bluuebunny/crossref_metadata_2025 huggingface dataset:
Pregnancy and the Postpartum Period as an Opportunity for Cardiovascular Risk Identification and Management
Authors: Smith Graeme N. , Louis Judette Marie , Saade George R.
Published: September 2019

Cardiovascular disease (CVD) is the leading cause of death in women. Because women generally present with more atypical symptoms of CVD than do men and because underlying CVD risk factors are often present for years before the onset of CVD, it is important to use innovative ways to identify women who should undergo CVD risk screening at a younger age. Pregnancy and the postpartum period afford us that opportunity, given that the development of certain pregnancy complications (hypertensive disorders of pregnancy, gestational diabetes, preterm birth, delivery of a neonate with fetal growth restriction, and significant placental abruption) can reliably identify women with underlying, often unrecognized, CVD risk factors. Women with one or more of these pregnancy complications should be identified at the time of delivery and referred for regular follow-up. This would ideally take the form of a multidisciplinary clinic including clinicians and allied health specialists to carry out physical and biochemical screening and counseling regarding lifestyle modification and possible therapeutic interventions. Longer-term follow-up and recommendations should be individualized based on findings and risks. There is also an opportunity for future pregnancy counseling and discussion about the importance of weight loss between pregnancies, initiation of a routine involving physical activity, use of preconception folic acid, and the potential initiation of low-dose aspirin for those women at risk for future preeclampsia and fetal growth restriction or the use of progesterone for women at risk for preterm labor. The link between pregnancy complications and future CVD affords us with the earliest opportunity for CVD risk assessment for health preservation and disease prevention.
Association Between Severe Maternal Morbidity and Psychiatric Illness Within 1 Year of Hospital Discharge After Delivery
Authors: Lewkowitz Adam K. , Rosenbloom Joshua I. , Keller Matt , López Julia D. , Macones George A. , Olsen Margaret A. , Cahill Alison G.
Published: September 2019

OBJECTIVE:

To estimate whether severe maternal morbidity is associated with increased risk of psychiatric illness in the year after delivery hospital discharge.

METHODS:

This retrospective cohort study used International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes within Florida's Healthcare Cost and Utilization Project's databases. The first liveborn singleton delivery from 2005 to 2015 was included; women with ICD-9-CM codes for psychiatric illness or substance use disorder during pregnancy were excluded. The exposure was ICD-9-CM codes during delivery hospitalization of severe maternal morbidity, as per the Centers for Disease Control and Prevention. The primary outcome was ICD-9-CM codes in emergency department encounter or inpatient admission within 1 year of hospital discharge of composite psychiatric morbidity (suicide attempt, depression, anxiety, posttraumatic stress disorder, psychosis, acute stress reaction, or adjustment disorder). The secondary outcome was a composite of ICD-9-CM codes for substance use disorder. We compared women with severe maternal morbidity with those without severe maternal morbidity using multivariable logistic regression adjusting for sociodemographic factors and medical comorbidities. Cox proportional hazard models identified the highest risk period after hospital discharge for the primary outcome.

RESULTS:

A total of 15,510 women with severe maternal morbidity and 1,178,458 without severe maternal morbidity were included. Within 1 year of hospital discharge, 2.9% (n=452) of women with severe maternal morbidity had the primary outcome compared with 1.6% (n=19,279) of women without severe maternal morbidity, resulting in an adjusted odds ratio (aOR) 1.74 (95% CI 1.58–1.91). The highest risk interval was within 4 months of discharge (adjusted hazard ratio [adjusted HR] 2.53 [95% CI 2.05–3.12]). Most severe maternal morbidity conditions were associated with higher risk of postpartum psychiatric illness. Women with severe maternal morbidity had nearly twofold higher risk of postpartum substance use disorder (170 [1.1%] vs 6,861 [0.6%]; aOR 1.91 [95% CI 1.64–2.23]).

CONCLUSION:

Though absolute numbers were modest, severe maternal morbidity was associated with increased risk of severe postpartum psychiatric morbidity and substance use disorder. The highest period of risk extended to 4 months after hospital discharge.
Outcomes of a Staged Midurethral Sling Strategy for Stress Incontinence and Pelvic Organ Prolapse
Authors: Giugale Lauren E. , Carter-Brooks Charelle M. , Ross James H. , Shepherd Jonathan P. , Zyczynski Halina M.
Published: September 2019

OBJECTIVE:

To evaluate the proportion of women who experienced resolution of stress urinary incontinence (SUI) symptoms after surgery for pelvic organ prolapse (POP) without a concomitant incontinence procedure.

METHODS:

We conducted a retrospective observational study of women with preoperative subjective and objective SUI who underwent minimally invasive sacrocolpopexy or uterosacral ligament suspension from 2009 to 2015. We excluded cases with incontinence procedures. The primary outcome was the proportion of women with subjective resolution of SUI postoperatively, defined as the absence of patient reported SUI symptoms during follow-up. Secondary outcomes included the proportion of women who underwent a subsequent staged midurethral sling (MUS) procedure and factors associated with resolution of SUI and staged MUS placement.

