by nitric oxide synthase inhibitors
Authors: Bujalska-Zadrożny Magdalena , Wolińska Renata , Leśniak Anna , Sacharczuk Mariusz
Published: August 2016

Nitric oxide synthases (NOSs) have been shown to participate in the mechanism of the antinociceptive action of tapentadol. The results obtained in this study indicate that tapentadol administered intrathecally at a range of doses (30–100 µg) increased nociceptive thresholds in the Randall–Selitto and tail-flick tests in rats; however, this effect was significant only for the higher doses. After intracerebroventricular administration of tapentadol at the same dose range, an antinociceptive effect was observed only in response to mechanical stimuli. In coadministration studies, l-NG-nitro arginine (l-NOArg) – a nonselective NOS inhibitor as well as selective inhibitors: 7-Nitroindazole (7-NI), l-N6(1-iminoethyl)lysine (l-NIL) or N5-(1-iminoethyl)-l-ornithine (l-NIO) for the respective neuronal, inducible, and endothelial NOSs enhanced the antinociceptive activity of intrathecally administered tapentadol in the Randall–Selitto test and to a lesser extent in the tail-flick test. A similar, although less pronounced effect of intracerebroventricular tapentadol was also observed after previous administration of NOS inhibitors in the Randall–Selitto test, but not in the tail-flick test. In conclusion, neuronal NOS, inducible NOS, and endothelial NOS influence the antinociceptive action of tapentadol at the spinal level and to a much lesser extent at the supraspinal level.
Molsidomine Attenuates Ventricular Electrical Remodeling and Arrhythmogenesis in Rats With Chronic β-Adrenergic Receptor Activation Through the NO/cGMP/PKG Pathway
Authors: Shan Yingguang , Wang Dandan , Li Ran , Huang Congxin
Published: August 2016

This study investigated the effects and associated underlying mechanisms of molsidomine, a nitric oxide (NO) donor, on cardiac electrical remodeling and ventricular tachycardias (VTs) induced by chronic isoprenaline (ISO) stimulation in rats. The rats were randomly divided into groups that were treated with saline (control group), ISO (ISO group), ISO + molsidomine (ISO + M group), and ISO + molsidomine + the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, ISO + M + O group) for 14 days. An electrophysiological study was performed to assess cardiac repolarization, action potential duration restitution, and the induction of action potential duration alternans and VTs in vitro. The properties of the Ca2+ transients, Ca2+ handling–related proteins, and NO/guanosine 3′5′-cyclic monophosphate (cGMP)/protein kinase G (PKG) pathway were examined. Compared with the control group, chronic ISO stimulation prolonged the cardiac repolarization, decreased the Ca2+ transient alternans and action potential duration alternans thresholds, and increased the maximum slope (Smax) of the action potential duration restitution curve and incidence of VTs in vitro. All these effects were attenuated by molsidomine treatment (P < 0.05). Moreover, molsidomine activated cGMP/PKG signaling and stabilized the expression of calcium handling–related proteins compared with the ISO group. However, the protective effects of molsidomine were partially inhibited by ODQ. Our results suggest that molsidomine stabilizes calcium handling and attenuates cardiac electrical remodeling and arrhythmogenesis in rats with chronic β-adrenergic receptor activation. These effects are at least partially mediated by the activation of NO/cGMP/PKG pathway.
Calcium plus vitamin D supplementation and height loss: findings from the Women's Health Initiative Calcium and Vitamin D clinical trial
Authors: Crandall Carolyn J. , Aragaki Aaron K. , LeBoff Meryl S. , Li Wenjun , Wactawski-Wende Jean , Cauley Jane A. , Margolis Karen L. , Manson JoAnn E.
Published: August 2016

Objective:

The aim of this study was to determine the associations between calcium + vitamin D supplementation (vs placebo) and height loss in 36,282 participants of the Women's Health Initiative Calcium and Vitamin D trial.

Methods:

Post hoc analysis of data from a double-blind randomized controlled trial of 1,000 mg of elemental calcium as calcium carbonate with 400 IU of vitamin D3 daily (CaD) or placebo in postmenopausal women at 40 US clinical centers. Height was measured annually (mean follow-up 5.9 y) with a stadiometer.

