Colorectal cancer screening at age 45 years in Israel: Cost-effectiveness and global implications.

BACKGROUND: Colorectal cancer (CRC) incidence at ages <50 years is increasing worldwide. Screening initiation was lowered to 45 years in the United States. The cost-effectiveness of initiating CRC screening at 45 years in Israel was assessed with the aim of informing national policy and addressing internationally relevant questions. METHODS: A validated CRC screening model was calibrated to Israeli data and examined annual fecal immunochemical testing (FIT) or colonoscopy every 10 years from 45 to 74 years (FIT45-74 or Colo45-74) versus from 50 to 74 years (FIT50-74 or Colo50-74). The addition of a fourth colonoscopy at 75 years was explored, subanalyses were performed by sex/ethnicity, and resource demands were estimated. RESULTS: FIT50-74 and Colo50-74 reduced CRC incidence by 57% and 70% and mortality by 70% and 77%, respectively, versus no screening, with greater absolute impact in Jews/Other versus Arabs but comparable relative impact. FIT45-74 further reduced CRC incidence and mortality by an absolute 3% and 2%, respectively. With Colo45-74 versus Colo50-74, CRC cases and deaths increased slightly as three colonoscopies per lifetime shifted to 5 years earlier but mean quality-adjusted life-years gained (QALYGs) per person increased. FIT45-74 and Colo45-74 cost 23,800-53,900 new Israeli shekels (NIS)/QALYG and 110,600-162,700 NIS/QALYG, with the lowest and highest values among Jewish/Other men and Arab women, respectively. A fourth lifetime colonoscopy cost 48,700 NIS/QALYG. Lowering FIT initiation to 45 years with modest participation required 19,300 additional colonoscopies in the first 3 years. CONCLUSIONS: Beginning CRC screening at 45 years in Israel is projected to yield modest clinical benefits at acceptable costs per QALYG. Despite different estimates by sex/ethnicity, a uniform national policy is favored. These findings can inform Israeli guidelines and serve as a case study internationally.

Pro-motility Preparation Protocol May Reduce the Rates of Failed Patency Capsule Among Patients with Crohn's Disease in Clinical Remission.

BACKGROUND: Patency capsule (PC) ingestion is commonly used to minimize capsule retention in high-risk patients with Crohn's disease (CD). However, false-positive rates remain high, precluding the use of video capsule endoscopy (VCE). We aimed to compare the efficacy of two preparation protocols in reducing failed PC rates in patients with CD. METHODS: This bi-center retrospective case-control study included adult patients with small-bowel CD in clinical remission who underwent PC ingestion. The pro-motility group followed a low-residue diet, then a clear fluid diet, and took bisacodyl after ingestion, while the control group followed only a clear fluid diet. The primary outcome was failed PC, defined as the absence of PC excretion or presence on abdominal X-ray at 30 h post-ingestion. Multivariable logistic regression was used to identify predictors of failed PC. RESULTS: Among 273 patients (83 in the pro-motility group, 190 controls), the pro-motility group was older (median 36 [27-48] vs. 31 [24-43], p = 0.012) and had a lower rate of B2/3 disease phenotype (32.5 vs. 53.1%, p = 0.002) compared to controls. The pro-motility group also had a lower failed PC rate (12.0 vs. 24.7%, p = 0.023). Longer disease duration (adjusted odds ratio (AOR) 1.053, 95% confidence interval (CI) 1.016-1.091, p = 0.005) increased the odds of failed PC, while the pro-motility protocol was protective (AOR 0.438, 95% CI 0.200-0.956, p = 0.038), outweighing the influence of B2/3 disease phenotype (AOR 1.743, 95% CI 0.912-3.332, p = 0.093). CONCLUSIONS: The pro-motility preparation protocol could substantially improve the success rates of the small-bowel patency test in patients with CD undergoing PC ingestion, potentially reducing the risk of capsule retention and associated complications.

Development and validation of a prediction model for histologic progression in patients with nondysplastic Barrett's esophagus.

