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.

68Ga-PSMA-PET/CT and Diffusion MRI Targeting for Cone-Beam CT-Guided Bone Biopsies of Castration-Resistant Prostate Cancer Patients.

INTRODUCTION: Precision medicine expands the treatment options for metastatic castration-resistant prostate cancer (mCRPC) by targeting druggable genetic aberrations. Aberrations can be identified following molecular analysis of metastatic tissue. Bone metastases, commonly present in mCRPC, hinder precision medicine due to a high proportion of biopsies with insufficient tumor cells for next-generation DNA sequencing. We aimed to investigate the feasibility of incorporating advanced target planning and needle guidance in bone biopsies and whether this procedure increases biopsy tumor yield and success rate of molecular analysis as compared to the current standards, utilizing only CT guidance. MATERIALS AND METHODS: In a pilot study, ten mCRPC patients received 68Ga-prostate-specific membrane antigen (PSMA)-PET/CT and diffusion-weighted MRI as biopsy planning images. These datasets were fused for targeting metastatic lesions with high tumor densities. Biopsies were performed under cone-beam CT (CBCT) guidance. Feasibility of target planning and needle guidance was assessed, and success of molecular analysis and tumor yield were reported. RESULTS: Fusion target planning and CBCT needle guidance were feasible. Nine out of ten biopsies contained prostate cancer cells, with a median of 39% and 40% tumor cells by two different sequencing techniques. Molecular analysis was successful in eight of ten patients (80%). This exceeds previous reports on CT-guided biopsies that ranged from 33 to 44%. In two patients, important druggable aberrations were found. DISCUSSION: A biopsy procedure using advanced target planning and needle guidance is feasible and can increase the success rate of molecular analysis in bone metastases, thereby having the potential of improving treatment outcome for patients with mCRPC. LEVEL OF EVIDENCE: Level 4, case series.

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.

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).

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.

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.

The merits of decision modelling in the earliest stages of the IDEAL framework: An innovative case in DIEP flap breast reconstructions.

BACKGROUND: The IDEAL framework aims at improving the evidence base of available surgical innovations. However, the development of such innovations and collection of evidence is costly. Surgical innovation can provide more value for money if innovations are evaluated at an early stage, where evaluations can inform the decision whether to stop or to further develop an innovation. We illustrate how decision modelling can be readily adopted at the earliest stages (0-1) of the IDEAL framework, using an innovation in bilateral DIEP flap breast reconstruction as an example. METHODS: We quantified expected costs and quality-adjusted life years (QALYs) of the current treatment and compared them with an innovation aimed at reducing complications and surgery time. The maximum effect of eliminating all complications (headroom analysis) was explored. Moreover, three scenarios with varying complications and surgery time reductions were modelled. Furthermore, the maximum price of the innovation was estimated in a threshold analysis according to its impact and societal willingness to pay. RESULTS: The headroom analysis showed that when all complications associated with the current treatment are prevented, up to €889 per patient is saved. Scenario analysis showed cost savings between €256 and €828 per patient. When surgery time is reduced by 15 min and complications by 50%, the innovation will remain cost-effective at €671 per patient. CONCLUSION: In a field struggling with cost containment, decision modelling can help to separate promising innovations from costly failures at an early stage. In this example, decision modelling showed that it seems worthwhile to further develop the innovation.

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.

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.

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.

Effectiveness of septoplasty versus non-surgical management for nasal obstruction due to a deviated nasal septum in adults: study protocol for a randomized controlled trial.