RESULTS:

Of 93 women, most were white (n=90, 98%) with stage III POP (n=55, 59%). Mean age was 59.5±8.9 years and body mass index 28.7±4.7. Seventy-three patients (78%) underwent minimally invasive sacrocolpopexy, and 20 (22%) underwent uterosacral ligament suspension. Median follow-up was 8.3 months (interquartile range 3.4–26.7). Postoperatively, 28 (30%) patients reported resolution of SUI, and 65 (70%) reported persistent SUI. Of the 93 patients, 47 (51%) were treated for persistent SUI and 34 (37%) underwent a staged MUS procedure. Among the staged MUS procedures, 27 (79%) were placed within 12 months. Median time to staged MUS procedure was 5.5 months (interquartile range 4.2–9.9). After controlling for degree of preoperative SUI bother, obese women were less likely to experience resolution of SUI after prolapse repair (odds ratio 0.28, 95% CI 0.08–0.95). We did not identify any factors that were significantly associated with undergoing a staged MUS procedure on univariate analyses (P>.05).

CONCLUSION:

Preoperative SUI resolved in nearly a third of women after prolapse surgery without a concomitant incontinence procedure. In a population typically offered a concomitant MUS procedure at the time of prolapse repair, a staged approach may result in nearly two-thirds fewer patients undergoing MUS procedures. This information may be helpful during preoperative shared decision making.
Referral Center Experience With Nonpalpable Contraceptive Implant Removals
Authors: Matulich Melissa C. , Chen Melissa J. , Schimmoeller Natasha R. , Hsia Jennifer K. , Uhm Suji , Wilson Machelle D. , Creinin Mitchell D.
Published: September 2019

OBJECTIVE:

To describe our experience with office removal of nonpalpable contraceptive implants at our referral center.

METHODS:

We performed a retrospective cohort study by reviewing the charts of patients referred to our family planning specialty center for nonpalpable or complex contraceptive implant removal from January 2015 through December 2018. We localized nonpalpable implants using high-frequency ultrasonography and skin mapping in radiology, followed by attempted removal in the office using local anesthesia and a modified vasectomy clamp. We abstracted information on demographics, implant location, and outcomes.

RESULTS:

Of 61 referrals, 55 patients attended their scheduled appointments. Seven patients had palpable implants; six elected removal. The other 48 patients had ultrasound localization, which identified 47 (98%) of the implants; the remaining patient had successful localization with computed tomography imaging. Nonpalpable implants were suprafascial (n=22), subfascial (n=25) and intrafascial (n=1); four of these patients opted to delay removal. Of 50 attempted office removals, all palpable (n=6), all nonpalpable suprafascial (n=21 [100%, 95% CI 83–100%]), and 19 out of 23 (83%, 95% CI 67–98%) subfascial implants were successful. Three of the four patients with failed subfascial implant office removal had successful operating room removal with a collaborative orthopedic surgeon; the other patient sought removal elsewhere. Transient postprocedure neuropathic complaints were noted in 7 out of 23 (30%, 95% CI 12–49%) subfascial and 1 out of 21 (5%, 95% CI 0–13%) suprafascial removals (P=.048). Nonpalpable implants were more likely to be subfascial in nonobese patients (24/34, 71%) as compared with obese (1/13, 8%) patients (P<.001). Seven (28%) of the 25 subfascially located implants had been inserted during a removal–reinsertion procedure through the same incision.

CONCLUSION:

Most nonpalpable contraceptive implants can be removed in the office by an experienced subspecialty health care provider after ultrasound localization. Some patients may experience transient postprocedure neuropathic pain. Nonpalpable implants in thinner women are more likely to be in a subfascial location.
Optimal Management of Endometriosis and Pain
Authors: Nezhat Camran , Vang Nataliya , Tanaka Pedro P. , Nezhat Ceana
Published: September 2019

The pathophysiology of endometriosis-associated pain involves inflammatory and hormonal alterations and changes in brain signaling pathways. Although medical treatment can provide temporary relief, most patients can achieve long-term sustained pain relief when it is combined with surgical intervention. Owing to its complexity, there is an ongoing debate about how to optimally manage endometriosis-associated pain. We believe optimal management for this condition requires: 1) possible egg preservation in affected young patients with and without endometriomas; 2) preoperative medical suppression to inhibit ovulation and to avoid removal of functional cysts that might look like endometriomas; and 3) postoperative hormonal suppression to decrease recurrence, but this treatment should be modified according to disease severity, symptoms, and fertility goals.
Closed Incision Negative Pressure Therapy in Morbidly Obese Women Undergoing Cesarean Delivery
Authors: Hussamy Deana J. , Wortman Alison C. , McIntire Donald D. , Leveno Kenneth J. , Casey Brian M. , Roberts Scott W.
Published: September 2019

OBJECTIVE:

To evaluate the efficacy of incisional negative pressure wound therapy in the prevention of postoperative wound morbidity in women with class III obesity undergoing cesarean delivery.

METHODS:

In an open label randomized controlled trial, women admitted for delivery with class III obesity (body mass index 40 or higher) measured within 2 weeks of admission for delivery were offered participation in the study. They were consented either in the outpatient maternal–fetal medicine specialty clinic, during admission to labor and delivery and before a decision to perform cesarean delivery, or in the preoperative area of the hospital before scheduled cesarean delivery. Exclusion criteria included anticoagulation therapy, human immunodeficiency virus infection, and silver or acrylic allergy. Those who ultimately underwent cesarean delivery were randomized to standard surgical dressing or incisional negative pressure wound therapy dressing. The primary outcome was wound morbidity. Preplanned secondary outcomes included characteristics of composite wound morbidity, and hospital, emergency room, and clinic utilization. The sample size estimate required randomization of 440 women to detect a 50% decrease in composite outcome.