OBJECTIVES: Patients with Barrett's esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). We developed a model to predict histologic progression in patients with nondysplastic BE (NDBE). METHODS: A longitudinal study in three referral centers was performed between January 2010 and December 2019. As progression to low-grade dysplasia (LGD) can be considered an indication for ablative therapy, the study end-point was histopathologic progression to LGD, high-grade dysplasia, or EAC at 3 years after diagnosis. We used logistic regression to create the model. Seventy percent of the cohort were used to stem the model and the remaining 30% for internal validation. RESULTS: A total of 542 patients were included, 69.4% of whom were male, mean age 62.2 years. Long-segment BE at index endoscopy was diagnosed in 20.8% of the patients. After a mean follow-up of 6.7 years, 133 patients (24.5%) had histologic progression. Our model identified a neutrophil-to-lymphocyte ratio (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.77-2.32, P < 0.001), BE length (OR 1.22, 95% CI 1.09-1.36, P < 0.001), age (OR 1.03, 95% CI 1.02-1.05, P = 0.02), smoking (OR 1.66, 95% CI 1.09-2.75, P = 0.04), and renal failure (OR 1.51, 95% CI 0.93-2.43, P = 0.07) as predictors of histologic progression at 3 years. The areas under the receiver operating characteristic curves of this model were 0.88 and 0.76 in the training and validation cohorts, respectively. CONCLUSION: This novel, internally validated model may predict histologic progression, even in patients with NDBE who generally have low rates of progression over time, and may contribute to enhanced patient selection for more intense surveillance programs.

Exploring Popular Social Media Networks for Patients With Inflammatory Bowel Diseases: Insights for Better Care.

GOAL: The aim was to assess topics of interest and concerns among patients with inflammatory bowel diseases (IBD) who are active online. BACKGROUND: Social media (SM) networks are a major communication tool for patients with IBD and health care professionals. PATIENTS AND METHODS: We performed an anonymized investigation of SM networks for IBD patients; I-a thematic analysis of patients' posts, II-an online survey advertised through Facebook and other popular SM networks throughout November 2019. RESULTS: Analyzing 2133 posts (2014 to 2019) revealed 18 topics of interest. The online survey was completed by 534 respondents [63%-Crohn's disease, 56%-female, median age-38 years (interquartile range: 28.7 to 51.0)]. Most respondents (70%) were followed in referral centers, and 45% were receiving biological therapy. Respondents reported high satisfaction with IBD care and health care provider professionalism. The top 5 topics of interest were diet, lifestyle, complementary and alternative medicine, diagnostic test interpretation, and specialist referrals and reviews. Cluster analysis demonstrated that gender, income, and education level were associated with specific interest and concerns. CONCLUSION: Patients' activity on SM is independent of their satisfaction with formal IBD care and rather reflects an ongoing need for information and support. These needs may be addressed both in clinical settings and through online tools.

Is molecular testing in patients with low risk papillary thyroid carcinoma justified? A Markovian model.

BACKGROUND: Current guidelines consider all cases of papillary thyroid carcinoma (PTC) smaller than 4 cm and without extrathyroidal extension (ETE) and/or lymph node metastases as belonging to the same prognostic group, and therefore the recommendation is for uniform treatment. Xing draws our attention to a small subgroup with Duet Mutations (BRAF E600 and TERT 3636 genes) that are aggressive biologically and should be treated differently. Thus the aim of the present study is to test the validity of this recommendation. METHODS: A Markovian Model is used to evaluate the above hypothesis. RESULTS: A Monte Carlo sensitivity test shows a 5.6 year survival advantage for patients with low-grade PTC, who have the Duet Mutations, and were treated by total thyroidectomy rather than hemithyroidectomy. CONCLUSIONS: We conclude that there is a place for routine molecular tests in low-risk patients with PTC.

Hepatitis C related cognitive impairment: Impact of viral and host factors and response to therapy.

