Journals

In Defense of the Employer Mandate: Hedging Against Uninsurance.

In Defense of the Employer Mandate: Hedging Against Uninsurance.

JAMA. 2014 Dec 18;

Authors: McDonough JE, Adashi EY

PMID: 25521209 [PubMed - as supplied by publisher]

Monitoring postcolonoscopy colorectal cancers: dangerous crossroads?

Monitoring postcolonoscopy colorectal cancers: dangerous crossroads?

Gut. 2014 Dec 17;

Authors: Sanduleanu S, Dubé C

PMID: 25520266 [PubMed - as supplied by publisher]

Evaluation of Opioid Modulation in Major Depressive Disorder.

Evaluation of Opioid Modulation in Major Depressive Disorder.

Neuropsychopharmacology. 2014 Dec 18;

Authors: Ehrich E, Turncliff R, Du Y, Leigh-Pemberton R, Fernandez E, Jones R, Fava M

Abstract

Although opioids have known antidepressant activity, their use in major depressive disorder (MDD) has been greatly limited by risk of abuse and addiction. Our aim was to determine whether opioid modulation achieved through a combination of a μ opioid partial agonist, buprenorphine (BUP), and a potent μ opioid antagonist, samidorphan (SAM), would demonstrate antidepressant activity without addictive potential. A placebo-controlled crossover study assessed the opioid pharmacodynamic profile following escalating doses of SAM co-administered with BUP in opioid-experienced adults. A subsequent one-week, placebo-controlled, parallel-group study was conducted in subjects with MDD and an inadequate response to standard antidepressant therapy. This second study evaluated safety and efficacy of ratios of BUP/SAM that were associated with partial and with maximal blockade of opioid responses in the initial study. Pupillometry, visual analog scale assessments and self-report questionnaires demonstrated that increasing amounts of SAM added to a fixed dose of BUP resulted in dose-dependent reductions in objective and subjective opioid effects, including euphoria and drug liking, in opioid-experienced adults. Following 7 days of treatment in subjects with MDD, a 1 : 1 ratio of BUP and SAM, the ratio associated with maximal antagonism of opioid effects, exhibited statistically significant improvement vs. placebo in HAM-D17 total score (p=0.032) and nearly significant improvement in MADRS total score (p=0.054). Overall, BUP/SAM therapy was well tolerated. A combination of BUP and SAM showed antidepressant activity in subjects with MDD. Balanced agonist-antagonist opioid modulation represents a novel and potentially clinically important approach to the treatment of MDD and other psychiatric disorders.Neuropsychopharmacology accepted article preview online, 18 December 2014. doi:10.1038/npp.2014.330.

PMID: 25518754 [PubMed - as supplied by publisher]

Association Study of Seven GWAS-Identified Common Variants with Nonalcoholic Fatty Liver Disease in Chinese Children.

Association Study of Seven GWAS-Identified Common Variants with Nonalcoholic Fatty Liver Disease in Chinese Children.

J Pediatr Gastroenterol Nutr. 2014 Dec 16;

Authors: Shang X, Song J, Liu F, Ma J, Wang H

Abstract

OBJECTIVES:: Three genome-wide association studies were previously done for nonalcoholic fatty liver disease (NAFLD) among individuals of western countries and identified several genetic variants associated with NAFLD. The study aimed to identify whether seven GWAS-identified common variants (GCKR rs780094, PDGFA rs343064, FDFT1 rs2645424, COL13A1 rs1227756, EHBP1L1 rs6591182, NCAN rs2228603, PNPLA3 rs738409) were associated with NAFLD in Chinese children.

METHODS:: The case-control study recruited 1,027 Chinese children aged 7 to 18, including 162 children with NAFLD and 865 children without NAFLD. Anthropometric measurements, alanine transaminase (ALT) detection, liver ultrasound examination and genotyping of 7 variants were performed.

