A multicentre cluster-randomized clinical trial to improve antibiotic use and reduce length of stay in hospitals: comparison of three measurement and feedback methods.

BACKGROUND: Various metrics of hospital antibiotic use might assist in guiding antimicrobial stewardship (AMS). OBJECTIVES: To compare patient outcomes in association with three methods to measure and feedback information on hospital antibiotic use when used in developing an AMS intervention. METHODS: Three methods were randomly allocated to 42 clusters from 21 Dutch hospitals: (1) feedback on quantity of antibiotic use [DDD, days-of-therapy (DOT) from hospital pharmacy data], versus feedback on (2) validated, or (3) non-validated quality indicators from point prevalence studies. Using this feedback together with an implementation tool, stewardship teams systematically developed and performed improvement strategies. The hospital length of stay (LOS) was the primary outcome and secondary outcomes included DOT, ICU stay and hospital mortality. Data were collected before (February-May 2015) and after (February-May 2017) the intervention period. RESULTS: The geometric mean hospital LOS decreased from 9.5 days (95% CI 8.9-10.1, 4245 patients) at baseline to 9.0 days (95% CI 8.5-9.6, 4195 patients) after intervention (P < 0.001). No differences in effect on LOS or secondary outcomes were found between methods. Feedback on quality of antibiotic use was used more often to identify improvement targets and was preferred over feedback on quantity of use. Consistent use of the implementation tool seemed to increase effectiveness of the AMS intervention. CONCLUSIONS: The decrease in LOS versus baseline likely reflects improvement in the quality of antibiotic use with the stewardship intervention. While the outcomes with the three methods were otherwise similar, stewardship teams preferred data on the quality over the quantity of antibiotic use.

Antibiotic treatment for 6 days versus 12 days in patients with severe cellulitis: a multicentre randomized, double-blind, placebo-controlled, non-inferiority trial.

OBJECTIVES: To investigate whether antibiotic treatment of 6 days' duration is non-inferior to treatment for 12 days in patients hospitalized for cellulitis. METHODS: This multicentre, randomized, double-blind, placebo-controlled, non-inferiority trial enrolled adult patients hospitalized for severe cellulitis who were treated with intravenous flucloxacillin. At day 6 participants with symptom improvement who were afebrile were randomized between an additional 6 days of oral flucloxacillin or placebo in a 1:1 ratio, stratified for diabetes and hospital. The primary outcome was cure by day 14, without relapse by day 28. Secondary outcomes included a modified cure assessment and relapse rate by day 90. RESULTS: Between August 2014 and June 2017, 151 of 248 included participants were randomized. The intention-to-treat population consisted of 76 and 73 participants allocated to 12 and 6 days of antibiotic therapy, respectively (mean age 62 years, 67% males, 24% diabetics); 38/76 (50.0%) and 36/73 (49.3%) were cured in the 12- and 6-day groups respectively (ARR 0.7 percentage points, 95%CI: -15.0 to 16.3). Cure rates were 56/76 (73.7%) and 49/73 (67.1%) with the modified cure assessment (ARR 6.6, 95%CI: -8.0 to 20.8). After initial cure without relapse, day 90 relapse rates were higher in the 6-day group (6% versus 24%, p < 0.05). CONCLUSIONS: Given the wide confidence intervals, we can neither confirm nor refute our hypothesis that 6 days of therapy is non-inferior to 12 days of therapy. However, a 6-day course resulted in significantly more frequent relapses by day 90. These findings require confirmation in future studies.

Heterogeneity of cost estimates in health economic evaluation research. A systematic review of stress urinary incontinence studies.

INTRODUCTION AND HYPOTHESIS: There is increased demand for an international overview of cost estimates and insight into the variation affecting these estimates. Understanding of these costs is useful for cost-effectiveness analysis (CEA) research into new treatment modalities and for clinical guideline development. METHODS: A systematic search was conducted in Ovid MEDLINE & other non-indexed materials and Ovid Embase for articles published between 1995 and 2017. The National Health Service Economic Evaluation Database (NHS-EED) filter and the McMaster sensitive therapy filter were combined with a bespoke search strategy for stress urinary incontinence (SUI). We extracted unit cost estimates, assessed variability and methodology, and determined transferability. RESULTS: We included 37 studies in this review. Four hundred and eighty-two cost estimates from 13 countries worldwide were extracted. Descriptive analysis shows that hospital stay in gynecology ranged between €82 and €1,292 per day. Costs of gynecological consultation range from €30 in France to €158 in Sweden. In the UK, costs are estimated at €228 per hour. Costs of a tension-free vaginal tape (TVT) device range from €431 in Finland to €994 in Canada. TVT surgery per minute costs €25 in France and €82 in Sweden. Total costs of TVT range from €1,224 in Ireland to €5,809 for inpatient care in France. Variation was explored. CONCLUSIONS: Heterogeneity was observed in cost estimates for all units at all levels of health care. CEAs of SUI interventions cannot be interpreted without bias when the base of these analyses-namely costs-cannot be compared and generalized.

