Adolescent survivors of childhood cancer: are they vulnerable for psychological distress?

OBJECTIVES: We aimed to (i) evaluate psychological distress in adolescent survivors of childhood cancer and compare them to siblings and a norm population; (ii) compare the severity of distress of distressed survivors and siblings with that of psychotherapy patients; and (iii) determine risk factors for psychological distress in survivors. METHODS: We sent a questionnaire to all childhood cancer survivors aged <16 years when diagnosed, who had survived ≥5 years and were aged 16-19 years at the time of study. Our control groups were same-aged siblings, a norm population, and psychotherapy patients. Psychological distress was measured with the Brief Symptom Inventory-18 (BSI-18) assessing somatization, depression, anxiety, and a global severity index (GSI). Participants with a T-score ≥57 were defined as distressed. We used logistic regression to determine risk factors. RESULTS: We evaluated the BSI-18 in 407 survivors and 102 siblings. Fifty-two survivors (13%) and 11 siblings (11%) had scores above the distress threshold (T ≥ 57). Distressed survivors scored significantly higher in somatization (p = 0.027) and GSI (p = 0.016) than distressed siblings, and also scored higher in somatization (p ≤ 0.001) and anxiety (p = 0.002) than psychotherapy patients. In the multivariable regression, psychological distress was associated with female sex, self-reported late effects, and low perceived parental support. CONCLUSIONS: The majority of survivors did not report psychological distress. However, the severity of distress of distressed survivors exceeded that of distressed siblings and psychotherapy patients. Systematic psychological follow-up can help to identify survivors at risk and support them during the challenging period of adolescence. Copyright © 2013 John Wiley & Sons, Ltd.

Anti-CD20 (rituximab) treatment improves atopic eczema

BACKGROUND: Atopic eczema (AE) is a chronic inflammatory skin disorder characterized by eczematous skin lesions, pruritus, and typical histopathologic features. OBJECTIVE: We asked whether depletion of B cells by monoclonal anti-CD20 antibody therapy (rituximab) would improve severe AE. METHODS: Six patients (4 women and 2 men) with severe AE received 2 intravenous applications of rituximab, each 1000 mg, 2 weeks apart. To evaluate the efficacy of rituximab, we monitored clinical parameters (eczema area and severity index, pruritus), total and allergen-specific IgE levels, skin histology, and inflammatory cells and cytokine expression in the skin and peripheral blood before and after therapy. RESULTS: All patients showed an improvement of their skin symptoms within 4 to 8 weeks. The eczema area and severity index significantly decreased (before therapy, 29.4 +/- 4.3; week 8, 8.4 +/- 3.6; P < .001). Histologic alterations such as spongiosis, acanthosis, and dermal infiltrate, including T and B cell numbers, also dramatically improved. However, whereas blood B cells were below detectable levels as a consequence of rituximab administration, skin B cells were reduced by approximately 50% only. Expression of IL-5 and IL-13 was reduced after therapy. Moreover, whereas allergen-specific IgE levels were not altered, we observed a slight reduction in total IgE concentrations in blood. CONCLUSIONS: B cells play a major role in AE pathogenesis. Treatment with an anti-CD20 antibody leads to an impressive improvement of AE in patients with severe disease.

Content comparison of health-related quality of life instruments for obstructive sleep apnea

BACKGROUND AND PURPOSE: Due to the increasing importance of quality of life assessments in obstructive sleep apnea (OSA) patients and due to an increased use of the International Classification of Functioning, Disability and Health (ICF), for comparative purposes it is essential to understand the relationship between health-related quality of life (HRQOL) instruments and the ICF. The purpose of this study was to compare the content covered by OSA-specific instruments using the ICF. PATIENTS AND METHODS: OSA-specific instruments were identified, including the Calgary Sleep Apnea Quality of Life Index, the Functional Outcomes of Sleep Questionnaire, the Obstructive Sleep Apnea Patient-Oriented Severity Index, and the Quebec Sleep Questionnaire, and linked to the ICF by six health professionals according to standardized guidelines. The degree of agreement between health professionals was calculated by means of the kappa statistic. RESULTS: A total of 308 concepts were identified and linked to 78 different ICF categories; 35 categories of the component body function, one category of the component body structure, 38 categories of the component activities and participation, and four categories of the component environmental factors. Only contents within the chapters mental functions, mobility and social life were addressed by all instruments. Forty-seven categories were covered by only one instrument. CONCLUSION: The ICF proved highly useful for the comparison of HRQOL instruments. This analysis may help researchers and clinicians to choose the most appropriate HRQOL instrument for a specific purpose as well as help to compare study outcomes of studies using different instruments for HRQOL assessment.