Results:

Average height loss was 1.28 mm/y among participants assigned to CaD versus 1.26 mm/y for women assigned to placebo (P = 0.35). Effect modification of the CaD intervention was not observed by age, race/ethnicity, or baseline intake of calcium or vitamin D. Randomization to the CaD group did not reduce the risk of clinical height loss (loss of ≥1.5 inches [3.8 cm]: hazard ratio (95% CI) = 1.00 (0.81, 1.23). A strong association (P < 0.001) was observed between age group and height loss. When we censored follow-up data in participants who became nonadherent to study pills, the results were similar to those of our primary analysis.

Conclusions:

Compared with placebo, the CaD supplement used in this trial did not prevent height loss in healthy postmenopausal women.
Use of systemic hormone therapy in BRCA mutation carriers
Authors: Domchek Susan , Kaunitz Andrew M.
Published: August 2016

As more women are being counseled and tested, clinicians increasingly encounter women with identified BRCA1 and BRCA2 gene mutations. Existing, albeit limited, data indicate that risks of breast cancer are not increased with use of systemic hormone therapy by menopausal BRCA mutation carriers with intact breasts. Young mutation carriers with or without intact breasts should not defer or avoid risk-reducing (and lifesaving) bilateral salpingo-oophorectomy because of concerns that subsequent use of systemic hormone therapy will elevate breast cancer risk.
Use of Innovative Technologies in Pediatric Lower Extremity Reconstruction
Authors: Mountziaris Paschalia M. , Soteropulos Carol E. , Rezak Kristen M. , Patel Ashit
Published: August 2016

The anterolateral thigh (ALT) free flap has proven to be a reliable option for the coverage of soft tissue defects in adults and more recently in the pediatric population. When considering the use of the ALT flap in the pediatric patient, there are few studies that detail techniques specific to pediatric free flap management. We present a unique case of a 14- × 8-cm ALT flap used for traumatic wound coverage in a distal tibial injury in a 6-year-old girl. This case highlights innovative techniques in pediatric perioperative free flap monitoring and the use of continuous external tissue expansion to achieve delayed primary closure of the donor site.
The Safety, Effectiveness, and Efficiency of Autologous Fat Grafting in Breast Surgery
Authors: Spear Scott L. , Coles Courtney N. , Leung Braden K. , Gitlin Matthew , Parekh Mousam , Macarios David
Published: August 2016

Background:

For years, the safety and effectiveness of autologous fat grafting (AFG) for breast reconstruction have been in question, with particular concern over fat necrosis, calcifications, cyst formation, and interfering with the detection of breast cancer. However, increasing evidence suggests that the complication rates and clinical results are generally acceptable to both clinicians and patients. The emerging challenge is the numerous AFG techniques and systems, where there are limited knowledge and data. The objective of this study was to conduct a literature review that focuses on the safety, effectiveness, and efficiency of various AFG techniques as applied to the breast.

Methods:

A PubMed search using terms related to AFG was performed over a 5-year period (April 1, 2010–April 30, 2015). Original articles focused on AFG to the breast, with outcomes on safety, effectiveness, and efficiency, were included.

Results:

Five hundred ninety-eight articles were identified with 36 articles included (n = 4306 patients). Satisfaction rates were high although the prevalence of complications was low—similar to previous findings. Seven studies reported average operating room time with an overall mean of 125 minutes (range: 40–210). The mean volume of fat harvested was 558 mL (range: 120–1299), and fat injected was 145 mL (range: 20–607). A positive association between injection volume and operating time was observed.

Conclusions:

This review validates previous findings on the safety and effectiveness of AFG to the breast and highlights its efficiency. The efficiency data available, although limited, suggest that there is an opportunity to achieve time and cost savings while not sacrificing safety and effectiveness.
Effect of Chronic Kidney Disease and Supplemental Polyunsaturated Fatty Acid Use on Exercise Levels During Cardiac Rehabilitation in Patients With Coronary Artery Disease
Authors: Pflum Adam , Gomadam Pallavi , Mehta Hardik , Sacrinty Matthew , Paladenech Connie C. , Robinson Killian
Published: August 2016

PURPOSE:

The correlation between chronic kidney disease (CKD) and increased cardiovascular disease-related mortality is well established. Cardiac rehabilitation (CR) improves exercise capacity, quality of life, and risk factors in patients with coronary artery disease (CAD). Data on the benefits of CR in patients with CKD are sparse. The purpose of this study was to compare outcomes after CR in patients with CAD but normal renal function, versus those with CAD and CKD.

METHODS:

We studied 804 patients with CAD entering an exercise-based CR program. Demographics, risk factors, exercise capacity in metabolic equivalent levels (METs), and estimated glomerular filtration rate (GFR) were recorded before and after the 3-month CR program. Use of polyunsaturated fatty acid (PUFA) was determined by medical records review. Stage III-V CKD (GFR <60 mL/min/1.73 m2) was present in 170 patients at baseline.

