Early closure of ileostomy is associated with less postoperative nausea and vomiting

Background/Aims: Temporary loop ileostomy is increasingly used in colorectal surgery but necessitates secondary closure. We evaluated postoperative complications, particularly nausea and vomiting, in patients with early, intermediate, or late elective ileostomy closure. Methods: We included all patients undergoing ileostomy closure from 2001 to 2008. Time from ileostomy construction to closure was classified as early (EC, <12 weeks), intermediate (IC, 12–18 weeks), and late (LC, >18 weeks). Using multivariable logistic regression, we compared the frequency of postoperative complications between the groups. Results: We included 134 patients (87 males; median age 71 years, range 29–91). Carcinoma of the rectum (n = 67, 50%) was the main reason for ileostomy construction. The median time to ileostomy closure was 103 days (range 8–461). Among patients with EC, IC, and LC, postoperative nausea occurred in 50.0, 73.1, and 78.6%, respectively (p = 0.006), and postoperative vomiting in 22.5, 57.7, and 59.5%, respectively (p = 0.001). Adjusting for important covariates, the odds ratio for postoperative nausea was 2.0 (95% CI 0.76–5.1) for IC and 4.1 (95% CI 1.2–14.3) for LC compared to EC (p = 0.069). For postoperative vomiting, adjusted odds ratios were 3.8 (95% CI 1.4–10.4) for IC and 4.6 (95% CI 1.4–15.5) for LC (p = 0.012). Other complications did not differ between the groups. Conclusions: These findings suggest that early ileostomy closure might reduce postoperative nausea and vomiting.

Alcohol consumption and binge drinking in young adult childhood cancer survivors

Background This study compared frequency of alcohol consumption and binge drinking between young adult childhood cancer survivors and the general population in Switzerland, and assessed its socio-demographic and clinical determinants. Procedure Childhood cancer survivors aged <16 years when diagnosed 1976–2003, who had survived >5 years and were currently aged 20–40 years received a postal questionnaire. Reported frequency of alcohol use and of binge drinking were compared to the Swiss Health Survey, a representative general population survey. Determinants of frequent alcohol consumption and binge drinking were assessed in a multivariable logistic regression. Results Of 1,697 eligible survivors, 1,447 could be contacted and 1,049 (73%) responded. Survivors reported more often than controls to consume alcohol frequently (OR = 1.7; 95%CI = 1.3–2.1) and to engage in binge drinking (OR = 2.9; 95%CI = 2.3–3.8). Peak frequency of binge drinking in males occurred at age 24–26 years in survivors, compared to age 18–20 in the general population. Socio-demographic factors (male gender, high educational attainment, French and Italian speaking, and migration background from Northern European countries) were most strongly associated with alcohol consumption patterns among both survivors and controls. Conclusions The high frequency of alcohol consumption found in this study is a matter of concern. Our data suggest that survivors should be better informed on the health effects of alcohol consumption during routine follow-up, and that such counseling should be included in clinical guidelines. Future research should study motives of alcohol consumption among survivors to allow development of targeted health interventions for this vulnerable group.

A PRISMA assessment of the reporting quality of systematic reviews in orthodontics

Abstract Objectives: To assess the reporting quality of Cochrane and non-Cochrane systematic reviews (SR) in orthodontics and to compare the reporting quality (PRISMA score) with methodological quality (AMSTAR criteria). Materials and Methods: Systematic reviews (n  =  109) published between January 2000 and July 2011 in five leading orthodontic journals were identified and included. The quality of reporting of the included reviews was assessed by two authors in accordance with the PRISMA guidelines. Each article was assigned a cumulative grade based on fulfillment of the applicable criteria, and an overall percentage score was assigned. Descriptive statistics and simple and multiple linear regression analyses were undertaken. Results: The mean overall PRISMA score was 64.1% (95% confidence interval [CI], 62%-65%). The quality of reporting was considerably better in reviews published in the Cochrane Database of Systematic Reviews (P < .001) than in non-Cochrane reviews. Both multivariable and univariable analysis indicated that journal of publication and number of authors was significantly associated with the PRISMA score. The association between AMSTAR score and modified PRISMA score was also found to be highly statistically significant. Conclusion: Compliance of orthodontic SRs published in orthodontic journals with PRISMA guidelines was deficient in several areas. The quality of reporting assessed using PRISMA guidelines was significantly better in orthodontic SRs published in the Cochrane Database of Systematic Reviews.