Prevalence of anaemia in inflammatory bowel disease in Switzerland: A cross-sectional study in patients from private practices and university hospitals

BACKGROUND: Anaemia represents a common complication of inflammatory bowel disease (IBD). Most studies on anaemia in IBD patients have been performed in tertiary referral centres (RC) and data from gastroenterologic practices (GP) are lacking. We investigated the frequency and severity of anaemia in IBD patients from tertiary referral centres and gastroenterologic practices compared to the general population. METHODS: Data were acquired from patients included in the Swiss IBD Cohort Study. IBD activity was evaluated by CDAI and modified Truelove and Witts severity index (MTWSI). Anaemia was defined as haemoglobin ≤120g/L in women and ≤130g/L in men. RESULTS: 125 patients from RC (66 with Crohn's disease (CD) and 59 with ulcerative colitis (UC)) and 116 patients from GP (71 CD and 45 UC) were included and compared to 6074 blood donors. Anaemia was found in 21.2% (51/241) of the IBD patients and more frequently in patients from RC as compared to GP and healthy controls (28.8% vs. 12.9% vs. 3.4%; P<0.01). IBD patients from RC suffered more frequently from active disease compared to IBD patients in GP (36% vs. 23%, P=0.032). Supplementation therapy (iron, vitamin B12, folic acid) was performed in 40% of anaemic IBD patients in GP as compared to 43% in RC. CONCLUSIONS: Anaemia is a common complication in patients with IBD and significantly more prevalent in patients from referral centres as compared to patients from gastroenterologic practices. Physicians treating IBD patients should pay attention to the presence of anaemia and ensure sufficient supplementation therapy.

Mental health-care utilization in survivors of childhood cancer and siblings: the Swiss childhood cancer survivor study

PURPOSE We aimed to (1) describe the utilization of mental health-care in survivors and siblings, the association with severity of distress, and visits to other professionals in distressed survivors not utilizing mental health-care; and (2) identify factors associated with utilization of mental health-care in distressed survivors. METHODS Within the Swiss Childhood Cancer Survivor Study, we sent postal questionnaires to all participants aged <16 years at diagnosis (1976-2003), who survived ≥5 years after diagnosis and were aged ≥16 years at study. Survivors and siblings could indicate if they utilized mental health-care in the past year. Psychological distress was assessed with the Brief Symptom Inventory-18 (BSI-18). Participants with scores T ≥ 57 on two of three scales or the Global Severity Index were considered distressed. RESULTS We included 1,602 survivors and 703 siblings. Overall, 160 (10 %) and 53 (8 %), utilized mental health-care and 203 (14 %) and 127 (14 %) were considered distressed. Among these, 69 (34 %) survivors and 20 (24 %) siblings had utilized mental health-care. Participants with higher distress were more likely to utilize mental health-care. Distressed survivors not utilizing mental health-care were more likely to see a medical specialist than nondistressed. In the multivariable regression, factors associated with utilizing mental health-care were higher psychological distress and reporting late effects. CONCLUSIONS Our results underline the importance of developing interventional programs and implementing psychological screening in follow-up of survivors. It is also important to systematically address siblings' needs. In follow-up, patients at risk should be informed about existing possibilities or advised to visit mental health professionals.

