bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaccine strategies for lowering LDL by immunization against proprotein convertase subtilisin/kexin type 9
Authors: Chackerian Bryce , Remaley Alan
Published: April 2016

Purpose of review

mAbs targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) have the potential to become groundbreaking therapies for the treatment of hypercholesterolemia. However, one major drawback of mAb-based therapy for a chronic condition like dyslipidemia is its relatively high cost. This review summarizes two recent studies describing novel vaccine approaches for lowering LDL-cholesterol by active immunization against PCSK9.

Recent findings

PCSK9 is a plasma protein secreted by the liver that controls cholesterol homeostasis by enhancing endosomal and lysosomal degradation of the LDL receptor. Two PCSK9 inhibitory mAbs (evolocumab and alirocumab) have recently been approved by the Food and Drug Administration and a third mAb (bococizumab) is in late stage clinical trials. Treatment with PCSK9 mAbs, in combination with statins, reduces LDL-cholesterol levels by as much as 40–60%. As an alternative to mAbs, there have been two recent studies describing the development of vaccines that target PCSK9. These studies have shown that PCSK9 vaccines can effectively induce high-titer antibody responses that reduce proatherogenic lipoproteins in animal models.

A PCSK9 vaccine-based approach could serve as a more widely applicable and a more cost-effective approach than mAb therapy for controlling hypercholesteremia and associated cardiovascular disease.
Mode of Delivery Determines Neonatal Pharyngeal Bacterial Composition and Early Intestinal Colonization
Authors: Brumbaugh David E. , Arruda Jaime , Robbins Kristen , Ir Diana , Santorico Stephanie A. , Robertson Charles E. , Frank Daniel N.
Published: April 2016

Objectives:

Bacterial colonization and succession of the human intestine shape development of immune function and risk for allergic disease, yet these processes remain poorly understood. We investigated the relations between delivery mode, initial bacterial inoculation of the infant oropharynx (OP), and intestinal colonization.

Methods:

We prospectively collected maternal rectal and vaginal swabs, infant OP aspirates, and infant stool from 23 healthy mother/infant pairs delivering by cesarean (CS) or vaginal delivery (VD) in an academic hospital. Bacterial abundance (16S rRNA sequencing) and community similarity between samples were compared by delivery mode. Shotgun DNA metagenomic sequencing of infant stool was performed.

Results:

VD infants had higher abundance of Firmicutes (mainly lactobacilli) in OP aspirates whereas CS OP aspirates were enriched in skin bacteria. OP aspirates were more similar to maternal vaginal and rectal microbiomes in VD compared with CS. Bacteroidetes were more abundant through 6 weeks in stool of VD infants. Infant fecal microbiomes in both delivery groups did not resemble maternal rectal or vaginal microbiomes. Differences in fecal bacterial gene potential between CS and VD at 6 weeks clustered in metabolic pathways and were mediated by abundance of Proteobacteria and Bacteroidetes.

Conclusions:

CS infants exhibited different microbiota in the oral inoculum, a chaotic pattern of bacterial succession, and a persistent deficit of intestinal Bacteroidetes. Pioneer OP bacteria transferred from maternal vaginal and intestinal communities were not prominent constituents of the early infant fecal microbiome. Oral inoculation at birth may impact the intestinal microenvironment, thereby modulating early succession of intestinal bacteria.
NASPGHAN Clinical Report
Authors: Ardura Monica I. , Toussi Sima S. , Siegel Jane D. , Lu Ying , Bousvaros Athos , Crandall Wallace
Published: April 2016

Children and adolescents with inflammatory bowel disease (IBD) receiving therapy with tumor necrosis factor α inhibitors (anti‐TNFα) pose a unique challenge to health care providers in regard to the associated risk of infection. Published experience in adult populations with distinct autoinflammatory and autoimmune diseases treated with anti‐TNFα therapies demonstrates an increased risk of serious infections with intracellular bacteria, mycobacteria, fungi, and some viruses; however, there is a paucity of robust pediatric data. With a rising incidence of pediatric IBD and increasing use of biologic therapies, heightened knowledge and awareness of infections in this population is important for primary care pediatricians, pediatric gastroenterologists, and infectious disease (ID) physicians. This clinical report is the result of a consensus review performed by pediatric ID and gastroenterology physicians detailing relevant published literature regarding infections in pediatric patients with IBD receiving anti‐TNFα therapies. The objective of this document is to provide comprehensive information for prevention, surveillance, and diagnosis of infections based on current knowledge, until additional pediatric data are available to inform evidence‐based recommendations.
Effect of Formula Containing Lactobacillus reuteri DSM 17938 on Fecal Microbiota of Infants Born by Cesarean‐Section
Authors: Garcia Rodenas Clara L. , Lepage Melissa , Ngom‐Bru Catherine , Fotiou Aikaterini , Papagaroufalis Konstantinos , Berger Bernard
Published: April 2016

Objectives:

Microbiota modulation by probiotics in infants born by cesarean (C)‐section is poorly understood. We aimed at assessing the response of C‐section–delivered infant microbiota to a formula containing Lactobacillus reuteri Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSM) 17938 and comparing it with that of vaginally delivered infants.

Methods:

Infants delivered by C‐section (C) and vaginally (V) were randomized to receive either control formula (CCt, n = 10; VCt, n = 10) or the same formula containing L reuteri (CLr, n = 11; VLr, n = 9) within 72 hours following birth. Stool samples were collected at 2 weeks and 4 months of age. Microbial DNA was extracted, amplified, and pyrosequenced.