Do Central Hypersensitivity and Altered Pain Modulation Predict the Course of Chronic Low Back and Neck Pain?

OBJECTIVES:: Widespread central hypersensitivity and altered conditioned pain modulation (CPM) have been documented in chronic pain conditions. Information on their prognostic values is limited. This study tested the hypothesis that widespread central hypersensitivity (WCH) and altered CPM, assessed during the chronic phase of low back and neck pain, predict poor outcome. METHODS:: A total of 169 consecutive patients with chronic low back or neck pain, referred to the pain clinic during 1 year, were analyzed. Pressure pain tolerance threshold at the second toe and tolerance time during cold pressor test at the hand assessed WCH. CPM was measured by the change in pressure pain tolerance threshold (test stimulus) after cold pressor test (conditioning stimulus). A structured telephone interview was performed 12 to 15 months after testing to record outcome parameters. Linear regression models were used, with average and maximum pain intensity of the last 24 hours at follow-up as endpoints. Multivariable analyses included sex, age, catastrophizing scale, Beck Depression Inventory, pain duration, intake of opioids, and type of pain syndrome. RESULTS:: Statistically significant reductions from baseline to follow-up were observed in pain intensity (P<0.001). No evidence for an association between the measures of WCH or CPM and intensity of chronic pain at follow-up was found. DISCUSSION:: A major predictive value of the measures that we used is unlikely. Future studies adopting other assessment modalities and possibly standardized treatments are needed to further elucidate the prognostic value of WCH and altered CPM in chronic pain.

Physical performance limitations in adolescent and adult survivors of childhood cancer and their siblings

Purpose This study investigates physical performance limitations for sports and daily activities in recently diagnosed childhood cancer survivors and siblings. Methods The Swiss Childhood Cancer Survivor Study sent a questionnaire to all survivors (≥16 years) registered in the Swiss Childhood Cancer Registry, who survived >5 years and were diagnosed 1976–2003 aged <16 years. Siblings received similar questionnaires. We assessed two types of physical performance limitations: 1) limitations in sports; 2) limitations in daily activities (using SF-36 physical function score). We compared results between survivors diagnosed before and after 1990 and determined predictors for both types of limitations by multivariable logistic regression. Results The sample included 1038 survivors and 534 siblings. Overall, 96 survivors (9.5%) and 7 siblings (1.1%) reported a limitation in sports (Odds ratio 5.5, 95%CI 2.9-10.4, p<0.001), mainly caused by musculoskeletal and neurological problems. Findings were even more pronounced for children diagnosed more recently (OR 4.8, CI 2.4–9.6 and 8.3, CI 3.7–18.8 for those diagnosed <1990 and ≥1990, respectively; p = 0.025). Mean physical function score for limitations in daily activities was 49.6 (CI 48.9–50.4) in survivors and 53.1 (CI 52.5–53.7) in siblings (p<0.001). Again, differences tended to be larger in children diagnosed more recently. Survivors of bone tumors, CNS tumors and retinoblastoma and children treated with radiotherapy were most strongly affected. Conclusion Survivors of childhood cancer, even those diagnosed recently and treated with modern protocols, remain at high risk for physical performance limitations. Treatment and follow-up care should include tailored interventions to mitigate these late effects in high-risk patients.

