A systematic review on the effectiveness of robot-assisted minimally invasive gastrectomy.

BACKGROUND: Robot-assisted minimally invasive gastrectomy (RAMIG) is increasingly used as a surgical approach for gastric cancer. This study assessed the effectiveness of RAMIG and studied which stages of the IDEAL-framework (1 = Idea, 2A = Development, 2B = Exploration, 3 = Assessment, 4 = Long-term follow-up) were followed. METHODS: The Cochrane Library, Embase, Pubmed, and Web of Science were searched for studies on RAMIG up to January 2023. Data collection included the IDEAL-stage, demographics, number of participants, and study design. For randomized controlled trials (RCTs) and long-term studies, data on intra-, postoperative, and oncologic outcomes, survival, and costs of RAMIG were collected and summarized. RESULTS: Of the 114 included studies, none reported the IDEAL-stage. After full-text reading, 18 (16%) studies were considered IDEAL-2A, 75 (66%) IDEAL-2B, 4 (4%) IDEAL-3, and 17 (15%) IDEAL-4. The IDEAL-stages were followed sequentially (2A-4), with IDEAL-2A studies still ongoing. IDEAL-3 RCTs showed lower overall complications (8.5-9.2% RAMIG versus 17.6-19.3% laparoscopic total/subtotal gastrectomy), equal 30-day mortality (0%), and equal length of hospital stay for RAMIG (mean 5.7-8.5 days RAMIG versus 6.4-8.2 days open/laparoscopic total/subtotal gastrectomy). Lymph node yield was similar across techniques, but RAMIG incurred significantly higher costs than laparoscopic total/subtotal gastrectomy ($13,423-15,262 versus $10,165-10,945). IDEAL-4 studies showed similar or improved overall/disease-free survival for RAMIG. CONCLUSION: During worldwide RAMIG implementation, the IDEAL-framework was followed in sequential order. IDEAL-3 and 4 long-term studies showed that RAMIG is similar or even better to conventional surgery in terms of hospital stay, lymph node yield, and overall/disease-free survival. In addition, RAMIG showed reduced postoperative complication rates, despite higher costs.

Arthroscopic partial meniscectomy vs non-surgical or sham treatment in patients with MRI-confirmed degenerative meniscus tears: a systematic review and meta-analysis with individual participant data from 605 randomised patients.

OBJECTIVE: To identify subgroups of patients with magnetic resonance imaging (MRI)-confirmed degenerative meniscus tears who may benefit from arthroscopic partial meniscectomy (APM) in comparison with non-surgical or sham treatment. METHODS: Individual participant data (IPD) from four RCTs were pooled (605 patients, mean age: 55 (SD: 7.5), 52.4% female) as to investigate the effectiveness of APM in patients with MRI-confirmed degenerative meniscus tears compared to non-surgical or sham treatment. Primary outcomes were knee pain, overall knee function, and health-related quality of life, at 24 months follow-up (0-100). The IPD were analysed in a one- and two-stage meta-analyses. Identification of potential subgroups was performed by testing interaction effects of predefined patient characteristics (e.g., age, gender, mechanical symptoms) and APM for each outcome. Additionally, generalized linear mixed-model trees were used for subgroup detection. RESULTS: The APM group showed a small improvement over the non-surgical or sham group on knee pain at 24 months follow-up (2.5 points (95% CI: 0.8-4.2) and 2.2 points (95% CI: 0.9-3.6), one- and two-stage analysis, respectively). Overall knee function and health-related quality of life did not differ between the two groups. Across all outcomes, no relevant subgroup of patients who benefitted from APM was detected. The generalized linear mixed-model trees did also not identify a subgroup. CONCLUSIONS: No relevant subgroup of patients was identified that benefitted from APM compared to non-surgical or sham treatment. Since we were not able to identify any subgroup that benefitted from APM, we recommend a restrained policy regarding meniscectomy in patients with degenerative meniscus tears.

Septoplasty versus non-surgical management for nasal obstruction in adults with a deviated septum: economic evaluation alongside a randomized controlled trial.