How to measure quantitative antibiotic use in order to support antimicrobial stewardship in acute care hospitals: a retrospective observational study.

A cornerstone of antimicrobial stewardship programs (ASPs) is monitoring quantitative antibiotic use. Frequently used metrics are defined daily dose (DDD) and days of therapy (DOT). The purpose of this study was (1) to explore for the hospital setting the possibilities of quantitative data retrieval on the level of medical specialty and (2) to describe factors affecting the usability and interpretation of these quantitative metrics. We performed a retrospective observational study, measuring overall systemic antibiotic use at specialty level over a 1-year period, from December 1st 2014 to December 1st 2015, in one university and 13 non-university hospitals in the Netherlands. We distinguished surgical and non-surgical adult specialties. The association between DDDs, calculated from aggregated dispensing data, and DOTs, calculated from patient-level prescription data, was explored descriptively and related to organizational factors, data sources (prescription versus dispensing data), data registration, and data extraction. Twelve hospitals were able to extract dispensing data (DDD), three of which on the level of medical specialty; 13 hospitals were able to extract prescription data (DOT), 11 of which by medical specialty. A large variation in quantitative antibiotic use was found between hospitals and the correlation between DDDs and DOTs at specialty level was low. Differences between hospitals related to organizational factors, data sources, data registration, and data extraction procedures likely contributed to the variation in quantitative use and the low correlation between DDDs and DOTs. The differences in healthcare organization, data sources, data registration, and data extraction procedures contributed to the variation in reported quantitative use between hospitals. Uniform registration and extraction procedures are necessary for appropriate measurement and interpretation and benchmarking of quantitative antibiotic use.

Pessary for prevention of preterm birth in twin pregnancy with short cervix: 3-year follow-up study.

OBJECTIVE: A recent randomized clinical trial (ProTWIN) showed that a cervical pessary prevented preterm birth and improved neonatal outcome in women with multiple pregnancy and cervical length (CL) < 38 mm. In this follow-up study, the long-term developmental outcome of these children was evaluated at 3 years' corrected age. METHODS: This was a follow-up study of ProTWIN, a multicenter trial conducted between 2009 and 2012 in which asymptomatic women with a multiple pregnancy were randomized to placement of a cervical pessary or no intervention. Current follow-up and analysis were limited to mothers with a mid-trimester CL < 38 mm (78 women (157 children) in the pessary group and 55 women (111 children) in the control group). At 3 years of corrected age, surviving children were invited for a Bayley Scales of Infant and Toddler Development-third edition (Bayley-III) assessment. Death after randomization or neurodevelopmental disability (Bayley-III score of ≤ 85, 1 SD below mean) rates were compared between the pessary and control groups, according to the intention-to-treat principle and using multiple imputation for missing data. Mean Bayley-III scores in surviving children were also assessed. A linear mixed-effects model was used to adjust for correlation between children of one mother. RESULTS: From the time of entry in the ProTWIN trial until follow-up at 3 years of age, a total of 27 children had died (six (5%) in the pessary vs 21 (26%) in the control group; odds ratio (OR), 0.13; 95% CI, 0.04-0.48). Bayley-III outcomes were collected for 173/241 (72%) surviving children (114 (75%) in the pessary vs 59 (66%) in the control group). The cumulative incidence of death or survival with a neurodevelopmental disability was 12 (10%) in the pessary vs 23 (29%) in the control group (OR, 0.26; 95% CI, 0.09-0.73). No statistical or clinically relevant differences were found with respect to cognitive, language and motor development among surviving children between the groups. Comparable results were found after multiple imputation. CONCLUSION: In women with twin pregnancy and a CL < 38 mm, the use of a cervical pessary strongly improved survival of the children without affecting neurodevelopment at 3 years' corrected age. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Cost-effectiveness of diagnostic testing strategies including cervical-length measurement and fibronectin testing in women with symptoms of preterm labor.

