Six-Month Follow-up of a Trial of Spinal Cord Burst Stimulation vs Placebo Stimulation and Disability in Patients With Chronic Radicular Pain After Lumbar Spine Surgery.

This follow-up study examines back pain­related disability at 6 months following a randomized trial of spinal cord burst stimulation for chronic radicular pain after lumbar spine surgery.

Effect of Spinal Cord Burst Stimulation vs Placebo Stimulation on Disability in Patients With Chronic Radicular Pain After Lumbar Spine Surgery: A Randomized Clinical Trial.

Importance: The use of spinal cord stimulation for chronic pain after lumbar spine surgery is increasing, yet rigorous evidence of its efficacy is lacking. Objective: To investigate the efficacy of spinal cord burst stimulation, which involves the placement of an implantable pulse generator connected to electrodes with leads that travel into the epidural space posterior to the spinal cord dorsal columns, in patients with chronic radiculopathy after surgery for degenerative lumbar spine disorders. Design, Setting, and Participants: This placebo-controlled, crossover, randomized clinical trial in 50 patients was conducted at St Olavs University Hospital in Norway, with study enrollment from September 5, 2018, through April 28, 2021. The date of final follow-up was May 20, 2022. Interventions: Patients underwent two 3-month periods with spinal cord burst stimulation and two 3-month periods with placebo stimulation in a randomized order. Burst stimulation consisted of closely spaced, high-frequency electrical stimuli delivered to the spinal cord. The stimulus consisted of a 40-Hz burst mode of constant-current stimuli with 4 spikes per burst and an amplitude corresponding to 50% to 70% of the paresthesia perception threshold. Main Outcomes and Measures: The primary outcome was difference in change from baseline in the self-reported Oswestry Disability Index (ODI; range, 0 points [no disability] to 100 points [maximum disability]; the minimal clinically important difference was 10 points) score between periods with burst stimulation and placebo stimulation. The secondary outcomes were leg and back pain, quality of life, physical activity levels, and adverse events. Results: Among 50 patients who were randomized (mean age, 52.2 [SD, 9.9] years; 27 [54%] were women), 47 (94%) had at least 1 follow-up ODI score and 42 (84%) completed all stimulation randomization periods and ODI measurements. The mean ODI score at baseline was 44.7 points and the mean changes in ODI score were -10.6 points for the burst stimulation periods and -9.3 points for the placebo stimulation periods, resulting in a mean between-group difference of -1.3 points (95% CI, -3.9 to 1.3 points; P = .32). None of the prespecified secondary outcomes showed a significant difference. Nine patients (18%) experienced adverse events, including 4 (8%) who required surgical revision of the implanted system. Conclusions and Relevance: Among patients with chronic radicular pain after lumbar spine surgery, spinal cord burst stimulation, compared with placebo stimulation, after placement of a spinal cord stimulator resulted in no significant difference in the change from baseline in self-reported back pain-related disability. Trial Registration: ClinicalTrials.gov Identifier: NCT03546738.

Incidence and case fatality of aneurysmal subarachnoid hemorrhage admitted to hospital between 2008 and 2014 in Norway.

BACKGROUND: To provide age- and sex-specific incidence and case fatality rates for non-traumatic aneurysmal subarachnoid hemorrhage (aSAH) in Norway. We also studied time trends in incidence and case fatality, as well as predictors of death following aSAH. METHODS: A nationwide study using discharge data for patients admitted with aSAH between 2008 and 2014. RESULTS: A total of 1732 patients with aSAH were included. The mean age was 60 years (SD 14) and 63% were females. Crude annual incidence was 5.7 per 100,000 person-years (95% CI 5.4-6.0) and was higher in females (6.3 per 100,000, 95% CI 5.9-6.7) compared with males (4.9 per 100,000, 95% CI 4.5-5.3). The annual decline in aSAH incidence was 3.2% per year (p = 0.007). The cumulative proportions of fatalities at days 30, 90, and 1 year were 22%, 25%, and 37%, respectively. The 30-day mortality rate did not change during the study period. Age (HR 0.7-2.2) and aneurysms in the posterior circulation (HR 1.7, 95% CI 1.3-2.3, p = 0.001) were associated with higher 30-day case fatality following aSAH, while aneurysm repair (HR 0.2, 95% CI 0.2-0.3, p < 0.001) was associated with lower risk. CONCLUSIONS: The incidence of aSAH declined in Norway between 2008 and 2014. Case fatality following aSAH continues to be high, and the 30-day mortality during the study period was unchanged. Increasing age and aneurysms in the posterior circulation were associated with increased risk of death within 30 days following aSAH.