RESULTS:: The G-allele of PNPLA3 rs738409 was associated with NAFLD (OR = 1.55, 95%CI: 1.13-2.11, P = 0.006) and moderate to severe steatosis (OR = 3.77, 95%CI: 1.78-7.98, P = 0.001) adjusted for age, gender and BMI standard deviation score (BMI-SDS). Additionally we found each G-allele of rs738409 increased ALT level by 1.09 IU/L (P = 0.011). Subjects carrying 10 or more risk alleles of 7 variants had an odds ratio of 4.76 (P = 0.025) for NAFLD compared with subjects carrying 3 or fewer risk alleles.

CONCLUSIONS:: The PNPLA3 rs738409 G-allele was associated with NAFLD and ALT level in Chinese children. It had stronger association with moderate to severe steatosis. Children carrying 10 or more risk alleles of 7 variants were susceptible for NAFLD.

PMID: 25522307 [PubMed - as supplied by publisher]

Antibodies to Deamidated Gliadin Peptide in Diagnosis of Celiac Disease in Children.

Antibodies to Deamidated Gliadin Peptide in Diagnosis of Celiac Disease in Children.

J Pediatr Gastroenterol Nutr. 2014 Dec 16;

Authors: Lammi A, Arikoski P, Simell S, Kinnunen T, Simell V, Paavanen-Huhtala S, Hinkkanen A, Veijola R, Knip M, Toppari J, Vaarala O, Simell O, Ilonen J

Abstract

OBJECTIVES:: Determinationof antibodies to synthetic deamidatedgliadin peptides (anti-DGP) may work as an alternative or complement the commonly used test for tissue transglutaminase antibodies (TGA) in the diagnosis of celiac disease (CD). We analyzed the performance of a time-resolved immunofluorometry (TR-IFMA) based anti-DGP assay in the diagnosis of CD in children and also retrospectively analyzed the appearance of anti-DGP antibodies before TGA seroconversion.

METHODS:: The study included 92 children with biopsy-confirmed CD. Serum samples were taken at the time or just before the clinical diagnosis. The control group comprised of 82 TGA-negative children who were positive for HLA-DQ2 or -DQ8.

RESULTS:: Based on receiver operating characteristics (ROC) curves, the optimal cut-off value for IgA anti-DGP positivity was 153 arbitrary units (AU) with a sensitivity of 92.4% and specificity of 97.6% and that for IgG anti-DGP 119 AU, with a sensitivity of 97.8% and specificity of 97.6%. All of the 92 children with CD were either IgA or IgG anti-DGP positive at the time of diagnosis. Sera from 48 children with CD were also analyzed retrospectively before the diagnosis. Anti-DGP antibodies preceded TGA positivity in 35 of 48 CD children and appeared a median of one year earlier.

CONCLUSIONS:: The TR-IFMA assay for detecting anti-DGP antibodies shows high sensitivity and specificity for the diagnosis of CD in children. In a majority of our study population anti-DGP seropositivity preceded TGA positivity, indicating that earlier detection of CD may be possible by monitoring anti-DGP antibodies frequently in genetically susceptible children.

PMID: 25522308 [PubMed - as supplied by publisher]

Reevaluation of Acetylcholinesterase Staining for the Diagnosis of Hirschsprung’s Disease and Allied Disorders.

Reevaluation of Acetylcholinesterase Staining for the Diagnosis of Hirschsprung’s Disease and Allied Disorders.

J Pediatr Gastroenterol Nutr. 2014 Dec 16;

Authors: Budianto IR, Obata S, Kinoshita Y, Yoshimaru K, Yanagi Y, Miyata J, Nagata K, Ieiri S, Taguchi T

Abstract

OBJECTIVES:: Acetylcholinesterase (AChE) staining has become the gold standard for definitively diagnosing Hirschsprung’s disease (HD), although some pitfalls have been reported. We reevaluated a large series at our institute in order to validate the accuracy of AChE staining for detecting HD.

METHODS:: A retrospective study of the rectal mucosal specimens of all children with suspected HD over a 13-year period was performed. The specimens were stained according to the modified Karnovsky-Roots method for AChE staining. The final diagnosis, prognosis and management after the histopathological diagnosis were analyzed with a questionnaire sent to the patient’s original hospital.

