Does weight management research for adults with severe obesity represent them? Analysis of systematic review data.

OBJECTIVE: Our objective was to determine the extent to which current evidence from long-term randomised controlled trials (RCTs) of weight management is generalisable and applicable to underserved adult groups with obesity (body mass index (BMI) ≥35 kg/m2). METHODS: Descriptive analysis of 131 RCTs, published after 1990-May 2017 with ≥1 year of follow-up, included in a systematic review of long-term weight management interventions for adults with BMI ≥35 kg/m2 (the REBALANCE Project). Studies were identified from MEDLINE, EMBASE, PsychINFO, SCI, CENTRAL and from hand searching. Reporting of trial inclusion and exclusion criteria, trial recruitment strategies, baseline characteristics and outcomes were analysed using a predefined list of characteristics informed by the PROGRESS (Place of residence, Race/ethnicity/culture/language, Occupation, Gender/sex, Religion, Education, Socioeconomic status, Social capital)-Plus framework and the UK Equality Act 2010. RESULTS: Few (6.1%) trials reported adapting recruitment to appeal to underserved groups. 10.0% reported culturally adapting their trial materials. Only 6.1% of trials gave any justification for their exclusion criteria, yet over half excluded participation for age or mental health reasons. Just over half (58%) of the trials reported participants' race or ethnicity, and one-fifth reported socioeconomic status. Where outcomes were reported for underserved groups, the most common analysis was by sex (47.3%), followed by race or ethnicity (16.8%). 3.1% of trials reported outcomes according to socioeconomic status. DISCUSSION: Although we were limited by poor trial reporting, our results indicate inadequate representation of people most at risk of obesity. Guidance for considering underserved groups may improve the appropriateness of research and inform greater engagement with health and social care services. FUNDING: National Institute for Health Research Health Technology Assessment Programme (project number: 15/09/04). PROSPERO REGISTRATION NUMBER: CRD42016040190.

Pre-hospital and emergency department treatment of convulsive status epilepticus in adults: an evidence synthesis.

BACKGROUND: Convulsive status epilepticus is defined as ≥ 5 minutes of either continuous seizure activity or repetitive seizures without regaining consciousness. It is regarded as an emergency condition that requires prompt treatment to avoid hospitalisation and to reduce morbidity and mortality. Rapid pre-hospital first-line treatment of convulsive status epilepticus is currently benzodiazepines, administered either by trained caregivers in the community (e.g. buccal midazolam, rectal diazepam) or by trained health professionals via intramuscular or intravenous routes (e.g. midazolam, lorazepam). There is a lack of clarity about the optimal treatment for convulsive status epilepticus in the pre-hospital setting. OBJECTIVES: To assess the current evidence on the clinical effectiveness and cost-effectiveness of treatments for adults with convulsive status epilepticus in the pre-hospital setting. DATA SOURCES: We searched major electronic databases, including MEDLINE, EMBASE, PsycInfo®, CINAHL, CENTRAL, NHS Economic Evaluation Database, Health Technology Assessment Database, Research Papers in Economics, and the ISPOR Scientific Presentations Database, with no restrictions on publication date or language of publication. Final searches were carried out on 21 July 2020. REVIEW METHODS: Systematic review of randomised controlled trials assessing adults with convulsive status epilepticus who received treatment before or on arrival at the emergency department. Eligible treatments were any antiepileptic drugs offered as first-line treatments, regardless of their route of administration. Primary outcomes were seizure cessation, seizure recurrence and adverse events. Two reviewers independently screened all citations identified by the search strategy, retrieved full-text articles, extracted data and assessed the risk of bias of the included trials. Results were described narratively. RESULTS: Four trials (1345 randomised participants, of whom 1234 were adults) assessed the intravenous or intramuscular use of benzodiazepines or other antiepileptic drugs for the pre-hospital treatment of convulsive status epilepticus in adults. Three trials at a low risk of bias showed that benzodiazepines were effective in stopping seizures. In particular, intramuscular midazolam was non-inferior to intravenous lorazepam. The addition of levetiracetam to clonazepam did not show clear advantages over clonazepam alone. One trial at a high risk of bias showed that phenobarbital plus optional phenytoin was more effective in terminating seizures than diazepam plus phenytoin. The median time to seizure cessation from drug administration varied from 1.6 minutes to 15 minutes. The proportion of people with recurrence of seizures ranged from 10.4% to 19.1% in two trials reporting this outcome. Across trials, the rates of respiratory depression among participants receiving active treatments were generally low (from 6.4% to 10.6%). The mortality rate ranged from 2% to 7.6% in active treatment groups and from 6.2% to 15.5% in control groups. Only one study based on retrospective observational data met the criteria for economic evaluation; therefore, it was not possible to draw any robust conclusions on cost-effectiveness. LIMITATIONS: The limited number of identified trials and their differences in terms of treatment comparisons and outcomes hindered any meaningful pooling of data. None of the included trials was conducted in the UK and none assessed the use of buccal midazolam or rectal diazepam. The review of economic evaluations was hampered by lack of suitable data. CONCLUSIONS: Both intravenous lorazepam and intravenous diazepam administered by paramedics are more effective than a placebo in the treatments of adults with convulsive status epilepticus, and intramuscular midazolam is non-inferior to intravenous lorazepam. Large well-designed clinical trials are needed to establish which benzodiazepines are more effective and preferable in the pre-hospital setting. STUDY REGISTRATION: This study is registered as PROSPERO CRD42020201953. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 26, No. 20. See the NIHR Journals Library website for further project information.

Epilepsy is a common condition that results from abnormal electrical activity in the brain and causes seizures (stiffening and uncontrolled jerking ­ known as a 'fit'). The most severe form of epilepsy is called 'convulsive status epilepticus', which involves continuous seizure activity for 5 minutes or more, or repetitive seizures without recovery of consciousness. Convulsive status epilepticus can be very dangerous and requires prompt treatment to avoid hospitalisation and prevent complications. Although several drugs are available for the treatment of convulsive status epilepticus in the community or in the emergency department, it is unclear which one is most effective in stopping seizures. We brought together results from all available clinical studies that looked at the use of drugs to treat adults with convulsive status epilepticus either before arriving at hospital or on arrival at the emergency department. In the literature, we found four studies (1234 adults) assessing drugs delivered by paramedics through an injection into a vein or into muscle. In general, the drugs used by paramedics (benzodiazepines) were effective in stopping seizures, but we were unable to identify any particular drug or way of administering it as being more successful than others. Future research is needed to establish which drugs are most effective and preferable. It is also important to improve adherence to clinical guidelines with regard to the use of these drugs. For the pre-hospital treatment of convulsive status epilepticus, little evidence was available to decide which drug treatment is the best in terms of value for money. Future studies could assess the (1) impact of treatments on costs and outcomes over the whole course of a seizure episode (2) long-term impact of different treatments on patients' quality of life and (3) health and social care needs.

Open versus laparoscopic repair of inguinal hernia: an overview of systematic reviews of randomised controlled trials.