Chronic hepatitis C virus (HCV) infection is associated with cognitive impairment via several suggested mechanisms including direct neurotoxicity and minimal hepatic encephalopathy. The prevalence of HCV-related cognitive impairment and whether it is reversed by anti-viral therapy is unknown. We aimed to assess predictors and reversibility of cognitive impairment of HCV-infected patients after successful treatment. Consecutive HCV patients treated during the EMERALD study (AbbVie 3D regimen for protease inhibitors failure) underwent neuropsychological (number connection test A [NCTA] and digital symbol test [DST]) and neurophysiological (critical flicker frequency [CFF]) tests at baseline and at 12 weeks post-treatment. Patient self-reported outcomes (PROs) were prospectively collected. Patients with a history of hepatic encephalopathy were excluded. Thirty-two patients underwent the cognitive tests at baseline. Seven of them had abnormal CFF test findings. Twenty-five (25/32, 78%) patients had repeated evaluations 3 months post-treatment. High viral loads were significantly associated with abnormal CFF across fibrosis levels (area under the ROC curve 0.817). CFF results significantly improved following viral eradication, from 40.9 (interquartile range 38.6-42.9) at baseline to 41.5 (39.8-44), p = .042, at follow-up. Both NCTA and DST results improved, but not significantly. There was improvement in the PROs of general health perception and vitality. The NCTA and DST results were more significantly associated with PROs than CFF. This prospective interventional study showed greater cognitive impairment in HCV patients with high viral load and demonstrated partial reversibility of HCV neurotoxicity and subsequent improvement in PROs following treatment.

Preimplantation genetic testing for BRCA gene mutation carriers: a cost effectiveness analysis.

BACKGROUND: Gynecologic oncologists should be aware of the option of conception through IVF/PGT-M for families with high BRCA related morbidity or mortality. Our objective was to investigate the cost-effectiveness of preimplantation genetic testing for selection and transfer of BRCA negative embryo in BRCA mutation carriers compared to natural conception. METHODS: Cost-effectiveness of two strategies, conception through IVF/PGT-M and BRCA negative embryo transfer versus natural conception with a 50% chance of BRCA positive newborn for BRCA mutation carriers was compared using a Markovian process decision analysis model. Costs of the two strategies were compared using quality adjusted life years (QALYs'). All costs were discounted at 3%. Incremental cost effectiveness ratio (ICER) compared to willingness to pay threshold was used for cost-effectiveness analysis. RESULTS: IVF/ PGT-M is cost-effective with an ICER of 150,219 new Israeli Shekels, per QALY gained (equivalent to 44,480 USD), at a 3% discount rate. CONCLUSIONS: IVF/ PGT-M and BRCA negative embryo transfer compared to natural conception among BRCA positive parents is cost effective and may be offered for selected couples with high BRCA mutation related morbidity or mortality. Our results could impact decisions regarding conception among BRCA positive couples and health care providers.

Modeling Social Distancing Strategies to Prevent SARS-CoV-2 Spread in Israel: A Cost-Effectiveness Analysis.

OBJECTIVES: While highly effective in preventing SARS-CoV-2 spread, national lockdowns come with an enormous economic price. Few countries have adopted an alternative "testing, tracing, and isolation" approach to selectively isolate people at high exposure risk, thereby minimizing the economic impact. To assist policy makers, we performed a cost-effectiveness analysis of these 2 strategies. METHODS: A modified Susceptible, Exposed, Infectious, Recovered, and Deceased (SEIRD) model was employed to assess the situation in Israel, a small country with ∼9 million people. The incremental cost-effectiveness ratio (ICER) of these strategies as well as the expected number of infected individuals and deaths were calculated. RESULTS: A nationwide lockdown is expected to save, on average, 274 (median 124, interquartile range: 71-221) lives compared to the "testing, tracing, and isolation" approach. However, the ICER will be, on average, $45 104 156 (median $49.6 million, interquartile range: 22.7-220.1) to prevent 1 case of death. CONCLUSION: A national lockdown has a moderate advantage in saving lives with tremendous costs and possible overwhelming economic effects. These findings should assist decision makers dealing with additional waves of this pandemic.

Early post-liver transplantation infections and their effect on long-term survival.