BACKGROUND: For years, the benefits of septoplasty have been questioned. Due to the scarce and inconclusive literature, several National Health Service (NHS) Clinical Commissioning Groups in England decided to add septal surgery to their list of restricted procedures with low clinical value. Recently, evidence was obtained that septoplasty is actually more effective than non-surgical management for nasal obstruction in adults with a deviated septum. However, the relation between costs and effects of septoplasty remains unknown. METHODS: We conducted an economic evaluation alongside an open, multicenter, pragmatic randomized controlled trial in two tertiary and 16 secondary referral hospitals in the Netherlands. Adults with nasal obstruction and a deviated septum were randomized to (1) septoplasty with or without concurrent turbinate surgery or (2) non-surgical management consisting of (a combination of) medical treatment and watchful waiting. Analyses were performed on an intention-to-treat basis. Single imputation nested in the bootstrap percentile method (using 5000 bootstrap replications) was performed to assess the effect of missing data. After 12 and 24 months, we assessed the incremental costs per quality-adjusted life year (QALY) gained from a healthcare and a societal perspective. RESULTS: A total of 203 adults were randomly assigned to septoplasty (N = 102) or non-surgical management (N = 101). After 12 months, the mean cost difference between septoplasty and non-surgical management using a healthcare or societal perspective was €1181 (95%CI €1038 to €1323) or €2192 per patient (95%CI €1714 to €2670), respectively. The mean QALY difference was 0.03 per patient (95%CI - 0.01 to 0.07). Incremental costs per QALY gained from a healthcare or societal perspective were €41,763 or €77,525, respectively. After 24 months, the mean cost difference between the two groups using a healthcare or societal perspective decreased to €936 (95%CI €719 to €1153) or €1671 per patient (95%CI €952 to €2390), respectively. The mean QALY difference increased to 0.05 per patient (95%CI - 0.03 to 0.14). Incremental costs per QALY gained from a healthcare or societal perspective became €17,374 or €31,024, respectively. Analyses of imputed data did not alter our findings. CONCLUSIONS: Depending on the selected perspective, cost-effectiveness threshold, and time horizon, septoplasty has the potential to be cost-effective. Despite considerable uncertainty, septoplasty seems to be cost-effective from a healthcare perspective, after 24 months against a threshold of €20,000 per QALY. From a societal perspective, septoplasty is not yet cost-effective after 24 months, but it comes closer to the cost-effectiveness threshold as time passes by. TRIAL REGISTRATION: Nederlands Trial Register, NTR3868 (https://www.trialregister.nl/trial/3698). Prospectively registered on February 21, 2013.

The caries-related cost and effects of a tax on sugar-sweetened beverages.

OBJECTIVES: While taxes on sugar-sweetened beverages (SSBs) have frequently been proposed to reduce non-communicable diseases like obesity and type 2 diabetes, relatively little is known about the caries-related impacts of SSB taxation. We assessed the effect of a 20% ad valorem tax on SSBs on dental caries and related treatment costs, specifically taking into account that consumers may switch from SSBs to other (non-taxed) sugar-containing drinks. STUDY DESIGN: Cost-effectiveness analysis. METHODS: A tooth-level Markov model was developed to evaluate the cost and effects of SSB taxation. Tax-related changes in sugar consumption were calculated using available evidence on SSBs price and cross-price elasticities, thereby taking changes in drinks consumption behaviors into account. The model was used to establish lifetime disease-free tooth years, caries lesions prevented, caries-related treatment costs avoided, tax revenues, and administrative costs (reference case: the Netherlands). Deterministic and probabilistic sensitivity analyses were performed to address uncertainties. RESULTS: A 20% SSB taxation would result in an average of 2.13 (95% uncertainty interval [UI] 2.12-2.13) caries-free tooth years per person and, on population level, prevention of 1,030,163 (95% UI 1,027,903-1,032,423) caries lesions. The intervention was found to save an aggregate total of € 159.01 (95% UI 158.67-159.35) million in terms of dental care expenditures. The estimated lifetime tax revenues (€3.49billion) were larger than the administrative costs for taxation (€37.3 million). CONCLUSIONS: Our results show that SSB taxation may substantially improve oral health and reduce the caries-related economic burden. Benefits would be the greatest for younger age groups.

Arthroscopic meniscectomy for degenerative meniscal tears reduces knee pain but is not cost-effective in a routine health care setting: a multi-center longitudinal observational study using data from the osteoarthritis initiative.