Drug-related emergency department visits by elderly patients presenting with non-specific complaints

BACKGROUND Since drug-related emergency department (ED) visits are common among older adults, the objectives of our study were to identify the frequency of drug-related problems (DRPs) among patients presenting to the ED with non-specific complaints (NSC), such as generalized weakness and to evaluate responsible drug classes. METHODS Delayed type cross-sectional diagnostic study with a prospective 30 day follow-up in the ED of the University Hospital Basel, Switzerland. From May 2007 until April 2009, all non-trauma patients presenting to the ED with an Emergency Severity Index (ESI) of 2 or 3 were screened and included, if they presented with non-specific complaints. After having obtained complete 30-day follow-up, two outcome assessors reviewed all available information, judged whether the initial presentation was a DRP and compared their judgment with the initial ED diagnosis. Acute morbidity ("serious condition") was allocated to individual cases according to predefined criteria. RESULTS The study population consisted of 633 patients with NSC. Median age was 81 years (IQR 72/87), and the mean Charlson comorbidity index was 2.5 (IQR 1/4). DRPs were identified in 77 of the 633 cases (12.2%). At the initial assessment, only 40% of the DRPs were correctly identified. 64 of the 77 identified DRPs (83%) fulfilled the criteria "serious condition". Polypharmacy and certain drug classes (thiazides, antidepressants, benzodiazepines, anticonvulsants) were associated with DRPs. CONCLUSION Elderly patients with non-specific complaints need to be screened systematically for drug-related problems. TRIAL REGISTRATION ClinicalTrials.gov: NCT00920491.

Cardiac biomarkers and clinical scores for risk stratification in elderly patients with non-high-risk pulmonary embolism.

OBJECTIVE To determine the prognostic accuracy of cardiac biomarkers alone and in combination with clinical scores in elderly patients with non-high-risk pulmonary embolism (PE). DESIGN Ancillary analysis of a Swiss multicentre prospective cohort study. SUBJECTS A total of 230 patients aged ≥65 years with non-high-risk PE. MAIN OUTCOME MEASURES The study end-point was a composite of PE-related complications, defined as PE-related death, recurrent venous thromboembolism or major bleeding during a follow-up of 30 days. The prognostic accuracy of the Pulmonary Embolism Severity Index (PESI), the Geneva Prognostic Score (GPS), the precursor of brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) was determined using sensitivity, specificity, predictive values, receiver operating characteristic (ROC) curve analysis, logistic regression and reclassification statistics. RESULTS The overall complication rate during follow-up was 8.7%. hs-cTnT achieved the highest prognostic accuracy [area under the ROC curve: 0.75, 95% confidence interval (CI): 0.63-0.86, P < 0.001). At the predefined cut-off values, the negative predictive values of the biomarkers were above 95%. For levels above the cut-off, the risk of complications increased fivefold for hs-cTnT [odds ratio (OR): 5.22, 95% CI: 1.49-18.25] and 14-fold for NT-proBNP (OR: 14.21, 95% CI: 1.73-116.93) after adjustment for both clinical scores and renal function. Reclassification statistics indicated that adding hs-cTnT to the GPS or the PESI significantly improved the prognostic accuracy of both clinical scores. CONCLUSION In elderly patients with nonmassive PE, NT-proBNP or hs-cTnT could be an adequate alternative to clinical scores for identifying low-risk individuals suitable for outpatient management.

Derivation and validation of multimarker prognostication for normotensive patients with acute symptomatic pulmonary embolism.

RATIONALE Not all patients with acute pulmonary embolism (PE) have a high risk of an adverse short-term outcome. OBJECTIVES This prospective cohort study aimed to develop a multimarker prognostic model that accurately classifies normotensive patients with PE into low and high categories of risk of adverse medical outcomes. METHODS The study enrolled 848 outpatients from the PROTECT (PROgnosTic valuE of Computed Tomography) study (derivation cohort) and 529 patients from the Prognostic Factors for Pulmonary Embolism (PREP) study (validation cohort). Investigators assessed study participants for a 30-day complicated course, defined as death from any cause, hemodynamic collapse, and/or adjudicated recurrent PE. MEASUREMENTS AND MAIN RESULTS A complicated course occurred in 63 (7.4%) of the 848 normotensive patients with acute symptomatic PE in the derivation cohort and in 24 patients (4.5%) in the validation cohort. The final model included the simplified Pulmonary Embolism Severity Index, cardiac troponin I, brain natriuretic peptide, and lower limb ultrasound testing. The model performed similarly in the derivation (c-index of 0.75) and validation (c-index of 0.85) cohorts. The combination of the simplified Pulmonary Embolism Severity Index and brain natriuretic peptide testing showed a negative predictive value for a complicated course of 99.1 and 100% in the derivation and validation cohorts, respectively. The combination of all modalities had a positive predictive value for the prediction of a complicated course of 25.8% in the derivation cohort and 21.2% in the validation cohort. CONCLUSIONS For normotensive patients who have acute PE, we derived and validated a multimarker model that predicts all-cause mortality, hemodynamic collapse, and/or recurrent PE within the following 30 days.