BACKGROUND: Inguinal hernia has a lifetime incidence of 27% in men and 3% in women. Surgery is the recommended treatment, but there is no consensus on the best method. Open repair is most popular, but there are concerns about the risk of chronic groin pain. Laparoscopic repair is increasingly accepted due to the lower risk of chronic pain, although its recurrence rate is still unclear. The aim of this overview is to compare the risk of recurrence and chronic groin pain in laparoscopic versus open repair for inguinal hernia. METHODS: We searched Ovid MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews for systematic reviews and meta-analyses. Only reviews of randomised controlled trials (RCTs) in adults published in English were included. Conference proceedings and editorials were excluded. The quality of the systematic reviews was assessed using the AMSTAR 2 checklist. Two outcomes were considered: hernia recurrence and chronic pain. RESULTS: Twenty-one systematic reviews and meta-analyses were included. Laparoscopic repair was associated with a lower risk of chronic groin pain compared with open repair. In the four systematic reviews assessing any laparoscopic versus any open repairs, laparoscopic repair was associated with a statistically significant (range: 26-46%) reduction in the odds or risk of chronic pain. Most reviews showed no difference in recurrence rates between laparoscopic and open repairs, regardless of the types of repair considered or the types of hernia that were studied, but most reviews had wide confidence intervals and we cannot rule out clinically important effects favouring either type of repair. CONCLUSION: Meta-analyses suggest that laparoscopic repairs have a lower incidence of chronic groin pain than open repair, but there is no evidence of differences in recurrence rates between laparoscopic and open repairs.

Biomarkers for assessing acute kidney injury for people who are being considered for admission to critical care: a systematic review and cost-effectiveness analysis.

BACKGROUND: Acute kidney injury is a serious complication that occurs in the context of an acute critical illness or during a postoperative period. Earlier detection of acute kidney injury may facilitate strategies to preserve renal function, prevent further disease progression and reduce mortality. Acute kidney injury diagnosis relies on a rise in serum creatinine levels and/or fall in urine output; however, creatinine is an imperfect marker of kidney function. There is interest in the performance of novel biomarkers used in conjunction with existing clinical assessment, such as NephroCheck® (Astute Medical, Inc., San Diego, CA, USA), ARCHITECT® urine neutrophil gelatinase-associated lipocalin (NGAL) (Abbott Laboratories, Abbott Park, IL, USA), and urine and plasma BioPorto NGAL (BioPorto Diagnostics A/S, Hellerup, Denmark) immunoassays. If reliable, these biomarkers may enable earlier identification of acute kidney injury and enhance management of those with a modifiable disease course. OBJECTIVE: The objective was to evaluate the role of biomarkers for assessing acute kidney injury in critically ill patients who are considered for admission to critical care. DATA SOURCES: Major electronic databases, conference abstracts and ongoing studies were searched up to June 2019, with no date restrictions. MEDLINE, EMBASE, Health Technology Assessment Database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, Web of Science, World Health Organization Global Index Medicus, EU Clinical Trials Register, International Clinical Trials Registry Platform and ClinicalTrials.gov were searched. REVIEW METHODS: A systematic review and meta-analysis were conducted to evaluate the performance of novel biomarkers for the detection of acute kidney injury and prediction of other relevant clinical outcomes. Random-effects models were adopted to combine evidence. A decision tree was developed to evaluate costs and quality-adjusted life-years accrued as a result of changes in short-term outcomes (up to 90 days), and a Markov model was used to extrapolate results over a lifetime time horizon. RESULTS: A total of 56 studies (17,967 participants), mainly prospective cohort studies, were selected for inclusion. No studies addressing the clinical impact of the use of biomarkers on patient outcomes, compared with standard care, were identified. The main sources of bias across studies were a lack of information on blinding and the optimal threshold for NGAL. For prediction studies, the reporting of statistical details was limited. Although the meta-analyses results showed the potential ability of these biomarkers to detect and predict acute kidney injury, there were limited data to establish any causal link with longer-term health outcomes and there were considerable clinical differences across studies. Cost-effectiveness results were highly uncertain, largely speculative and should be interpreted with caution in the light of the limited evidence base. To illustrate the current uncertainty, 15 scenario analyses were undertaken. Incremental quality-adjusted life-years were very low across all scenarios, ranging from positive to negative increments. Incremental costs were also small, in general, with some scenarios generating cost savings with tests dominant over standard care (cost savings with quality-adjusted life-year gains). However, other scenarios generated results whereby the candidate tests were more costly with fewer quality-adjusted life-years, and were thus dominated by standard care. Therefore, it was not possible to determine a plausible base-case incremental cost-effectiveness ratio for the tests, compared with standard care. LIMITATIONS: Clinical effectiveness and cost-effectiveness results were hampered by the considerable heterogeneity across identified studies. Economic model predictions should also be interpreted cautiously because of the unknown impact of NGAL-guided treatment, and uncertain causal links between changes in acute kidney injury status and changes in health outcomes. CONCLUSIONS: Current evidence is insufficient to make a full appraisal of the role and economic value of these biomarkers and to determine whether or not they provide cost-effective improvements in the clinical outcomes of acute kidney injury patients. FUTURE WORK: Future studies should evaluate the targeted use of biomarkers among specific patient populations and the clinical impact of their routine use on patient outcomes and management. STUDY REGISTRATION: This study is registered as PROSPERO CRD42019147039. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 26, No. 7. See the NIHR Journals Library website for further project information.

Among people who are very ill or have undergone surgery, the kidneys may suddenly stop working properly. This is known as acute kidney injury. Acute kidney injury can progress to serious kidney problems and can be fatal. Currently, to decide whether or not acute kidney injury is present, doctors use the level of creatinine (a waste product filtered by the kidneys) in the blood or urine. However, creatinine levels are not a precise indicator and they can take hours or days to rise; this may lead to delays in acute kidney injury recognition. Novel biomarkers may help doctors to recognise the presence of acute kidney injury earlier and treat patients promptly. This work evaluates current evidence on the use of biomarkers for acute kidney injury with respect to clinical usefulness and costs. We reviewed the current evidence on the use of biomarkers for assessing the risk of acute kidney injury among people who are very ill, and assessed whether or not the evidence was of good value for the NHS. We assessed the ARCHITECT^® urine neutrophil gelatinase-associated lipocalin (NGAL) (Abbott Laboratories, Abbott Park, IL, USA), urine and plasma BioPorto NGAL (BioPorto Diagnostics A/S, Hellerup, Denmark) and urine NephroCheck^® (Astute Medical, Inc., San Diego, CA, USA) biomarkers. We checked studies published up to June 2019 and found 56 relevant studies (17,967 patients). Most studies were conducted outside the UK and investigated people already admitted to critical care. We combined the results of the studies and found that NephroCheck and NGAL biomarkers might be useful in identifying acute kidney injury or pre-empting acute kidney injury in some circumstances. However, studies differed in patient characteristics, clinical setting and the way in which biomarkers were used. This could explain why the number of people correctly identified and missed by the biomarkers varied across studies. Hence, we do not completely trust the pooled results. We also found that acute kidney injury is associated with substantial costs for the NHS, but there was insufficient good-quality evidence to decide which biomarker (if any) offered the best value for money.