A prediction model for assessing residential radon concentration in Switzerland

Indoor radon is regularly measured in Switzerland. However, a nationwide model to predict residential radon levels has not been developed. The aim of this study was to develop a prediction model to assess indoor radon concentrations in Switzerland. The model was based on 44,631 measurements from the nationwide Swiss radon database collected between 1994 and 2004. Of these, 80% randomly selected measurements were used for model development and the remaining 20% for an independent model validation. A multivariable log-linear regression model was fitted and relevant predictors selected according to evidence from the literature, the adjusted R², the Akaike's information criterion (AIC), and the Bayesian information criterion (BIC). The prediction model was evaluated by calculating Spearman rank correlation between measured and predicted values. Additionally, the predicted values were categorised into three categories (50th, 50th-90th and 90th percentile) and compared with measured categories using a weighted Kappa statistic. The most relevant predictors for indoor radon levels were tectonic units and year of construction of the building, followed by soil texture, degree of urbanisation, floor of the building where the measurement was taken and housing type (P-values <0.001 for all). Mean predicted radon values (geometric mean) were 66 Bq/m³ (interquartile range 40-111 Bq/m³) in the lowest exposure category, 126 Bq/m³ (69-215 Bq/m³) in the medium category, and 219 Bq/m³ (108-427 Bq/m³) in the highest category. Spearman correlation between predictions and measurements was 0.45 (95%-CI: 0.44; 0.46) for the development dataset and 0.44 (95%-CI: 0.42; 0.46) for the validation dataset. Kappa coefficients were 0.31 for the development and 0.30 for the validation dataset, respectively. The model explained 20% overall variability (adjusted R²). In conclusion, this residential radon prediction model, based on a large number of measurements, was demonstrated to be robust through validation with an independent dataset. The model is appropriate for predicting radon level exposure of the Swiss population in epidemiological research. Nevertheless, some exposure misclassification and regression to the mean is unavoidable and should be taken into account in future applications of the model.

Long-lasting protection of activity of nucleoside reverse transcriptase inhibitors and protease inhibitors (PIs) by boosted PI containing regimens

Background The accumulation of mutations after long-lasting exposure to a failing combination antiretroviral therapy (cART) is problematic and severely reduces the options for further successful treatments. Methods We studied patients from the Swiss HIV Cohort Study who failed cART with nucleoside reverse transcriptase inhibitors (NRTIs) and either a ritonavir-boosted PI (PI/r) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). The loss of genotypic activity <3, 3–6, >6 months after virological failure was analyzed with Stanford algorithm. Risk factors associated with early emergence of drug resistance mutations (<6 months after failure) were identified with multivariable logistic regression. Results Ninety-nine genotypic resistance tests from PI/r-treated and 129 from NNRTI-treated patients were analyzed. The risk of losing the activity of ≥1 NRTIs was lower among PI/r- compared to NNRTI-treated individuals <3, 3–6, and >6 months after failure: 8.8% vs. 38.2% (p = 0.009), 7.1% vs. 46.9% (p<0.001) and 18.9% vs. 60.9% (p<0.001). The percentages of patients who have lost PI/r activity were 2.9%, 3.6% and 5.4% <3, 3–6, >6 months after failure compared to 41.2%, 49.0% and 63.0% of those who have lost NNRTI activity (all p<0.001). The risk to accumulate an early NRTI mutation was strongly associated with NNRTI-containing cART (adjusted odds ratio: 13.3 (95% CI: 4.1–42.8), p<0.001). Conclusions The loss of activity of PIs and NRTIs was low among patients treated with PI/r, even after long-lasting exposure to a failing cART. Thus, more options remain for second-line therapy. This finding is potentially of high relevance, in particular for settings with poor or lacking virological monitoring.

Minor protease inhibitor mutations at baseline do not increase the risk for a virological failure in HIV-1 subtype B infected patients