OBJECTIVES: It is disputed whether arthroscopic meniscectomy is an (cost-) effective treatment for degenerative meniscus tears in day-to-day clinical practice. The objective of this study was to assess the cost-effectiveness of arthroscopic meniscectomy in subjects with knee osteoarthritis, in routine clinical practice, while taking into account the increased risk for future knee replacement surgery. We compared cost-effectiveness of arthroscopic meniscectomy compared to no surgery. DESIGN: We used a state transition (Markov) simulation model to evaluate the cost-effectiveness of arthroscopic meniscectomy compared to no surgery in subjects with knee osteoarthritis (age range 45-79 years). Data used in the preparation of the current study were obtained from the Osteoarthritis Initiative (AOI) database. We applied a 9 years' time horizon (which is equal to the current OAI study follow up period), and evaluated cost-effectiveness from a societal perspective. The main outcome measure was the incremental cost-effectiveness ratio (Euros per quality adjusted life-year (QALY) gained). RESULTS: Arthroscopic meniscectomy was associated with 8.09 (SD ± 0.07) QALYs at a cost of € 21,345 (SD ± 841), whereas the no surgery was associated with 8.05 (SD ± 0.07) QALYs at a cost of € 16,284 (SD ± 855). For arthroscopic meniscectomy, the incremental cost per QALY gained was € 150,754. CONCLUSIONS: In day-to-day clinical practice, arthroscopic meniscectomy in subjects with knee osteoarthritis is associated with € 150,754 per QALY gained, which exceeds the generally accepted willingness to pay (WTP) (range € 20,000-€ 80,000).

Robot assisted radical cystectomy versus open radical cystectomy in bladder cancer (RACE): study protocol of a non-randomized comparative effectiveness study.

BACKGROUND: Despite the fact that the cost-effectiveness of robot-assisted radical cystectomy (RARC) is not yet proven, and open radical (ORC) cystectomy is recommended as the standard of care in patients with high-risk non-muscle-invasive and muscle-invasive bladder cancer, the use of RARC is still increasing. The objective of the current ongoing comparative effectiveness trial therefore is to study the (cost-)effectiveness of RARC compared to ORC, both in terms of objective (complication rates, oncological outcomes) and patient-reported (health-related quality of life) outcome measures. METHODS: This study is designed as a non-randomized, multicentre comparative effectiveness trial. Centres with an annual caseload of > 20 radical cystectomies can include patients after informed consent has been given. Centres that perform RARC must have passed the (initial) learning curve of 40 cases. A total of 338 (2 × 169) patients will be enrolled from 23 participating centres (12 ORC, 10 RARC and 1 LRC). Follow-up visits will be scheduled at 1, 3, 6 and 12 months. During each follow-up visit, clinical data and health-related quality of life questionnaires will be administered. Costs will be studied using a monthly resource usage questionnaire. Impact on complications and quality of life will be calculated as the average difference between the groups with 95% confidence intervals, adjusted for potential baseline differences by means of propensity score matching. DISCUSSION: This study aims to contribute to the development of evidence-based guidelines regarding the most cost-effective surgical technique for radical cystectomy. TRIAL REGISTRATION: Nederlands Trial Register/Dutch Trial Registry, trial identifying number: NTR5362. Registered on 14 August 2015. ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5362 ).

Septoplasty for nasal obstruction due to a deviated nasal septum in adults: a systematic review.

BACKGROUND: The status of current evidence for the effectiveness of septoplasty is unclear. This systematic review evaluates the effectiveness of a) septoplasty (with or without concurrent turbinate surgery) versus non-surgical management, and b) septoplasty with concurrent turbinate surgery versus septoplasty alone, for nasal obstruction due to a deviated nasal septum in adults. METHODOLOGY: Eligible for inclusion were randomised controlled trials and non-randomised designs comparing treatment strategies. Risk of bias was assessed using Cochrane's tool. Standardised mean differences and risk differences with 95% confidence intervals were calculated. Substantial heterogeneity between included studies did not allow meta-analyses. RESULTS: No studies were found comparing septoplasty (with or without concurrent turbinate surgery) to non-surgical management, but 11 articles were included to compare septoplasty with concurrent turbinate surgery to septoplasty alone. Five studies described both subjective and objective outcomes; six studies reported one or the other. Risk of bias was overall high. Although outcomes generally improved after treatment, eight out of nine studies on subjective measures and five out of seven studies on objective measures found no additional benefit of turbinate surgery. CONCLUSIONS: Despite the routine application of septoplasty in clinical practice, the current body of evidence does not support firm conclusions on its effectiveness.

Diagnostic accuracy of high-resolution T2-weighted MRI vs contrast-enhanced T1-weighted MRI to screen for cerebellopontine angle lesions in symptomatic patients.