RESULTS:

Between January 1, 2015, and July 31, 2016, 850 women were screened and 677 women with class III obesity were enrolled. Of these, 441 underwent cesarean delivery and were subsequently randomized (219 to standard dressing and 222 to incisional negative pressure wound therapy). The primary outcome, overall composite wound morbidity rate, was 18%. This was not different between the two cohorts (incisional negative pressure wound therapy 17% vs standard dressing 19%, relative risk 0.9 [95% CI 0.5–1.4]).

CONCLUSION:

Prophylactic incisional negative pressure wound therapy use did not reduce postoperative wound morbidity when compared with a standard surgical dressing in women with class III obesity.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02289157.
Effects of Shared Decision Making on Opioid Prescribing After Hysterectomy
Authors: Vilkins Annmarie L. , Sahara Michael , Till Sara R. , Ceci Christina , Howard Ryan , Griffith Kendall C. , Waljee Jennifer F. , Lim Courtney S. , Skinner Bethany D. , Clauw Daniel J. , Brummett Chad M. , As-Sanie Sawsan
Published: September 2019

OBJECTIVE:

To evaluate the effects of shared decision making using a simple decision aid for opioid prescribing after hysterectomy.

METHODS:

We conducted a prospective quality initiative study including all patients undergoing hysterectomy for benign, nonobstetric indications between March 1, 2018, and July 31, 2018, at our academic institution. Using a visual decision aid, patients received uniform education regarding postoperative pain management. They were then educated on the department's guidelines regarding the maximum number of tablets recommended per prescription and the mean number of opioid tablets used by a similar cohort of patients in a previously published study at our institution. Patients were then asked to choose their desired number of tablets to receive on discharge. Structured telephone interviews were conducted 14 days after surgery. The primary outcome was total opioids prescribed before compared with after implementation of the decision aid. Secondary outcomes included opioid consumption, patient satisfaction, and refill requests after intervention implementation.

RESULTS:

Of 170 eligible patients, 159 (93.5%) used the decision aid (one patient who used the decision aid was subsequently excluded from the analysis owing to significant perioperative complications), including 110 (69.6%) laparoscopic, 40 (25.3%) vaginal, and eight (5.3%) abdominal hysterectomies. Telephone surveys were completed for 89.2% (n=141) of participants. Student’s t-test showed that patients who participated in the decision aid (post–decision aid cohort) were discharged with significantly fewer oral morphine equivalents than patients who underwent hysterectomy before implementation of the decision aid (pre–decision aid cohort) (92±35 vs 160±81, P<.01), with no significant change in the number of requested refills (9.5% [n=15] vs 5.7% [n=14], P=.15). In the post–decision aid cohort, 76.6% of patients (n=121) chose fewer tablets than the guideline-allotted maximum. Approximately 76% of patients (n=102) reported having leftover tablets.

CONCLUSION:

This quality improvement initiative illustrates that a simple decision aid can result in a significant decrease in opioid prescribing without compromising patient satisfaction or postoperative pain management.
Pulmonary involvement in antisynthetase syndrome
Authors: Gasparotto Michela , Gatto Mariele , Saccon Francesca , Ghirardello Anna , Iaccarino Luca , Doria Andrea
Published: September 2019

Purpose of review

Lung involvement is a distinctive feature of antisynthetase syndrome (ASS) and it is considered a basic disease-classifying criterion. In this review, we go over clinical features, radiological patterns, prognostic factors, pathogenesis and treatment of lung involvement in ASS patients, focusing on the clinical differences linked to the different antibody specificities known so far.

Recent findings

The lung is the most common extramuscular organ involved in ASS and has the greatest impact on patient prognosis. The pulmonary disease-defining manifestation in ASS is interstitial lung disease (ILD), yet a proportion of patients also develop pulmonary arterial hypertension and, less frequently, obstructive bronchiolitis or acute respiratory failure according to drivers not yet fully understood but likely associated with the underlying autoantibody pattern. Clinical presentation of pulmonary involvement can range from milder forms to a rapidly progressive disease which may lead to chronic lung damage if misdiagnosed and not properly treated.

The knowledge of risk factors associated with progressive or refractory lung damage is important to identify and properly treat patients with the poorest prognosis. For those with a disease not responsive to conventional therapy the efficacy of other therapeutic option is under evaluation.
Interpreting neonatal hip sonography: intraobserver and interobserver variability
Authors: Pedrotti Luisella , Crivellari Ilaria , Degrate Alessandro , De Rosa Federica , Ruggiero Francesca , Mosconi Mario
Published: September 2019

The purpose of this study is to state the reliability of neonatal hip ultrasound interpretation, defining the intra and interoperator variability in the evaluation of the scans. We considered a sample of 2071 scans (coming from 798 patients who attended the screening programme for hip dysplasia), which were interpreted by the operator who obtained and read the images at the screening time and then by a different operator who saw the images for the first time. Both the intra and interoperator variability of α and β angles’ values resulted statistically not significative (intraclass correlation coefficient > 0.8) and determining a class shift (according to the Graf’s classification) in a nonstatistically significative number of cases (agreement percentage >91% and Cohen’s
κ
>0.8). Hip sonography can reliably detect hip dysplasia and the intra and interoperator variability in the interpretation of the exam is NS when the examination is correctly executed.
Antitumor effect of a short peptide on p53-null SKOV3 ovarian cancer cells
Authors: Huang Yi-shan , Wang Tian-xiang , Lin Xiao-mian , Wang Heng , Li Rong-zhen , Zeng Xiangfeng , Zhu Cairong , Chen Lian-kuai , Guo Qiuxiao , Liu Hongjiao , Wu Xiao-ping
Published: September 2019