Results:

The phylogenetic profiles of the CLr, VCt, and VLr microbiota were not significantly different at any age but diverged from that of CCt at 2 weeks. Compared with VCt, CCt displayed lower Bifidobacterium and higher Enterobacter, unclassified Enterobacteriaceae, Enterococcus, Clostridium, and unclassified Clostridiaceae relative abundance at 2 weeks, as well as lower Collinsella and higher Enterococcus and Coprococcus abundance at 4 months. The level of most of these taxa was not significantly different between the CLr and the vaginal‐delivery groups. Compared with VCt, the only difference observed in VLr microbiota was higher Lactobacillus at the 2 study ages and Coprococcus at 4 months.

Conclusions:

Our results show that a formula containing L reuteri DSM 17938 does not essentially alter the microbiota in vaginally born infants. In C‐section–delivered infants, however, this strain seems to play the role of keystone species by modulating the early development of the microbiota toward the composition found after vaginal delivery.
Prebiotics and Bioactive Milk Fractions Affect Gut Development, Microbiota, and Neurotransmitter Expression in Piglets
Authors: Berding Kirsten , Wang Mei , Monaco Marcia H. , Alexander Lindsey S. , Mudd Austin T. , Chichlowski Maciej , Waworuntu Rosaline V. , Berg Brian M. , Miller Michael J. , Dilger Ryan N. , Donovan Sharon M.
Published: April 2016

Objective:

This study tested the hypothesis that the addition of prebiotics and 2 functional milk ingredients to infant formula would maintain normal growth and gut development, and modify microbiota composition and neurotransmitter gene expression in neonatal piglets.

Methods:

Two‐day‐old male piglets (n = 24) were fed formula (CONT) or formula with polydextrose (1.2 g/100 g diet), galactooligosaccharides (3.5 g/100 g diet), bovine lactoferrin (0.3 g/100 g diet), and milk fat globule membrane‐10 (2.5 g/100 g diet) (TEST) for 30 days. On study day 31, intestinal samples, ileal and colonic contents, and feces were collected. Intestinal histomorphology, disaccharidase activity, serotonin (5'HT), vasoactive intestinal peptide (VIP), and tyrosine hydroxylase (TH) were measured. Gut microbiota composition was assessed by pyrosequencing of the V3–V5 regions of 16S rRNA and quantitative polymerase chain reaction.

Results:

Body weight of piglets on TEST was greater (P ⩽ 0.05) than CONT on days 17 to 30. Both groups displayed growth patterns within the range observed for sow‐reared pigs. TEST piglets had greater jejunal lactase (P = 0.03) and higher (P = 0.003) ileal VIP expression. TEST piglets tended to have greater (P = 0.09) sucrase activity, longer (P = 0.08) ileal villi, and greater (P = 0.06) duodenal TH expression. Microbial communities of TEST piglets differed from CONT in ascending colon (AC, P = 0.001) and feces (P ⩽ 0.05). CONT piglets had greater relative abundances of Mogibacterium, Collinsella, Klebsiella, Escherichia/Shigella, Eubacterium, and Roseburia compared with TEST piglets in AC. In feces, CONT piglets harbored lower (P ⩽ 0.05) proportions of Parabacteroides, Clostridium IV, Lutispora, and Sutterella than TEST piglets.

Conclusions:

A mixture of bioactive ingredients improved weight gain and gut maturation, modulated colonic and fecal microbial composition, and reduced the proportions of opportunistic pathogens.
Health‐Related Quality of Life and Parental Stress in Children With Fecal Incontinence
Authors: Cushing Christopher C. , Martinez‐Leo Bruno , Bischoff Andrea , Hall Jennifer , Helmrath Michael , Dickie Belinda H. , Levitt Marc A. , Peña Alberto , Zeller Meg H. , Frischer Jason S.
Published: April 2016

Objective:

The aim of the present study was to describe the quality of life and parenting stress associated with a child with fecal incontinence (FI).

Methods:

Female caregivers (n = 170) of children of 3 to 12 years age with FI completed a broad and general measure of quality of life and a measure of parenting stress. Results were compared with proxy reports for a normative sample of healthy children.

Results:

Caregivers of children with FI reported significantly impaired quality of life for their children and increased parenting stress in all of the respective domains relative to healthy controls. Impairments reported by caregivers were large in magnitude. Similarly, rates of parenting stress were at or greater than the 98th percentile for caregivers of children with FI.

Conclusions:

Children with fecal incontinence and their families are in need of interventions targeting their quality of life and the stress associated with caregiving. FI appears to be particularly stressful for caregivers who may be in need of support beyond medical management of their child's bowel. Moreover, additional refinements in disease‐specific quality of life assessment are needed in this population. Such refinement would allow for more precise measurement of the quality of life processes that are unique to FI.
Effect of Psychotherapy on Health Care Utilization in Children With Inflammatory Bowel Disease and Depression
Authors: Keerthy Divya , Youk Ada , Srinath Arvind I. , Malas Nasuh , Bujoreanu Simona , Bousvaros Athos , Keljo David , DeMaso David R. , Szigethy Eva M.
Published: April 2016

Objectives:

Pediatric patients with inflammatory bowel disease (IBD) are at an increased risk of developing depression compared with community controls. Depression often negatively influences illness behaviors such as resource utilization. We sought to investigate the effects of treating depression on utilization of medical resources in depressed pediatric patients with IBD by comparing rates of health care utilization 1 year before and after psychotherapy.