OBJECTIVE: To evaluate the cost-effectiveness of combining cervical-length (CL) measurement and fetal fibronectin (fFN) testing in women with symptoms of preterm labor between 24 and 34 weeks' gestation. METHODS: This was a model-based cost-effectiveness analysis evaluating seven test-treatment strategies based on CL measurement and/or fFN testing in women with symptoms of preterm labor from a societal perspective, in which neonatal outcomes and costs were weighted. Estimates of disease prevalence, test accuracy and costs were based on two recently performed nationwide cohort studies in The Netherlands. RESULTS: Strategies using fFN testing and CL measurement separately to predict preterm delivery are associated with higher costs and incidence of adverse neonatal outcomes compared with strategies that combine both tests. Additional fFN testing when CL is 15-30 mm was considered cost effective, leading to a cost saving of €3919 per woman when compared with a treat-all strategy, with a small deterioration in neonatal health outcomes, namely one additional perinatal death and 21 adverse outcomes per 10 000 women with signs of preterm labor (incremental cost-effectiveness ratios €39 million and €1.9 million, respectively). Implementing this strategy in The Netherlands, a country with about 180 000 deliveries annually, could lead to an annual cost saving of between €2.4 million and €7.6 million, with only a small deterioration in neonatal health outcomes. CONCLUSION: In women with symptoms of preterm labor at 24-34 weeks' gestation, performing additional fFN testing when CL is between 15 and 30 mm is a viable and cost-saving strategy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

[From record keeping to scientific research: obstacles and opportunities for research with electronic health records]. / Van statusvoering naar wetenschappelijk onderzoek.

As a result of increasing digitisation of medical record keeping, electronic health records (EHRs) are an attractive source for data reuse. However, such record-based research is still suffering from poor quality of data stored in EHRs. Lack of consent for reuse of data also plays an impeding role, especially in retrospective record-based research. That said, increasing cooperation between healthcare institutions and current attention for EHR organisation also offer opportunities for record-based research. Patient data can be recorded in more standardised ways and in increasingly harmonised EHRs. In addition, if healthcare institutions were to establish a generic consent procedure - preferably with national scope - the potential of EHRs for scientific research could be exploited in considerably better ways.

Effect of an antibiotic checklist on length of hospital stay and appropriate antibiotic use in adult patients treated with intravenous antibiotics: a stepped wedge cluster randomized trial.

OBJECTIVES: Quality indicators (QIs) have been developed to define appropriate antibiotic use in hospitalized patients. We evaluated whether a checklist based on these QIs affects appropriate antibiotic use and length of hospital stay. METHODS: An antibiotic checklist for patients treated with intravenous antibiotics was introduced in nine Dutch hospitals in a stepped wedge cluster randomized trial. Prophylaxis was excluded. We included a random sample before (baseline), and all eligible patients after (intervention) checklist introduction. Baseline and intervention outcomes were compared. Primary endpoint was length of stay (LOS), analysed by intention to treat. Secondary endpoints, including QI performances, QI sum score (performance on all QIs per patient), and quality of checklist use, were analysed per protocol. RESULTS: Between 1 November 2014 and 1 October 2015 we included 853 baseline and 5354 intervention patients, of whom 993 (19%) had a completed checklist. The LOS did not change (baseline geometric mean 10.0 days (95% CI 8.6-11.5) versus intervention 10.1 days (95% CI 8.9-11.5), p 0.8). QI performances increased between +3.0% and +23.9% per QI, and the percentage of patients with a QI sum score above 50% increased significantly (OR 2.4 (95% CI 2.0-3.0), p<0.001). Higher QI sum scores were significantly associated with shorter LOS. Discordance existed between checklist-answers and actual performance. CONCLUSIONS: Use of an antibiotic checklist resulted in a significant increase in appropriateness of antibiotic use, but not in a reduction of LOS. Low overall checklist completion rates and discordance between checklist-answers and actual provided care might have attenuated the impact of the checklist.