Metformin in Pregnancy Study (MiPS): protocol for a systematic review with individual patient data meta-analysis.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a common disorder of pregnancy and contributes to adverse pregnancy outcomes. Metformin is often used for the prevention and management of GDM; however, its use in pregnancy continues to be debated. The Metformin in Pregnancy Study aims to use individual patient data (IPD) meta-analysis to clarify the efficacy and safety of metformin use in pregnancy and to identify relevant knowledge gaps. METHODS AND ANALYSIS: MEDLINE, EMBASE and all Evidence-Based Medicine will be systematically searched for randomised controlled trials (RCT) testing the efficacy of metformin compared with placebo, usual care or other interventions in pregnant women. Two independent reviewers will assess eligibility using prespecified criteria and will conduct data extraction and quality appraisal of eligible studies. Authors of included trials will be contacted and asked to contribute IPD. Primary outcomes include maternal glycaemic parameters and GDM, as well as neonatal hypoglycaemia, anthropometry and gestational age at delivery. Other adverse maternal, birth and neonatal outcomes will be assessed as secondary outcomes. IPD from these RCTs will be harmonised and a two-step meta-analytic approach will be used to determine the efficacy and safety of metformin in pregnancy, with a priori adjustment for covariates and subgroups to examine effect moderators of treatment outcomes. Sensitivity analyses will assess heterogeneity, risk of bias and the impact of trials which have not provided IPD. ETHICS AND DISSEMINATION: All IPD will be deidentified and studies contributing IPD will have ethical approval from their respective local ethics committees. This study will provide robust evidence regarding the efficacy and safety of metformin use in pregnancy, and may identify subgroups of patients who may benefit most from this treatment modality. Findings will be published in peer-reviewed journals and disseminated at scientific meetings, providing much needed evidence to inform clinical and public health actions in this area.

Surgery for herniated lumbar disc in private vs public hospitals: A pragmatic comparative effectiveness study.

BACKGROUND: There is limited evidence on the comparative performance of private and public healthcare. Our aim was to compare outcomes following surgery for lumbar disc herniation (LDH) in private versus public hospitals. METHODS: Data were obtained from the Norwegian registry for spine surgery. Primary outcome was change in Oswestry disability index (ODI) 1 year after surgery. Secondary endpoints were quality of life (EuroQol EQ-5D), back and leg pain, complications, and duration of surgery and hospital stays. RESULTS: Among 5221 patients, 1728 in the private group and 3493 in the public group, 3624 (69.4%) completed 1-year follow-up. In the private group, mean improvement in ODI was 28.8 points vs 32.3 points in the public group (mean difference - 3.5, 95% CI - 5.0 to - 1.9; P for equivalence < 0.001). Equivalence was confirmed in a propensity-matched cohort and following mixed linear model analyses. There were differences in mean change between the groups for EQ-5D (mean difference - 0.05, 95% CI - 0.08 to - 0.02; P = 0.002) and back pain (mean difference - 0.2, 95% CI - 0.2, - 0.4 to - 0.004; P = 0.046), but after propensity matching, the groups did not differ. No difference was found between the two groups for leg pain. Complication rates was lower in the private group (4.5% vs 7.2%; P < 0.001), but after propensity matching, there was no difference. Patients operated in private clinics had shorter duration of surgery (48.4 vs 61.8 min) and hospital stay (0.7 vs 2.2 days). CONCLUSION: At 1 year, the effectiveness of surgery for LDH was equivalent in private and public hospitals.

Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have an increased risk of pregnancy complications. Epi-analysis of two previous randomised controlled trials that compared metformin with placebo during pregnancy in women with PCOS showed a significant reduction in late miscarriages and preterm births in the metformin group. The aim of this third randomised trial (PregMet2) was to test the hypothesis that metformin prevents late miscarriage and preterm birth in women with PCOS. METHODS: PregMet2 was a randomised, placebo-controlled, double-blind, multicentre trial done at 14 hospitals in Norway, Sweden, and Iceland. Singleton pregnant women with PCOS aged 18-45 years were eligible for inclusion. After receiving information about the study at their first antenatal visit or from the internet, women signed up individually to participate in the study. Participants were randomly assigned (1:1) to receive metformin or placebo by computer-generated random numbers. Randomisation was in blocks of ten for each country and centre; the first block had a random size between one and ten to assure masking. Participants were assigned to receive oral metformin 500 mg twice daily or placebo during the first week of treatment, which increased to 1000 mg twice daily or placebo from week 2 until delivery. Placebo tablets and metformin tablets were identical and participants and study personnel were masked to treatment allocation. The primary outcome was the composite incidence of late miscarriage (between week 13 and week 22 and 6 days) and preterm birth (between week 23 and week 36 and 6 days), analysed in the intention-to-treat population. Secondary endpoints included the incidence of gestational diabetes, preeclampsia, pregnancy-induced hypertension, and admission of the neonate to the neonatal intensive care unit. We also did a post-hoc individual participant data analysis of pregnancy outcomes, pooling data from the two previous trials with the present study. The study was registered with ClinicalTrials.gov, number NCT01587378, and EudraCT, number 2011-002203-15. FINDINGS: The study took place between Oct 19, 2012, and Sept 1, 2017. We randomly assigned 487 women to metformin (n=244) or placebo (n=243). In the intention-to-treat analysis, our composite primary outcome of late miscarriage and preterm birth occurred in 12 (5%) of 238 women in the metformin group and 23 (10%) of 240 women in the placebo group (odds ratio [OR] 0·50, 95% CI 0·22-1·08; p=0·08). We found no significant differences for our secondary endpoints, including incidence of gestational diabetes (60 [25%] of 238 women in the metformin group vs 57 [24%] of 240 women in the placebo group; OR 1·09, 95% CI 0·69-1·66; p=0·75). We noted no substantial between-group differences in serious adverse events in either mothers or offspring, and no serious adverse events were considered drug-related by principal investigators. In the post-hoc pooled analysis of individual participant data from the present trial and two previous trials, 18 (5%) of 397 women had late miscarriage or preterm delivery in the metformin group compared with 40 (10%) of 399 women in the placebo group (OR 0·43, 95% CI 0·23-0·79; p=0·004). INTERPRETATION: In pregnant women with PCOS, metformin treatment from the late first trimester until delivery might reduce the risk of late miscarriage and preterm birth, but does not prevent gestational diabetes. FUNDING: Research Council of Norway, Novo Nordisk Foundation, St Olav's University Hospital, and Norwegian University of Science and Technology.

Intrauterine metformin exposure and offspring cardiometabolic risk factors (PedMet study): a 5-10 year follow-up of the PregMet randomised controlled trial.

BACKGROUND: Metformin is increasingly used to treat gestational diabetes and type 2 diabetes in pregnancy, and in attempts to improve pregnancy outcomes in polycystic ovary syndrome and obesity. It passes across the placenta with possible long-term consequences for the offspring. We previously explored the effect of metformin, given to women with polycystic ovary syndrome during pregnancy, on children's growth up to 4 years of age. In this 5-10 year follow-up, we examined the cardiometabolic risk factors in these children. METHODS: This is a follow-up of children from the PregMet study, a double-blind, randomised controlled trial comparing metformin with placebo in polycystic ovary syndrome pregnancies. In the PregMet study, between Feb 4, 2005, and Jan 27, 2009, 257 pregnant women aged 18-45 years with polycystic ovary syndrome according to the Rotterdam criteria were included with 274 singleton pregnancies at 5-12 weeks of gestation at 11 study centres in Norway. 17 women participated twice. Pregnant women were randomised to metformin (2000 mg/day) or placebo from inclusion in the first trimester to birth. Randomisation was stratified according to metformin use at conception. In this follow-up, the primary endpoint was body-mass index (BMI) in the offspring at 5-10 years of age assessed by the standard deviation score (Z score). The primary endpoint was analysed with independent sample t tests. ClinicalTrials.gov number NCT00159536. FINDINGS: Of the 255 invited children from the PregMet study, 141 (55%) consented to participate and were included between April 29, 2014, and July 12, 2016. Maternal baseline characteristics in the first trimester were similar between groups. Children in the metformin group had a higher BMI Z score than those in the placebo group (difference in means=0·41, 95% CI 0·03-0·78, p=0·03). INTERPRETATION: The increased BMI in metformin-exposed children might indicate a potential risk of inferior cardiometabolic health. Implications for adult health cannot be excluded. FUNDING: The Research Council of Norway, Novo Nordisk Foundation, St Olavs University Hospital, and the Norwegian University of Science and Technology.