Management of the first stage of convulsive status epilepticus in adults: a systematic review of current randomised evidence.

BACKGROUND: Convulsive status epilepticus is the most severe form of epilepsy and requires urgent treatment. We synthesised the current evidence on first-line treatments for controlling seizures in adults with convulsive status epilepticus before, or at, arrival at hospital. METHODS: We conducted a systematic review of randomised controlled trials (RCTs) assessing antiepileptic drugs offered to adults as first-line treatments. Major electronic databases were searched. RESULTS: Four RCTs (1234 adults) were included. None were conducted in the UK and none assessed the use of buccal or intranasal midazolam. Both intravenous lorazepam and intravenous diazepam administered by paramedics were more effective than placebo and, notably, intramuscular midazolam was non-inferior to intravenous lorazepam. Overall, median time to seizure cessation from drug administration varied from 2 to 15 min. Rates of respiratory depression among participants receiving active treatments ranged from 6.4 to 10.6%. Mortality ranged from 2 to 7.6% in active treatment groups and 6.2 to 15.5% in control groups. CONCLUSIONS: Intravenous and intramuscular benzodiazepines are safe and effective in this clinical context. Further research is needed to establish the most clinically and cost-effective first-line treatment and preferable mode of administration. Head-to-head trials comparing buccal versus intranasal midazolam versus rectal diazepam would provide useful information to inform the management of the first stage of convulsive status epilepticus in adults, especially when intravenous or intramuscular access is not feasible. Approaches to improve adherence to clinical guidelines on the use of currently available benzodiazepines for the first-line treatment of convulsive status epilepticus should also be considered.

Minimally invasive treatments for benign prostatic hyperplasia: a Cochrane network meta-analysis.

OBJECTIVE: To assess the comparative effectiveness and ranking of minimally invasive treatments (MITs) for lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We searched multiple databases up to 24 February 2021. We included randomized controlled trials assessing the following treatments: convective radiofrequency water vapour thermal therapy (WVTT; or Rezum); prostatic arterial embolization (PAE); prostatic urethral lift (PUL; or Urolift); temporary implantable nitinol device (TIND); and transurethral microwave thermotherapy (TUMT) compared to transurethral resection of the prostate (TURP) or sham surgery. We performed a frequentist network meta-analysis. RESULTS: We included 27 trials involving 3017 men. The overall certainty of the evidence of most outcomes according to GRADE was low to very low. Compared to TURP, we found that PUL and PAE may result in little to no difference in urological symptoms, while WVTT, TUMT and TIND may result in worse urological symptoms. MITs may result in little to no difference in quality of life, compared to TURP. MITs may result in a large reduction in major adverse events compared to TURP. We were uncertain about the effects of PAE and PUL on retreatment compared to TURP, however, TUMT may result in higher retreatment rates. We were very uncertain of the effects of MITs on erectile function and ejaculatory function. Among MITs, PUL and PAE had the highest likelihood of being the most efficacious for urinary symptoms and quality of life, TUMT for major adverse events, WVTT and TIND for erectile function and PUL for ejaculatory function. Excluding WVTT and TIND, for which there were only studies with short-term (3-month) follow-up, PUL had the highest likelihood of being the most efficacious for retreatment. CONCLUSIONS: Minimally invasive treatments may result in similar or worse effects concerning urinary symptoms and quality of life compared to TURP at short-term follow-up.

Cost-effectiveness and value of information analysis of NephroCheck and NGAL tests compared to standard care for the diagnosis of acute kidney injury.

BACKGROUND: Early and accurate acute kidney injury (AKI) detection may improve patient outcomes and reduce health service costs. This study evaluates the diagnostic accuracy and cost-effectiveness of NephroCheck and NGAL (urine and plasma) biomarker tests used alongside standard care, compared with standard care to detect AKI in hospitalised UK adults. METHODS: A 90-day decision tree and lifetime Markov cohort model predicted costs, quality adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) from a UK NHS perspective. Test accuracy was informed by a meta-analysis of diagnostic accuracy studies. Clinical trial and observational data informed the link between AKI and health outcomes, health state probabilities, costs and utilities. Value of information (VOI) analysis informed future research priorities. RESULTS: Under base case assumptions, the biomarker tests were not cost-effective with ICERs of £105,965 (NephroCheck), £539,041 (NGAL urine BioPorto), £633,846 (NGAL plasma BioPorto) and £725,061 (NGAL urine ARCHITECT) per QALY gained compared to standard care. Results were uncertain, due to limited trial data, with probabilities of cost-effectiveness at £20,000 per QALY ranging from 0 to 99% and 0 to 56% for NephroCheck and NGAL tests respectively. The expected value of perfect information (EVPI) was £66 M, which demonstrated that additional research to resolve decision uncertainty is worthwhile. CONCLUSIONS: Current evidence is inadequate to support the cost-effectiveness of general use of biomarker tests. Future research evaluating the clinical and cost-effectiveness of test guided implementation of protective care bundles is necessary. Improving the evidence base around the impact of tests on AKI staging, and of AKI staging on clinical outcomes would have the greatest impact on reducing decision uncertainty.

Minimally invasive treatments for lower urinary tract symptoms in men with benign prostatic hyperplasia: a network meta-analysis.