OBJECTIVE: To evaluate diagnostic accuracy of high-resolution T2-weighted MRI (T2w) for detecting cerebellopontine angle (CPA) lesions compared to a combined protocol including gadolinium enhanced T1-weighted MRI (GdT1w). SETTING: Department of Radiology & Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands. PARTICIPANTS: A random sample of MRIs from 350 patients (700 CPAs) with asymmetrical audiovestibular complaints was used, acquired between 2013 and 2016. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values of T2w results compared to GdT1w and, in patients with any suggestion of CPA pathology, to the complete examination (T1w, GdT1w and T2w). Inter-rater agreement between an experienced neuroradiologist and a less experienced observer was calculated. RESULTS: Results of 678 CPAs in 340 patients were analysed. On T2w, the neuroradiologist identified all 27 lesions >2 mm in size out of a total of 30 CPA lesions (sensitivity: 90% [95% CI: 73.5%-97.9%]). Negative predictive value reached 99.5% (95% CI: 98.7-99.9). One missed lesion of 2 mm would have been detected in clinical practice, as this was one of 14 patients for which additional GdT1w would have been ordered based on T2w alone, increasing sensitivity to 93% (95% CI: 77.9%-99.2%) and negative predictive value to 99.7% (95% CI: 98.9%-100%). Inter-rater agreement for T2w was 98% (95% CI: 96.4-98.8). CONCLUSION: T2w has a very high diagnostic accuracy for the presence of CPA lesions in patients with asymmetrical audiovestibular complaints. However, in a screening protocol with T2w only, smallest vestibular schwannomas as well as rare differential diagnoses that probably only would be detected on GdT1w may remain unnoticed.

Potential savings in the diagnosis of vestibular schwannoma.

INTRODUCTION: Magnetic resonance imaging (MRI) is used to screen patients at risk for vestibular schwannoma (VS). These MRIs are costly and have an extremely low yield; only 3% of patients in the screening population has an actual VS. It might be worthwhile to develop a test to predict VS and refer only a subset of all patients for MRI. OBJECTIVE: To examine the potential savings of such a hypothetical diagnostic test before MRI. DESIGN: We built a decision analytical model of the diagnostic strategy of VS. Input was derived from literature and key opinion leaders. The current strategy was compared to hypothetical new strategies, assigning MRI to the following: (i) all patients with pathology, (ii) all patients with important pathology and (iii) only patients with VS. This resulted in potential cost savings for each strategy. We conducted a budget impact analysis to predict nationwide savings for the Netherlands and the United Kingdom (UK), and a probabilistic sensitivity analysis to address uncertainty. RESULTS: Mean savings ranged from €256 (95%CI €250 - €262) or approximately US$284 (95%CI US$277 - US$291) per patient for strategy 1 to €293 (95%CI €290 - €296) or approximately US$325 (95%CI US$322 - US$328) per patient for strategy 3. Future diagnostic strategies can cost up to these amounts per patient and still be cost saving. Annually, for the Netherlands, €2.8 to €3.2 million could be saved and €10.8 to €12.3 million for the UK. CONCLUSIONS: The model shows that substantial savings could be generated if it is possible to further optimise the diagnosis of VS.

Increased risk for knee replacement surgery after arthroscopic surgery for degenerative meniscal tears: a multi-center longitudinal observational study using data from the osteoarthritis initiative.

OBJECTIVE: The primary objective was to assess whether patients with knee osteoarthritis and whom undergo arthroscopic meniscectomy have an increased risk for future knee replacement surgery. DESIGN: Data used were obtained from the Osteoarthritis Initiative (OAI) study. SETTING: Participants were enrolled, in four clinical centers, between February 2004 and May 2006 and were followed up on an annual basis up to and including 108-months from enrollment. PARTICIPANTS: 4674 participants (58.4% female), aged 45-79, of all ethnic groups, who had, and those who were at high risk for developing, symptomatic knee osteoarthritis were included, of which 3337 (71.4%) were included in the final follow up visit. MAIN OUTCOME MEASURES: Hazard ratio of knee replacement surgery for participants who underwent arthroscopic meniscectomy during follow up compared to propensity score matched participants who did not undergo arthroscopic meniscectomy during follow up. RESULTS: 335 participants underwent arthroscopic meniscectomy during follow up, of which 63 (18.8%) underwent knee replacement surgery in the same knee. Of the 335 propensity score matched participants 38 (11.1%) underwent knee replacement surgery during follow up. Results from the Cox-proportional hazards model demonstrated that the hazard ratio of knee replacement surgery was 3.03 (95% CI (1.67-5.26)) for participants who underwent arthroscopic meniscectomy relative to the propensity score matched participants who did not undergo arthroscopic meniscectomy. CONCLUSIONS: In patients with knee osteoarthritis arthroscopic knee surgery with meniscectomy is associated with a three fold increase in the risk for future knee replacement surgery.