Fibroblast growth factor-2 (FGF2) is a protein ligand, which exerts essential roles in development, angiogenesis, and tumor progression via activation of the downstream signaling cascades. Accumulating evidence has demonstrated that FGF2 is involved in the progression of ovarian cancer, providing a novel potential target for ovarian cancer therapy. In this study, we showed that FGF2 is significantly increased in ovarian tumors, and is negatively associated with the overall survival of ovarian cancer by database analysis. A short peptide obtained from a heptapeptide phage display library suppressed FGF2-induced proliferation, migration, and invasion of the p53-null epithelial ovarian cancer (EOC) cells. Further investigations revealed that the short peptide antagonized the effects of FGF2 on G0/G1 to S cell phase promotion, cyclin D1 expression, and MAPK and Akt signaling activation, which might contribute to the mechanism underlying the inhibitory effects of the short peptide on the aggressive phenotype of the ovarian cancer cells triggered by FGF2. Moreover, the short peptide might have the potentials of reversing FGF2-induced resistance to the doxorubicin via downregulation of the antiapoptotic proteins and counteracting of the antiapoptotic effects of FGF2 on p53-null EOC cells. Taken together, the short peptide targeting FGF2 may provide a novel strategy for improving the therapeutic efficiency in a subset of EOC.
Screening of MYH7 gene mutation sites in hypertrophic cardiomyopathy and its significance
Authors: Liu Hui-Ting , Ji Fang-Fang , Wei Ling , Zuo An-Jun , Gao Yu-Xiu , Qi Lin , Jin Bu , Wang Ji-Gang , Zhao Peng
Published: September 2019

Background:

There have been few reports of mutations in the beta-myosin heavy chain (MYH7) gene in hypertrophic cardiomyopathy (HCM), which is associated with sudden cardiac death caused by HCM. This study aimed to screen the mutation sites in the sarcomeric gene MYH7 in Chinese patients with HCM. We also planned to analyze the pathogenicity of the mutation site as well as its significance in clinical and forensic medicine.

Methods:

From January 2006 to June 2017, autopsy cases were collected from the Department of Pathology, the Affiliated Hospital of Qingdao University. The experiment was to detect MYH7 gene status in formalin-fixed paraffin-embedded tissues from 18 independent autopsy cases who suffered HCM related sudden death (fatal HCM) and 20 cases without cardiomyopathy. Common mutation exon fragments of MYH7 gene were amplified by polymerase chain reaction. The end-of-deoxygenation method and gene cloning method were further performed to analyze the mutation sites. Homologous comparison among mutant sites was conducted using BLAST online database.

Results:

The 1336th nucleotide of MYH7 gene at exon 14 was converted from T to G in one HCM case, resulting in the conversion of threonine (Thr) at position 446 to proline (Pro). In another case, the 1402th nucleotide at exon 14 was converted from T to C, resulting in the conversion of phenylalanine (Phe) at position 468 to leucine (Leu). Homologous comparison results showed that the two amino acid residues of Thr446 and Phe468 are highly conserved among different species.

Conclusions:

Our results showed fatal HCM harbored mutations of Thr446Pro and Phe468Leu in the MYH7 gene. It is significant for clinical and forensic medicine to further explore the functions and detailed mechanisms of these mutations.
Phase I/II Trial of Neoadjuvant Oregovomab-based Chemoimmunotherapy Followed by Stereotactic Body Radiotherapy and Nelfinavir For Locally Advanced Pancreatic Adenocarcinoma
Authors: Lin Chi , Verma Vivek , Lazenby Audrey , Ly Quan P. , Berim Lyudmyla D. , Schwarz James K. , Madiyalakan Madi , Nicodemus Christopher F. , Hollingsworth Michael A. , Meza Jane L. , Are Chandrakanth , Padussis James , Grem Jean L.
Published: September 2019

Objective:

Cancer antigen (CA)-125 influences progression, metastasis, and outcomes in pancreatic cancer. This phase I/II trial (NCT01959672) evaluated the safety, efficacy, and immunologic correlates of chemoimmunotherapy (CIT) with oregovomab (anti–CA-125), followed by stereotactic body radiotherapy (SBRT) with the radiosensitizer nelfinavir.

Materials and Methods:

Following imaging, pathologic confirmation, and staging laparoscopy, subjects received three 3-week cycles of CIT (gemcitabine/leucovorin/fluorouracil/oregovomab). Thereafter, nelfinavir was delivered (1250 mg bid) for 5 weeks, with SBRT (40 Gy/5 fractions) occurring during the third week of nelfinavir. Following another cycle of CIT, pancreaticoduodenectomy was performed if resectable. Three more cycles of CIT were then delivered (total 7 cycles). In subjects with high (≥10 U/mL) CA-125, oregovomab (2 mg) was administered for 7 total doses (3 pre-SBRT, 1 between SBRT and resection, and 3 postoperatively). The enzyme-linked immunospot assay evaluated the development of CA-125–specific CD8 T-lymphocytes.