RESULTS:

After CR, METs improved in all patients, although increases in patients with a GFR 30 to 59 mL/min/1.73 m2 (Δ1.6) and a GFR <30 (Δ1.2) were smaller than those in patients with a GFR ≥60 (Δ2.6, P < .05 vs GFR 30-59 and GFR <30). In patients with a GFR ≥60 mL/min/1.73 m2, PUFA use was associated with a 20% greater increase in MET levels compared with nonusers (Δ3.0 vs Δ2.5, P = .02); and in patients with a GFR 30 to 59, PUFA use was associated with 30% increase in MET level compared with nonusers (Δ2.0 vs Δ1.4, P = .03). These observations persisted after multivariable adjustment for baseline MET level, demographics, and risk factors.

CONCLUSIONS:

Potential mitigation by PUFA of the smaller improvement in exercise capacity with decreasing GFR requires confirmation in prospective randomized trials.
INTRAVITREAL RANIBIZUMAB AS AN ADJUNCTIVE TREATMENT FOR COATS DISEASE (6-YEAR FOLLOW-UP)
Authors: Giannakopoulos Marios , Drimtzias Evangelos , Panteli Vasiliki , Vasilakis Panagiotis , Gartaganis Sotirios P.
Published: August 2016

Purpose:

To evaluate the effectiveness of intravitreal ranibizumab in combination with laser photocoagulation in the management of Coats disease.

Method:

Six intravitreal injections of 0.5 mg (0.05 mL) ranibizumab were performed, each 4 weeks apart. Correspondence to therapy was evaluated using visual acuity measurements and optical coherence tomography images. Six months after the initiation of treatment, laser photocoagulation was applied on the telangiectasias and on the surrounding ischemic areas, followed by a single intravitreal ranibizumab injection. Three months later, laser photocoagulation was repeated in purpose to prevent recurrence.

Results:

In the sixth month, no improvement in visual acuity was recorded, as thick circinate hard exudates still remained in the submacular space. Nevertheless, retinal detachment had completely subsided, and fluorescein angiography showed a significant decrease of leakage from the telangiectatic vessels. At the 12-month follow-up visit, an impressive improvement was recorded, with total absorption of the submacular exudate and visual acuity being 20/30. At the 20-month follow-up visit, his visual acuity was 20/20 and the retina was flat with no signs of macular edema or exudates. At the 6-year follow-up visit, the patient was absolutely stable.

Discussion:

Elevated vascular endothelial growth factor levels have been demonstrated in Coats disease. Anti–vascular endothelial growth factor agents assist to the decrease of vascular permeability of the capillary endothelial cells, thus increasing the efficiency of laser application.
SUCCESSFUL TREATMENT OF REFRACTORY PROLIFERATIVE RETINOPATHY OF INCONTINENTIA PIGMENTI BY INTRAVITREAL RANIBIZUMAB AS ADJUNCT THERAPY IN A 4-YEAR-OLD CHILD
Authors: Ho Mary , Yip Wilson W. K. , Chan Vesta C. K. , Young Alvin L.
Published: August 2016

Purpose:

To describe a case of incontinentia pigmenti with proliferative retinopathy successfully treated by combination of repeated retinal laser photocoagulation and intravitreal ranibizumab injection.

Methods:

Single interventional case report of a 4-year-old girl, known case of incontientia pigmenti, first screened at the age of two, presented with proliferative retinopathy. Sole treatment by panretinal laser photocoagulation failed to control the progression of retinal neovascularization. Intravitreal ranibizumab injections were used as an adjunct therapy.

Results:

The proliferative retinopathy was brought under control and halted till this date with repeated intravitreal ranibizumab and panretinal photocoagulation. No systemic side effect was noted.

Conclusion:

Intravitreal ranibizumab can be considered as an adjunct therapy in proliferative retinopathy secondary to incontinentia pigmenti when monotherapy with panretinal photocoagulation fails. Intravitreal ranibizumab may quickly inhibit the intraocular vascular endothelial growth factor and may prevent devastating complications like tractional retinal detachment. Extra caution has to be taken in adopting different dosages and injection regimes especially in pediatric cases.
Additive Effect of Risk Factors for Trabeculectomy Failure in Glaucoma Patients: A Risk-group From a Cohort Study
Authors: Issa de Fendi Ligia , Cena de Oliveira Tiago , Bigheti Pereira Carolina , Pereira Bigheti Carina , Viani Gustavo A.
Published: August 2016

Purpose of the Study:

The purpose of the study was to assess the role of significant risk factors and develop a risk-group category related to the trabeculectomy (Trab) failure.