Method:

Two hundred seventeen subjects ages 9 to 17 years with IBD and depression received 3 months of psychotherapy for depression as part of a multicenter randomized controlled trial. Of these 217 subjects, 70 had utilization data available 1 year prior and 1 year after receiving 3 months of psychotherapy. Primary outcomes included frequency of hospitalizations, inpatient hospital days, outpatient gastrointestinal visits, and number of emergency room visits, radiological examinations, and endoscopies. Within subject analyses were completed comparing health care utilization 12 months before psychotherapy compared with the 12 months after the conclusion of psychotherapy.

Results:

Fifty‐one and 19 patients had CD and UC, respectively. A total of 55.7% of patients had major depression and 44.3% had minor depression. Overall, all study measures of health care utilization were significantly reduced after psychotherapy (P < 0.01)—including gastrointestinal‐related (mean values) hospitalization frequency, inpatient days, outpatient visit, emergency room visits, radiological examinations, and endoscopies.

Conclusions:

Psychotherapy for comorbid depression in pediatric patients with IBD is associated with decreased GI‐related health care utilization. The present study highlights the importance of screening for depression in a pediatric population with IBD, and that psychotherapy may be a reasonable adjunctive treatment for pediatric patients with IBD and comorbid depression.
Healthcare Utilization and Spending for Constipation in Children With Versus Without Complex Chronic Conditions
Authors: Stephens John R. , Steiner Michael J. , DeJong Neal , Rodean Jonathan , Hall Matt , Richardson Troy , Berry Jay G.
Published: April 2016

Objectives:

The aim of the study was to examine the prevalence of diagnosis and treatment for constipation among children receiving Medicaid and to compare healthcare utilization and spending for constipation among children based on number of complex chronic conditions (CCCs).

Methods:

Retrospective cohort study of 4.9 million children ages 1 to 17 years enrolled in Medicaid from 2009 to 2011 in 10 states in the Truven Marketscan Database. Constipation was identified using International Classification of Disease, 9th revision codes for constipation (564.0x), intestinal impaction (560.3x), or encopresis (307.7). Outpatient and inpatient utilization and spending for constipation were assessed. CCC status was identified using validated methodology.

Results:

A total of 267,188 children (5.4%) were diagnosed with constipation. Total constipation spending was $79.5 million. Outpatient constipation spending was $66.8 million (84.1%) during 406,814 visits, mean spending $120/visit. Among children with constipation, 1363 (0.5%) received inpatient treatment, accounting for $12.2 million (15.4%) of constipation spending, mean spending $7815/hospitalization. Of children hospitalized for constipation, 552 (40.5%) did not have an outpatient visit for constipation before admission. Approximately 6.8% of children in the study had ≥1 CCC; these children accounted for 33.5% of total constipation spending, 70.3% of inpatient constipation spending, and 19.8% of emergency department constipation spending. Constipation prevalence was 11.0% for children with 1 CCC, 16.6% with 2 CCCs, and 27.1% with ≥3 CCCs.

Conclusions:

Although the majority of pediatric constipation treatment occurs in the outpatient setting, inpatient care accounts for a sizable percentage of spending. Children with CCCs have a higher prevalence of constipation and account for a disproportionate amount of constipation healthcare utilization and spending.
Concomitant Fundoplication With Gastrostomy
Authors: Fox David , Campagna Elizabeth J. , Finnell S. Maria E. , Partrick David A. , Kempe Allison
Published: April 2016

Objectives:

We sought to determine whether practice differences for fundoplication exist between 2 geographically distinct states, and to determine the reflux medication use pattern associated with concomitant fundoplication.

Methods:

A retrospective observational cohort study of children in Colorado (CO) and North Carolina (NC) insured by Medicaid from 2006 to 2008. Children who received a surgical gastrostomy during the study period were included, and our primary outcome measure was the performance of a concomitant gastric fundoplication. Thirty‐day prescription fills for reflux medications were examined before and after gastrostomy procedure.

Results:

We examined 969 surgical gastrostomy admission in both states over the 3‐year study period (CO, n = 341 and NC, n = 628). Patients in each state had similar age (median age, 6 months, P = 0.97). Use of pH probe (CO: 15%, NC: 11%) and diagnosis of reflux (CO: 84%, NC: 72%) differed in each state. Concomitant fundoplication was performed in 60% of patients in CO and 43% in NC (P < 0.01). Age less than 6 months was associated with an increased adjusted odds of fundoplication in CO (OR 9.77, CI, 3.91, 24.43), but less so in NC (OR 2.73, CI, 1.48, 5.04). Among patients undergoing gastrostomy, the proportion of patients on reflux medication 4 to 6 months post‐discharge did not differ between those receiving fundoplication and those that did not in either state.

Conclusions:

Rates of concomitant fundoplication varied in the 2 states despite patients having similar demographic and clinical characteristics. Antireflux surgery was not associated with a reduction in reflux medications in either state.
Effect of Oral Lipid Matrix Supplement on Fat Absorption in Cystic Fibrosis
Authors: Stallings Virginia A. , Schall Joan I. , Maqbool Asim , Mascarenhas Maria R. , Alshaikh Belal N. , Dougherty Kelly A. , Hommel Kevin , Ryan Jamie , Elci Okan U. , Shaw Walter A.
Published: April 2016