Diagnostic workup for postmenopausal bleeding: a randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of hysteroscopy for the detection and treatment of endometrial polyps versus expectant management in women with postmenopausal bleeding (PMB), a thickened endometrium and benign endometrial sampling. DESIGN: Multicentre, randomised controlled trial. SETTING: Three academic hospitals and nine non-academic teaching hospitals in the Netherlands. POPULATION: Women with PMB, an endometrial thickness >4 mm and benign result from endometrial sampling. METHODS: Women were randomised to either further diagnostic workup by hysteroscopy (preceded by saline infusion sonography) or expectant management. MAIN OUTCOMES: The primary outcome measure was recurrence of PMB within a year after randomisation. Secondary outcome measures were time to recurrent bleeding and recurrent bleeding after more than 1 year. In the hysteroscopy group, the presence of polyps and the results of their histology were registered. RESULTS: Between January 2010 and October 2013, 200 women were randomised; 98 to hysteroscopy and 102 to expectant management. Within 1 year a total of 15 women (15.3%) in the hysteroscopy group experienced recurrent bleeding, versus 18 (18.0%) in the expectant management group (relative risk 0.85 (95% CI 0.46-1.59). In the hysteroscopy group, 50/98 (51%) polyps were diagnosed of which 6/98 (6%) showed evidence of endometrial (pre)malignancy; final pathology results after hysterectomy showed three women with hyperplasia with atypia and three women with endometrial cancer. CONCLUSION: In women with PMB, a thickened endometrium and benign endometrial sampling, operative hysteroscopy does not reduce recurrent bleeding. Hysteroscopy detected focal endometrial (pre)malignancy in 6% of women who had benign endometrial sampling. This finding indicates that in these women, further diagnostic workup is warranted to detect focal (pre)malignancies, missed by blind endometrial sampling. TWEETABLE ABSTRACT: In women with PMB, hysteroscopy does not reduce recurrent bleeding but is warranted to detect focal malignancy.

A prospective randomized controlled trial comparing infliximab and etanercept in patients with moderate-to-severe chronic plaque-type psoriasis: the Psoriasis Infliximab vs. Etanercept Comparison Evaluation (PIECE) study.

BACKGROUND: There are currently no independent data available comparing infliximab and etanercept for the treatment of psoriasis. OBJECTIVES: To compare these biologics without funding from pharmaceutical companies. METHODS: Overall, 50 patients were randomized to etanercept (n = 23) 50 mg subcutaneously twice weekly or infliximab (n = 25) 5 mg kg-1 intravenously at week 0, 2, 6, 14 and 22. After 24 weeks, 19 patients stopped and 22 continued treatment and were followed up to week 48. The primary outcome was ≥ 75% improvement of Psoriasis Area and Severity Index (PASI 75) at week 24. The secondary outcomes included PASI 75 at week 6 (onset of action) and week 12, Investigator's Global Assessment (IGA), Patient Global Assessment, impact on quality of life (Skindex-17 and SF-36), Treatment Satisfaction Questionnaire of Medication, duration of remission, maintenance treatment and safety. RESULTS: At week 24, PASI 75 was achieved in 72% (infliximab) vs. 35% (etanercept) (P = 0·01). The onset of action was achieved in 52% (infliximab) and 4% (etanercept). At week 12, 76% (infliximab) and 22% (etanercept) achieved PASI 75 (P < 0·001). At week 24, IGA 'clear or almost clear' was observed in 76% (infliximab) and 30% (etanercept) (P = 0·01). Skindex-17 symptom score was significantly better for infliximab. Maintenance treatment achieved PASI 75 for 67% (n = 6) infliximab vs. 50% (n = 5) etanercept, at week 48 (P = 0·65). Mild adverse events were reported in 76% (infliximab) vs. 66% (etanercept). CONCLUSIONS: Infliximab showed a rapid and significant higher level of efficacy until week 24 compared with etanercept. Long-term data showed no significant differences between both groups at week 48. Safety parameters were comparable.

Cost analysis of laparoscopic lavage compared with sigmoid resection for perforated diverticulitis in the Ladies trial.