Results:

The trial was prematurely closed because gemcitabine/leucovorin/fluorouracil was replaced by FOLFIRINOX and gemcitabine/nab-paclitaxel as the standard of care. Median follow-up was 13 months. Of 11 enrolled patients, 10 had high CA-125; 1 patient suffered an unexpected cardiac-related death, so 9 subjects received oregovomab. Ten received SBRT and 4 underwent resection. Overall, 6/11 patients experienced any grade ≥3 event. The median survival and time to progression were 13 and 8.6 months, respectively. Five patients had samples available for immunospot testing, of whom 2 (40%) developed CA-125–specific CD8 T-lymphocytes.

Conclusion:

A combined pancreatic cancer multimodality approach using CIT and radiosensitized radiotherapy is feasible and safe; delivery of immunotherapy can lead to T-cell immunity. Re-evaluation with modern systemic paradigms is recommended.
Deletion of mu opioid receptors reduces palatable solution intake in a mouse model of binge eating
Authors: Awad Gaëlle , Roeckel Laurie-Anne , Massotte Dominique , Olmstead Mary C. , Befort Katia
Published: September 2019

Binge eating in humans is driven by hedonic properties of food, suggesting that brain reward systems may contribute to this behaviour. We examined the role of mu opioid receptors (MOP) in binge eating by examining sweet solution intake in mice with genetic deletion of the MOP. Wildtype and MOP knockout mice had 4 hours access to food in the home cage combined with limited (4 hours) access to sucrose (17.1% w/v) or saccharin (0.09% w/v), or continuous (24 hours) access to sucrose. Only limited access groups exhibited binge intake, measured as increased solution consumption during the first hour. Knockout mice consumed less solution and food during the first hour as well as less food each day compared with wildtype mice. Limited access groups consumed more food and gained more weight than continuous access groups, and the effect was magnified in saccharin-consuming mice. Indeed, the increased food consumption in animals given limited access to saccharin was so excessive that caloric intake of this group was significantly higher than either of the sucrose groups (limited or continuous access). Within this group, females consumed more food per bodyweight than males, highlighting important sex differences in feeding behaviours under restricted access schedules.
Ultra-low doses of the transient receptor potential vanilloid 1 agonist, resiniferatoxin, prevents vomiting evoked by diverse emetogens in the least shrew (Cryptotis parva)
Authors: Darmani Nissar A. , Henry Denise A. , Zhong Weixia , Chebolu Seetha
Published: September 2019

Published studies have shown that the transient receptor potential vanilloid 1 (TRPV1) receptor agonist, resiniferatoxin (RTX), has pro and antiemetic effects. RTX can suppress vomiting evoked by a variety of nonselective emetogens such as copper sulfate and cisplatin in several vomit-competent species. In the least shrew, we have already demonstrated that combinations of ultra-low doses of RTX and low doses of the cannabinoid CB1/2 receptor agonist delta-9-tetrahydrocannabinol (Δ9-THC) produce additive antiemetic effects against cisplatin-evoked vomiting. In the current study, we investigated the broad-spectrum antiemetic potential of very low nonemetic doses of RTX against a diverse group of specific emetogens including selective and nonselective agonists of serotonergic 5-hydroxytrptamine (5-HT3) receptor (5-HT and 2-Me-5-HT), dopaminergic D2 receptor (apomorphine and quinpirole), cholinergic M1 receptor (pilocarpine and McN-A-343), as well as the selective substance P neurokinin NK1 receptor agonist GR73632, the selective L-Type calcium channel agonist FPL64176, and the sarcoplasmic endoplasmic reticulum calcium ATPase (SERCA) inhibitor thapsigargin. When administered subcutaneously, ultra-low (0.01 µg/kg) to low (5.0 µg/kg) doses of RTX suppressed vomiting induced by the aforementioned emetogens in a dose-dependent fashion with 50% inhibitory dose values ranging from 0.01 to 1.26 µg/kg. This study is the first to demonstrate that low nanomolar nonemetic doses of RTX have the capacity to completely abolish vomiting caused by diverse receptor specific emetogens in the least shrew model of emesis.
Differential effects of d-amphetamine and atomoxetine on risk-based decision making of Lewis and Fischer 344 rats
Authors: Ozga-Hess Jenny E. , Anderson Karen G.
Published: September 2019

Individuals with attention-deficit/hyperactivity disorder tend to make risker choices during probabilistic-discounting procedures. Thus, how common attention-deficit/hyperactivity disorder medications affect probabilistic discounting is of interest. In general, d-amphetamine increases risk-taking while atomoxetine has produced mixed effects in rats. Results from previous studies may result from genetic factors. Lewis and F344 rats have neurochemical differences that may be relevant to probabilistic discounting and how drugs affect such behavior. In this study, we evaluated dose-dependent effects of d-amphetamine and atomoxetine on probabilistic discounting of Lewis and F344. Male Lewis and F344 chose between one food pellet delivered 100% of the time and three food pellets delivered following decreasing probabilities of delivery (i.e. 100%, 66.7%, 33.3%, 16.5%, and 8.25%). Saline, d-amphetamine (0.1–1.8 mg/kg), and atomoxetine (0.1–7.8 mg/kg) were tested acutely. Lewis and F344 did not differ in choice at baseline. d-Amphetamine increased risky choice for both rat strains at low-to-moderate doses, although it did so at a lower dose (0.1 and 0.3 mg/kg) for F344 as compared to Lewis (0.3 mg/kg only). At high doses (1.0 and 1.8 mg/kg), d-amphetamine disrupted choice, increased frequencies of omitted trials, and reduced reinforcer sensitivity. Although atomoxetine increased frequencies of omitted trials at high doses (5.6 and 7.8 mg/kg), it had no effect on probabilistic discounting for either rat strain. Although Lewis and F344 differ in various types of impulsivity (i.e. motor, choice), with Lewis being the more impulsive of the two, the present results suggest that Lewis and F344 do not differ in risk-based decision-making. Effects of d-amphetamine on probabilistic discounting may be biology-dependent and differ from effects of atomoxetine.
Pharmacological inhibition of glycogen synthase kinase 3 increases operant alcohol self-administration in a manner associated with altered pGSK-3β, protein interacting with C kinase and GluA2 protein expression in the reward pathway of male C57BL/6J mice
Authors: Faccidomo Sara , Holstein Sarah E. , Santanam Taruni S. , Saunders Briana L. , Swaim Katarina S. , Reid Grant T. , O’Neill Conor , Eastman Vallari R. , Hodge Clyde W.
Published: September 2019