Background Minor protease inhibitor (PI) mutations often exist as polymorphisms in HIV-1 sequences from treatment-naïve patients. Previous studies showed that their presence impairs the antiretroviral treatment (ART) response. Evaluating these findings in a larger cohort is essential. Methods To study the impact of minor PI mutations on time to viral suppression and time to virological failure, we included patients from the Swiss HIV Cohort Study infected with HIV-1 subtype B who started first-line ART with a PI and two nucleoside reverse transcriptase inhibitors. Cox regression models were performed to compare the outcomes among patients with 0 and ≥1 minor PI mutation. Models were adjusted for baseline HIV-1 RNA, CD4 cell count, sex, transmission category, age, ethnicity, year of ART start, the presence of nucleoside reverse transcriptase inhibitor mutations, and stratified for the administered PIs. Results We included 1199 patients of whom 944 (78.7%) received a boosted PI. Minor PI mutations associated with the administered PI were common: 41.7%, 16.1%, 4.7% and 1.9% had 1, 2, 3 or ≥4 mutations, respectively. The time to viral suppression was similar between patients with 0 (reference) and ≥1 minor PI mutation (multivariable hazard ratio (HR): 1.1 [95% confidence interval (CI): 1.0–1.3], P = .196). The time to virological failure was also similar (multivariable HR:.9 [95% CI:.5–1.6], P = .765). In addition, the impact of each single minor PI mutation was analyzed separately: none was significantly associated with the treatment outcome. Conclusions The presence of minor PI mutations at baseline has no effect on the therapy outcome in HIV infected individuals.

Prognostic impact of lymph node ratio outperforms positive lymph nodes and lymph nodes harvested: a time-dependent analysis in mismatch repair-proficient and –deficient colrectal cancers

Objective: We compare the prognostic strength of the lymph node ratio (LNR), positive lymph nodes (+LNs) and collected lymph nodes (LNcoll) using a time-dependent analysis in colorectal cancer patients stratified by mismatch repair (MMR) status. Method: 580 stage III-IV patients were included. Multivariable Cox regression analysis and time-dependent receiver operating characteristic (tROC) curve analysis were performed. The Area under the Curve (AUC) over time was compared for the three features. Results were validated on a second cohort of 105 stage III-IV patients. Results: The AUC for the LNR was 0.71 and outperformed + LNs and LNcoll by 10–15 % in both MMR-proficient and deficient cancers. LNR and + LNs were both significant (p<0.0001) in multivariable analysis but the effect was considerably stronger for the LNR [LNR: HR=5.18 (95 % CI: 3.5–7.6); +LNs=1.06 (95 % CI: 1.04–1.08)]. Similar results were obtained for patients with >12 LNcoll. An optimal cut off score for LNR=0.231 was validated on the second cohort (p<0.001). Conclusion: The LNR outperforms the + LNs and LNcoll even in patients with >12 LNcoll. Its clinical value is not confounded by MMR status. A cut-of score of 0.231 may best stratify patients into prognostic subgroups and could be a basis for the future prospective analysis of the LNR.

Impact of Lifetime Alcohol Use on Liver Fibrosis in a Population of HIV-Infected Patients With and Without Hepatitis C Coinfection

BACKGROUND: The effect of alcohol on liver disease in HIV infection has not been well characterized. METHODS: We performed a cross-sectional multivariable analysis of the association between lifetime alcohol use and liver fibrosis in a longitudinal cohort of HIV-infected patients with alcohol problems. Liver fibrosis was estimated with 2 noninvasive indices, "FIB-4," which includes platelets, liver enzymes, and age; and aspartate aminotransferase/platelet ratio index ("APRI"), which includes platelets and liver enzymes. FIB-4 <1.45 and APRI <0.5 defined the absence of liver fibrosis. FIB-4 >3.25 and APRI >1.5 defined advanced liver fibrosis. The main independent variable was lifetime alcohol consumption (<150 kg, 150 to 600 kg, >600 kg). RESULTS: Subjects (n = 308) were 73% men, mean age 43 years, 49% with hepatitis C virus (HCV) infection, 60% on antiretroviral therapy, 49% with an HIV RNA load <1,000 copies/ml, and 18.7% with a CD4 count <200 cells/mm(3) . Forty-five percent had lifetime alcohol consumption >600 kg, 32.7% 150 to 600 kg, and 22.3% <150 kg; 33% had current heavy alcohol use, and 69% had >9 years of heavy episodic drinking. Sixty-one percent had absence of liver fibrosis and 10% had advanced liver fibrosis based on FIB-4. In logistic regression analyses, controlling for age, gender, HCV infection, and CD4 count, no association was detected between lifetime alcohol consumption and the absence of liver fibrosis (FIB-4 <1.45) (adjusted odds ratio [AOR] = 1.12 [95% CI: 0.25 to 2.52] for 150 to 600 kg vs. <150 kg; AOR = 1.11 [95% CI: 0.52 to 2.36] for >600 kg vs. <150 kg; global p = 0.95). Additionally, no association was detected between lifetime alcohol use and advanced liver fibrosis (FIB-4 >3.25). Results were similar using APRI, and among those with and without HCV infection. CONCLUSIONS: In this cohort of HIV-infected patients with alcohol problems, we found no significant association between lifetime alcohol consumption and the absence of liver fibrosis or the presence of advanced liver fibrosis, suggesting that alcohol may be less important than other known factors that promote liver fibrosis in this population.