BACKGROUND: Laparoscopic peritoneal lavage is an alternative to sigmoid resection in selected patients presenting with purulent peritonitis from perforated diverticulitis. Although recent trials have lacked superiority for lavage in terms of morbidity, mortality was not compromised, and beneficial secondary outcomes were shown. These included shorter duration of surgery, less stoma formation and less surgical reintervention (including stoma reversal) for laparoscopic lavage versus sigmoid resection respectively. The cost analysis of laparoscopic lavage for perforated diverticulitis in the Ladies RCT was assessed in the present study. METHODS: This study involved an economic evaluation of the randomized LOLA (LaparOscopic LAvage) arm of the Ladies trial (comparing laparoscopic lavage with sigmoid resection in patients with purulent peritonitis due to perforated diverticulitis). The actual resource use per individual patient was documented prospectively and analysed (according to intention-to-treat) for up to 1 year after randomization. RESULTS: Eighty-eight patients were randomized to either laparoscopic lavage (46) or sigmoid resection (42). The total medical costs for lavage were lower (mean difference € - 3512, 95 per cent bias-corrected and accelerated c.i. -16 020 to 8149). Surgical reintervention increased costs in the lavage group, whereas stoma reversal increased costs in the sigmoid resection group. Differences in favour of laparoscopy were robust when costs were varied by ±20 per cent in a sensitivity analysis (mean cost difference € - 2509 to -4438). CONCLUSION: Laparoscopic lavage for perforated diverticulitis is more cost-effective than sigmoid resection.

MisoREST: surgical versus expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for miscarriage: a randomized controlled trial.

STUDY QUESTION: Is curettage more effective than expectant management in case of an incomplete evacuation after misoprostol treatment for first trimester miscarriage? SUMMARY ANSWER: Curettage leads to a higher chance of complete evacuation but expectant management is successful in at least 76% of women with an incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage. WHAT IS KNOWN ALREADY: In 5-50% of the women treated with misoprostol, there is a suspicion of incomplete evacuation of the uterus on sonography. Although these women generally have minor symptoms, such a finding often leads to additional curettage. STUDY DESIGN, SIZE, DURATION: From June 2012 until July 2014, we conducted a nationwide multicenter randomized controlled trial (RCT). Women who had had primary misoprostol treatment for miscarriage with sonographic evidence of incomplete evacuation of the uterus were randomly allocated to either curettage or expectant management (1:1), using a web-based application. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 59 women in 27 hospitals; 30 were allocated to curettage and 29 were allocated to expectant management. A successful outcome was defined as sonographic finding of an empty uterus 6 weeks after randomization. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics of both groups were comparable. Empty uterus on sonography or uneventful clinical follow-up was seen in 29/30 women (97%) allocated to curettage compared with 22/29 women (76%) allocated to expectant management (RR 1.3, 95% CI 1.03-1.6) with complication rates of 10% versus 10%, respectively (RR 0.97, 95% CI 0.21-4.4). In the group allocated to curettage, no woman required re-curettage, while two women (6.7%) underwent hysteroscopy (for other or unknown reasons). In the women allocated to expectant management, curettage was performed in four women (13.8%) and three women (10.3%) underwent hysteroscopy. LIMITATIONS, REASONS FOR CAUTION: Due to a strong patient preference, mainly for expectant management, the targeted sample size could not be included and the trial was stopped prematurely. WIDER IMPLICATIONS OF THE FINDINGS: In women suspected of incomplete evacuation of the uterus after misoprostol, curettage is more effective than expectant management. However, expectant management is equally safe and prevents curettage for most of the women. This finding could further restrain the use of curettage in the treatment of first trimester miscarriage. STUDY FUNDING/COMPETING INTERESTS: This study was funded by ZonMw, a Dutch organization for Health Research and Development, project number 80-82310-97-12066. There were no conflicts of interests. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR3310, http://www.trialregister.nl TRIAL REGISTRATION DATE: 27 February 2012. DATE OF FIRST PATIENT'S ENROLMENT: 12 June 2012.

[Better antibiotic use in complicated urinary tract infections; multicentre cluster randomised trial of 2 improvement strategies]. / Beter antibioticagebruik bij gecompliceerde urineweginfecties.