Uterine Artery Doppler in Pregnancy: Women with PCOS Compared to Healthy Controls.

The objective of this study was to investigate possible differences in uterine artery pulsatility index (UtAPI) between pregnant women with PCOS and healthy controls and to explore possible effects of metformin on UtAPI. Material and Methods. The study was conducted in a tertiary center. Forty-eight pregnant women diagnosed with PCOS before pregnancy and 124 healthy pregnant women were included. Women with PCOS were randomly assigned to metformin 2000 mg daily or a placebo. UtAPI was measured five times during 1st and 2nd trimesters of pregnancy in women with PCOS and four times in healthy controls. Results. There was no difference in UtAPI between PCOS women and healthy controls at any point in time (p = 0.34-0.77). In women with PCOS, randomly assigned to metformin 2000 mg or placebo, UtAPI was unaffected by metformin two hours after intake of the first dose of study medication (p = 0.34). All PCOS women, regardless of randomization, had higher UtAPI two hours after intake of study medication and a meal compared to before a meal (p = 0.02). Conclusions. In the first and second trimesters of pregnancy, there was no difference in UtAPI between women with PCOS and healthy controls. Metformin had no immediate effect on the UtAPI. Interestingly, blood flow decreased after a meal, suggesting that time since last meal should be taken into consideration when interpreting the results of UtAPI measurements in pregnancy. This trial is registered with ClinicalTrials.gov (NCT00466622) Metformin in Pregnant PCOS women (PregMet) (NCT00159536).

Risk of intracranial hemorrhage (RICH) in users of oral antithrombotic drugs: Nationwide pharmacoepidemiological study.

BACKGROUND: The risks of intracranial haemorrhage (ICH) associated with antithrombotic drugs outside clinical trials are gaining increased attention. The aim of this nationwide study was to investigate the risk of ICH requiring hospital admission in users of antithrombotic drugs. METHODS AND FINDINGS: Data from the Norwegian Patient Registry and Norwegian Prescription Database were linked on an individual level. The primary outcome was incidence rates of ICH associated with use of antithrombotic drugs. Secondary endpoints were risk of ICH and fatal outcome following ICH assessed by Cox models. Among 3,131,270 individuals ≥18 years old observed from 2008 through 2014, there were 729,818 users of antithrombotic medications and 22,111 ICH hospitalizations. Annual crude ICH rates per 100 person-years were 0.076 (95% CI, 0.075-0.077) in non-users and 0.30 (95% CI, 0.30-0.31) in users of antithrombotic medication, with the highest age and sex adjusted rates observed for aspirin-dipyridamole plus clopidogrel (0.44; 95% CI, 0.19-0.69), rivaroxaban plus aspirin (0.36; 95% CI, 0.16-0.56), warfarin plus aspirin (0.34; 95% CI, 0.26-0.43), and warfarin plus aspirin and clopidogrel (0.33; 95% CI, 0.073-0.60). With no antithrombotic medication as reference, the highest adjusted hazard ratios (HR) for ICH were observed for aspirin-dypiridamole plus clopidogrel (6.29; 95% CI 3.71-10.7), warfarin plus aspirin and clopidogrel (4.38; 95% CI 2.71-7.09), rivaroxaban plus aspirin (3.82; 95% CI, 2.46-5.95), and warfarin plus aspirin (3.40; 95% CI, 2.99-3.86). All antithrombotic medication regimens were associated with an increased risk of ICH, except dabigatran monotherapy (HR 1.20; 95% CI, 0.88-1.65) and dabigatran plus aspirin (HR 1.79; 95% CI, 0.96-3.34). Fatal outcome within 90 days was more common in users (2,603 of 8,055) than non-users (3,228 of 14,056) of antithrombotic medication (32.3% vs 23.0%, p<0.001), and was associated with use of warfarin plus aspirin and clopidogrel (HR 2.89; 95% CI, 1.49-5.60), warfarin plus aspirin (HR 1.37; 95% CI, 1.11-1.68), aspirin plus clopidogrel (HR 1.30; 95% CI, 1.05-1.61), and warfarin (HR 1.19; 95% CI, 1.09-1.31). Increased one-year mortality was observed in users of antithrombotic medication following hemorrhagic stroke, subdural hemorrhage, subarachnoid hemorrhage, and traumatic ICH (all p<0.001). Limitations include those inherent to observational studies including the inability to make causal inferences, certain assumptions regarding drug exposure, and the possibility of residual confounding. CONCLUSIONS: The real-world incidence rates and risks of ICH were generally higher than reported in randomized controlled trials. There is still major room for improvement in terms of antithrombotic medication safety (clinicaltrials.gov NCT02481011).