Materials and Methods:

A retrospective cohort study was developed between January 2009 and June 2014. In total, 120 eyes included in this study had a glaucoma diagnosis and undergone to Trab with mitomycin. The main outcome measures were surgical success and failure rate. Multivariate (Cox proportional hazards regression model) analyses were used to examine the predictive value of significant factors. A risk-group category was build based on the number of significant risk factors for patients. The risk group category was tested using the Kaplan-Meier method and log-rank test.

Results:

With a median follow-up of 33 months (3 to 72 mo), the complete surgical success in 1, 2, 3, and 4 years was 82%, 63.5%, 52%, and 27.6%, respectively. The probability of freedom from a complete surgical failure was 88%, 84.5%, 78%, and 70% in 1, 2, 3, and 4 years, respectively. Glaucoma type (P=0.008), previous ophthalmic surgery (P=0.04), glaucoma medication use ≥3 years (P=0.010) and 4 glaucoma medication use pre-Trab (P=0.038) were identified as risk factors for surgical failure. The probability of freedom of surgical failure in 3 years was 93%, 83%, and 37.6% (P=0.003), for low (no factors), intermediate (1 to 2 factors), and high-risk group (3 to 4 factors).

Conclusions:

Trab with mitomycin produces satisfactory intraocular pressure control over time. However, several risk factors influence the efficacy of the surgical procedure. Our data show that there seems to exist an additive effect among risk factors with similar pathophysiology.
Achromobacter Bacteremia in Patients With Cancer
Authors: Stutzman Tyler , Sánchez-Vargas Flor Maria , Nanjappa Sowmya , Velez Ana Paula , Greene John N.
Published: August 2016

Background

Achromobacter species are Gram-negative waterborne bacteria that occasionally cause bacteremia primarily in immunocompromised hosts. Cancer patients have increased risk due to their use of intravascular catheters and immunosuppression from neoplasm, chemotherapy, and prolonged steroids. In this study, we investigated the clinical characteristics of cancer patients with Achromobacter bacteremia and identified risk factors, outcomes, and susceptibility patterns in this selective population.

Methods

We retrospectively reviewed all cases of Achromobacter bacteremia occurring from March 2010 to March 2015 at Moffitt Cancer Center. Data collected included age, sex, comorbidities, underlying malignancy, neutropenia status, prior bacteremia, treatment course, and patterns of susceptibilities of the isolates. We also reviewed outcomes such as discharge disposition and death.

Results

Eleven patients were identified with positive blood cultures for Achromobacter species. Central venous catheters were infected in 9 patients (82%), and 2 patients had recurrent bacteremia, which resolved after removal of the catheter. Eight (73%) patients had a history of prior bacteremia. Patients were treated with meropenem (n = 4), piperacillin/tazobactam (n = 3), cefepime, ceftazidime, and trimethoprim-sulfamethoxazole (TMP-SMX). The isolates were susceptible to meropenem (8 of 8 isolates), piperacillin/tazobactam (10 of 10), ceftazidime (7 of 7), and TMP-SMX (8 of 8). Most of isolates were resistant to aminoglycosides and fluoroquinolones.

Conclusions

The major predisposing factors for Achromobacter bacteremia were infected intravascular catheters and prior history of bacteremia. Infections can be treated with piperacillin/tazobactam, a carbapenem, or TMP-SMX. Compared with other studies, we observed similar risk factors and morbidity but with a higher rate of intravascular catheter infections.
Antidepressant Medication Treatment and Risk of Death
Authors: Zivin Kara , Kim H. Myra , Yosef Matheos , Maust Donovan T. , Valenstein Marcia , Smith Eric G. , Davydow Dimitry S.
Published: August 2016

Objective

Although previous studies have assessed whether depression is a mortality risk factor, few have examined whether antidepressant medications (ADMs) influence mortality risk.

Methods

We estimated hazards of 1-year all-cause mortality associated with ADMs, with use occurring within 90 days of depression diagnosis among 720 821 patients who received treatment in a Veterans Health Administration facility during fiscal year 2006. We addressed treatment selection biases using conventional Cox regression, propensity-stratified Cox regression (propensity score), and 2 forms of marginal structural models. Models accounted for multiple potential clinical and demographic confounders, and sensitivity analyses compared findings by antidepressant class.