Clinimetric properties of the Glasgow Health Status Inventory, Glasgow Benefit Inventory, Peak Nasal Inspiratory Flow, and 4-Phase Rhinomanometry in adults with nasal obstruction.

BACKGROUND: The validity of many measurement instruments frequently used in rhinology is unknown. This study describes clinimetric properties of well-known subjective and objective outcomes, i.e., the Glasgow Health Status Inventory, Glasgow Benefit Inventory, Peak Nasal Inspiratory Flow, and 4-Phase Rhinomanometry, in adults with nasal obstruction. METHODOLOGY: Construct validity and responsiveness were determined in 111 patients. Inter-rater and intra-rater reliability were analysed in 30 patients. We assessed content validity by interviewing patients and ENT-surgeons; construct validity by comparing hypothesised associations to calculated correlations between the outcomes; inter-rater reliability by having two researchers perform objective measurements in the same patients; intra-rater reliability by having one rater administer all instruments twice within a two-week interval; and responsiveness by comparing patients scores at baseline and three months after septoplasty or non-surgical management. RESULTS: All instruments demonstrated adequate content validity, inter-, and intra-rater reliability. Analyses of construct validity yielded low Pearsons correlations between the subjective and objective outcomes. Comparing septoplasty to non-surgical management, only the Glasgow Health Status Inventory scores were different between the two groups (mean difference 10.4, 95% CI 6.9 - 13.9). CONCLUSION: All measurement instruments scored appropriately on content validity and reliability, but only the subjective GHSI scored well on responsiveness.

The diagnostic accuracy of non-imaging screening protocols for vestibular schwannoma in patients with asymmetrical hearing loss and/or unilateral audiovestibular dysfunction: a diagnostic review and meta-analysis.

BACKGROUND: Currently, all patients presenting with asymmetrical sensorineural hearing loss and/or unilateral audiovestibular dysfunction (i.e. tinnitus, dizziness) undergo MRI, leading to a substantial amount of MRIs with negative findings as the incidence of vestibular schwannoma (VS) in this screening population varies between 1% and 4.7% (i.e. more than 95% of MRIs are negative for VS). OBJECTIVE OF REVIEW: The aim was to assess the diagnostic accuracy of different non-imaging screening protocols that can be used prior to MRI to select patients at high risk of VS. TYPE OF REVIEW: Diagnostic review and meta-analysis. SEARCH STRATEGY: We systematically searched MEDLINE, Embase and The Cochrane Library as from inception up to 28 July 2016. We included studies that compared non-imaging screening protocols to MRI as gold reference standard. EVALUATION METHOD: Methodological quality was assessed by two independent reviewers using the Quality Assessment of Diagnostic Accuracy Studies tool. Data necessary to complete 2 × 2 tables were obtained, and patient, study, screening and imaging characteristics were extracted. We calculated sensitivity and specificity of all tests and obtained pooled estimates using a bivariate random effects model. RESULTS: We analysed 12 studies (4969 patients) of poor to moderate quality according to the quality assessment. Most studies tested diagnostic accuracy of multiple screening protocols. Five pure-tone audiometry (PTA) protocols were studied by multiple authors; pooled estimates for sensitivity ranged from 88% [95% CI: 84-91] to 91% [95% CI: 52-99] and specificity from 31% [95% CI: 10-66] to 58% [95% CI: 49-65]. Due to heterogeneity, we were unable to pool other tests. In five studies testing auditory brainstem response, sensitivity values ranged from 37% [95% CI: 23-52] to 100% [95% CI: 40-100] and specificity from 57% to 96% [95% CI: 87-100]. Two authors studied PTA shape as a screening test. Presenting symptoms, electronystagmography, caloric irrigation and hyperventilation test were assessed by one study each. All reported low diagnostic accuracy. CONCLUSIONS: All identified studies had a moderate-to-high risk of bias, and none of the currently available non-imaging screening protocols appear to be accurate in detecting VSs.