Metformin Use in PCOS Pregnancies Increases the Risk of Offspring Overweight at 4 Years of Age: Follow-Up of Two RCTs.

Context: Metformin is used in pregnancy in women with gestational diabetes mellitus, polycystic ovary syndrome (PCOS), and obesity. Metformin passes the placenta. Objective: To explore the effects of metformin use in PCOS pregnancies on offspring growth to 4 years of age. Design: Follow-up study of two randomized, double-blind, placebo-controlled trials. Setting: Secondary care centers. Eleven public hospitals in Norway. Participants: One hundred eighty-two children of mothers with PCOS who participated in two randomized controlled trials. Intervention: Metformin 1700 or 2000 mg/d or placebo from first trimester to delivery in the original studies. No intervention in the current study. Main Outcome Measures: Height, weight, body mass index (BMI), and overweight/obesity at 4 years of age and head circumference at 1 year of age, converted to z scores. Results: The difference in height z score means between the groups at 4 years of age was nonsignificant (0.07 [95% confidence interval (CI): -0.22 to 0.36]; P = 0.651). At 4 years of age, the metformin group had higher weight z score than the placebo group [difference in means: 0.38 (0.07 to 0.69); P = 0.017] and higher BMI z score [difference in means: 0.45 (0.11 to 0.78); P = 0.010]. There were more overweight/obese children in the metformin group [26 (32%)] than in the placebo group [14 (18%)] at 4 years of age [odds ratio: 2.17 (1.04 to 4.61); P = 0.038]. The difference in mean head circumference z score at 1 year of age was 0.27 (-0.04 to 0.58; P = 0.093). Conclusion: Metformin-exposed children had higher BMI and increased prevalence of overweight/obesity at 4 years of age.

Uterine artery Doppler measurements during first and second trimesters of normal pregnancy.

INTRODUCTION: The aim of this study was to construct a reference curve based on longitudinal Doppler blood flow measurements of the uterine artery during the first and second trimesters of normal pregnancy. MATERIAL AND METHODS: Healthy pregnant women (n = 124) between 18 and 38 years of age were included. The uterine artery pulsatility index (UtAPI) was measured with transvaginal ultrasound in the first trimester (gestational weeks 8-10 and 11-13) and with transabdominal ultrasound in the second trimester (gestational weeks 18 and 24). Individual longitudinal curves were constructed and a reference curve was created. RESULTS: A centile curve with the normal distribution of the UtAPI during the first and second trimesters was constructed. We found that 90% of the women alternated between quartiles during the four examinations between gestational weeks 8 and 24, but 75% remained within the higher or lower range. CONCLUSIONS: A UtAPI reference curve was constructed for the first and second trimesters of pregnancy. Although the mean UtAPI values may vary from one examination to the next, most mean UtAPI values remain within the higher or lower range, i.e. above or below the 50th centile.

Open discectomy vs microdiscectomy for lumbar disc herniation - a protocol for a pragmatic comparative effectiveness study.