Results

Antidepressant medication use compared with no use was associated with significantly lower hazards of 1-year mortality risk in Cox (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.90–0.97) and propensity score estimates (HR, 0.94; 95% CI, 0.91–0.98), whereas marginal structural model–based estimates showed no difference in mortality risk when the exposure was specified as “as-treated” in every 90-day intervals of the 1-year follow-up (HR, 0.91; 95% CI, 0.66–1.26) but showed increased risk when specified as “intent-to-treat” (HR, 1.07; 95% CI, 1.02–1.13).

Conclusions

Among patients treated with ADMs belonging to a single class in the first 90 days, there were no significant differences in 1-year all-cause mortality risks. When accounting for clinical and demographic characteristics and treatment selection bias, ADM use was associated with no excess harm.
Comparison of Subjective Experiences and Effectiveness of First-Generation Long-Acting Injectable Antipsychotics and Risperidone Long-Acting Injectables in Patients With Schizophrenia
Authors: Chen Wen-Yin , Lin Shih-Ku
Published: August 2016

We conducted a cross-sectional study to compare the subjective experiences and clinical effects of first-generation long-acting injectable (FGA-LAI) antipsychotics with those of risperidone long-acting injectables (RIS-LAIs) in 434 schizophrenia patients. Compared with the RIS-LAI group, the patients treated with FGA-LAIs had a significantly longer duration of illness and LAI treatment and were older. Our results suggest that patients treated with FGA-LAI have more satisfactory subjective experiences compared with patients treated with RIS-LAI and that both FGA-LAI and RIS-LAI treatments can prevent relapses and hospitalization. Additional longitudinal studies determining the long-term benefits of RIS-LAI are warranted.
Sore on the Neck
Authors: Jacob Sharon E. , Love Justin
Published: August 2016

Teledermatology is a term to describe the provision of dermatologic medical services through telecommunication technology. In this modality, there is transfer of medical information electronically (including history and visual data) on a patient in one location to a provider who is in another location. The construct of this column is such that cases are presented in a standardized teledermatology reader format. This is a case of a sore on the neck.
Topical Metronidazole in the Management of Rosacea
Authors: Hill Hannah E. , Pham Quy , Jacob Sharon E.
Published: August 2016

By definition, a drug is a medicine or substance that exerts a physiologic effect on an organism. In dermatology, medications and substances are utilized on a daily basis from topical treatments to anesthetics in micrographic surgery. The purpose of this section is to focus on some of the more common substances, specifically how they work, how they are utilized, and routine alternatives (if available). This article gives an overview of rosacea and discusses the role of topical metronidazole in the management of rosacea as well as details the mechanism of action, adverse effects, and alternative treatments.
Humor: Power Conveying Social Structures Inside Forensic Mental Health Nursing
Authors: Gildberg Frederik A. , Paaske Kristian J. , Rasmussen Vivian L. , Nissen Ricko D. , Bradley Stephen K. , Hounsgaard Lise
Published: August 2016

According to research literature, humor inside the staff–patient interaction seems to be significant in the area of forensic mental healthcare. However, existing literature on the subject is limited. Therefore, the aim of this study was to explore the characteristics of the use humor by forensic mental health staff members in interactions with forensic mental health inpatients. The study included 32 forensic mental health staff members, used 307 hours of participant observations, 48 informal interviews, and seven formal semistructured interviews. Outcomes identify four themes concerning the conveyance of power to, from, and between forensic mental health staff and patients as they interact: (a) “the informal use: the human-to-human approach,” characterized by an informal use of humor and without any reference to mental health issues; (b) the “formal use of humor: the staff–patient approach,” characterized as formal with a view on the patient as mentally ill, unable to understand humor, and with the aim of using humor to prevent conflicts or negative behavior; (c) “protest against requested care: the human–patient approach,” characterized by the use of humor as a protest against requested care; and the use of (d) “inadequacy humor: the staff–human approach,” characterized by the use of inadequacy—humor referring to, for example, patients’ physical features. Recommendations and clinical implications are discussed.
An Expectorated “Stent”
Authors: Zamora Felix D. , Moughrabieh Anas , Gibson Heidi , Podgaetz Eitan , Dincer H. Erhan
Published: August 2016