BACKGROUND: Septoplasty, i.e., surgical correction of the deviated nasal septum, is the most common ear, nose and throat (ENT) operation in adults. Currently the main indication to perform septoplasty is nasal obstruction. However, the effectiveness of septoplasty for nasal obstruction in adults with a deviated nasal septum remains uncertain. Scientific evidence is scarce and inconclusive, and internationally accepted guidelines are lacking. Moreover, there is no consensus on whether or not septoplasty should be combined with concurrent turbinate surgery. The objective of the current ongoing trial is to study the effectiveness of septoplasty (with or without concurrent turbinate surgery) as compared to non-surgical management for nasal obstruction in adults with a deviated nasal septum, both in terms of subjective (health-related quality of life) as well as objective (nasal patency) outcome measures. METHODS/DESIGN: The study is designed as a pragmatic, multicenter, parallel-group, randomized controlled trial. A total of 200 adults will be enrolled with nasal obstruction based on a deviated nasal septum and an indication for septoplasty according to current medical practice in the Netherlands. Participants will be randomized to either septoplasty (with or without concurrent turbinate surgery as originally indicated by the otorhinolaryngologist) or a non-surgical watchful waiting strategy. Follow-up visits will be scheduled at 0, 3, 6, 12, and 24 months. During each follow-up visit, health-related quality of life questionnaires will be administered and measurements of four-phase rhinomanometry and peak nasal inspiratory flow will be performed. Costs will be studied using a patient-based diary. Effects of septoplasty on health-related quality of life (primary outcome) and nasal patency will be calculated as mean differences with 95 % confidence intervals. Subgroup analyses according to gender, age, and severity of the septal deviation will be performed. All analyses will be performed on an intention-to-treat basis. DISCUSSION: With the results of this study we aim to contribute to the development of evidence-based guidelines regarding indications for septoplasty. TRIAL REGISTRATION: Nederlands Trial Register/Dutch Trial Registry ( www.trialregister.nl ), trial identifying number: NTR3868 . Registered on 21 February 2013.

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.

The effects of clinical and statistical heterogeneity on the predictive values of results from meta-analyses.

Variance between studies in a meta-analysis will exist. This heterogeneity may be of clinical, methodological or statistical origin. The last of these is quantified by the I(2) -statistic. We investigated, using simulated studies, the accuracy of I(2) in the assessment of heterogeneity and the effects of heterogeneity on the predictive value of meta-analyses. The relevance of quantifying I(2) was determined according to the likely presence of heterogeneity between studies (low, high, or unknown) and the calculated I(2) (low or high). The findings were illustrated by published meta-analyses of selective digestive decontamination and weaning protocols. As expected, I(2) increases and the likelihood of drawing correct inferences from a meta-analysis decreases with increasing heterogeneity. With low levels of heterogeneity, I(2) does not appear to be predictive of the accuracy of the meta-analysis result. With high levels of heterogeneity, even meta-analyses with low I(2) -values have low predictive values. Most commonly, the level of heterogeneity in a meta-analysis will be unknown. In these scenarios, I(2) determination may help to identify estimates with low predictive values (high I(2) ). In this situation, the results of a meta-analysis will be unreliable. With low I(2) -values and unknown levels of heterogeneity, predictive values of pooled estimates may range extensively, and findings should be interpreted with caution. In conclusion, quantifying statistical heterogeneity through I(2) -statistics is only helpful when the amount of clinical heterogeneity is unknown and I(2) is high. Objective methods to quantify the levels of clinical and methodological heterogeneity are urgently needed to allow reliable determination of the accuracy of meta-analyses.

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.

Effectiveness of adenoidectomy in children with recurrent upper respiratory tract infections: open randomised controlled trial.

OBJECTIVE: To assess the effectiveness of adenoidectomy in children with recurrent upper respiratory tract infections. DESIGN: Open randomised controlled trial. SETTING: 11 general hospitals and two academic centres. PARTICIPANTS: 111 children aged 1-6 with recurrent upper respiratory tract infections selected for adenoidectomy. INTERVENTION: A strategy of immediate adenoidectomy with or without myringotomy or a strategy of initial watchful waiting. Main outcome measure Primary outcome measure: number of upper respiratory tract infections per person year calculated from data obtained during the total follow-up (maximum 24 months). SECONDARY OUTCOME MEASURES: days with upper respiratory tract infection per person year, middle ear complaints with fever in episodes and days, days with fever, prevalence of upper respiratory tract infections, and health related quality of life. RESULTS: During the median follow-up of 24 months, there were 7.91 episodes of upper respiratory tract infections per person year in the adenoidectomy group and 7.84 in the watchful waiting group (difference in incidence rate 0.07, 95% confidence interval -0.70 to 0.85). No relevant differences were found for days of upper respiratory tract infections and middle ear complaints with fever in episodes and days, nor for health related quality of life. The prevalence of upper respiratory tract infections decreased over time in both groups. Children in the adenoidectomy group had significantly more days with fever than the children in the watchful waiting group. Two children had complications related to surgery. CONCLUSION: In children selected for adenoidectomy for recurrent upper respiratory tract infections, a strategy of immediate surgery confers no clinical benefits over a strategy of initial watchful waiting. Trial registration Dutch Trial Register NTR968: ISRCTN03720485.