Glycogen synthase kinase 3 (GSK-3) is a constitutively active serine-threonine kinase that regulates numerous signaling pathways and has been implicated in neurodegenerative and neuropsychiatric diseases. Alcohol exposure increases GSK-3β (ser9) phosphorylation (pGSK-3β); however, few studies have investigated whether GSK-3 regulates the positive reinforcing effects of alcohol, which drive repetitive drug use. To address this goal, male C57BL/6J mice were trained to lever press on a fixed-ratio 4 schedule of sweetened alcohol or sucrose-only reinforcement in operant conditioning chambers. The GSK-3 inhibitor CHIR 99021 (0–10 mg/kg, i.p.) was injected 45 minutes prior to self-administration sessions. After completion of the self-administration dose–effect curve, potential locomotor effects of the GSK-3 inhibitor were assessed. To determine molecular efficacy, CHIR 99021 (10 mg/kg, i.p.) was evaluated on pGSK-3β, GSK-3β, protein interacting with C kinase (PICK1), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA2 subunit protein expression in amygdala, nucleus accumbens (NAcb), and frontal cortex. Results showed that CHIR 99021 (10 mg/kg) dose-dependently increased alcohol reinforced responding with no effect on sucrose self-administration or locomotor activity. CHIR 99021 (10 mg/kg) significantly decreased pGSK-3β expression in all brain regions tested, reduced PICK1 and increased GluA2 total expression only in the NAcb. We conclude that GSK-3 inhibition increased the reinforcing effects of alcohol in mice. This was associated with reduced pGSK-3β and PICK1, and increased GluA2 expression. Given prior results showing that AMPA receptor activity regulates alcohol self-administration, we propose that signaling through the GSK-3/PICK1/GluA2 molecular pathway drives the positive reinforcing effects of the drug, which are required for abuse liability.
Factors Associated With Interhospital Transfer of Trauma Victims
Authors: Viel Isabelle Lauria , Moura Bruna Roberta Siqueira , Martuchi Sérgio Dias , de Souza Nogueira Lilia
Published: September 2019

This study aimed to identify the factors associated with interhospital transfer of trauma victims treated in the emergency department of a nontertiary hospital. Retrospective analysis of medical records of trauma victims treated from January to July 2014 in the emergency department of a hospital not specialized in trauma care and located in Brazil was undertaken. The inclusion criteria were as follows: being 15 years or older; being a trauma victim; having received prehospital care; and being admitted to the hospital directly from the scene of the accident. Pearson's chi-square, Mann–WhitneyU, Fisher's exact tests, and multiple logistic regression were used in the analyses. The sample was made up of 246 patients, mostly men (67.9%) and blunt trauma victims (97.6%). The mean age of the trauma victims was 44.2 (SD= 22.1). Falls were the most frequent external cause (41.1%). Forty patients were transferred to a tertiary care center, mostly for orthopedic treatment (70%). The factors associated with interhospital transfer of victims were severity of the trauma according to the Injury Severity Score ([ISS]; mean ±SDof ISS = 8.1 ± 4.5; odds ratio = 1.14; 95% confidence interval [1.06, 1.24];p= .001) and extremities/pelvic girdle as the body region most severely injured (mean ±SDof extremities/pelvic girdle Abbreviated Injury Scale score = 2.9 ± 0.5; odds ratio = 3.86; 95% confidence interval [1.71, 8.72;p= .001). Identification of the risk factors for interhospital transfer of trauma victims treated in hospitals without a trauma center provides important information for the creation of referral and counter-referral policies to facilitate the process and ensure definitive early treatment and improved patient survival.
A Review of Two Heparin Prophylaxes for Trauma
Authors: Yu Hyunmin (David)
Published: September 2019

Venous thromboembolism (VTE) prophylaxis has a significant impact on mortality and morbidity in trauma patients. This article reviews 9 published studies that investigate and compare low-dose unfractionated heparin (LDUH) with low-molecular-weight heparin (LMWH) for prophylaxis of VTE in the trauma patient population in terms of efficacy, safety, and cost. There is no difference between LDUH and LMWH for VTE prophylaxis. Four databases were utilized to find 9 relevant studies whose patient population was adult trauma patients: PubMed, CINAHL, EMBASE and Scopus. Two studies found statistically significant differences in deep venous thrombosis, and 3 found differences in pulmonary embolism between LDUH and LMWH. Only 1 study demonstrated a significant difference in bleeding complications between the 2 treatment regimens. Two statedthat using LDUH resulted in remarkable cost savings versus LMWH. The 9 studies all came to different conclusions. Contrary findings may have been affected by population variety, different dosing regimens, various applications of mechanical VTE prophylaxis, and/or different VTE-screening tools. All of the studies had major variances leading to conflicting results, which made this review unable to draw concrete conclusions. Limitations of each study, population variety, and disparity of dosing regimens made it difficult for this review to make recommendations for practice.
MICROtransplant to refractory acute myeloid leukemia in Egyptian population
Authors: Emarah Ziad , Shamaa Sameh , El-Zaafarany Maha , Eisa Noha , Khalaf Mohamed
Published: September 2019

Purpose of review

The purpose of this review is to outline Egyptian experience of nonengraftment haploidentical cellular therapy [microtransplantation (MST)] for patients with refractory acute myeloid leukemia.