Endobronchial ultrasound-guided transbronchial needle aspiration has a low complication rate and is a cost-effective procedure for mediastinal staging and diagnosis when compared with the more invasive mediastinoscopy. There are increasing case reports of unexpected complications including equipment failures with and without significant medical consequences. Knowledge of complications, including those that are rare, is essential for the physician performing this minimally invasive procedure. We report a case of a retained foreign body from the unexpected separation of a distal spring/coil mechanism from the Olympus ViziShot Aspiration needle following early needle deployment within the working channel of the bronchoscope.
Endoscopic Bubble Trouble
Authors: Cooper Jeffrey S. , Thomas Jason , Singh Shailender , Brakke Tarra
Published: August 2016

Gas embolism is a rare but potentially devastating complication of endoscopic procedures. We describe 3 cases of gas embolism which were associated with endoscopic procedures (esophagogastroduodenoscopy and endoscopic retrograde cholangiopancreatography). We treated these at our hyperbaric medicine center with 3 different outcomes: complete resolution, death, and disability. We review the literature regarding this unusual complication of endoscopy and discuss the need for prompt identification and referral for hyperbaric oxygen therapy. Additional adjunctive therapies are also discussed.
Value of Oral Proton Pump Inhibitors in Acute, Nonvariceal Upper Gastrointestinal Bleeding
Authors: Rodriguez Eduardo A. , Donath Elie , Waljee Akbar K. , Sussman Daniel A.
Published: August 2016

Background:

Intravenous (IV) proton pump inhibitors (PPI) are the standard medical treatment in acute nonvariceal upper gastrointestinal bleeding (ANVGIB). Optimal route of PPI delivery has been questioned.

Aim:

The aim was to perform a systematic review and network meta-analysis for the endpoints of risk of rebleeding, length of stay (LOS), surgery (ROS), mortality, and total units of blood transfused (UBT) among trials evaluating acid suppressive medications in ANVGIB.

Methods:

A total of 39 studies using IV PPI drip, IV scheduled PPI, oral PPI, H2-receptor antagonists, and placebo were identified. Network meta-analysis was used for indirect comparisons and Bayesian Markov Chain Monte Carlo methods for calculation of probability superiority.

Results:

No difference was observed between IV PPI drip and scheduled IV PPI for mortality (relative risk=1.11; 95% credibility interval, 0.56-2.21), LOS (0.04, −0.49 to 0.44), ROS (1.27, 0.64-2.35) and risk of rebleeding within 72 hours, 1 week, and 1 month [(0.98, 0.48-1.95), (0.59, 0.13-2.03), (0.82, 0.28-2.16)]. Oral PPIs were as effective as IV scheduled PPIs and IV PPI drip for LOS (0.22, −0.61 to 0.79 and 0.16, −0.56 to 0.80) and UBT (−0.25, −1.23 to 0.65 and −0.06, −0.71 to 0.65) and superior to IV PPI drip for ROS (0.30, 0.10 to 0.78).

Conclusion:

Scheduled IV PPIs were as effective as IV PPI drip for most outcomes. Oral PPIs were comparable to scheduled IV for LOS and UBT and superior to IV PPI drip for ROS. Conclusions should be tempered by low frequency endpoints such as ROS, but question the need for IV PPI drip in ANVGIB.
Real-World Data
Authors: Basu Anirban , Axelsen Kirsten , Grabowski David C. , Meltzer David O. , Polsky Daniel , Ridley David B. , Wiederkehr Daniel , Philipson Tomas J.
Published: August 2016

As real-world data (RWD) in health care begin to cross over to the Big Data realms, a panel of health economists was gathered to establish how well the current US policy environment further the goals of RWD and, if not, what can be done to improve matters. This report summarizes these discussions spanning the current US landscape of RWD availability and usefulness, private versus public development of RWD assets, the current inherent bias in terms of access to RWD, and guiding principles in providing quality assessments of new RWD studies. Three main conclusions emerge: (1) a business case is often required to incentivize investments in RWD assets. However, access restrictions for public data assets have failed to generate a proper market for these data and hence may have led to an underinvestment of public RWDs; (2) Very weak empirical evidence exist on for-profit entities misusing public RWD data entities to further their own agendas, which is the basis for supporting access restrictions of public RWD data; and (3) perhaps developing standardized metrics that could flag misuse of RWDs in an efficient way could help quell some of the fear of sharing public RWD assets with for-profit entities. It is hoped that these discussions and conclusions would pave the way for more rigorous and timely debates on the greater availability and accessibility of RWD assets.
Reference Pricing, Consumer Cost-Sharing, and Insurer Spending for Advanced Imaging Tests
Authors: Robinson James C. , Whaley Christopher , Brown Timothy T.
Published: August 2016

Background:

Fees charged for similar imaging tests often vary dramatically within the same market, leading to wide variation in insurer spending and consumer cost-sharing. Reference pricing is an insurance design that offers good coverage to patients up to a defined contribution limit but requires the patients who select high-priced facilities to pay the remainder out of pocket.