Pancreatic enzyme therapy does not normalize dietary fat absorption in patients with cystic fibrosis and pancreatic insufficiency. Efficacy of LYM‐X‐SORB (LXS), an easily absorbable lipid matrix that enhances fat absorption, was evaluated in a 12‐month randomized, double‐blinded, placebo‐controlled trial with plasma fatty acids (FA) and coefficient of fat absorption (CFA) outcomes. A total of 110 subjects (age 10.4 ± 3.0 years) were randomized. Total FA increased with LXS at 3 and 12 months (+1.58, +1.14 mmol/L) and not with placebo (P = 0.046). With LXS, linoleic acid (LA) increased at 3 and 12 months (+298, +175 nmol/mL, P ⩽ 0.046), with a 6% increase in CFA (P < 0.01). LA increase was significant in LXS versus placebo (445 vs 42 nmol/mL, P = 0.038). Increased FA and LA predicted increased body mass index Z scores. In summary, the LXS treatment improved dietary fat absorption compared with placebo as indicated by plasma FA and LA and was associated with better growth status.
Baseline Wall Thickness Is Lower in Mucosa‐Healed Segments 1 Year After Infliximab in Pediatric Crohn Disease Patients
Authors: Kang Ben , Choi So Yoon , Chi Sangah , Lim Yaeji , Jeon Tae Yeon , Choe Yon Ho
Published: April 2016

Objectives:

We aimed to quantitatively investigate the therapeutic response to combined immunosuppression treatment by magnetic resonance enterography (MRE) in active luminal Crohn disease (CD) in the pediatric population.

Methods:

Pediatric patients with moderate‐to‐severe luminal CD, who received scheduled infliximab and azathioprine, were included in this preliminary study. Ileocolonoscopy and MRE were performed at baseline and at 1 year, and Simple Endoscopic Score for Crohn's Disease (SES‐CD) and Magnetic Resonance Index of Activity (MaRIA) scores were calculated. The correlation between SES‐CD and MaRIA scores were investigated with analysis per person and per segment.

Results:

A total of 167 segments from 17 patients were evaluated by both Ileocolonoscopy and MRE. SES‐CD and MaRIA scores showed significant correlations on both per‐person analysis (ρ = 0.699, P < 0.001) and per‐segment analysis (ρ = 0.596, P < 0.001). Analysis according to ileocolonic location of each segment revealed that the correlation strength was strongest in the right colon (ρ = 0.653, P < 0.001), whereas the correlation in the rectum was statistically insignificant (ρ = 0.29, P = 0.096). A comparative analysis of MaRIA components revealed a significantly thinner bowel wall thickness at baseline in endoscopically healed segments (50/65) compared with unhealed segments (15/65) (median 4.3 vs 7.2 mm, P = 0.036).

Conclusions:

Therapeutic response to combined immunosuppression at 1 year assessed by MRE correlates with ileocolonoscopy in pediatric patients with CD. Bowel wall thickness of the involved segments at baseline may affect treatment response to combined immunosuppression.
CT and MRI of Rare Extraintestinal Manifestations of Inflammatory Bowel Disease in Children and Adolescents
Authors: Raymond Scott B. , Gee Michael S. , Anupindi Sudha A. , Shailam Randheer , Kaplan Jess L. , Nimkin Katherine
Published: April 2016

Inflammatory bowel disease (IBD) is associated with a spectrum of extraintestinal manifestations (EIMs) affecting many organ systems. EIMs can occur in more than 40% of patients with IBD and are associated with significant morbidity. They occur at any time point in the course of disease, often during an active phase of bowel inflammation, but sometimes preceding bowel disease. Prompt recognition of EIMs enables timely and more effective therapy. Physicians who image patients with IBD should be aware of the myriad extraintestinal conditions that may be detected on imaging studies, both within and outside of the abdomen, as they may predate the diagnosis of IBD. Cross‐sectional imaging of unusual conditions associated with IBD will be presented, including pathology in the hepatobiliary, pancreatic, genitourinary, musculoskeletal, mucocutaneous, vascular, neurologic, and pulmonary systems.
Yoga Therapy for Abdominal Pain‐Related Functional Gastrointestinal Disorders in Children
Authors: Korterink Judith J. , Ockeloen Lize E. , Hilbink Mirrian , Benninga Marc A. , Deckers‐Kocken Judith M.
Published: April 2016

Objectives:

The aim of the present study was to compare effects of 10 weeks of yoga therapy (YT) and standard medical care (SMC) on abdominal pain and quality of life (QoL) in children with abdominal pain–related functional gastrointestinal disorders (AP‐FGIDs).

Methods:

Sixty‐nine patients, ages 8 to 18 years, with AP‐FGIDs, were randomized to SMC complemented with YT or SMC alone. YT is a mixture of yoga poses, meditation, and relaxation exercises and was given once a week in group sessions. SMC consisted of education, reassurance, dietary advice, and fibers/mebeverine, if necessary. Pain intensity (pain intensity score [PIS] 0–5) and frequency (pain frequency score [PFS] 0–4) were scored in a pain diary, and QoL was measured with KIDSCREEN‐27. Follow‐up was 12 months. Treatment response was defined as ≥50% reduction of weekly pain scores.

Results:

At 1‐year follow‐up, treatment response was accomplished in 58% of the YT group and in 29% of the control group (P = 0.01); no significant differences for other time points were found. YT, and not SMC, resulted in a significant reduction of PIS (P < 0.01) and PFS (P < 0.01) after 12 months. During the study, however, YT was not significantly superior compared with SMC. Subanalyses for time points demonstrated a significant greater reduction of PIS at 12 months in favor of YT. No differences were found for QoL. YT was more effective in the reduction of reported monthly school absence (P = 0.03).

Conclusion:

At 1‐year follow‐up, YT in addition to standard care was superior compared with SMC according to treatment success, PIS, and reduction of school absence. YT, however, was not significantly more effective in improving PFS or QoL, compared with SMC.
Quality of Life in Women With Breast Cancer Treated With or Without Chemotherapy
Authors: Tiezzi Maria Fernanda Barbirato da Mata , de Andrade Jurandyr Moreira , Romão Adriana Peterson Mariano Salata , Tiezzi Daniel Guimarães , Lerri Maria Rita , Carrara Hélio Angotti Humberto , Lara Lúcia Alves Silva
Published: April 2016

Background:

The diagnosis and treatment of breast cancer may negatively affect the quality of life (QOL) of women.