BACKGROUND: A variety of minimally invasive treatments are available as an alternative to transurethral resection of the prostate (TURP) for management of lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). However, it is unclear which treatments provide better results. OBJECTIVES: Our primary objective was to assess the comparative effectiveness of minimally invasive treatments for lower urinary tract symptoms in men with BPH through a network meta-analysis. Our secondary objective was to obtain an estimate of relative ranking of these minimally invasive treatments, according to their effects. SEARCH METHODS: We performed a comprehensive search of multiple databases (CENTRAL, MEDLINE, Embase, Scopus, Web of Science and LILACS), trials registries, other sources of grey literature, and conference proceedings, up to 24 February 2021. We had no restrictions on language of publication or publication status. SELECTION CRITERIA: We included parallel-group randomized controlled trials assessing the effects of the following minimally invasive treatments, compared to TURP or sham treatment, on men with moderate to severe LUTS due to BPH: convective radiofrequency water vapor therapy (CRFWVT); prostatic arterial embolization (PAE); prostatic urethral lift (PUL); temporary implantable nitinol device (TIND); and transurethral microwave thermotherapy (TUMT). DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, extracted data, and assessed risk of bias. We performed statistical analyses using a random-effects model for pair-wise comparisons and a frequentist network meta-analysis for combined estimates. We interpreted them according to Cochrane methods. We planned subgroup analyses by age, prostate volume, and severity of baseline symptoms. We used risk ratios (RRs) with 95% confidence intervals (CIs) to express dichotomous data and mean differences (MDs) with 95% CIs to express continuous data. We used the GRADE approach to rate the certainty of evidence. MAIN RESULTS: We included 27 trials involving 3017 men, mostly over age 50, with severe LUTS due to BPH. The overall certainty of evidence was low to very low due to concerns regarding bias, imprecision, inconsistency (heterogeneity), and incoherence. Based on the network meta-analysis, results for our main outcomes were as follows. Urologic symptoms (19 studies, 1847 participants): PUL and PAE may result in little to no difference in urologic symptoms scores (MD of International Prostate Symptoms Score [IPSS]) compared to TURP (3 to 12 months; MD range 0 to 35; higher scores indicate worse symptoms; PUL: 1.47, 95% CI -4.00 to 6.93; PAE: 1.55, 95% CI -1.23 to 4.33; low-certainty evidence). CRFWVT, TUMT, and TIND may result in worse urologic symptoms scores compared to TURP at short-term follow-up, but the CIs include little to no difference (CRFWVT: 3.6, 95% CI -4.25 to 11.46; TUMT: 3.98, 95% CI 0.85 to 7.10; TIND: 7.5, 95% CI -0.68 to 15.69; low-certainty evidence). Quality of life (QoL) (13 studies, 1459 participants): All interventions may result in little to no difference in the QoL scores, compared to TURP (3 to 12 months; MD of IPSS-QoL score; MD range 0 to 6; higher scores indicate worse symptoms; PUL: 0.06, 95% CI -1.17 to 1.30; PAE: 0.09, 95% CI -0.57 to 0.75; CRFWVT: 0.37, 95% CI -1.45 to 2.20; TUMT: 0.65, 95% CI -0.48 to 1.78; TIND: 0.87, 95% CI -1.04 to 2.79; low-certainty evidence). Major adverse events (15 studies, 1573 participants): TUMT probably results in a large reduction of major adverse events compared to TURP (RR 0.20, 95% CI 0.09 to 0.43; moderate-certainty evidence). PUL, CRFWVT, TIND and PAE may also result in a large reduction in major adverse events, but CIs include substantial benefits and harms at three months to 36 months; PUL: RR 0.30, 95% CI 0.04 to 2.22; CRFWVT: RR 0.37, 95% CI 0.01 to 18.62; TIND: RR 0.52, 95% CI 0.01 to 24.46; PAE: RR 0.65, 95% CI 0.25 to 1.68; low-certainty evidence). Retreatment (10 studies, 799 participants): We are uncertain about the effects of PAE and PUL on retreatment compared to TURP (12 to 60 months; PUL: RR 2.39, 95% CI 0.51 to 11.1; PAE: RR 4.39, 95% CI 1.25 to 15.44; very low-certainty evidence). TUMT may result in higher retreatment rates (RR 9.71, 95% CI 2.35 to 40.13; low-certainty evidence). Erectile function (six studies, 640 participants): We are very uncertain of the effects of minimally invasive treatments on erectile function (MD of International Index of Erectile Function [IIEF-5]; range 5 to 25; higher scores indicates better function; CRFWVT: 6.49, 95% CI -8.13 to 21.12; TIND: 5.19, 95% CI -9.36 to 19.74; PUL: 3.00, 95% CI -5.45 to 11.44; PAE: -0.03, 95% CI -6.38, 6.32; very low-certainty evidence). Ejaculatory dysfunction (eight studies, 461 participants): We are uncertain of the effects of PUL, PAE and TUMT on ejaculatory dysfunction compared to TURP (3 to 12 months; PUL: RR 0.05, 95 % CI 0.00 to 1.06; PAE: RR 0.35, 95% CI 0.13 to 0.92; TUMT: RR 0.34, 95% CI 0.17 to 0.68; low-certainty evidence). TURP is the reference treatment with the highest likelihood of being the most efficacious for urinary symptoms, QoL and retreatment, but the least favorable in terms of major adverse events, erectile function and ejaculatory function. Among minimally invasive procedures, PUL and PAE have the highest likelihood of being the most efficacious for urinary symptoms and QoL, TUMT for major adverse events, PUL for retreatment, CRFWVT and TIND for erectile function and PUL for ejaculatory function. AUTHORS' CONCLUSIONS: Minimally invasive treatments may result in similar or worse effects concerning urinary symptoms and QoL compared to TURP at short-term follow-up. They may result in fewer major adverse events, especially in the case of PUL and PAE; resulting in better rankings for symptoms scores. PUL may result in fewer retreatments compared to other interventions, especially TUMT, which had the highest retreatment rates at long-term follow-up. We are very uncertain about the effects of these interventions on erectile function. There was limited long-term data, especially for CRFWVT and TIND. Future high-quality studies with more extended follow-up, comparing different, active treatment modalities, and adequately reporting critical outcomes relevant to patients, including those related to sexual function, could provide more information on the relative effectiveness of these interventions.

Successful laparoscopic extirpation of a vasoactive intestinal polypeptide-secreting neuroblastoma originating from the right adrenal gland: A report of an infantile case.

We herein report a 10-month-old female infant with a 4-month history of diarrhea with electrolyte abnormalities and growth impairment. A 4-cm right adrenal tumor was detected by computed tomography. No metastasis or accumulation on I123 -metaiodobenzylguanidine scintigraphy was recognized in the tumor. A vasoactive intestinal peptide-secreting neuroblastic tumor was suspected, and octreotide was started, but the diarrhea persisted. Tumor extirpation was laparoscopically performed. After tumor removal, the symptoms improved immediately, and her growth caught up by 9 months after surgery. A minimally invasive approach for pediatric solid tumor is difficult, especially for neuroblastoma, but may be beneficial for the patient's recovery.

Interventions for treating people with symptoms of bladder pain syndrome: a network meta-analysis.