RESULTS:: Three hundred and fifty-eight specimens were collected. One hundred and twenty-two (34%) specimens were diagnosed as HD, 198 (55%) as non-Hirschsprung’s disease (non-HD), 25 (7%) as “undetermined” and 13 (4%) as “inappropriate.” The non-HD group contained 190 (96%) specimens with a normal appearance and eight (4%) specimens with suspected intestinal neuronal dysplasia (IND). Three hundred and six of 358 questionnaires were returned. The final diagnosis showed that no specimens first diagnosed as HD were identified as non-HD and vice versa, for a sensitivity and specificity of 100%. Four cases were finally diagnosed as chronic idiopathic intestinal pseudo-obstruction (CIIP) in the non-HD group. All HD patients underwent radical surgery. Most non-HD patients were managed conservatively, although some continued to have constipation.

CONCLUSIONS:: AChE staining is an accurate tool for differentiating between HD and non-HD with high sensitivity and specificity. CIIP can be included in cases of non-HD; therefore, careful follow-up is mandatory.

PMID: 25522309 [PubMed - as supplied by publisher]

A cross sectional analysis of satisfaction in open access versus traditional referral for upper endoscopy in children.

A cross sectional analysis of satisfaction in open access versus traditional referral for upper endoscopy in children.

J Pediatr Gastroenterol Nutr. 2014 Dec 16;

Authors: Isaac DM, Persad R, Huynh HQ, Shirton L, Turner JM

Abstract

OBJECTIVES:: In traditional access endoscopy (TAE), patients are booked for endoscopy following a gastroenterology clinic assessment. In contrast, open access endoscopy (OAE) patients are seen for the first time on the day of the procedure, providing same day procedural consent. Controversy exists over the use of OAE in adults, both with the consent process and patient satisfaction. No literature exists describing satisfaction with OAE in pediatrics. We therefore aimed to assess pediatric patient and caregiver satisfaction in OAE compared to TAE.

METHODS:: Consecutive pediatric patients, and their caregivers, undergoing elective upper endoscopy from May to December of 2012 at the Stollery Children’s Hospital (Edmonton, Alberta) were consented for a cross-sectional survey. Seven pre- and five post-procedure questions were completed regarding mood, satisfaction with the wait time and with the information provided. Group demographics and endoscopy wait times were collected.

RESULTS:: Median wait time with OAE was less compared to TAE (57 days vs 196 days; p < 0.001). OAE patients reported worse mood pre-procedure than TAE patients (35.3% vs 10.7%; p = 0.046). OAE caregivers and patients reported more mood disturbance if required to wait longer for endoscopy by attending clinic pre-procedure (OAE caregivers 62.2%; OAE patients 64.7%).

CONCLUSIONS:: OAE is associated with worse pre-endoscopy patient mood, however children and caregivers seem concerned about longer wait times associated with TAE. Given the significantly shorter wait times in OAE, identifying methods to minimize current limitations of OAE will be useful to improve clinical practices in pediatric gastroenterology.

PMID: 25522310 [PubMed - as supplied by publisher]

Randomized trial of micafungin for the prevention of invasive fungal infection in high-risk liver transplant recipients.

Randomized trial of micafungin for the prevention of invasive fungal infection in high-risk liver transplant recipients.

Clin Infect Dis. 2014 Dec 17;

Authors: Saliba F, Pascher A, Cointault O, Laterre PF, Cervera C, De Waele JJ, Cillo U, Langer RM, Lugano M, Göran-Ericzon B, Phillips S, Tweddle L, Karas A, Brown M, Fischer L, on behalf of the TENPIN study investigators

Abstract

BACKGROUND:  Invasive fungal infection (IFI) following liver transplantation is associated with significant morbidity and mortality. Antifungal prophylaxis is rational for liver transplant patients at high IFI risk.