Objectives:

The aim of this study is to assess QOL in women with breast cancer who were treated with or without chemotherapy and to identify factors associated with improved or worsening QOL in these women.

Methods:

This cross-sectional study enrolled 112 women who were treated with chemotherapy (CTX group, with 85 [75.9%] women) or without chemotherapy (non-CTX group, with 27 [24.1%] women) for breast cancer. The Short-Form Health Survey (SF-36) assessed QOL and the Hospital Anxiety and Depression scale assessed anxiety and depression.

Results:

The overall mean SF-36 score was below 50 in all domains. Relative to CTX women, non-CTX women were significantly older (P = .001) and more likely to engage in physical exercise (P = .002). The non-CTX group had higher scores in the Physical Functioning (P = .001) and Role-Physical (P = .0009) domains of the SF-36 relative to the CTX group, and the fluoruracil + epirubicin + cyclophosphamide group had significantly lower scores in the SF-36 domains Physical Functioning (P = .009) and Role-Physical (P = .02).

Conclusion:

Chemotherapy treatment for breast cancer worsens QOL in the Physical Functioning and the Role-Physical domains of the SF-36 relative to women treated without chemotherapy.

Implications for Practice:

Nurses should assess Physical Functioning and the Role-Physical before treatment, as a woman who was not physically active before breast cancer is not likely to become physically active after treatment. Establishing support groups and providing educational sessions about the disease and its management, supportive care can improve the QOL of this population.
The Integration of Emotional, Physiologic, and Communication Responses to Medical Oncology Surveillance Appointments During Breast Cancer Survivorship
Authors: Clayton Margaret F. , Dingley Catherine , Donaldson Gary
Published: April 2016

Background:

Breast cancer survivors regularly interact with providers during routine surveillance medical oncology visits, discussing uncertainty and anxiety about potential cancer recurrence for many years after treatment. Physiologic alteration can also occur as a stress response, triggered by an upcoming surveillance visit. Survivor-provider communication can theoretically allay emotional distress.

Objective:

The aim of this study was to evaluate associations between emotional (uncertainty, anxiety, concerns about recurrence) and physiologic responses (cytokine levels, lymphocyte counts), and survivor-provider communication (women’s plans for their visit, negotiation of decision-making roles).

Methods:

Twenty-seven community-dwelling breast cancer survivors participated. Blood specimens, and self-reported data focusing on the previous month, were collected immediately before and the morning after a regularly scheduled medical oncology visit.

Results:

Global concerns about cancer recurrence and acute anxiety and uncertainty were associated with changes in immune status before and after the visit. Postvisit natural killer cells increased in 70% of women, and uncertainty/anxiety decreased. Thirty-three percent of women reported a previous minor illness. Most women had a visit plan; 66% successfully negotiated decision-making roles with providers.

Conclusions:

Triggered by an upcoming medical oncology visit, women experience uncertainty, anxiety, and altered immunity, potentially placing them at risk of disease exacerbations.

Implications for Practice:

Not all women respond similarly to a routine surveillance visit; thus, providers must determine who may be at increased risk of emotional distress and physiologic alteration. Survivor-provider communication facilitates immediate resolution of concerns. Explanations of symptom meaning reduce anxiety and uncertainty and by extension may help resolve immune alteration. Between visits, this could be done by nurse-operated telephone-based “help lines.”
Coping With Pain Severity, Distress, and Consequences in Women With Ovarian Cancer
Authors: Gilbertson-White Stephanie , Campbell Grace , Ward Sandra , Sherwood Paula , Donovan Heidi
Published: April 2016

Background:

Self-regulation can be useful in understanding pain management efforts in women with ovarian cancer. Self-regulation is a parallel process of problem- and emotion-focused coping; problem-focused coping involves efforts aimed at solving/reducing the problem directly, whereas emotion-focused coping is aimed at managing negative emotions.

Objectives:

The aims of this study were to describe the types of problem- and emotion-focused coping strategies used to manage pain severity, distress, and consequences and to evaluate whether there was evidence of parallel processing (ie, use of a combination of both problem- and emotion-focused strategies).

Methods:

Women (n = 162) from a cross-sectional study of cancer symptoms who reported pain as a most noticed symptom in the past week were included. Pearson correlations and t tests were used to evaluate relationships among the variables.

Results:

Mean pain severity was 5.5 (SD, 2.7) on a 0- to 10-point scale. An average of 4.6 (SD, 2.1) coping strategies were reported. Actively manage and planning were the most frequent problem-focused strategies; relaxation was the most frequent emotion-focused strategy. Higher total number of coping strategies attempted, expressing emotions, and seeking emotional support were associated with higher pain distress and consequences scores, and actively managing pain was associated with higher pain severity.

Conclusion:

Women with a history of ovarian cancer continue to experience severe pain. Partial support for parallel processing was found.

Implications for Practice:

The relative benefits of the 2 types of coping strategies are unclear. Thorough assessment of pain and the effectiveness of coping strategies is needed to help women identify strategies that work best for them.
Hypersensitivity to Cold Stimuli in Symptomatic Contact Lens Wearers
Authors: Situ Ping , Simpson Trefford , Begley Carolyn
Published: April 2016

Purpose

To examine the cooling thresholds and the estimated sensation magnitude at stimulus detection in controls and symptomatic and asymptomatic contact lens (CL) wearers, to determine whether detection thresholds depend on the presence of symptoms of dryness and discomfort.