BACKGROUND: Infections post-liver transplantation are major drivers for morbidity and mortality. However, the impact of infections within 180 days post-liver transplantation on long-term survival is not clear. METHODS: We present a retrospective cohort of 317 liver transplant patients for whom all infectious episodes were prospectively collected during a mean follow-up of 4.4 years. RESULTS: A total of 143/317 (45%) of patients suffered from any infectious episode during the first 6 months following liver transplantation. Patients with surgical site infections have a reduced survival compared to those with no infection (HR 0.33, 95% CI 0.172-0.636, P = .001), whereas infections from other sources, including pneumonia, UTI, and line-related infections, were not associated with increased mortality. Furthermore, even though the presence of any infection within 30 days or 6 months post-transplantation did not affect survival, more than a single infectious episode per patient was significantly associated with increased mortality (HR 1.70, CI 1.12-2.60, P = .013). In a multivariate analysis, the number of infectious episodes remained statistically significant (HR 1.58, 95% CI 1.03-2.43, P = .035) upon adjustment for other major variables associated with comorbidities and infection risk. CONCLUSIONS: Surgical site infections and the number of infectious episodes within 180 days post-liver transplantation are major determinants of long-term survival among these patients.

Is parotidectomy justified in elderly patients with pleomorphic adenoma? A decision analysis model.

PURPOSE: The value of parotidectomy in older patients is unclear. This study presents a decision model to help resolve this question. MATERIALS & METHODS: A Markov model with Monte Carlo simulation was used to compare outcomes in patients of different ages with pleomorphic adenoma of the parotid gland treated by surgery or surveillance. RESULTS: In 30-year-old patients, surgery conferred a 3.5-year gain in life expectancy whereas in 75-year-olds, it was only 0.74 months. The expected rate of malignant transformation at age 30 years was 6.5% after surgery and 26.5% after surveillance; at age 65, corresponding rates were 0.8% and 10.7%. Sensitivity analysis showed that age was the only parameter that significantly contributed to life expectancy. The benefit of surgery was restricted in older patients. CONCLUSION: Our Markov decision-analysis model suggests that patients older than 65 years with pleomorphic adenoma have a limited survival advantage with surgery compared to surveillance.

Median Survival or Mean Survival: Which Measure Is the Most Appropriate for Patients, Physicians, and Policymakers?

INTRODUCTION: Understanding the efficacy of treatments is crucial for patients, physicians, and policymakers. Median survival, the most common measure used in the outcome reporting of oncology clinical trials, is easy to understand; however, it describes only a single time point. The interpretation of the hazard ratio is difficult, and its underlying statistical assumptions are not always met. The objective of this study was to evaluate alternative measures based on the mean benefit of novel oncology treatments. MATERIALS AND METHODS: We reviewed all U.S. Food and Drug Administration (FDA) approvals for oncology agents between 2013 and 2017. We digitized survival curves as reported in the clinical trials used for the FDA approvals and implemented statistical transformations to calculate for each trial the restricted mean survival time (RMST), as well as the mean survival using Weibull distribution. We compared the mean survival with the median survival benefit in each clinical trial. RESULTS: The FDA approved 83 solid tumor indications for oncology agents between 2013 and 2017, of which 27 approvals based on response rates, whereas 49 approvals were based on survival endpoints (progression-free survival and overall survival). The average improvement in median overall survival or progression-free survival was 4.6 months versus 3.6 months improvement in the average RMST and 6.1 months improvement in mean survival using Weibull distribution. CONCLUSION: Mean survival may supply valuable information for different stakeholders. Its inclusion should be considered in the reporting of prospective clinical trials. IMPLICATIONS FOR PRACTICE: Mean survival may supply valuable information for different stakeholders. Its inclusion should be considered in the reporting of clinical trials.

A Cost-Effectiveness Analysis of Nivolumab and Ipilimumab Versus Sunitinib in First-Line Intermediate- to Poor-Risk Advanced Renal Cell Carcinoma.