Risk factors, prevalence, and course of severe fatigue after breast cancer treatment: a meta-analysis involving 12 327 breast cancer survivors.

BACKGROUND: This meta-analysis aimed to (i) examine demographic, disease-related, and treatment-related risk factors, (ii) estimate the prevalence, and (iii) describe the course of severe fatigue following breast cancer (BC) treatment. METHODS: PubMed, PsycINFO, Cochrane, CINAHL, and Web of Science were systematically searched from inception up to 23 November 2015. Risk factors and prevalence rates were analyzed with inverse variance random-effects analyses. Heterogeneity was studied with sensitivity analyses. RESULTS: Twenty-seven studies were included (N = 12 327). Breast cancer survivors (BCS) with a partner were at lower risk for severe fatigue than survivors without a partner [risk ratio (RR) 0.96, 95% confidence interval (CI) 0.93-0.98]. Survivors with stage II or III cancer, and survivors treated with chemotherapy were at higher risk for severe fatigue than survivors with stage 0 or I cancer and without chemotherapy (RR respectively 1.18, 95% CI 1.08-1.28; 1.12, 95% CI 1.06-1.19). Survivors treated with surgery, radiotherapy, and chemotherapy, and survivors with this combination plus hormone therapy were at higher risk than survivors with other treatment combinations (RR respectively 1.18, 95% CI 1.05-1.33; 1.38, 95% CI 1.15-1.66). Survivors treated with surgery and surgery plus radiotherapy were at lower risk than survivors with additional treatments (RR respectively 0.83, 95% CI 0.70-0.98; 0.87, 95% CI 0.78-0.96). Hormone and targeted therapy were no significant risk factors. The pooled prevalence of severe fatigue was 26.9% (95% CI 23.2-31.0), but this should be interpreted with caution because of high heterogeneity. A relatively large decrease in the prevalence of severe fatigue seemed to occur in the first half year after treatment completion. CONCLUSIONS: Approximately one in four BCS suffer from severe fatigue. Risk factors of severe fatigue were higher disease stages, chemotherapy and receiving the combination of surgery, radiotherapy, and chemotherapy, both with and without hormone therapy. Having a partner, receiving only surgery, and surgery plus radiotherapy decreased the risk.

Evidence supporting see-and-treat management of cervical intraepithelial neoplasia: a systematic review and meta-analysis.

BACKGROUND: Studies of see-and-treat management of cervical intraepithelial neoplasia (CIN) vary in their inclusion criteria, resulting in a broad range of overtreatment rates. OBJECTIVES: To determine overtreatment rates in see-and-treat management of women referred for colposcopy because of suspected CIN, in order to define circumstances supporting see-and-treat management. SEARCH STRATEGY: MEDLINE, EMBASE, and the Cochrane Library were searched from inception up to 12 May 2014. SELECTION CRITERIA: Studies of see-and-treat management in women with a reported cervical smear result, colposcopic impression, and histology result were included. DATA COLLECTION AND ANALYSIS: Methodological quality was assessed with the Newcastle-Ottawa scale. We used the inverse variance method for pooling incidences, and a random-effects model was used to account for heterogeneity between studies. Overtreatment was defined as treatment in patients with no CIN or CIN1. MAIN RESULTS: Thirteen studies (n = 4611) were included. The overall overtreatment rate in women with a high-grade cervical smear and a high-grade colposcopic impression was 11.6% (95% CI 7.8-15.3%). The overtreatment rate in women with a high-grade cervical smear and low-grade colposcopic impression was 29.3% (95% CI 16.7-41.9%), and in the case of a low-grade smear and high-grade colposcopic impression it was 46.4% (95% CI 15.7-77.1%). In women with a low-grade smear and low-grade colposcopic impression, the overtreatment rate was 72.9% (95% CI 68.1-77.7%). AUTHOR'S CONCLUSIONS: The pooled overtreatment rate in women with a high-grade smear and high-grade colposcopic impression is at least comparable with the two-step procedure, which supports the use of see-and-treat management in this subgroup of women. TWEETABLE ABSTRACT: See-and-treat management is justified in the case of a high-grade smear and a high-grade colposcopic impression.

Quality of life after different procedures for regional control in oral cancer patients: cross-sectional survey.