OBJECTIVE: To compare the effectiveness of two strategies to improve antibiotic use in patients with a complicated urinary tract infection. DESIGN: Multicentre cluster randomised unblinded trial. METHOD: The departments of Internal Medicine and Urology from 19 hospitals in the Netherlands took part in this trial. Based on retrospective patient record investigations we performed baseline measurements on the scores of a validated set of quality indicators for antibiotic use in a minimum of 50 patients with a complicated urinary tract infection per department in 2009. A similar post-trial measurement took place in 2012. In 2010 we randomised the hospitals between 2 improvement strategies: a multifaceted strategy that included results of the baseline measurements, education, reminders and assistance with optional improvement interventions, and a competitive feedback strategy, in which the departments only received results of the baseline measurements and non-anonymous results from the other departments in this study arm. The primary outcome measure was improvement of the quality indicator scores. Secondary outcome measures were determinants of improvement of the indicators. (Netherlands Trial Register: NTR1742) RESULTS: The baseline and post-trial measurements were performed on 1,964 patients and 2,027 patients, respectively. Post-trial measurements revealed a significant, but limited, improvement of several indicators compared with baseline measurements. We found no significant difference in improvement between the two strategies for any indicator. The intensity with which the departments implemented improvement strategies was mostly suboptimal, but intensive implementation of a strategy was associated with greater improvement. CONCLUSION: The effectiveness of both improvement strategies was comparable, but limited. For real improvement in antibiotic use in patients with complicated urinary tract infections, improvement interventions should be developed and applied by local professionals themselves.

Mode of childbirth and neonatal outcome after external cephalic version: A prospective cohort study.

OBJECTIVE: to assess the mode of childbirth and adverse neonatal outcomes in women with a breech presentation with or without an external cephalic version attempt, and to compare the mode of childbirth among women with successful ECV to women with a spontaneous cephalic presentation. DESIGN: prospective matched cohort study. SETTING: 25 clusters (hospitals and its referring midwifery practices) in the Netherlands. Data of the Netherlands perinatal registry for the matched cohort. PARTICIPANTS: singleton pregnancies from January 2011 to August 2012 with a fetus in breech presentation and a childbirth from 36 weeks gestation onwards. Spontaneous cephalic presentations (selected from national registry 2009 and 2010) were matched in a 2:1 ratio to cephalic presentations after a successful version attempt. Matching criteria were maternal age, parity, gestational age at childbirth and fetal gender. Main outcomes were mode of childbirth and neonatal outcomes. MEASUREMENTS AND FINDINGS: of 1613 women eligible for external cephalic version, 1169 (72.5%) received an ECV attempt. The overall caesarean childbirth rate was significantly lower compared to women who did not receive a version attempt (57% versus 87%; RR 0.66 (0.62-0.70)). Women with a cephalic presentation after ECV compared to women with a spontaneous cephalic presentation had a decreased risk for instrumental vaginal childbirth (RR 0.52 (95% CI 0.29-0.94)) and an increased risk of overall caesarean childbirth (RR 1.7 (95%CI 1.2-2.5)). KEY CONCLUSIONS: women who had a successful ECV are at increased risk for a caesarean childbirth but overall, ECV is an important tool to reduce the caesarean rate. IMPLICATION FOR PRACTICE: ECV is an important tool to reduce the caesarean section rates.

A Structured Assessment to Decrease the Amount of Inconclusive Endometrial Biopsies in Women with Postmenopausal Bleeding.

OBJECTIVE: To determine whether structured assessment of outpatient endometrial biopsies decreases the number of inconclusive samples. DESIGN: Retrospective cohort study. SETTING: Single hospital pathology laboratory. POPULATION: Endometrial biopsy samples of 66 women with postmenopausal bleeding, collected during the usual diagnostic work-up and assessed as insufficient for a reliable histological diagnosis. METHODS: Endometrial biopsy samples were requested from the pathology laboratories. The retrieved samples were systematically reassessed by a single pathologist specialized in gynecology. MAIN OUTCOME MEASURE: Disagreement between initial assessment and conclusion after structured reassessment. RESULTS: We retrieved 36 of 66 endometrial biopsy samples from six different pathology laboratories. Structured reassessment of the retrieved samples by a single pathologist specialized in gynecology did not change the conclusion in 35 of the 36 samples. The remaining sample contained a large amount of endometrial tissue and the diagnosis at reassessment was endometrial hyperplasia without atypia. All other samples contained insufficient material for a reliable diagnosis. CONCLUSION: A structured reassessment of endometrial biopsies samples, which were classified as inconclusive due to insufficient material, did not change the conclusion. Although it might be helpful for pathologists to have diagnostic criteria for adequacy and/or inadequacy of an endometrial biopsy sample, the gain in efficiency is likely to be small.

Quantitative fetal fibronectin testing in combination with cervical length measurement in the prediction of spontaneous preterm delivery in symptomatic women.