Objectives:

To measure the association between implementation of reference pricing and patient choice of facility, test prices, out-of-pocket spending, and insurer spending for advanced imaging (CT and MRI) procedures.

Research Design:

Difference-in-differences multivariable analysis of insurance claims data. Study included 4751 employees of a national grocery chain (treatment group) and 23,428 enrollees in the nation’s largest private insurance plan (comparison group) that used CT or MRI tests between 2010 and 2013.

Measures:

Patient choice of facility, price paid per test, patient out-of-pocket cost-sharing, and employer spending.

Results:

Compared with trends in prices paid by insurance enrollees not subject to reference pricing, and after adjusting for characteristics of tests and patients, implementation of reference pricing was associated with a 12.5% (95% CI, −25.0%, 2.1%) reduction in average price paid per test by the end of the second full year of the program for CT scans and a 10.5% (95% CI, −16.9%, 3.6%) for MRIs. Out-of-pocket cost-sharing by patients declined by $71,508 (13.8%). The savings accruing to employees amounted to 45.5% of total savings from reference pricing, with the remainder accruing to the employer.

Conclusions:

Implementation of reference pricing led to reductions in payments by both employer and employees.
Constructing Episodes of Inpatient Care
Authors: Peng Mingkai , Li Bing , Southern Danielle A. , Eastwood Cathy A. , Quan Hude
Published: August 2016

Background:

Hospital administrative health data create separate records for each hospital stay of patients. Treating a hospital transfer as a readmission could lead to biased results in health service research.

Methods:

This is a cross-sectional study. We used the hospital discharge abstract database in 2013 from Alberta, Canada. Transfer cases were defined by transfer institution code and were used as the reference standard. Four time gaps between 2 hospitalizations (6, 9, 12, and 24 h) and 2 day gaps between hospitalizations [same day (up to 24 h), ≤1 d (up to 48 h)] were used to identify transfer cases. We compared the sensitivity and positive predictive value (PPV) of 6 definitions across different categories of sex, age, and location of residence. Readmission rates within 30 days were compared after episodes of care were defined at the different time gaps.

Results:

Among the 6 definitions, sensitivity ranged from 93.3% to 98.7% and PPV ranged from 86.4% to 96%. The time gap of 9 hours had the optimal balance of sensitivity and PPV. The time gaps of same day (up to 24 h) and 9 hours had comparable 30-day readmission rates as the transfer indicator after defining episode of care.

Conclusions:

We recommend the use of a time gap of 9 hours between 2 hospitalizations to define hospital transfer in inpatient databases. When admission or discharge time is not available in the database, a time gap of same day (up to 24 h) can be used to define hospital transfer.
Dipeptidyl peptidase-4 inhibition: insights from the bench and recent clinical studies
Authors: Zhong Jixin , Kankanala Saumya , Rajagopalan Sanjay
Published: August 2016

Purpose of review

Atherosclerosis is the leading cause of death globally. The pathophysiology of atherosclerosis is not fully understood. Recent studies suggest dipeptidyl peptidase-4 (DPP4), a regulator of inflammation and metabolism, may be involved in the development of atherosclerotic diseases. Recent advances in the understanding of DPP4 function in atherosclerosis will be discussed in this review.

Recent findings

Multiple preclinical and clinical studies suggest DPP4/glucagon-like peptide-1 axis is involved in the development of atherosclerotic disease. However, several recent trials assessing the cardiovascular effects of DPP4 inhibition indicate enzymatic inhibition of DPP4 lacks beneficial effects on cardiovascular disease.

Catalytic inhibition of DPP4 with DPP4 inhibitors alters pathways that could favor cardioprotection. Glucagon-like peptide-1 receptor-independent aspects of DPP4 function may contribute to the overall neutral effects on cardiovascular outcome seen in the outcome trials.
The Natural History of Primary Sclerosing Cholangitis in Children
Authors: Valentino Pamela L. , Wiggins Shanna , Harney Sarah , Raza Roshan , Lee Christine K. , Jonas Maureen M.
Published: August 2016

Objectives:

Data regarding pediatric primary sclerosing cholangitis (PSC) natural history are limited. We describe a large pediatric PSC cohort with longitudinal follow‐up.