OBJECTIVES: To examine health utilities in patients with cT1-2 oral cavity squamous cell carcinoma following different diagnostic and treatment modalities for the neck and to investigate the relation between shoulder morbidity and health utility. DESIGN: Cross-sectional survey. SETTING: Two Dutch hospitals. PARTICIPANTS: Four subgroups of patients with oral cavity cancer who underwent watchful waiting, sentinel lymph node biopsy, elective supraomohyoid neck dissection or therapeutic modified radical neck dissection. MAIN OUTCOME MEASURES: Patients received the EuroQol-5D-3L questionnaire and the shoulder disability questionnaire. Mean health utility, visual analogue scale and shoulder disability scores were calculated. RESULTS: A total of 181 patients (62%) returned the questionnaires. Mean health utilities, adjusted for age, gender and time since treatment were 0.804, 0.863, 0.834 and 0.794 for the watchful waiting, sentinel lymph node biopsy, supraomohyoid neck dissection and modified radical neck dissection subgroups, respectively. Mean shoulder disability scores (higher score means more shoulder complaints) for these subgroups were 8.64, 10.57, 18.92 and 33.66. Patients with shoulder complaints had a mean utility of 0.78 while patients without shoulder complaints had a mean utility of 0.90. CONCLUSIONS: This study shows that more invasive procedures appear to result in lower health utility. The high health utility for patients after sentinel lymph node biopsy supports a role for this procedure in patients with oral cancer.

The Course and Predictors of Health-Related Quality of Life in Living Kidney Donors: A Systematic Review and Meta-Analysis.

A better understanding of the course and risk factors for impaired long-term health-related quality of life (HRQoL; ie, physical, psychological, and social-relational functioning) after kidney donation might help clinicians improve the care of live kidney donors. This systematic review and meta-analysis summarizes prospective studies about the course and predictors of HRQoL in living kidney donors. Studies indicate that shortly after donation, donors have lower HRQoL, with minor to moderate changes in psychological and social-relational functioning and major changes in physical functioning. At 3-12 months after donation, HRQoL returned to baseline or was slightly reduced, particularly for fatigue, but scores were still comparable to general population norms. Results were mainly robust across surgery techniques. A limited number of studies examined risk factors for impaired HRQoL, with low psychological functioning before donation as the most consistent predictor. Based on these results, clinicians can inform potential donors that, on average, kidney donors have high long-term HRQoL; however, donors with low psychological functioning at baseline are those most at risk of impaired long-term HRQoL. Future studies should focus on other potentially relevant predictors of postdonation HRQoL, including donor eligibility criteria and donor-recipient relationships, to optimize screening and interventions for donors at risk.

Comparing responses to different selenium sources and dosages in laying hens.

Developing new sources of organic Se has potential benefit for animal production and human nutrition via animal-based foods enriched in Se. The objectives of this trial were to compare L-selenomethionine with another organic Se source, Se-enriched yeast (SelPlex 2300), and sodium selenite, an inorganic Se source, against a commercial control diet. The effect of source and the dosage of Se supplementation on Se in eggs and blood variables was investigated. Ten treatments were used with 18 laying hens per group. In addition to the control diet, the control diet was supplemented with L-selenomethionine, Se-enriched yeast, or sodium selenite at 0.1, 0.3, or 0.5 mg/kg of Se. The feeding trial lasted 8 wk. Birds in the different treatment groups all showed good performance. At d 0 and 56, Se and glutathione peroxidase (GPx) were analyzed in 10 blood samples per group. After supplementing the diets for 56 d, significantly higher Se levels in serum and egg contents were reached for the Se-supplemented groups compared with the control. Supplementing 0.3 and 0.5 mg/kg of L-selenomethionine or Se-enriched yeast instead of 0.1 mg/kg significantly increased the serum Se levels, whereas no significant increase was found for sodium selenite. No effect of Se source or dosage was observed on serum GPx levels. Selenium in eggs was significantly affected by dosage and source of Se. The Se supplementation level in the feed was reflected in the eggs, with the highest and lowest values for 0.5 and 0.1 mg/kg, respectively, and values in between for the 0.3 mg/kg supplementation level. A dose response was most pronounced for L-selenomethionine, followed by Se-enriched yeast, and was least when Se was added as sodium selenite. It can be concluded that Se from organic sources was more bioavailable than the inorganic Se source as evidenced by blood and egg Se levels. Within the organic Se sources, L-selenomethionine showed higher Se transfer to eggs than Se-enriched yeast.