Recent findings

The use of granulocyte colony-stimulating factor primed halo-identical MST appears to be a biologically active therapy in patients with refractory acute myeloid leukemia (AML), especially in patients received less than four previous chemotherapy lines, fludarabine-free previous chemotherapy, response naïve and young age patients.

Refractory AML is still challenging. MST is promising, however the optimum conditioning, stem-cell dose, matching degree are factors should be optimized.
Improving Post‐induction Antitumor Necrosis Factor Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease
Authors: Guido Amy J. , Crandall Wallace , Homan Emily , Dotson Jennifer , Maltz Ross M. , Donegan Amy , Drobnic Barbara , Oates Melanie , Boyle Brendan
Published: September 2019

Objectives:

Adequate serum drug levels of tumor necrosis factor‐alpha inhibitors (anti‐TNF) have been shown to improve outcomes in patients with inflammatory bowel disease. We aim to describe the quality improvement (QI) methods used at our institution to improve post‐induction therapeutic drug monitoring (TDM) in children initiating anti‐TNF therapy (infliximab and adalimumab) and describe the frequency of subtherapeutic anti‐TNF levels.

Methods:

Beginning in February 2016, all patients initiating anti‐TNF therapy were identified and tracked. Interventions to improve TDM, including the initiation of therapy plans for infliximab, real‐time reminders for practitioners, and scheduling modifications for those initiating anti‐TNF therapies were implemented using the Institute for Healthcare Improvement Plan‐Do‐Study‐Act cycle approach. Statistical process control charts were used to demonstrate improvement over time. Anti‐TNF levels and presence of antidrug antibodies were also recorded.

Results:

Using QI methodology, we improved post‐induction anti‐TNF TDM from a baseline of 43% in 2015 to >80% by the end of 2017, with sustained improvement. Infliximab post‐induction TDM improved from a baseline of 59% to 82%, whereas adalimumab post‐induction TDM improved from baseline of 14% to 79%. In total, 36% of all anti‐TNF post‐induction levels were <5 μg/mL, with nearly 60% of post‐induction infliximab levels being <5 μg/mL.

Conclusions:

Through incremental QI approaches, we improved the utilization of anti‐TNF post‐induction TDM with sustained improvement, approaching our goal of 90%. Subtherapeutic post‐induction infliximab levels were common, indicating a strong need for anti‐TNF TDM and an opportunity for dose optimization.
Neurodevelopmental Outcomes in Preschool and School Aged Children With Biliary Atresia and Their Native Liver
Authors: Squires James E. , Lee Ng Vicky , Hawthorne Kieran , Henn Lisa L. , Sorensen Lisa G. , Fredericks Emily M. , Alonso Estella M. , Murray Karen F. , Loomes Kathleen M. , Karpen Saul J. , Cavallo Laurel A. , Molleston Jean P. , Bezerra Jorge A. , Rosenthal Philip , Squires Robert H. , Wang Kasper S. , Schwarz Kathleen B. , Arnon Ronen , Magee John C. , Sokol Ronald J. ,   Childhood Liver Disease Research Network (ChiLDReN)
Published: September 2019

Objectives:

The aim of the study was to assess neurodevelopmental outcomes among children with biliary atresia (BA) surviving with their native liver at ages 3 to 12 years and evaluate variables that associate with neurodevelopment.

Methods:

Participants (ages 3–12 years) in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with Weschler Preschool and Primary Scale of Intelligence, 3rd edition (WPPSI‐III, ages 3–5 years) and Weschler Intelligence Scale for Children, 4th edition (WISC‐IV, ages 6–12 years). Continuous scores were analyzed using Kolmogorov‐Smironov tests compared with a normal distribution (mean = 100 ± 15). Effect of covariates on Full‐Scale Intelligence Quotient (FSIQ) was analyzed using linear regression.

Results:

Ninety‐three participants completed 164 WPPSI‐III (mean age 3.9) and 51 WISC‐IV (mean age 6.9) tests. WPPSI‐III FSIQ (104 ± 14, P < 0.02), Verbal IQ (106 ± 14, P < 0.001), and General Language Composite (107 ± 16, P < 0.001) distributions were shifted higher compared with test norms. WISC‐IV FSIQ (105 ± 12, P < 0.01), Perceptual Reasoning Index (107 ± 12, P < 0.01), and Processing Speed Index (105 ± 10, P < 0.02) also shifted upwards. In univariate and multivariable analysis, parent education (P < 0.01) was a significant predictor of FSIQ on WPPSI‐III and positively associated with WISC‐IV FSIQ. Male sex and higher total bilirubin and gamma glutamyl transferase (GGT) predicted lower WPPSI‐III FSIQ. Portal hypertension was predictive of lower WISC‐IV FSIQ.