BACKGROUND: Bladder pain syndrome (BPS), which includes the condition of interstitial cystitis, is a poorly understood clinical condition for which patients present with varying symptoms. Management of BPS is challenging for both patients and practitioners. At present, there is no universally accepted diagnosis and diverse causes have been proposed. This is reflected in wide-ranging treatment options, used alone or in combination, with limited evidence. A network meta-analysis (NMA) simultaneously comparing multiple treatments may help to determine the best treatment options for patients with BPS. OBJECTIVES: To conduct a network meta-analysis to assess the effects of interventions for treating people with symptoms of bladder pain syndrome (BPS). SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL, in the Cochrane Library), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and handsearched journals and conference proceedings (searched 11 May 2018) and the reference lists of relevant articles. We conducted a further search on 5 June 2019, which yielded four small studies that were screened for eligibility but were not incorporated into the review. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs of interventions for treating adults with BPS. All types of interventions (including conservative, pharmacological and surgical) were eligible. DATA COLLECTION AND ANALYSIS: We assessed the risk of bias of included studies using Cochrane's 'Risk of bias' tool. Primary outcomes were the number of people cured or improved, pain, frequency and nocturia. For each outcome, random-effects NMA models were fitted using WinBUGS 1.4. We monitored median odds ratios (ORs) for binary outcomes and mean differences (MDs) for continuous outcomes with 95% credible intervals (Crls). We compared results of the NMA with direct evidence from pairwise meta-analysis of head-to-head trials. We used the CINeMA tool to assess the certainty of evidence for selected treatment categories. MAIN RESULTS: We included 81 RCTs involving 4674 people with a median of 38 participants (range 10 to 369) per RCT. Most trials compared treatment against control; few trials compared two active treatments. There were 65 different active treatments, and some comparisons were informed by direct evidence from only one trial. To simplify, treatments were grouped into 31 treatment categories by mode of action. Most studies were judged to have unclear or high risk of bias for most domains, particularly for selection and detection bias. Overall, the NMA suggested that six (proportion cured/improved), one (pain), one (frequency) and zero (nocturia) treatment categories were effective compared with control, but there was great uncertainty around estimates of effect. Due to the large number of intervention comparisons in this review, we focus on three interventions: antidepressants, pentosan polysulfate (PPS) and neuromuscular blockade. We selected these interventions on the basis that they are given 'strong recommendations' in the EAU Guidelines for management of BPS (EAU Guidelines 2019). We found very low-certainty evidence suggesting that antidepressants were associated with greater likelihood of cure or improvement compared with control (OR 5.91, 95% CrI 1.12 to 37.56), but it was uncertain whether they reduced pain (MD -1.27, 95% CrI -3.25 to 0.71; low-certainty evidence), daytime frequency (MD -2.41, 95% CrI -6.85 to 2.05; very low-certainty evidence) or nocturia (MD 0.01, 95% CrI -2.53 to 2.50; very low-certainty evidence). There was no evidence that PPS had improved cure/improvement rates (OR 0.14, 95% CrI 0.40 to 3.35; very low-certainty evidence) or reduced pain (MD 0.42, 95% CrI -1.04 to 1.91; low-certainty evidence), frequency (MD -0.37, 95% CrI -5.00 to 3.44; very low-certainty evidence) or nocturia (MD -1.20, 95% CrI -3.62 to 1.28; very low-certainty evidence). There was evidence that neuromuscular blockade resulted in greater cure or improvement (OR 5.80, 95% CrI 2.08 to 18.30) but no evidence that it improved pain (MD -0.33, 95% CrI -1.71 to 1.03), frequency (MD -0.91, 95% CrI -3.24, 1.29) or nocturia (MD -0.04, 95% CrI -1.35 to 1.27). The certainty of this evidence was always very low. AUTHORS' CONCLUSIONS: We are uncertain whether some treatments may be effective in treating patients with BPS because the certainty of evidence was generally low or very low. Data were available for a relatively large number of trials, but most had small sample sizes and effects of treatments often could not be estimated with precision. An NMA was successfully conducted, but limited numbers of small trials for each treatment category hampered our ability to fully exploit the advantages of this analysis. Larger, more focused trials are needed to improve the current evidence base.

Economic evaluation of surgical treatments for women with stress urinary incontinence: a cost-utility and value of information analysis.

OBJECTIVES: Stress urinary incontinence (SUI) and stress-predominant mixed urinary incontinence (MUI) are common conditions that can have a negative impact on the quality of life of patients and serious cost implications for healthcare providers. The objective of this study was to assess the cost-effectiveness of nine different surgical interventions for treatment of SUI and stress-predominant MUI from a National Health Service and personal social services perspective in the UK. METHODS: A Markov microsimulation model was developed to compare the costs and effectiveness of nine surgical interventions. The model was informed by undertaking a systematic review of clinical effectiveness and network meta-analysis. The main clinical parameters in the model were the cure and incidence rates of complications after different interventions. The outcomes from the model were expressed in terms of cost per quality-adjusted life-years (QALYs) gained. In addition, expected value of perfect information (EVPI) analyses were conducted to quantify the main uncertainties facing decision-makers. RESULTS: The base-case results suggest that retropubic mid-urethral sling (retro-MUS) is the most cost-effective surgical intervention over a 10-year and lifetime time horizon. The probabilistic results show that retro-MUS and traditional sling are the interventions with the highest probability of being cost-effective across all willingness-to-pay thresholds over a lifetime time horizon. The value of information analysis results suggest that the largest value appears to be in removing uncertainty around the incidence rates of complications, the relative treatment effectiveness and health utility values. CONCLUSIONS: Although retro-MUS appears, at this stage, to be a cost-effective intervention, research is needed on possible long-term complications of all surgical treatments to provide reassurance of safety, or earlier warning of unanticipated adverse effects. The value of information analysis supports the need, as a first step, for further research to improve our knowledge of the actual incidence of complications.

Surgical treatments for women with stress urinary incontinence: a systematic review of economic evidence.

BACKGROUND: Surgical interventions for the treatment of stress urinary incontinence (SUI) in women are commonly employed following the failure of minimally invasive therapies. Due to the limited information available on the relative cost-effectiveness of available surgeries for treating SUI, a de novo economic analysis was conducted to assess costs and effects of all relevant surgeries. To inform the economic analysis, the objective of this review was to identify and assess the quality of existing economic evaluation studies on different surgical interventions for the treatment of SUI in women. METHODS: The following databases were searched during the review process: Medical Literature Analysis and Retrieval System Online (MEDLINE), MEDLINE In-Process, Excerpta Medica Database (Embase), National Health Service Economic Evaluation Database (NHS EED), and Health Management Information Consortium and Cost-Effectiveness Analysis Registry (CEA registry). The key criteria for inclusion were that the study population included women with SUI and that the surgical interventions considered were utilised as either a primary or a follow-up surgery. The review included only full economic evaluations. Studies were quality assessed using the Drummond checklist for economic evaluations. No quantitative synthesis of the results by meta-analysis was conducted due to the high methodological heterogeneity. RESULTS: Twenty-six economic evaluations were included, of which 13 were model-based analyses. Surgical treatments assessed most frequently were mid-urethral slings and open and laparoscopic colposuspension. There were some differences in the methodological approaches taken, including differences in type of economic analysis, perspective, time horizon, types of resource use, and costs and outcomes that were included in the analysis. The majority of studies conducted a cost-utility analysis from a health system perspective and applied a time horizon of between 1 and 5 years. The cost-effectiveness results suggest that single-incision mini-sling and mid-urethral slings are among the most cost-effective options. CONCLUSIONS: The review has shown that methods used for the economic evaluation of surgical treatments for SUI vary widely in terms of study design, analysis type, compared alternatives, time horizon, costing methodologies and effect outcomes. Future economic evaluation studies on surgical treatments for SUI may be improved by the application of available guidelines. SYSTEMATIC REVIEW REGISTRATION: Registered in PROSPERO in 2016, CRD42016049339.

Celecoxib as a Potential Treatment for Intractable Lymphatic Malformation.