Methods:

The present study records review of pediatric patients with PSC diagnosed between 1984 and 2014.

Results:

N = 120 (63% M) ages 1 to 21 years (median 14 years) at diagnosis. 27% (31/113) had autoimmune sclerosing cholangitis (ASC), 24% had exclusive small duct PSC, METAVIR stage was F3‐F4 in 41%. Eighty‐one percent of patients with PSC had inflammatory bowel disease (IBD); most had ulcerative/indeterminate colitis (72/97), typically pancolitis (40/72). PSC‐IBD was more common than ASC‐IBD (85% vs 68%, P = 0.03). Median follow‐up was 3.7 years (interquartile range [IQR] 1.5, 6.9). Median gamma glutamyl transferase decreased from baseline of 221 U/L (IQR 110, 425) to 104 U/L by 1 year postdiagnosis ([IQR 18,229], P < 0.0001), and then changed little. Mean fibrosis stage at diagnosis was 2.3 ± 1.4 (N = 91), and at 1 to 5 years was 2.6 ± 1.3 (N = 20). Transplant‐free survival at 10 year was 89%; there were 6 liver transplants, 2 in patients with small duct PSC and 4 with diffuse large duct PSC. Although the cirrhosis rate was not significantly different in PSC with IBD versus without (22% vs 41%, P = 0.06), the former had a lower rate of liver transplantation (2% vs 18%, P = 0.01). The rate of cirrhosis was lower in patients diagnosed with IBD before PSC (15% vs 31%, P = 0.05).

Conclusions:

In this largest reported pediatric PSC cohort, liver transplantation rate at 10 years was lower than that reported in adults. ASC and PSC had similar biochemical abnormalities and degree of fibrosis at diagnosis. PSC that developed after IBD diagnosis had a milder course, possibly reflecting earlier disease detection or milder phenotype.
The effects of different types of ankle-foot orthoses on postural responses in individuals with walking impairments
Authors: Cikajlo Imre , Osrečki Ksenija , Burger Helena
Published: August 2016

The aim of this study was to examine the immediate and long-term effects of different ankle-foot orthosis (AFO) types on postural responses in patients with various pathological conditions who, because of their walking disorders, wore an AFO. A total of 37 patients with different pathological conditions who visited the outpatient clinic for orthotics because of walking problems, already used or were referred for an AFO and had no other impairments that may influence balance were included in the study. The participants were divided into four groups according to the type of AFO that they wore. The postural responses were assessed with and without AFO using two force-plates following perturbations in different directions at the level of the pelvis. The centre of pressure was examined in the sagittal and frontal plane and compared with the normative data from healthy individuals. The results showed an improvement in postural responses to the lateral and backward perturbation directions when wearing the AFO, particularly responses in the anterior–posterior direction. The best results were achieved with the custom-made posterior leaf spring AFO for correction of equinovarus deformity. The time of wearing the AFO had an impact on postural responses in perturbation directions where the patients could not rely only on AFO. The custom-made AFO improved overall postural responses, especially dynamic stability, in lateral directions, whereas all stiff AFOs contributed towards an improvement in responses to all perturbations to the affected side. Results showed that long-term use of an AFO can be important for the overall improvement of postural responses.
Interlimb weight adjustments between the lower and upper limbs relate to inaccurate performance during the lateral body weight-shifting task
Authors: Watanabe Miyoko , Higuchi Takahiro , Imanaka Kuniyasu
Published: August 2016

The lateral body weight-shifting task is commonly used in therapeutic programs for patients with orthopedic complaints or hemiparesis. Although the patients usually support themselves using the upper limbs during the task, it is unclear whether the use of upper limbs affects performance accuracy of lateral body weight shifting. Therefore, the aim of this study was to investigate the effects of support by the upper limbs on performance accuracy, particularly on the central tendency effects (i.e. overshooting for light targets and undershooting for heavy targets). Twenty-three able-bodied, neurologically intact individuals, who were right-handed and right-footed participants performed the lateral body weight-shifting task to shift one-third or two-thirds of their body weight toward the left and right lower limbs using support by the upper limbs. The result of correlation coefficients between interlimb weight adjustment and errors showed that the use of the upper limbs and interlimb weight adjustment related to the enhanced central tendency effects. The use of upper limbs generally contributes toward stabilizing posture, however, this is not the case with performance of the lateral body weight shifting. Moreover, the effects of using the upper limb on performance accuracy differed among leftward and rightward weight shifting. This result might be owing to the dominant side of the hand/foot and hemisphere lateralization.