Association of cardiovascular risk factors with pattern of lower limb atherosclerosis in 2659 patients undergoing angioplasty

OBJECTIVES: Aim of this study is to correlate distribution pattern of lower limb atherosclerosis with cardiovascular risk factor profile of patients with peripheral arterial occlusive disease (PAD). PATIENTS AND METHODS: Analysis is based on a consecutive series of 2659 patients (1583 men, 1076 women, 70+/-11 years) with chronic PAD of atherosclerotic origin undergoing primary endovascular treatment of lower extremity arteries. Pattern of atherosclerosis was grouped into iliac (n=1166), femoropopliteal (n=2151) and infrageniculate (n=888) disease defined according to target lesions treated. A multivariable multinomial logistic regression analysis was performed to assess relation with age, gender and classical cardiovascular risk factors (diabetes mellitus, arterial hypertension, hypercholesterolemia, cigarette smoking) using femoropopliteal disease as reference. RESULTS: Iliac disease was associated with younger age (RRR 0.95 per year of age, 95%-CI 0.94-0.96, p<0.001), male gender (RRR 1.32, 95%-CI 1.09-1.59, p=0.004) and cigarette smoking (RRR 2.02, 95%-CI 1.68-2.42, p<0.001). Infrageniculate disease was associated with higher age (RRR 1.02, 95%-CI 1.01-1.02, p<0.001), male gender (RRR 1.23, 95%-CI 1.06-1.41, p=0.005) and diabetes mellitus (RRR 1.68, 95%-CI 1.47-1.92, p<0.001). Hypercholesterolemia was less prevalent in patients with lesions below the knee (RRR 0.82, 95%-CI 0.71-0.94, p=0.006), whereas no distinct pattern was apparent related to arterial hypertension. CONCLUSION: Clinical phenotype of peripheral atherosclerosis varies with prevalence of cardiovascular risk factors suggesting differences in mechanisms involved in iliac as compared with infrageniculate lesions. Identification of molecular mechanism might have influence on future therapeutic strategies in PAD patients.

First trimester markers for pre-eclampsia: placental vs. non-placental protein serum levels

BACKGROUND/AIM: Parallel investigation, in a matched case-control study, of the association of different first-trimester markers with the risk of subsequent pre-eclampsia (PE). METHOD: The levels of different first trimester serum markers and fetal nuchal translucency thickness were compared between 52 cases of PE and 104 control women by non-parametric two-group comparisons and by calculating matched odds ratios. RESULTS: In univariable analysis increased concentrations of inhibin A and activin A were associated with subsequent PE (p < 0.02). Multivariable conditional logistic regression models revealed an association between increased risk of PE and increased inhibin A and translucency thickness and respectively reduced pregnancy-associated plasma protein A (PAPP-A) and placental lactogen . However, these associations varied with the gestational age at sample collection. For blood samples taken in pregnancy weeks 12 and 13 only, increased levels of activin A, inhibin A and nuchal translucency thickness, and lower levels of placenta growth factor and PAPP-A were associated with an increased risk of PE. CONCLUSIONS: Members of the inhibin family and to some extent PAPP-A and placental growth factor are superior to other serum markers, and the predictive value of these depends on the gestational age at blood sampling. The availability of a single, early pregnancy 'miracle' serum marker for PE risk assessment seems unlikely in the near future.