BACKGROUND: The treatment paradigm of advanced renal cell carcinoma (RCC) has changed rapidly in recent years. In first-line treatment of intermediate- to poor-risk patients, the CheckMate 214 study demonstrated a significant survival advantage for nivolumab and ipilimumab versus sunitinib. The high cost of combined immune-modulating agents warrants an understanding of the combination's value by considering both efficacy and cost. The objective of this study was to estimate the cost-effectiveness of nivolumab and ipilimumab compared with sunitinib for first-line treatment of intermediate- to poor-risk advanced RCC from the U.S. payer perspective. MATERIALS AND METHODS: A Markov model was developed to compare the costs and effectiveness of nivolumab and ipilimumab with those of sunitinib in the first-line treatment of intermediate- to poor-risk advanced RCC. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Drug costs were based on Medicare reimbursement rates in 2017. We extrapolated survival beyond the trial closure using Weibull distribution. Model robustness was addressed in univariable and probabilistic sensitivity analyses. RESULTS: The total mean cost per-patient of nivolumab and ipilimumab versus sunitinib was $292,308 and $169,287, respectfully. Nivolumab and ipilimumab generated a gain of 0.978 QALYs over sunitinib. The incremental cost-effectiveness ratio (ICER) for nivolumab and ipilimumab was $125,739/QALY versus sunitinib. CONCLUSION: Our analysis established that the base case ICER in the model for nivolumab and ipilimumab versus sunitinib is below what some would consider the upper limit of the theoretical willingness-to-pay threshold in the U.S. ($150,000/QALY) and is thus estimated to be cost-effective. IMPLICATIONS FOR PRACTICE: This article assessed the cost-effectiveness of nivolumab and ipilimumab versus sunitinib for treatment of patients with intermediate- to poor-risk metastatic kidney cancer, from the U.S. payer perspective. It would cost $125,739 to gain 1 quality-adjusted life-year with nivolumab and ipilimumab versus sunitinib in these patients.

Liver steatosis is a major predictor of poor outcomes in chronic hepatitis C patients with sustained virological response.

Sustained virological response (SVR) results in reduced incidence of hepatocellular carcinoma (HCC) and mortality among chronic hepatitis C (CHC) patients with advanced fibrosis. Since both advanced fibrosis and liver steatosis (LS) may coexist in CHC patients, we evaluated their individual effects on a composite outcome of all-cause mortality and HCC in CHC patients with SVR following direct-acting antivirals (DAA) treatment. We retrospectively evaluated inception cohort of 515 CHC patients who achieved SVR following treatment with DAA, with a mean follow-up of 24 months. Baseline liver fibrosis was assessed by transient elastography, and LS was validated by at least three independent ultrasonographic examinations. 211 of 515 patients (41%) had baseline LS. Patients with LS had a higher cumulative rate of all-cause mortality and HCC at 2 years of follow-up compared to patients without LS (15.75% and 2.79%, respectively, P < 0.001), although they did not have increased incidence of advanced fibrosis or cirrhosis. Consistently, multivariate analysis showed that LS was associated with a significant 7.5-fold increased risk of all-cause mortality and HCC (HR 7.51, 95% C.I 3.61-13.36, P < 0.001) even upon adjustment to components of the metabolic syndrome, whereas advanced fibrosis showed only a trend towards statistical significance (HR 2.32, 95% C.I 0.97-6.59, P = 0.06). In conclusion, LS is a major predictor of all-cause mortality and HCC in patients who achieved SVR following DAA treatment regardless of fibrosis stage. These patients should be rigorously screened for HCC.

Sex, Ethnicity, and Socioeconomic Status Affect on Israeli Pediatric Lipid Testing Despite Equality in National Healthcare Services.

BACKGROUND: In Israel, coronary heart disease mortality rates are significantly higher among the Arab population than the Jewish population. Dyslipidemia prevention should begin in childhood. OBJECTIVES: To identify sociodemographic disparities in the preventive health measurement of lipid profile testing and lipoprotein levels among Israeli children and adolescents. METHODS: A cross-sectional analysis of 1.2 million children and adolescents insured by Clalit Health Services between 2007 and 2011 was conducted using sociodemographic data and serum lipid concentrations. RESULTS: Overall, 10.1% individuals had undergone lipid testing. Those with male sex (odds ratio [OR] = 0.813, 95% confidence interval [95%CI] 0.809-0.816), Arab ethnicity (OR = 0.952, 95%CI 0.941-0.963), and low socioeconomic status (SES) (OR = 0.740, 95%CI 0.728-0.752) were less likely to be tested. By 2010, differences among economic sectors narrowed and Arab children were more likely to be tested (OR = 1.039, 95%CI 1.035-1.044). Girls had higher total cholesterol, triglyceride, low-density lipoprotein-cholesterol, and non-high-density lipoprotein-cholesterol levels compared to boys (P < 0.001). Jewish children had higher cholesterol and low-density and high-density lipoprotein-cholesterol, as well as lower triglyceride levels than Arabs (P < 0.001). Children with low SES had lower cholesterol, low-density and high-density lipoprotein-cholesterol, and non-high-density lipoprotein-cholesterol levels (P < 0.001). CONCLUSIONS: We found that boys, Arab children, and those with low SES were less likely to be tested. Over time there was a gradual reduction in these disparities. Publicly sponsored healthcare services can diminish disparities in the provision of preventive health among diverse socioeconomic groups that comprise the national population.