Lymphatic malformation (LM) is a congenital disorder resulting from an abnormal development of lymphatic vessels. LM may result in problems of cosmesis and functional impairment, including airway compression. An 11-year-old girl was referred to our department with increasing dysphagia caused by a large left cervical LM with a long history of treatment. Because of the LM location, surgical resection was not an option, and various therapies, including use of picibanil, had proven ineffective. Celecoxib treatment (100 mg/day) was initiated for local pain management. Softening of the lesion was observed 2 weeks after treatment initiation, and the dose was increased to 200 mg/day with additional shrinking of the LM over the next 2 weeks. With parental consent, celecoxib was continued, with a 65% reduction in volume achieved at 6 months. The patient discontinued treatment at 12 months, and the LM volume increased. Control over the LM was achieved with resumption of celecoxib treatment. After 2 years of treatment, the LM persists, but the size of the malformation is significantly smaller. No adverse effects of celecoxib treatment were observed. The anti-cyclooxygenase-2 effect of celecoxib prevented lymphatic vessel growth through an inhibition of cyclooxygenase-2 activity in the conversion of prostaglandin to prostaglandin E2. In conclusion, celecoxib may be a promising therapeutic agent for LM management.

Surgical interventions for women with stress urinary incontinence: systematic review and network meta-analysis of randomised controlled trials.

OBJECTIVES: To compare the effectiveness and safety of surgical interventions for women with stress urinary incontinence. DESIGN: Systematic review and network meta-analysis. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials evaluating surgical interventions for the treatment of stress urinary incontinence in women. METHODS: Identification of relevant randomised controlled trials from Cochrane reviews and the Cochrane Incontinence Specialised Register (searched May 2017), which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Medline In-Process, Medline Epub Ahead of Print, CINAHL, ClinicalTrials.gov, and WHO ICTRP. The reference lists of relevant articles were also searched. Primary outcomes were "cure" and "improvement" at 12 months, analysed by means of network meta-analyses, with results presented as the surface under the cumulative ranking curve (SUCRA). Adverse events were analysed using pairwise meta-analyses. Risk of bias was assessed using the Cochrane risk of bias tool. The quality of evidence for network meta-analysis was assessed using the GRADE approach. RESULTS: 175 randomised controlled trials assessing a total of 21 598 women were included. Most studies had high or unclear risk across all risk of bias domains. Network meta-analyses were based on data from 105 trials that reported cure and 120 trials that reported improvement of incontinence symptoms. Results showed that the interventions with highest cure rates were traditional sling, retropubic midurethral sling (MUS), open colposuspension, and transobturator MUS, with rankings of 89.4%, 89.1%, 76.7%, and 64.1%, respectively. Compared with retropubic MUS, the odds ratio of cure for traditional sling was 1.06 (95% credible interval 0.62 to 1.85), for open colposuspension was 0.85 (0.54 to 1.33), and for transobtrurator MUS was 0.74 (0.59 to 0.92). Women were also more likely to experience an improvement in their incontinence symptoms after receiving retropubic MUS or transobturator MUS compared with other surgical procedures. In particular, compared with retropubic MUS, the odds ratio of improvement for transobturator MUS was 0.76 (95% credible interval 0.59 to 0.98), for traditional sling was 0.69 (0.39 to 1.26), and for open colposuspension was 0.65 (0.41 to 1.02). Quality of evidence was moderate for retropubic MUS versus transobturator MUS and low or very low for retropubic MUS versus the other two interventions. Data on adverse events were available mainly for mesh procedures, indicating a higher rate of repeat surgery and groin pain but a lower rate of suprapubic pain, vascular complications, bladder or urethral perforation, and voiding difficulties after transobturator MUS compared with retropubic MUS. Data on adverse events for non-MUS procedures were sparse and showed wide confidence intervals. Long term data were limited. CONCLUSIONS: Retropubic MUS, transobturator MUS, traditional sling, and open colposuspension are more effective than other procedures for stress urinary incontinence in the short to medium term. Data on long term effectiveness and adverse events are, however, limited, especially around the comparative adverse events profiles of MUS and non-MUS procedures. A better understanding of complications after surgery for stress urinary incontinence is imperative. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016049339.

Extended versus standard lymph node dissection for urothelial carcinoma of the bladder in patients undergoing radical cystectomy.

BACKGROUND: In the treatment of urothelial carcinoma of the bladder, we are currently uncertain of the benefits and harms of standard pelvic lymph node dissection (PLND) compared to extended PLND. OBJECTIVES: To assess the effects of extended versus standard PLND in patients undergoing cystectomy to treat muscle-invasive (cT2 and cT3) and treatment-refractory, non-muscle-invasive (cT1 with or without carcinoma in situ) urothelial carcinoma of the bladder. SEARCH METHODS: We performed a comprehensive literature search using multiple databases (PubMed, Embase, Cochrane Controlled Trials, Web of Science, and LILACS), trial registries, and conference proceedings published up to April 29, 2019, with no restrictions on the language or status of publication. SELECTION CRITERIA: We included randomized controlled trials in which participants underwent radical cystectomy (RC) for muscle-invasive or therapy-refractory non-muscle-invasive urothelial carcinoma of the bladder with either an extended PLND with a superior extent reaching as far cranially as the inferior mesenteric vein, or a standard PLND with a superior extent of the bifurcation of the internal and external iliac artery, with otherwise the same anatomical boundaries. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the included studies and extracted data from them for the primary outcomes: time to death from any cause, time to death from bladder cancer and Clavien-Dindo classification of surgical complications grade III-V, and the secondary outcomes: time to recurrence, Clavien-Dindo I-II complications and disease-specific quality of life.We performed statistical analyses using a random-effects model and rated the certainty of evidence according to the GRADE approach. MAIN RESULTS: The search identified one multicenter trial based in Germany that enrolled 401 participants with histologically confirmed T1 grade 3 or muscle-invasive urothelial carcinoma. The median age was 67 years (range: 59 to 74) and the majority of participants were male (78.3%). No participant received neoadjuvant chemotherapy; a small subset received adjuvant chemotherapy (14.5%).Primary outcomesOur results indicate that extended PLND may reduce the risk of death from any cause over time as compared to standard PLND, but the confidence interval includes the possibility of no effect (hazard ratio [HR]: 0.78, 95% confidence interval [CI]: 0.57 to 1.07, 401 participants, low-certainty evidence). After five years of follow-up, this may result in 83 fewer deaths (95% CI: 174 fewer to 24 more overall deaths) per 1000 participants: 420 deaths for extended PLND compared to 503 deaths per 1000 for standard PLND. We downgraded the certainty of evidence by two levels due to study limitations and imprecision.Our results indicate that extended PLND may reduce the risk of death from bladder cancer over time as compared to standard PLND but, again, the confidence interval includes the possibility of no effect (HR: 0.70, 95% CI: 0.45 to 1.07, participants = 401, low-certainty evidence). After five years of follow-up, this corresponds to 91 fewer deaths per 1000 participants (95% CI: 176 fewer to 19 more bladder cancer deaths): 264 deaths for extended PLND compared to 355 deaths per 1000 for standard PLND. We downgraded the certainty of evidence by two levels due to study limitations and imprecision.Based on follow-up of up to 30 days, we are uncertain whether extended PLND leads to more grade III-V complications as compared to standard PLND, because of study limitations and imprecision (risk ratio [RR]: 1.13, 95% CI: 0.84 to 1.52, participants = 401, very low-certainty evidence).Secondary outcomesWe are uncertain whether extended PLND reduces the risk of recurrence over time as compared to standard PLND, because of study limitations and imprecision (HR: 0.84, 95% CI: 0.58 to 1.22, participants = 401, very low-certainty evidence).Based on follow-up of up to 30 days, we are uncertain whether extended PLND leads to similar grade I-II complications as compared to standard PLND because of study limitations and imprecision (RR: 0.94, 95% CI: 0.74 to 1.19, participants = 401, very low-certainty evidence).We found no trials that reported on disease-specific quality of life. AUTHORS' CONCLUSIONS: Results from a single trial indicate that extended PLND in patients undergoing radical cystectomy for invasive urothelial carcinoma of the bladder may reduce death from any cause and death from bladder cancer over time; however, the results include the possibility of no effect. We are uncertain whether the risk of serious complications up to 30 days may be increased. We are also uncertain as to whether the risk of recurrence over time or the risk of minor complications up to 30 days changes. We were unable to conduct any of the preplanned subgroup analyses, in particular, analyses based on extended lymph node dissection templates, clinical tumor stage, and use of neoadjuvant chemotherapy that may be important effect modifiers. Important additional data is expected from a larger, ongoing trial that will also consider the role of neoadjuvant chemotherapy. Inclusion of this trial in the meta-analysis may help address the issue of imprecision which was a common reason for downgrading the certainty of the evidence.