Methods

Forty-nine adapted CL wearers and 15 non–lens wearing controls had room temperature pneumatic thresholds measured using a custom Belmonte esthesiometer, during Visits 1 and 2 (Baseline CL), Visit 3 (2 weeks no CL wear), and Visit 4 (2 weeks after resuming CL wear). CL wearers were subdivided into symptomatic and asymptomatic groups based on comfortable wearing time (CWT) and CLDEQ-8 score (<8 hours CWT and ≥14 CLDEQ-8 stratified the symptom groups). Detection thresholds were estimated using an ascending method of limits and each threshold was the average of the three first-reported flow rates. The magnitude of intensity, coolness, irritation, and pain at detection of the stimulus were estimated using a 1–100 scale (1 very mild, 100 very strong).

Results

In all measurement conditions, the symptomatic CL wearers were the most sensitive, the asymptomatic CL wearers were the least sensitive, and the control group was between the two CL wearing groups (group factor p < 0.001, post hoc asymptomatic vs. symptomatic group, all p’s < 0.015). Similar patterns were found for the estimated magnitude of intensity and irritation (group effect p = 0.027 and 0.006 for intensity and irritation, respectively) but not for cooling (p > 0.05) at detection threshold.

Conclusions

Symptomatic CL wearers have higher cold detection sensitivity and report greater intensity and irritation sensation at stimulus detection than the asymptomatic wearers. Room temperature pneumatic esthesiometry may help to better understand the process of sensory adaptation to CL wear.
Modified Photodynamic Therapy Treatment of Central Serous Chorioretinopathy
Authors: Putnam Christopher M. , Vang See S.
Published: April 2016

Purpose

Central serous chorioretinopathy (CSC) is a condition characterized by serous detachment of the neurosensory retina at the level of the retinal pigmented epithelium (RPE) as a result of leakage from the choriocapillaris. The pathophysiology of CSC is not completely understood rendering treatment and management decisions more complex. When an observational approach and topical medical therapy are unsuccessful, a surgical intervention may be necessary. Here, we examine the role of modified photodynamic therapy (PDT) in recurrent CSC with multiple points of RPE leakage.

Case Report

A 37-year-old male patient presented a case of recurrent CSC in the left eye. After an initial presentation of a large area of submacular fluid, near complete resolution was seen in 8 weeks using a topical NSAID protocol and close monitoring. Two weeks later, a second serous neurosensory detachment larger than the first occurred. The recurrent CSC was successfully treated with focal grid laser photocoagulation and modified PDT resulting in complete resolution and return of visual function 4 months after the initial presentation.

Conclusions

CSC is a multifactorial condition with the potential to severely impair daily visual function. Spectral domain optical coherence tomography retinal imaging has provided a remarkable tool in the diagnosis and monitoring of CSC. The addition of FA and ICG can create a highly precise picture of the subretinal fluid. Although most patients will spontaneously resolve, a subset of patients may benefit from medical therapy including topical nepafenac 0.1%. A smaller subset will require surgical intervention. Modified PDT with ICG-guided laser photocoagulation has a growing body of evidence as an effective treatment for recurrent CSC. Modified PDT may be the best course of action for chronic, non-resolving RPE leakage for both paramacular and foveal leaks leading to minimization of adverse visual effects.
Association Between Contact Lens Discomfort and Pre-lens Tear Film Kinetics
Authors: Guillon Michel , Dumbleton Kathryn A. , Theodoratos Panagiotis , Wong Stephanie , Patel Kishan , Banks Gaidig , Patel Trisha
Published: April 2016

Purpose

The relationship between contact lens wettability and comfort has been extensively evaluated; however, a direct correlation between the characteristics of the pre-lens tear film and the symptoms associated with contact lens discomfort has yet to be established. In addition, there is relatively limited knowledge relating to the entire tear film kinetics during the inter-blink period in contact lens wearers. The purpose of this analysis was to identify the characteristics of the pre-lens tear film kinetics that may be associated with the symptoms of contact lens discomfort.

Methods

The study population comprised 202 soft (hydrogel and silicone hydrogel) contact lens wearers attending pre-screening visits at the OTG-i research clinic. All participants completed the Ocular Surface Disease Index (OSDI) questionnaire and the tear film was quantified via post hoc, masked analysis of high definition digital Tearscope videos recorded at the visit. The tear film kinetics of the least symptomatic wearers (OSDI lowest quintile scores, n = 45) were compared to the tear film kinetics of the most symptomatic wearers (OSDI highest quintile scores, n = 43). The hypothesis tested was that the tear film kinetics of asymptomatic wearers were better than tear film kinetics of symptomatic wearers.

Results

The distribution of lens types worn was as follows: Daily Disposable 46.5%, 1-Month Replacement 39.6%, and 2-Week Replacement 13.6%. 48.2% of lenses were silicone hydrogel and 51.8% hydrogel. Symptomatic wearers had a shorter break-up time (4.7 s vs. 6.0 s; p = 0.003), lesser surface coverage by the tear film during the interblink period (95.1% vs. 98.5%; p < 0.001) and greater surface exposure at the time of the blink (9.4% vs. 3.9%; p = 0.001).