Low neonatal Toll-like receptor 4-mediated interleukin-10 production is associated with subsequent atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) and respiratory syncytial virus lower respiratory tract infection (RSV LRTI) are common diseases during early life. Impaired Th1-cell polarizing Toll-like receptor (TLR) responses play an important role in the pathogenesis of both diseases. Neonatal TLR-mediated production of Th1-type cytokines is decreased at birth, but rapidly increases during the first month of life. OBJECTIVE: To determine whether decreased TLR-mediated production of Th1-polarizing cytokines, at the age of 1 month is associated with subsequent AD or RSV LRTI. METHODS: A prospective healthy birth cohort study was performed. Whole blood concentrations of innate immune cells and TLR-mediated cytokine responses were measured at the age of 1 month in 291 neonates. AD was determined by a physician questionnaire at the age of 1 year and RSV LRTI was defined as parent-reported respiratory symptoms and presence of RSV RNA in a nose-throat specimen. RESULTS: Of participating neonates, 45 (15%) developed AD and 41 (14%) developed RSV LRTI. Risks of AD and RSV LRTI were not associated (χ(2) , P = 1.00). AD was associated with decreased concentrations of basophils (7.6 vs. 14.0 × 10(6) /mL, P = 0.002) and plasmacytoid dendritic cells (17.0 vs. 20.5 × 10(6) /mL, P = 0.04), increased concentrations of NK-cells (79.7 vs. 45.1 × 10(6) /mL, P = 0.03), and twofold lower TLR4-mediated IL-10 production (P = 0.001). In contrast, RSV LRTI was associated neither with neonatal concentrations of innate immune cells, nor with TLR-mediated TNF-α, IL-12p70, IL-10 or IFN-α production. CONCLUSIONS AND CLINICAL RELEVANCE: Atopic dermatitis, but not RSV LRTI, is associated with distinct pre-symptomatic differences in the innate immune system. We hypothesize that decreased neonatal IL-10-mediated immune regulation during early life might play a causal role in the initiation of AD.

Breastfeeding modulates neonatal innate immune responses: a prospective birth cohort study.

BACKGROUND: Neonatal Toll-like receptor (TLR) responses are biased toward Th2-polarizing responses at birth and rapidly mature toward more balanced responses during the first month of life. Postnatal TLR maturation may be guided by environmental exposure. AIMS: To determine the environmental determinants of neonatal TLR function. MATERIALS AND METHODS: A prospective birth cohort study was performed in 291 healthy term neonates. Mode of delivery, breastfeeding, birth month, siblings, pets and parental smoking were analyzed in relation to neonatal innate immune parameters at the age of 1 month. Whole blood concentrations of innate immune cells were measured by flow cytometry. In vitro TLR-mediated cytokine production was determined by ELISA. RESULTS: Breastfeeding was the major determinant of neonatal innate immunity, associated with 5 (31%) of neonatal innate immune parameters, of which the association with TLR7-mediated IL-10 production was most significant (76 pg/ml in breastfed neonates vs. 293 pg/ml in formula-fed neonates, p = 0.001). Of innate immune variables, TLR3-mediated IL-12p70 production was highly associated with environmental exposures (pets, breastfeeding and mode of delivery), whereas TLR9-mediated cytokine responses were not associated with any environmental factor. CONCLUSION: Neonatal innate immune responses are differentially modulated by environmental exposure in the first month of life. The protective effect of breastfeeding against subsequent infections and atopy might be explained by its innate immune modulatory effects in the first month of life.

Trends in primary-care consultations, comorbidities, and antibiotic prescriptions for respiratory infections in The Netherlands before implementation of pneumococcal vaccines for infants.

The burden of respiratory infections is mainly seen in primary healthcare. To evaluate the potential impact of new preventive strategies against respiratory infections, such as the implementation of pneumococcal conjugate vaccines for infants in 2006 in The Netherlands, we conducted a baseline retrospective cohort study of electronic primary-care patient records to assess consultation rates, comorbidities and antibiotic prescription rates for respiratory infections in primary care. We found that between 1995 and 2005, overall registered consultation rates for lower respiratory tract infections had increased by 42·4%, upper respiratory infections declined by 4·9%, and otitis media remained unchanged. Concomitantly, there was a steady rise in overall comorbidity (75·7%) and antibiotic prescription rates (67·7%). Since Dutch primary-care rates for respiratory infections changed considerably between 1995 and 2005, these changes must be taken into account to properly evaluate the effect of population-based preventive strategies on primary-care utilization.