Surgical treatments for women with stress urinary incontinence: the ESTER systematic review and economic evaluation.

BACKGROUND: Urinary incontinence in women is a distressing condition that restricts quality of life and results in a large economic burden to both the NHS and women themselves. OBJECTIVE: To evaluate the clinical effectiveness, safety and cost-effectiveness of surgical treatment for stress urinary incontinence (SUI) in women and explore women's preferences. DESIGN: An evidence synthesis, a discrete choice experiment (DCE) and an economic decision model, with a value-of-information (VOI) analysis. Nine surgical interventions were compared. Previous Cochrane reviews for each were identified and updated to include additional studies. Systematic review methods were applied. The outcomes of interest were 'cure' and 'improvement'. Both a pairwise and a network meta-analysis (NMA) were conducted for all available surgical comparisons. A DCE was undertaken to assess the preferences of women for treatment outcomes. An economic model assessed the cost-effectiveness of alternative surgeries and a VOI analysis was undertaken. RESULTS: Data from 175 studies were included in the effectiveness review. The majority of included studies were rated as being at high or unclear risk of bias across all risk-of-bias domains. The NMA, which included 120 studies that reported data on 'cure' or 'improvement', showed that retropubic mid-urethral sling (MUS), transobturator MUS, traditional sling and open colposuspension were more effective than other surgical procedures for both primary outcomes. The results for other interventions were variable. In general, rate of tape and mesh exposure was higher after transobturator MUS than after retropubic MUS or single-incision sling, whereas the rate of tape or mesh erosion/extrusion was similar between transobturator MUS and retropubic MUS. The results of the DCE, in which 789 women completed an anonymous online questionnaire, indicate that women tend to prefer surgical treatments associated with no pain or mild chronic pain and shorter length of hospital stay as well as those treatments that have a smaller risk for urinary symptoms to reoccur after surgery. The cost-effectiveness results suggest that, over a lifetime, retropubic MUS is, on average, the least costly and most effective surgery. However, the high level of uncertainty makes robust estimates difficult to ascertain. The VOI analysis highlighted that further research around the incidence rates of complications would be of most value. LIMITATIONS: Overall, the quality of the clinical evidence was low, with limited data available for the assessment of complications. Furthermore, there is a lack of robust evidence and significant uncertainty around some parameters in the economic modelling. CONCLUSIONS: To our knowledge, this is the most comprehensive assessment of published evidence for the treatment of SUI. There is some evidence that retropubic MUS, transobturator MUS and traditional sling are effective in the short to medium term and that retropubic MUS is cost-effective in the medium to long term. The VOI analysis highlights the value of further research to reduce the uncertainty around the incidence rates of complications. There is a need to obtain robust clinical data in future work, particularly around long-term complication rates. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016049339. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Urinary incontinence, defined as involuntary leakage of urine, is a common condition that varies in type and severity and can have a huge impact on the quality of life of women. The aim of this project was to summarise the evidence on the clinical effectiveness, safety and cost-effectiveness of nine surgical operations for stress urinary incontinence in women and assess the need for further research. Women's preferences for surgery were also explored. Currently there is no agreement among decision-makers, doctors and patients about which of the available surgical operations is best. Based on previous Cochrane reviews, the effects and safety of each operation were systematically reviewed and analysed. Their cost-effectiveness and the value of conducting further research were also evaluated. To better understand the preference of women, an online survey containing a discrete choice experiment was conducted. Finally, patient representatives were consulted to help us to understand the consequences of the findings from a patient's perspective. The evidence on surgical operations was predominantly short to medium term (up to 12 months). This analysis found that the quality of the evidence varied, with the majority of trials being subject to high or unclear risk of bias, making the conclusions that can be drawn less robust. The findings of the clinical evidence review suggest that retropubic sling procedures, transobturator sling procedures and traditional sling procedures are more effective than other surgical procedures for both 'cure' and 'improvement' of stress urinary incontinence. The results of the economic analyses support these findings, suggesting that retropubic mid-urethral sling is the most cost-effective surgical operation. However, data on complications were lacking, limiting any strong conclusions. The results suggest that there is value in undertaking further research to reduce the uncertainty around the medium- to long-term complications of all surgical treatments and this was reflected in patients' views.