Fracture Risk Assessment With FRAX Using Real-World Data in a Population-Based Cohort From Israel.

The predictive value of the World Health Organization's Fracture Risk Assessment Tool (FRAX) was evaluated using real-world community data. A population-based cohort of 141,320 women aged 50-90 years (median age, 58 years; interquartile range, 54-67) in 2004 was extracted from the central database of a large Israeli health-care services provider and insurer. Retrospective FRAX scores were calculated using computerized health records and compared with actual incidence of major osteoporotic fractures (MOFs) during the following 10 years. Fracture proportions of 6.9% for MOFs and 2.2% for hip fractures were expected, as opposed to 13.5% and 2.9% observed. The area under the receiver operating characteristic curve (AUC) of FRAX scores calculated without the inclusion of bone mineral density (BMD) data was 0.65 (95% confidence interval: 0.65, 0.66) for MOF and 0.82 (95% confidence interval: 0.81, 0.82) for hip fracture. A total of 16,578 subjects had BMD data at the index date, and their risk estimates based solely on BMD exhibited lower predictive performance for both MOFs (AUC = 0.62 vs. 0.65; P = 0.003) and hip fractures (AUC = 0.78 vs. 0.84; P < 0.001) as compared with FRAX. FRAX scores based on electronic health records provided reasonable discrimination despite some underestimation of the absolute risk of nonhip fractures. Integration of FRAX with routine clinical systems could increase implementation in daily practice and improve risk detection, especially for patients without BMD data.

Predicting Efficacy of Plastic Stents for Posttransplantation Biliary Strictures.

BACKGROUND: Biliary strictures (BS) are a common complication of liver transplantation. The standard treatment is sequential insertion of increasing numbers of plastic stents by endoscopic retrograde cholangiopancreatography (ERCP). Despite high success rates, some strictures fail to resolve and require surgery as definitive treatment. GOALS: To identify predictors of response or failure of standard endoscopic treatment, allowing earlier referral to alternative modalities when needed and avoiding unnecessary procedures. STUDY: Database of Gastroenterology Department at Tel Aviv Medical Center was retrospectively reviewed, and data regarding patients who underwent liver transplantation and developed BS were analyzed. RESULTS: Thirty-one patients met the study criteria. Twenty-four (77.4%) resolved with plastic stenting and 7 ultimately required surgery. There were no significant differences between stent responders and nonresponders regarding demographics, transplant and postoperative hospitalization data, time from transplantation to presentation with stricture, total number of ERCP sessions, or maximal number of stents.A trend toward difference was noted in the time elapsed between the first and the second ERCP, whereby ERCP nonresponders required a second procedure sooner than responders. Patients presenting to their second procedure as scheduled ultimately had a 95% endoscopic success rate, whereas those presenting urgently with acute cholangitis had a 55% failure rate (P=0.02). CONCLUSIONS: Urgent repeat ERCP is a harbinger of ultimate failure of plastic stent treatment for BS after liver transplant. This finding may assist earlier triage of these patients toward alternative treatment such as metal stents or surgery, thus sparing needless procedures and complications.

Sinonasal debridement versus no debridement for the postoperative care of patients undergoing endoscopic sinus surgery.