Conclusions

The current study demonstrated that the tear film kinetics of asymptomatic and symptomatic contact lens wearers were different, the findings supporting the hypothesis of poorer tear film kinetics for symptomatic than asymptomatic wearers in a general contact lens wearing population.
Investigating Various Thresholds as Immunohistochemistry Cutoffs for Observer Agreement
Authors: Ali Asif , Bell Sarah , Bilsland Alan , Slavin Jill , Lynch Victoria , Elgoweini Maha , Derakhshan Mohammad H. , Jamieson Nigel B. , Chang David , Brown Victoria , Denley Simon , Orange Clare , McKay Colin , Carter Ross , Oien Karin A. , Duthie Fraser R.
Published: April 2016

Background:

Clinical translation of immunohistochemistry (IHC) biomarkers requires reliable and reproducible cutoffs or thresholds for interpretation of immunostaining. Most IHC biomarker research focuses on the clinical relevance (diagnostic, prognostic, or predictive utility) of cutoffs, with less emphasis on observer agreement using these cutoffs. From the literature, we identified 3 commonly used cutoffs of 10% positive epithelial cells, 20% positive epithelial cells, and moderate to strong staining intensity (+2/+3 hereafter) to use for investigating observer agreement.

Materials and Methods:

A series of 36 images of microarray cores stained for 4 different IHC biomarkers, with variable staining intensity and percentage of positive cells, was used for investigating interobserver and intraobserver agreement. Seven pathologists scored the immunostaining in each image using the 3 cutoffs for positive and negative staining. Kappa (κ) statistic was used to assess the strength of agreement for each cutoff.

Results:

The interobserver agreement between all 7 pathologists using the 3 cutoffs was reasonably good, with mean κ scores of 0.64, 0.59, and 0.62, respectively, for 10%, 20%, and +2/+3 cutoffs. A good agreement was observed for experienced pathologists using the 10% cutoff, and their agreement was statistically higher than for junior pathologists (P=0.02). In addition, the mean intraobserver agreement for all 7 pathologists using the 3 cutoffs was reasonably good, with mean κ scores of 0.71, 0.60, and 0.73, respectively, for 10%, 20%, and +2/+3 cutoffs. For all 3 cutoffs, a positive correlation was observed with perceived ease of interpretation (P<0.003). Finally, cytoplasmic-only staining achieved higher agreement using all 3 cutoffs than mixed staining patterns.

Conclusions:

All 3 cutoffs investigated achieve reasonable strength of agreement, modestly decreasing interobserver and intraobserver variability in IHC interpretation. These cutoffs have previously been used in cancer pathology, and this study provides evidence that these cutoffs can be reproducible between practicing pathologists.
Histologic Typing in Oropharyngeal Squamous Cell Carcinoma
Authors: Gondim Dikson Dibe , Haynes Wesley , Wang Xiaowei , Chernock Rebecca D. , El-Mofty Samir K. , Lewis James S.
Published: April 2016

Oropharyngeal squamous cell carcinomas (OPSCCs) associated with human papillomavirus (HPV) represent a distinct clinical and pathologic entity. The majority of HPV-related OPSCCs have a characteristic nonkeratinizing morphology. This study sought to determine the strength of the association between nonkeratinizing histology and HPV status compared with other squamous cell carcinoma variants in 4 years of routine clinical practice on a high-volume head and neck service. Primary and/or nodal metastatic tumors in all cases of OPSCC from 2010 to 2013 were typed by 1 of 3 head and neck pathologists as keratinizing, nonkeratinizing, nonkeratinizing with maturation, or another defined variant. All were assessed for p16 by immunohistochemistry with a 70% nuclear and cytoplasmic positivity cutoff as part of routine clinical practice. In addition, 70 consecutive cases from 1 year were “audited” for high-risk HPV mRNA by reverse transcription polymerase chain reaction and in situ hybridization. Of the 435 cases, the majority (90%) consisted of 1 of the 3 main types described and the rest (10%) of uncommon variants. Nonkeratinizing morphology had 99.1% and 100.0% positive predictive value for p16 and high-risk HPV mRNA positivity, respectively. Nonkeratinizing with maturation, keratinizing, and other specific squamous cell carcinoma variants were p16 positive in 91.8%, 22.8%, and 79.5%, respectively. All 47 nonkeratinizing OPSCCs tested for HPV mRNA were positive. In summary, strictly defined nonkeratinizing OPSCC (which constitutes ∼55% of all tumors) essentially implies positivity for both p16 and transcriptionally active high-risk HPV.
Intracranial Hypertension and Cerebral Hypoperfusion in Children With Severe Traumatic Brain Injury: Thresholds and Burden in Accidental and Abusive Insults
Authors: Miller Ferguson Nikki , Shein Steven L. , Kochanek Patrick M. , Luther Jim , Wisniewski Stephen R. , Clark Robert S. B. , Tyler-Kabara Elizabeth C. , Adelson P. David , Bell Michael J.
Published: April 2016

Objectives:

The evidence to guide therapy in pediatric traumatic brain injury is lacking, including insight into the intracranial pressure/cerebral perfusion pressure thresholds in abusive head trauma. We examined intracranial pressure/cerebral perfusion pressure thresholds and indices of intracranial pressure and cerebral perfusion pressure burden in relationship with outcome in severe traumatic brain injury and in accidental and abusive head trauma cohorts.

Design:

A prospective observational study.

Setting:

PICU in a tertiary children’s hospital.

Patients:

Children less than18 years old admitted to a PICU with severe traumatic brain injury and who had intracranial pressure monitoring.

Interventions:

None.