OBJECTIVE: To evaluate whether in symptomatic women, the combination of quantitative fetal fibronectin (fFN) testing and cervical length (CL) improves the prediction of preterm delivery (PTD) within 7 days compared with qualitative fFN and CL. DESIGN: Post hoc analysis of frozen fFN samples of a nationwide cohort study. SETTING: Ten perinatal centres in the Netherlands. POPULATION: Symptomatic women between 24 and 34 weeks of gestation. METHODS: The risk of PTD <7 days was estimated in predefined CL and fFN strata. We used logistic regression to develop a model including quantitative fFN and CL, and one including qualitative fFN (threshold 50 ng/ml) and CL. We compared the models' capacity to identify women at low risk (<5%) for delivery within 7 days using a reclassification table. MAIN OUTCOME MEASURES: Spontaneous delivery within 7 days after study entry. RESULTS: We studied 350 women, of whom 69 (20%) delivered within 7 days. The risk of PTD in <7 days ranged from 2% in the lowest fFN group (<10 ng/ml) to 71% in the highest group (>500 ng/ml). Multivariable logistic regression showed an increasing risk of PTD in <7 days with rising fFN concentration [10-49 ng/ml: odds ratio (OR) 1.3, 95% confidence interval (95% CI) 0.23-7.0; 50-199 ng/ml: OR 3.2, 95% CI 0.79-13; 200-499 ng/ml: OR 9.0, 95% CI 2.3-35; >500 ng/ml: OR 39, 95% CI 9.4-164] and shortening of the CL (OR 0.86 per mm, 95% CI 0.82-0.90). Use of quantitative fFN instead of qualitative fFN resulted in reclassification of 18 (5%) women from high to low risk, of whom one (6%) woman delivered within 7 days. CONCLUSION: In symptomatic women, quantitative fFN testing does not improve the prediction of PTD within 7 days compared with qualitative fFN testing in combination with CL measurement in terms of reclassification from high to low (<5%) risk, but it adds value across the risk range. TWEETABLE ABSTRACT: Quantitative fFN testing adds value to qualitative fFN testing with CL measurement in the prediction of PTD.

Dilatation and curettage increases the risk of subsequent preterm birth: a systematic review and meta-analysis.

STUDY QUESTION: Could dilatation and curettage (D&C), used in the treatment of miscarriage and termination of pregnancy, increase the risk of subsequent preterm birth? SUMMARY ANSWER: A history of curettage in women is associated with an increased risk of preterm birth in a subsequent pregnancy compared with women without such history. WHAT IS KNOWN ALREADY: D&C is one of the most frequently performed procedures in obstetrics and gynaecology. Apart from the acknowledged but relatively rare adverse effects, such as cervical tears, bleeding, infection, perforation of the uterus, bowel or bladder, or Asherman syndrome, D&C has been suggested to also lead to an increased risk of preterm birth in the subsequent pregnancy. STUDY DESIGN, SIZE, DURATION: In the absence of randomized data, we conducted a systematic review and meta-analysis of cohort and case-control studies. PARTICIPANTS/MATERIALS, SETTING, METHODS: We searched OVID MEDLINE and OVID EMBASE form inception until 21 May 2014. We selected cohort and case-control studies comparing subsequent preterm birth in women who had a D&C for first trimester miscarriage or termination of pregnancy and a control group of women without a history of D&C. MAIN RESULTS AND THE ROLE OF CHANCE: We included 21 studies reporting on 1 853 017 women. In women with a history of D&C compared with those with no such history, the odds ratio (OR) for preterm birth <37 weeks was 1.29 (95% CI 1.17; 1.42), while for very preterm birth the ORs were 1.69 (95% CI 1.20; 2.38) for <32 weeks and 1.68 (95% CI 1.47; 1.92) for <28 weeks. The risk remained increased when the control group was limited to women with a medically managed miscarriage or induced abortion (OR 1.19, 95% CI 1.10; 1.28). For women with a history of multiple D&Cs compared with those with no D&C, the OR for preterm birth (<37 weeks) was 1.74 (95% CI 1.10; 2.76). For spontaneous preterm birth, the OR was 1.44 (95% CI 1.22; 1.69) for a history of D&C compared with no such history. LIMITATIONS, REASONS FOR CAUTION: There were no randomized controlled trials comparing women with and without a history of D&C and subsequent preterm birth. As a consequence, confounding may be present since the included studies were either cohort or case-control studies, not all of which corrected the results for possible confounding factors. WIDER IMPLICATIONS OF THE FINDINGS: This meta-analysis shows that D&C is associated with an increased risk of subsequent preterm birth. The increased risk in association with multiple D&Cs indicates a causal relationship. Despite the fact that confounding cannot be excluded, these data warrant caution in the use of D&C for miscarriage and termination of pregnancy, the more so since less invasive options are available. STUDY FUNDING/COMPETING INTERESTS: This study was funded by ZonMw, a Dutch organization for Health Research and Development, project number 80-82310-97-12066.