BACKGROUND: Endoscopic sinus surgery (ESS) is often recommended for symptomatic patients with recurrent acute or chronic rhinosinusitis who have failed conservative treatment. Postoperative care has been felt to be critical for both maintaining the surgical patency of the operated sinuses and improving patient symptoms. Debridement of the sinonasal cavities is one such postoperative care measure that has frequently been studied in the literature, often with conflicting conclusions. OBJECTIVES: To assess the effects of postoperative sinonasal debridement versus no debridement following endoscopic sinus surgery. SEARCH METHODS: The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL, via the Cochrane Register of Studies); PubMed; EMBASE; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 21 May 2018. SELECTION CRITERIA: Randomised controlled trials comparing postoperative nasal debridement versus no debridement in adult patients with recurrent acute or chronic rhinosinusitis undergoing endoscopic sinus surgery. We included studies in which the patients acted as self-controls (i.e. one side of the nose underwent debridement and the other side did not) only for the secondary endoscopy outcomes. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcome measures were: health-related quality of life, disease severity (patient-reported symptom scores) and significant adverse effects (bleeding requiring intervention, severe pain, iatrogenic injury). Secondary outcomes were: postoperative endoscopic appearance of the sinonasal surgical cavities (endoscopic scores), recorded use of postoperative medical treatment and rate of revision surgery. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. MAIN RESULTS: We included four studies (152 participants), with a follow-up duration ranging from three months to 12 months. In two studies patients acted as self-controls, i.e. one side of the nose underwent debridement and the other side did not ('split-nose' studies). The risk of bias in all studies was high, mostly due to the inability to blind the patients to the debridement procedure.Primary outcomesDisease-specific health-related quality of life scoresOnly one study (58 participants) provided data for disease-specific health-related quality of life. At six months follow-up, lower disease-specific health-related quality of life scores, measured using the Sino-Nasal Outcome Test-22 (SNOT-22, range 0 to 110), were noted in the debridement group but the difference was not statistically significant (9.7 in the debridement group versus 10.3 in the control group, P = 0.47) (low-quality evidence).Disease severity (patient-reported symptom score)Only one study (60 participants) provided data for disease severity measured by visual analogue scale (VAS) score. No significant differences in total symptom score were observed between groups postoperatively (low-quality evidence).Significant adverse effectsSignificant adverse effects related to the debridement procedure were not reported in any of the included studies, however it is not clear whether data regarding adverse effects were not collected or if none were indeed observed in any of the included studies.Secondary outcomesAll four studies assessed thepostoperative endoscopic appearance of the sinonasal cavities using the Lund-Kennedy score (range 0 to 10). A pooled analysis of endoscopic scores in the two non 'split-nose' studies revealed better endoscopic scores in the debridement group, however this was not a statistically significant difference (mean difference -0.31, 95% confidence interval (CI) -1.35 to 0.72; I² = 0%; two studies; 118 participants) (low-quality evidence). A sub-analysis of the adhesion formation component of the endoscopic score was available for all four studies and revealed a significantly lower adhesion rate in the debridement group (risk ratio 0.43, 95% CI 0.28 to 0.68; I² = 29%; four studies; 152 participants). Analysis of the number needed to treat to benefit revealed that for every three patients undergoing debridement, the endoscopic score would be decreased by one point in one patient. For every five patients undergoing debridement adhesion formation would be prevented in one patient.Use of postoperative medical treatment was reported in all studies, all of which recommended nasal douching. Steroids (systemic or nasal) were administered in two studies. However, the data were very limited and heterogeneous, therefore we could not analyse the impact of concomitant postoperative medical treatment.The rate of revision surgery was not reported in any of the included studies, however it is not clear whether these data were not recorded or if there were no revision surgeries in any of the included studies. AUTHORS' CONCLUSIONS: We are uncertain about the effects of postoperative sinonasal debridement due to high risk of bias in the included studies and the low quality of the evidence. Sinonasal debridement may make little or no difference to disease-specific health-related quality of life or disease severity. Low-quality evidence suggests that postoperative debridement is associated with a significantly lower risk of adhesions at three months follow-up. Whether this has any impact on longer-term outcomes is unknown.

Predicting neurofibromatosis type 1 risk among children with isolated café-au-lait macules.

BACKGROUND: Although isolated cafe-au-lait macules (CALMs) are a common skin finding, they are an early feature of neurofibromatosis type 1 (NF1). OBJECTIVE: We sought to develop an algorithm determining the risk of children with CALMs to have constitutional NF1. METHODS: We conducted a retrospective study of patients with isolated CALMs. Diagnosis of NF1 was based on detecting NF1 mutation in blood or fulfilling clinical criteria. RESULTS: In all, 170 of 419 (41%) and 21 of 86 (24%) children with isolated CALMs who underwent molecular testing and clinical follow-up, respectively, were given a diagnosis of NF1. Presence of fewer than 6 CALMs at presentation or atypical CALMs was associated with not having NF1 (P < .001). An algorithm based on age, CALMs number, and presence of atypical macules predicted NF1 in both cohorts. According to the algorithm, children older than 29 months with at least 1 atypical CALM or less than 6 CALMs have a 0.9% (95% confidence interval 0%-2.6%) risk for constitutional NF1 whereas children younger than 29 months with 6 or more CALMs have a high risk (80.4%, 95% confidence interval 74.6%-86.2%). LIMITATIONS: The study was designed to detect constitutional NF1 and not NF1 in mosaic form. CONCLUSIONS: A simple algorithm enables categorization of children with isolated CALMs as being at low or high risk for having NF1.