Measuring depression with a well-being index: Further evidence for the validity of the WHO Well-Being Index (WHO-5) as a measure of the severity of depression

BACKGROUND: In recent years, the WHO Wellbeing Index (WHO-5) has been used as a screening measure for depression. Nevertheless, research on the validity of this measure in the context of clinical depression is sparse. QUESTIONS: The aim of the present study was to investigate the measurement invariance of the WHO-5 across depressed and non-depressed individuals, as well as the shape and specificity of its relationship to measures of depression severity. METHOD: Of the 414 subjects who completed the WHO-5 and the Beck Depression Inventory-II (BDI-II), 207 had a diagnosis of a major depressive episode (MDE). A subsample also completed the Beck Anxiety Inventory (BAI) and was assessed by clinicians using the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A). RESULTS: The WHO-5 demonstrated strong measurement invariance regarding the presence or absence of a current MDE. The WHO-5 showed a very high negative association with self- and observer-rated measures of depressive symptoms, especially in the range of mild to moderate symptoms. These associations were still substantial after controlling for measures of anxiety symptoms. LIMITATIONS: In addition to a diagnostic interview, only one measure for self- and observer-rated symptoms of depression was used. Furthermore, the observer-rated measure was only assessed in one subsample that exhibited a somewhat restricted range of depression severity. CONCLUSION: Although this index was originally designed as a measure of well-being, the results support the use of the WHO-5 in the context of depression research.

Association between sleep apnea severity and blood coagulability: Treatment effects of nasal continuous positive airway pressure

A prothrombotic state may contribute to the elevated cardiovascular risk in patients with obstructive sleep apnea (OSA). We investigated the relationship between apnea severity and hemostasis factors and effect of continuous positive airway pressure (CPAP) treatment on hemostatic activity. We performed full overnight polysomnography in 44 OSA patients (mean age 47+/-10 years), yielding apnea-hypopnea index (AHI) and mean nighttime oxyhemoglobin saturation (SpO2) as indices of apnea severity. For treatment, subjects were double-blind randomized to 2 weeks of either therapeutic CPAP (n = 18), 3 l/min supplemental nocturnal oxygen (n = 16) or placebo-CPAP (<1 cm H2O) (n = 10). Levels of von Willebrand factor antigen (VWF:Ag), soluble tissue factor (sTF), D-dimer, and plasminogen activator inhibitor (PAI)-1 antigen were measured in plasma pre- and posttreatment. Before treatment, PAI-1 was significantly correlated with AHI (r = 0.47, p = 0.001) and mean nighttime SpO2 (r = -0.32, p = 0.035), but these OSA measures were not significantly related with VWF:Ag, sTF, and D-dimer. AHI was a significant predictor of PAI-1 (R2 = 0.219, standardized beta = 0.47, p = 0.001), independent of mean nighttime SpO2, body mass index (BMI), and age. A weak time-by-treatment interaction for PAI-1 was observed (p = 0.041), even after adjusting for age, BMI, pre-treatment AHI, and mean SpO2 (p = 0.046). Post hoc analyses suggested that only CPAP treatment was associated with a decrease in PAI-1 (p = 0.039); there were no changes in VWF:Ag, sTF, and D-dimer associated with treatment with placebo-CPAP or with nocturnal oxygen. Apnea severity may be associated with impairment in the fibrinolytic capacity. To the extent that our sample size was limited, the observation that CPAP treatment led to a decrease in PAI-1 in OSA must be regarded as tentative.