METHODS:  In this open-label, non-inferiority study, patients were randomized 1:1 to receive intravenous micafungin 100 mg or center-specific standard care (fluconazole, liposomal amphotericin B, or caspofungin) post-transplant. The primary endpoint was clinical success (absence of a proven/probable IFI and no need for additional antifungals) at end of prophylaxis (EOP). Non-inferiority (10% margin) of micafungin versus standard care was assessed in the per protocol (PPS) and full analysis sets (FAS). Safety assessments included adverse events (AEs), liver and kidney function tests.

RESULTS:  The FAS comprised 344 patients (172 micafungin; 172 standard care). Mean age was 51.2 years; 48.0% had a Model for End-Stage Liver Disease (MELD) score ≥20. At EOP (mean treatment duration 17 days), clinical success was 98.6% for micafungin and 99.3% for standard care (Δ standard care-micafungin [95% CI]: 0.7% [-2.7, 4.4]) in the PPS and 96.5% and 93.6%, respectively (-2.9% [-8.0, 1.9]), in the FAS. Incidences of drug-related AEs for micafungin and standard care were 11.6% and 16.3%, leading to discontinuation in 6.4% and 11.6% of cases, respectively. At EOP, liver function tests were similar but creatinine clearance was higher in micafungin- versus standard care-treated patients.

CONCLUSION:  Micafungin was non-inferior to standard care as antifungal prophylaxis in liver transplant patients at high IFI risk. AE profiles and liver function at EOP were similar although kidney function was better with micafungin.

PMID: 25520332 [PubMed - as supplied by publisher]

A Cluster-Randomized Controlled Trial of a Multicomponent Intervention Protocol for Pneumonia Prevention Among Nursing Home Elders.

A Cluster-Randomized Controlled Trial of a Multicomponent Intervention Protocol for Pneumonia Prevention Among Nursing Home Elders.

Clin Infect Dis. 2014 Dec 16;

Authors: Juthani-Mehta M, Van Ness PH, McGloin J, Argraves S, Chen S, Charpentier P, Miller L, Williams K, Wall D, Baker D, Tinetti M, Peduzzi P, Quagliarello VJ

Abstract

BACKGROUND:  Pneumonia remains an important public health problem among elderly nursing home residents. This clinical trial sought to determine if a multicomponent intervention protocol, including manual tooth/gum brushing plus 0.12% chlorhexidine oral rinse, twice per day, plus upright positioning during feeding, could reduce the incidence of radiographically documented pneumonia among nursing home residents, compared with usual care.

METHODS:  This cluster-randomized clinical trial was conducted in 36 nursing homes in Connecticut. Eligible residents >65 years with at least 1 of 2 modifiable risk factors for pneumonia (ie, impaired oral hygiene, swallowing difficulty) were enrolled. Nursing homes were randomized to the multicomponent intervention protocol or usual care. Participants were followed for up to 2.5 years for development of the primary outcome, a radiographically documented pneumonia, and secondary outcome, a lower respiratory tract infection (LRTI) without radiographic documentation.

RESULTS:  A total of 834 participants were enrolled: 434 to intervention and 400 to usual care. The trial was terminated for futility. The number of participants in the intervention vs control arms with first pneumonia was 119 (27.4%) vs 94 (23.5%), respectively, and with first LRTI, 125 (28.8%) vs 100 (25.0%), respectively. In a multivariable Cox regression model, the hazard ratio in the intervention vs control arms, respectively, was 1.12 (95% confidence interval [CI], .84-1.50; P = .44) for first pneumonia and 1.07 (95% CI, .79-1.46, P = .65) for first LRTI.

CONCLUSIONS:  The multicomponent intervention protocol did not significantly reduce the incidence of first radiographically confirmed pneumonia or LRTI compared with usual care in nursing home residents. Clinical Trials Registration. NCT00975780.

PMID: 25520333 [PubMed - as supplied by publisher]

Preventing Aspiration Pneumonia in High-Risk Nursing Home Residents: Role of Chlorhexidine-Based Oral Care Questioned Again.

Preventing Aspiration Pneumonia in High-Risk Nursing Home Residents: Role of Chlorhexidine-Based Oral Care Questioned Again.

Clin Infect Dis. 2014 Dec 16;

Authors: Mody L

PMID: 25520334 [PubMed - as supplied by publisher]