Conclusions:

This cohort of children with BA and native liver did not demonstrate higher prevalence of neurodevelopmental delays. Markers of advanced liver disease (higher total bilirubin and GGT for age ⩽5 years; portal hypertension for age ≥6) correlate with lower FSIQ and may identify a vulnerable subset of patients who would benefit from intervention.
Uncovering Demographic, Clinical, Triggering Factors Similarities Between Migraine and Irritable Bowel Syndrome
Authors: Hajj Aline , Mourad Diane , Ghossoub May , Hallit Souheil , Geagea Antoine , Abboud Halim , El Mouallem Hanna , Saniour Philippe , El Hachem Nabil , Rabbaa Khabbaz Lydia
Published: September 2019

The objective was to uncover demographical and clinical factors associated with migraine and irritable bowel syndrome (IBS) in a group of patients experiencing both painful disorders and to identify their triggering factors. A prospective study was performed between January 2016 and June 2017. Clinical characteristics and potential generating factors for both pathologies were then assessed using validated questionnaires. Our study showed that the percentage of patients diagnosed with migraine and having IBS was 34.3%. Compared with patients with migraine alone, patients having both diseases were identified with higher prevalence of concomitant chronic/psychiatric diseases, lower frequency of migraine attacks, and lower prevalence of throbbing/distressing/enervating pain and concentration difficulties than patients with migraine alone. Moreover, patients in this subgroup had moderate abdominal pain intensity, and constipation was the predominant stool type. Finally, some dietary and environmental factors seem to be significantly important triggering factors of migraine/IBS pain.
Developing Texting for Relapse Prevention: A Scalable mHealth Program for People With Schizophrenia and Schizoaffective Disorder
Authors: Ybarra Michele L. , Rodriguez Katrina , Madison Hannah , Mojtabai Ramin , Cullen Bernadette A.
Published: September 2019

Symptom relapse in people with schizophrenia and schizoaffective disorder is common and has a negative impact on the course of illness. Here, we describe the development of Texting for Relapse Prevention, a scalable, cost-effective text messaging relapse prevention program that queries patients' “early warning signs” daily. Results of development focus groups and content advisory teams with 25 patients and 19 providers suggest that patients were enthusiastic about the program and thought that receiving daily messages about their symptoms would help them feel supported. Providers also were positive about the idea but worried that the program might interfere with patient-provider communication if patients thought that the messages were coming from providers. Patients found the content positive and actionable. The program was improved to address this feedback. This iterative development process that included multiple stakeholders ensured that the program is feasible and acceptable to both patients and providers.
Paranoid Ideation Without Psychosis Is Associated With Depression, Anxiety, and Suicide Attempts in General Population
Authors: Na Eun Jin , Choi Kwan Woo , Hong Jin Pyo , Cho Maeng Je , Fava Maurizio , Mischoulon David , Jeon Hong Jin
Published: September 2019

This study aimed to characterize the association between paranoid ideation without psychosis (PIP) and suicide attempts in a general population. A total of 12,532 adults were randomly selected as the study sample through one-person-per-household method. Subjects completed a face-to-face interview. Among 12,532 subjects, 471 (3.76%) met criteria for the PIP group. The PIP group was younger with more divorced/widowed/separated and lower income than the non-PIP group. The PIP group showed more than fivefold higher lifetime suicide attempt (LSA) rates and ninefold multiple attempt rates than the non-PIP group. Among PIP symptoms, “spouse was being unfaithful” showed the strongest association with LSA (adjusted odds ratio [AOR], 4.49; 95% confidence interval, 2.95–6.85). Major depressive disorder (MDD) in combination with PIP was associated with a higher risk of LSA (AOR, 15.39; 95% confidence interval, 9.63–24.59) compared with subjects without MDD or PIP. In conclusion, PIP, especially “doubting spouse,” was significantly associated with LSA. PIP in combination with comorbid MDD showed higher risk of LSA than subjects without PIP or MDD.
Diglossia in the Etiology of Schizophrenia
Authors: Alherz Mohammad , Almusawi Hashemiah , Barry Denis S.
Published: September 2019

A hypothesis offering diglossia as a potential risk factor for schizophrenia is presented. This is supported primarily by an account of the numerous co-occurrences between the diglossic phenomenon and the established risk factors and features of schizophrenia, such as language impairment, working memory dysfunction, social adversity, urbanicity, migration, and ethnicity, as well as some of the broader educational elements including illiteracy, reading deficits, and poor academic attainment. With an emphasis on the inherent role of language in schizophrenia and the demand for elucidating a mechanism behind its risk factors, we propose that a diglossic environment in childhood may constitute a neurodevelopmental insult predisposing to the development of the disorder. This relationship may be mediated by the reduced lateralization of language in the brain, which has been observed in relation to schizophrenia.
A Practical Guide to Artificial Intelligence–Based Image Analysis in Radiology
Authors: Weikert Thomas , Cyriac Joshy , Yang Shan , Nesic Ivan , Parmar Victor , Stieltjes Bram
Published: September 2019

The use of artificial intelligence (AI) is a powerful tool for image analysis that is increasingly being evaluated by radiology professionals. However, due to the fact that these methods have been developed for the analysis of nonmedical image data and data structure in radiology departments is not “AI ready”, implementing AI in radiology is not straightforward. The purpose of this review is to guide the reader through the pipeline of an AI project for automated image analysis in radiology and thereby encourage its implementation in radiology departments. At the same time, this review aims to enable readers to critically appraise articles on AI-based software in radiology.