Naftopidil for the treatment of lower urinary tract symptoms compatible with benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common condition in ageing men that may cause lower urinary tract symptoms (LUTS). Treatment aims are to relieve symptoms and prevent disease-related complications. Naftopidil is an alpha-blocker (AB) that has a high affinity for the A1d receptor that may have advantages in treating LUTS in this setting. This is an update of a Cochrane Review first published in 2009. Since that time, several large randomised controlled trials (RCTs) have been reported, making this update relevant. OBJECTIVES: To evaluate the effects of naftopidil for the treatment of LUTS associated with BPH. SEARCH METHODS: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, LILAC, and Web of Science), trials registries, other sources of grey literature, and conference proceedings with no restrictions on the language of publication or publication status up to 31 May 2018 SELECTION CRITERIA: We included all parallel RCTs. We also included cross-over design trials. DATA COLLECTION AND ANALYSIS: Two review authors independently classified and abstracted data from the included studies. We performed statistical analyses using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. Primary outcomes were urological symptom scores, quality of life (QoL) and treatment withdrawals for any reason; secondary outcomes were treatment withdrawals due to adverse events, acute urinary retention, surgical intervention for BPH, and cardiovascular and sexual adverse events. We considered outcomes measured up to 12 months after randomisation as short term, and later than 12 months as long term. We rated the certainty of the evidence according to the GRADE approach. MAIN RESULTS: We included 22 RCTs with 2223 randomised participants across four comparisons for short-term follow-up. This abstract focuses on only two of four comparisons for which we found data since two comparators (i.e. propiverine and Eviprostat (phytotherapy)) are rarely used. One study comparing naftopidil to placebo did not report any relevant outcomes and was therefore excluded. There were no trials that compared to combination therapy with naftopidil or any 5-alpha reductase inhibitors (5-ARIs) to combination therapy with other ABs and any 5-ARIs.All included studies were conducted in Asian countries. Study duration ranged from four to 12 weeks. Mean age was 67.8 years, prostate volume was 35.4 mL, and International Prostate Symptom Score was 18.3. We were unable to perform any of the preplanned subgroup analyses based on age and baseline symptom score.Naftopidil versus tamsulosinBased on 12 studies with 965 randomised participants, naftopidil may have resulted in little or no difference in urological symptom score (mean difference (MD) 0.47, 95% confidence interval (CI) -0.09 to 1.04 measured on a scale from 0 to 35 with higher score representing increased symptoms), QoL (MD 0.11, 95% CI -0.09 to 0.30; measured on a scale from 0 to 6 with higher scores representing worse QoL), and treatment withdrawals for any reason (risk ratio (RR) 0.92, 95% CI 0.64 to 1.34; corresponding to 7 fewer per 1000 participants, 95% CI 32 fewer to 31 more). Naftopidil may have resulted in little to no difference in sexual adverse events (RR 0.54, 95% CI 0.24 to 1.22); this would result in 26 fewer sexual adverse events per 1000 participants (95% CI 43 fewer to 13 more). We rated the certainty of evidence as moderate for urological symptom score and low for the other outcomes.Naftopidil versus silodosinBased on five studies with 652 randomised participants, naftopidil may have resulted in little or no difference in the urological symptom scores (MD 1.04, 95% CI -0.78 to 2.85), QoL (MD 0.21, 95% CI -0.23 to 0.66), and treatment withdrawals for any reason (RR 0.80, 95% CI 0.52 to 1.23; corresponding to 26 fewer per 1000 participants, 95% CI 62 fewer to 32 more). We rated the certainty of evidence as low for all these outcomes. Naftopidil likely reduced sexual adverse events (RR 0.15, 95% CI 0.06 to 0.42; corresponding to 126 fewer sexual adverse events per 1000 participants, 95% CI 139 fewer to 86 fewer). We rated the certainty of evidence as moderate for sexual adverse events. AUTHORS' CONCLUSIONS: Naftopidil appears to have similar effects in the urological symptom scores and QoL compared to tamsulosin and silodosin. Naftopidil has similar sexual adverse events compared to tamsulosin but has fewer compared to silodosin.

A systematic review of implementation strategies to deliver guidelines on obstetric care practice in low- and middle-income countries.

BACKGROUND: Healthcare measures to prevent maternal deaths are well known. However, effective implementation of this knowledge to change practice remains a challenge. OBJECTIVES: To assess whether strategies to promote the use of guidelines can improve obstetric practices in low- and middle-income countries (LMICs). SEARCH STRATEGY: Electronic databases were searched up to February 7, 2014, using relevant terms for implementation strategies (e.g. "audit," "education," "reminder"), and maternal mortality. SELECTION CRITERIA: Randomized and non-randomized studies of implementation strategies targeting healthcare professionals within the formal health services in LMICs were included. DATA COLLECTION AND ANALYSIS: Cochrane methodological guidance was followed. Because of heterogeneity in the interventions, a narrative synthesis was completed. MAIN RESULTS: Nine studies met the inclusion criteria. Moderate-to-low-quality evidence was found to show improvement in the areas of doctor-patient communication (one study), analgesic provision (one study), the management of emergencies (two studies) and maternal and late neonatal mortality (one study each). Intervention effects were not consistent across studies. CONCLUSIONS: Implementation strategies targeting health professionals could lead to improvement in obstetric care in LMICs. Future research should explore what feature of an intervention is effective in one context and how this could be translated into another context. PROSPERO: CRD42014010310.

Systematic review of obstetric care from a women-centered perspective in Nigeria since 2000.

BACKGROUND: A women-centered approach can improve the quality of patient care. OBJECTIVE: To review issues in the provision of obstetric care from a patient-centered care perspective in Nigeria. SEARCH STRATEGY: Using terms related to maternal and perinatal mortality, in combination with "Nigeria", MEDLINE, Embase, CINAHL, Web of Knowledge, and African Journal Online were searched, between December 1, 2013 and January 31, 2014, for articles in any language. SELECTION CRITERIA: Articles published in a Nigerian setting after 2000 that investigated causes of and circumstance surrounding maternal deaths and complications, or clinical practice related to maternal care were included. DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers using a standardized abstraction form and were analyzed from a patient-centered perspective. MAIN RESULTS: The analysis included 57 studies. Clandestine induced abortions, lack of prenatal care, delays in seeking care, and the use of spiritual churches for delivery were found to contribute to adverse pregnancy outcomes. CONCLUSIONS: Healthcare systems respond inadequately to patients' needs in terms of abortion care, information sharing, transitioning between prenatal and obstetric care, and patients' non-medical needs. Data from clinician-led maternal death audits provided insights into how women-centered care can be provided; nonetheless, more-focused studies from a primarily patient-centered perspective are warranted.

Barriers and enablers to guideline implementation strategies to improve obstetric care practice in low- and middle-income countries: a systematic review of qualitative evidence.

BACKGROUND: Maternal mortality remains a major international health problem in low- and middle-income countries (LMIC), and most could have been prevented by quality improvement interventions already demonstrated to be effective, such as clinical guideline implementation strategies. The aim of this systematic review was to synthesise qualitative evidence on guideline implementation strategies to improve obstetric care practice in LMIC in order to identify barriers and enablers to their successful implementation. METHODS: We searched MEDLINE and CINAHL databases for articles reporting research findings on barriers and enablers to guideline implementation strategies in obstetric care practice in LMIC. We conducted a "best fit" framework synthesis of the included studies. We used an organisational "stages of change" model as our a priori framework for the synthesis. RESULTS: Nine studies were included: all were based in Sub-Saharan Africa and in hospital health care facilities. The majority of studies (seven) evaluated one particular guideline implementation strategy: clinical audit and feedback (both criterion-based audit and maternal death reviews), and a minority (two) evaluated educational interventions. A range of barriers and enablers to successful guideline implementation was identified. A key finding of the framework synthesis was that "high" and "low" intrinsic health care professional motivation are overall enablers and barriers, respectively, of successful guideline implementation. We developed a modified "stages of change" model to take account of these findings. CONCLUSION: We have identified a number of quality improvement processes that are amenable to change at limited or no additional cost, although some identified barriers may be difficult to address without increased resources. We note the pathways to implementation may be complex and require further research to develop our understanding of individual and organisational behaviours and motivation in LMIC settings. TRIAL REGISTRATION: PROSPERO CRD42015016062.