Measurements and Main Results:

A pediatric traumatic brain injury database was interrogated with 85 patients (18 abusive head trauma) enrolled. Hourly intracranial pressure and cerebral perfusion pressure (in mm Hg) were collated and compared with various thresholds. C-statistics for intracranial pressure and cerebral perfusion pressure data in the entire population were determined. Intracranial hypertension and cerebral hypoperfusion indices were formulated based on the number of hours with intracranial pressure more than 20 mm Hg and cerebral perfusion pressure less than 50 mm Hg, respectively. A secondary analysis was performed on accidental and abusive head trauma cohorts. All of these were compared with dichotomized 6-month Glasgow Outcome Scale scores. The models with the number of hours with intracranial pressure more than 20 mm Hg (C = 0.641; 95% CI, 0.523–0.762) and cerebral perfusion pressure less than 45 mm Hg (C = 0.702; 95% CI, 0.586–0.805) had the best fits to discriminate outcome. Two factors were independently associated with a poor outcome, the number of hours with intracranial pressure more than 20 mm Hg and abusive head trauma (odds ratio = 5.101; 95% CI, 1.571–16.563). As the number of hours with intracranial pressure more than 20 mm Hg increases by 1, the odds of a poor outcome increased by 4.6% (odds ratio = 1.046; 95% CI, 1.012–1.082). Thresholds did not differ between accidental versus abusive head trauma. The intracranial hypertension and cerebral hypoperfusion indices were both associated with outcomes.

Conclusions:

The duration of hours of intracranial pressure more than 20 mm Hg and cerebral perfusion pressure less than 45 mm Hg best discriminated poor outcome. As the number of hours with intracranial pressure more than 20 mm Hg increases by 1, the odds of a poor outcome increased by 4.6%. Although abusive head trauma was strongly associated with unfavorable outcome, intracranial pressure/cerebral perfusion pressure thresholds did not differ between accidental and abusive head trauma.
Fluid Overload Is Associated With Late Poor Outcomes in Neonates Following Cardiac Surgery*
Authors: Wilder Nicole S. , Yu Sunkyung , Donohue Janet E. , Goldberg Caren S. , Blatt Neal B.
Published: April 2016

Objectives:

Acute kidney injury is a severe complication of cardiac surgery associated with increased morbidity and mortality; yet, acute kidney injury classification for neonates remains challenging. We characterized patterns of postoperative fluid overload as a surrogate marker for acute kidney injury and as a risk factor of poor postoperative outcomes in neonates undergoing cardiac surgery.

Design:

Retrospective cohort study.

Setting:

Single, congenital heart center destination program.

Patients:

Four hundred thirty-five neonates undergoing cardiac surgery with cardiopulmonary bypass from January 2006 through December 2010.

Interventions:

None.

Measurements and Main Results:

Demographics, diagnosis, and perioperative clinical variables were collected, including daily weights and serum creatinine levels. A composite poor clinical outcome (death, need for renal replacement therapy or extracorporeal life support within 30 postoperative days) was considered the primary outcome measure. Twenty-one neonates (5%) had a composite poor outcome with 7 (2%) requiring renal replacement therapy, 8 (2%) requiring extracorporeal life support, and 14 (3%) dying between 3 and 30 days post surgery. Neonates with a composite poor outcome had significantly higher maximum fluid overload (> 20%) and were slower to diurese. A receiver-operating characteristic curve determined that fluid overload greater than or equal to 16% and serum creatinine greater than or equal to 0.9 on postoperative day 3 were the optimal cutoffs for significant discrimination on the primary outcome (area under the curve = 0.71 and 0.76, respectively). In multivariable analysis, fluid overload greater than or equal to 16% (adjusted odds ratio = 3.7) and serum creatinine adjusted odds ratio 0.9 (adjusted odds ratio = 6.6) on postoperative day 3 remained an independent risk factor for poor outcome. Fluid overload greater than or equal 16% was also significantly associated with cardiac arrest requiring cardiopulmonary resuscitation, prolonged ICU stay, and chest reexploration.

Conclusions:

This study highlights the importance of monitoring fluid balance in the neonatal cardiac surgical population and suggests that daily fluid overload, a readily available, noninvasive marker of renal function, may be a sensitive and specific predictor of adverse outcomes.
Mandible Fracture Complications and Infection: The Influence of Demographics and Modifiable Factors
Authors: Odom Elizabeth B. , Snyder-Warwick Alison K.
Published: April 2016

Background:

Mandible fractures account for 36 to 70 percent of all facial fractures. Despite their high prevalence, the literature lacks a comprehensive review of demographics, fracture patterns, timing of management, antibiotic selection, and outcomes, particularly when evaluating pediatric versus adult patients. The authors aim to determine the complication and infection rates after surgical treatment of mandibular fractures and the bacterial isolates and antibiotic sensitivities from mandible infections after open reduction and internal fixation at their institution.

Methods:

Data were collected retrospectively for all mandible fractures treated at the authors’ institution between 2003 and 2013. Patients were divided into pediatric (younger than 16 years) and adult (16 years or older) subgroups. Demographics, fracture location, fracture cause, comorbidities, antibiotic choice, and subsequent complications and infections were analyzed. Data were evaluated using appropriate statistical tests for each variable.

Results:

Three hundred ninety-five patients were evaluated. Demographics and fracture cause were similar to those reported in current literature. Of the 56 pediatric patients, complications occurred in 5.6 percent. Time from injury to operative intervention did not affect outcome. The complication rate was 17.5 percent and the infection rate was 9.4 percent in the adult subgroup. Time from injury to operative intervention, sex, and edentulism were not significant predictors of complication or infection. Tobacco use, number of fractures, number of fractures fixated, and surgical approach were predictors of complication and infection. Perioperative ampicillin-sulbactam had a significantly lower risk of infection.

Conclusions:

Certain demographic and operative factors lead to significantly higher risks of complications after surgical management of mandibular fractures. Ampicillin-sulbactam provides effective antibiotic prophylaxis. Risk factor modification may improve outcomes.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, IV.