Does probability guided hysteroscopy reduce costs in women investigated for postmenopausal bleeding?

OBJECTIVE: To evaluate whether a model to predict a failed endometrial biopsy in women with postmenopausal bleeding (PMB) and a thickened endometrium can reduce costs without compromising diagnostic accuracy. DESIGN, SETTING, AND POPULATION: Model based cost-minimization analysis. METHODS: A decision analytic model was designed to compare two diagnostic strategies for women with PMB: (I) attempting office endometrial biopsy and performing outpatient hysteroscopy after failed biopsy and (II) predicted probability of a failed endometrial biopsy based on patient characteristics to guide the decision for endometrial biopsy or immediate hysteroscopy. Robustness of assumptions regarding costs was evaluated in sensitivity analyses. MAIN OUTCOME MEASURES: Costs for the different strategies. RESULTS: At different cut-offs for the predicted probability of failure of an endometrial biopsy, strategy I was generally less expensive than strategy II. The costs for strategy I were always € 460; the costs for strategy II varied between € 457 and € 475. At a 65% cut-off, a possible saving of € 3 per woman could be achieved. CONCLUSIONS: Individualizing the decision to perform an endometrial biopsy or immediate hysteroscopy in women presenting with postmenopausal bleeding based on patient characteristics does not increase the efficiency of the diagnostic work-up.

Economic analysis of use of pessary to prevent preterm birth in women with multiple pregnancy (ProTWIN trial).

OBJECTIVE: To assess the cost-effectiveness of a cervical pessary to prevent preterm delivery in women with a multiple pregnancy. METHODS: The study design comprised an economic analysis of data from a randomized clinical trial evaluating cervical pessaries (ProTWIN). Women with a multiple pregnancy were included and an economic evaluation was performed from a societal perspective. Costs were estimated between the time of randomization and 6 weeks postpartum. The prespecified subgroup of women with a cervical length (CL) < 25(th) centile (< 38 mm) was analyzed separately. The primary endpoint was poor perinatal outcome occurring up to 6 weeks postpartum. Direct medical costs and health outcomes were estimated and incremental cost-effectiveness ratios for costs to prevent one poor outcome were calculated. RESULTS: Mean costs in the pessary group (n = 401) were € 21,783 vs € 21,877 in the group in which no pessary was used (n = 407) (difference, -€ 94; 95% CI, -€ 5975 to € 5609). In the prespecified subgroup of women with a CL < 38 mm we demonstrated a significant reduction in poor perinatal outcome (12% vs 29%; RR, 0.40; 95% CI, 0.19-0.83). Mean costs in the pessary group (n = 78) were € 25,141 vs € 30,577 in the no-pessary group (n = 55) (difference, -€ 5436 (95% CI, -€ 11,001 to € 1456). In women with a CL < 38 mm, pessary treatment was the dominant strategy (more effective and less costly) with a probability of 94%. CONCLUSION: Cervical pessaries in women with a multiple pregnancy involve costs comparable to those in women without pessary treatment. However, in women with a CL < 38 mm, treatment with a cervical pessary appears to be highly cost-effective.

The additional value of blood cultures in patients with complicated urinary tract infections.

We evaluated 800 hospitalized patients with a complicated urinary tract infection, from whom both a blood and a urine culture were obtained on the first day of antibiotic treatment. Urine cultures were positive in 70% of patients, and blood cultures were positive in 29%. In 7% of patients, uropathogens caused bacteraemia with a pathogen that was not isolated from urine. Receiving antibiotic therapy at the moment of hospitalization was the only factor independently associated with discordant culture results (OR, 2.06; 95% CI, 1.18-3.61). For those receiving antibiotics at the moment of hospitalization, blood cultures have additional diagnostic value over urine cultures.