Snoring in preschool children: prevalence, severity and risk factors

Epidemiological data on snoring from preschool children are scarce, although habitual snoring (snoring on almost all nights) has been associated with poor long-term outcomes. In a population survey of 6,811 children aged 1-4 yrs (from Leicestershire, UK) the present authors determined prevalence, severity and risk factors for snoring, especially habitual snoring. In 59.7% of the children, parents reported snoring in the previous 12 months, including 7.9% with habitual snoring and 0.9% with habitual snoring and sleep disturbance. Prevalence of habitual snoring increased with age from 6.6% in 1-yr-olds to 13.0% in 4-yr-olds. Habitual snoring was associated with: one and both parents smoking (adjusted odds ratio (OR) 1.46 and 2.09, respectively); road traffic (OR 1.23); single parent (OR 1.60); and in White but not South Asian children, socioeconomic deprivation (OR 1.25 and 2.03 for middle and upper thirds of Townsend score, respectively). Respiratory tract symptoms related to atopic disorders and to respiratory infections were strongly associated with snoring; however, body mass index was not. In conclusion, habitual snoring is common in preschool children with one-third of cases attributable to avoidable risk factors. The strong association with atopic disorders, viral infections and environmental exposures suggests a complex aetiology, based on a general vulnerability of the respiratory tract.

The influence of body mass index on injury pattern in polytrauma: thorax as the main source of complications

Background: Obesity is a growing problem in industrial nations. The aim of this study was to determine the relationship between the body mass index (BMI) and the pattern of injury after polytrauma. Methods: This retrospective study included 651 patients with an injury severity score (ISS) ≥16 and aged ≥16 years who were subdivided into three groups: BMI < 25 kg/m2, BMI 25–30 kg/m2, and BMI > 30 kg/m2. The Abbreviated Injury Scale (AIS) was used to quantify the injuries in the different anatomical regions. The Murray score was assessed at admission and at its maximum during hospitalization to evaluate pulmonary problems. Data are presented as means ± standard errors of the means. One way analysis of variance, χ2 test and Kruskal-Wallis test were used for the analyses and the significance level was set at p < 0.05. Results: The AIS of the thorax was 3.2 ± 0.1 in the BMI < 25 kg/m2 group, 3.3 ± 0.1 in the BMI 25–30 kg/m2 group, and 2.8 ± 0.2 in the BMI > 30 kg/m2 group; p < 0.05. The Murray score at admission increased significantly with increasing BMI (0.8 ± 0.8 for BMI < 25 kg/m2, 0.9 ± 0.9 for BMI 25–30 kg/m2, and 1.0 ± 0.8 for BMI > 30 kg/m2; p < 0.05) as was the maximum Murray score during hospitalization (1.2 ± 0.9 for BMI < 25 kg/m2, 1.6 ± 1.0 for BMI 25–30 kg/m2, and 1.5 ± 0.9 for BMI > 30 kg/m2; p < 0.001). The number of ventilator days was also elevated significantly with increasing BMI (5.9 ± 0.4 for BMI < 25 kg/m2, 7.7 ± 0.8 for BMI 25–30 kg/m2, and 7.9 ± 1.6 for BMI > 30 kg/m2; p < 0.05). Conclusion: Overweight and obesity lead to a higher incidence of thoracic trauma in a polytrauma situation and may additionally handicap ventilation in an obstructive manner.

Expanding the cone location and magnitude index to include corneal thickness and posterior surface information for the detection of keratoconus

PURPOSE To extend the capabilities of the Cone Location and Magnitude Index algorithm to include a combination of topographic information from the anterior and posterior corneal surfaces and corneal thickness measurements to further improve our ability to correctly identify keratoconus using this new index: ConeLocationMagnitudeIndex_X. DESIGN Retrospective case-control study. METHODS Three independent data sets were analyzed: 1 development and 2 validation. The AnteriorCornealPower index was calculated to stratify the keratoconus data from mild to severe. The ConeLocationMagnitudeIndex algorithm was applied to all tomography data collected using a dual Scheimpflug-Placido-based tomographer. The ConeLocationMagnitudeIndex_X formula, resulting from analysis of the Development set, was used to determine the logistic regression model that best separates keratoconus from normal and was applied to all data sets to calculate PercentProbabilityKeratoconus_X. The sensitivity/specificity of PercentProbabilityKeratoconus_X was compared with the original PercentProbabilityKeratoconus, which only uses anterior axial data. RESULTS The AnteriorCornealPower severity distribution for the combined data sets are 136 mild, 12 moderate, and 7 severe. The logistic regression model generated for ConeLocationMagnitudeIndex_X produces complete separation for the Development set. Validation Set 1 has 1 false-negative and Validation Set 2 has 1 false-positive. The overall sensitivity/specificity results for the logistic model produced using the ConeLocationMagnitudeIndex_X algorithm are 99.4% and 99.6%, respectively. The overall sensitivity/specificity results for using the original ConeLocationMagnitudeIndex algorithm are 89.2% and 98.8%, respectively. CONCLUSIONS ConeLocationMagnitudeIndex_X provides a robust index that can detect the presence or absence of a keratoconic pattern in corneal tomography maps with improved sensitivity/specificity from the original anterior surface-only ConeLocationMagnitudeIndex algorithm.