Distinct Lipoprotein Curves in Normal Weight, Overweight, and Obese Children and Adolescents.

OBJECTIVES: Pediatric lipoprotein curves are based on population-based samples. As obesity, may alter lipoprotein levels, cutoffs not adjusted for body mass index (BMI) are potentially inappropriate. We aimed to develop distinct serum lipid curves based on sex- and BMI-percentiles for children and adolescents. METHODS: Cross-sectional analysis included all healthy children and adolescents (age range 2-17 years) with available serum lipid concentrations (n = 152,820 of approximately 1.2 million children and adolescents per study year). These children and adolescents were categorized according to sex- and age-stratified BMI-percentiles: 100,375 normal weight (5th-85th percentile), 26,028 overweight (85th-95th percentile) and 26,417 obese (≥95th percentile) individuals. Excluded were individuals with hyperlipidemia, gastrointestinal disease, thyroid disease and lipid-lowering medications. Lambda-Mu-Sigma, smoothed percentile lipid curves were computed. RESULTS: Obese children had a lipid profile pattern throughout childhood and adolescence similar to that of normal weight subjects but with a significant upward shift in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TGs) and a downward shift in high-density lipoprotein-cholesterol (HDL-C). Obese boys had 13 mg/dL higher TC levels (P < 0.001), 11 mg/dL higher LDL-C levels, 15 mg/dL higher non-HDL-C levels, and 5 mg/dL lower HDL-C levels (P < 0.001). Obese girls had 6 mg/dL higher TC levels, 7 mg/dL higher LDL-C levels, 11 mg/dl higher non-HDL-C levels, and 6 mg/dL lower HDL-C levels (P < 0.001). CONCLUSIONS: Across a large, nationally representative cohort of children and adolescents, lipoprotein levels were found to vary in relation to weight status. On the basis of these findings, it is suggested that when evaluating the lipid profile in the pediatric population, in addition to sex-based curves, clinical decision making may require consideration of BMI-stratified curves.

Patients' Age Rather Than Model of End-Stage Liver Disease Score Predicts Survival After Liver Transplantation.

BACKGROUND: The model of end-stage liver disease (MELD) score is the standard tool for prioritizing patients awaiting liver transplantation. There is currently no definite high cutoff score reflecting disease severity that might exclude patients from transplantation. Furthermore, the age limit that used to disqualify patients from eligibility to transplantation was recently withdrawn in several countries. AIMS: The aims of this study were to assess the effects of MELD score and age at time of transplantation on patients' short- and long-term survival. METHODS: We conducted a retrospective single-center study on a cohort of patients transplanted for the first time due to non-fulminant liver failure. RESULTS: Four hundred and seventeen patients (mean age 50.2 years, 63% males) who underwent liver transplantation for the first time were included. Both higher patients' and donors' age were significantly associated with increased long-term mortality (p = 0.007, 95% CI 1.006-1.038 for patient age, p = 0.02, 95% CI 1.002-1.023 for donor age). Patients' age remained significantly associated with survival at 1 year post-transplantation, as well. We found no association between higher MELD score at transplantation and long-term mortality (p = 0.189, 95% CI 0.99-1.051) irrespective of patients' age. Specifically, when patients were divided according to their MELD score at transplantation (MELD < 15, MELD 15-25 and MELD > 25), no significant differences in long-term survival were detected between these three subgroups. Results did not differ significantly in a subgroup analysis of patients without hepatocellular carcinoma at the time of transplantation. CONCLUSIONS: Patients' and donors' age rather than patients' MELD score at transplantation determine survival following liver transplantation.