Association of biomarkers of lipid modification with functional and morphological indices of coronary stenosis severity in stable coronary artery disease

Biomarkers of blood lipid modification and oxidative stress have been associated with increased cardiovascular morbidity. We sought to determine whether these biomarkers were related to functional indices of stenosis severity among patients with stable coronary artery disease. We studied 197 consecutive patients with stable coronary artery disease due to single vessel disease. Fractional flow reserve (FFR) ≤ 0.80 was assessed as index of a functionally significant lesion. Serum levels of secretory phospholipase A2 (sPLA2) activity, secretory phospholipase A2 type IIA (sPLA2-IIA), myeloperoxydase (MPO), lipoprotein-associated phospholipase A2 (Lp-PLA2), and oxidized low-density lipoprotein (OxLDL) were assessed using commercially available assays. Patients with FFR > 0.8 had higher sPLA2 activity, sPLA2 IIA, and OxLDL levels than patients with FFR ≤ 0.8 (21.25 [16.03-27.28] vs 25.85 [20.58-34.63] U/mL, p < 0.001, 2.0 [1.5-3.4] vs 2.6 [2.0-3.4] ng/mL, p < 0.01; and 53.0 [36.0-71.0] vs 64.5 [50-89.25], p < 0.001 respectively). Patients with FFR > 0.80 had similar Lp-PLA2 and MPO levels versus those with FFR ≤ 0.8. sPLA2 activity, sPLA2 IIA significantly increased area under the curve over baseline characteristics to predict FFR ≤ 0.8 (0.67 to 0.77 (95 % confidence interval [CI]: 0.69-0.85) p < 0.01 and 0.67 to 0.77 (95 % CI: 0.69-0.84) p < 0.01, respectively). Serum sPLA2 activity as well as sPLA2-IIA level is related to functional characteristics of coronary stenoses in patients with stable coronary artery disease.

Development and Validation of a Symptom-Based Activity Index for Adults with Eosinophilic Esophagitis

BACKGROUND & Aims: Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE), to provide endpoints for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patients' assessments of disease severity. We also evaluated relationships between patients' assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings. METHODS We collected information from 186 patients with EoE in Switzerland and the US (69.4% male; median age, 43 years) via surveys (n = 135), focus groups (n = 27), and semi-structured interviews (n = 24). Items were generated for the instruments to assess biologic activity based on physician input. Linear regression was used to quantify the extent to which variations in patient-reported disease characteristics could account for variations in patients' assessment of EoE severity. The PRO instrument was prospectively used in 153 adult patients with EoE (72.5% male; median age, 38 years), and validated in an independent group of 120 patients with EoE (60.8% male; median age, 40.5 years). RESULTS Seven PRO factors that are used to assess characteristics of dysphagia, behavioral adaptations to living with dysphagia, and pain while swallowing accounted for 67% of the variation in patients' assessment of disease severity. Based on statistical consideration and patient input, a 7-day recall period was selected. Highly active EoE, based on endoscopic and histologic findings, was associated with an increase in patient-assessed disease severity. In the validation study, the mean difference between patient assessment of EoE severity and PRO score was 0.13 (on a scale from 0 to 10). CONCLUSIONS We developed and validated an EoE scoring system based on 7 PRO items that assesses symptoms over a 7-day recall period. Clinicaltrials.gov number: NCT00939263.