Introduction:  Since the introduction of lumbar microdiscectomy in the 1970's, many studies have attempted to compare the effectiveness of this method with that of standard open discectomy with conflicting results. This observational study is designed to compare the relative effectiveness of microdiscectomy (MD) with open discectomy (OD) for treating lumbar disc herniation, -within a large cohort, recruited from daily clinical practice. Methods and analysis:   This study will include patients registered in the Norwegian Registry for Spine Surgery (NORspine). This clinical registry collects prospective data, including preoperative and postoperative outcome measures as well as individual and demographic parameters. The primary outcome is change in Oswestry disability index between baseline and 12 months after surgery. Secondary outcome measures are improvement of leg pain and changes in health related quality of life measured by the Euro-Qol-5D between baseline and 12 months after surgery, complications to surgery, duration of surgical procedures and length of hospital stay.

Impact of sex and age on the performance of FINDRISC: the HUNT Study in Norway.

OBJECTIVE: The Finnish Diabetes Risk Score (FINDRISC) is recommended as a screening tool for diabetes risk. However, there is a lack of well-powered studies examining the performance of FINDRISC by sex and age. We aim to estimate, by sex and age, the prevalence of elevated FINDRISC and positive predictive value (PPV) of FINDRISC for identifying impaired glucose metabolism (IGM) in a general Norwegian population. RESEARCH DESIGN AND METHODS: We estimated the prevalence of elevated FINDRISC (≥15) among 47 694 adults in the third survey of the Nord-Trøndelag Health Study (HUNT3, 2006-08). Among 2559 participants who participated in oral glucose tolerance testing, we estimated the PPV of elevated FINDRISC for identifying unknown prevalent diabetes and other forms of IGM. RESULTS: The prevalence of elevated FINDRISC was 12.1% in women, 9.6% in men, and increased from 1.5% at age 20-39 to 25.1% at age 70-79 years. The PPVs of elevated FINDRISC were 9.8% for diabetes, 16.9% for impaired glucose tolerance, 8.2% for impaired fasting glucose, and 34.9% for any form of IGM. The PPV for IGM was lower in women (31.2%) than in men (40.4%), and increased from 19.1% at age 20-39 to 55.5% at age ≥80 years. CONCLUSIONS: FINDRISC identified more women than men as high-risk individuals for diabetes. FINDRISC had a high PPV for detecting prevalent IGM, and the PPV was higher in men than in women and in the older individuals. Our data indicate that the impact of sex and age on diabetes risk is not fully captured by FINDRISC, and that refinements to it might improve diabetes prediction.

Cervical Length and Androgens in Pregnant Women With Polycystic Ovary Syndrome: Has Metformin Any Effect?

CONTEXT: Women with polycystic ovary syndrome (PCOS) have increased risk of preterm delivery. Shortening of the cervix is a sign of preterm delivery. OBJECTIVE: This study aimed to investigate potential effect of metformin on cervical length and whether androgen levels correlate with cervical length in PCOS pregnancies. DESIGN AND SETTING: This was a sub-study of a randomized, placebo-controlled, multicenter study (The PregMet study) performed at 11 secondary or tertiary centers from 2005 to 2009. PARTICIPANTS: Two-hundred sixty-one pregnancies of 245 women with PCOS, age 18-42 years participated. INTERVENTIONS: Participants were randomly assigned to metformin or placebo from first trimester to delivery. OUTCOME MEASUREMENTS: We compared cervical length and androgen levels in metformin and placebo groups at gestational weeks 19 and 32. We also explored whether cervical length correlated with androgen levels. RESULTS: We found no difference in cervical length between the metformin and the placebo groups at gestational week 19 and 32. Dehydroepiandrosterone (DHEAS) tended to be higher in the metformin group. There were no correlations between androgens and cervical length at week 19. At gestational week 32, androstenedione (P = .02) and DHEAS (P = .03) showed a trend toward negative correlation to cervical length. High androstenedione level correlated with shortening of cervical length from week 19 to 32 when adjusted for confounders (P = .003). T (P = .03), DHEAS (P = .02), and free testosterone index (P = .03) showed a similar trend. CONCLUSION: Metformin in pregnancy did not affect cervical length in women with PCOS. High maternal androgen levels correlated with cervical shortening from the second to the third trimester of pregnancy, as a sign of cervical ripening.

Does AMH Reflect Follicle Number Similarly in Women with and without PCOS?

CONTEXT: Increased Anti-Mullerian Hormone in polycystic ovary syndrome, may be due to overactive follicles rather than reflect antral follicle count. OBJECTIVE: Does Anti-Mullerian Hormone reflect antral follicle count similarly in women with or without polycystic ovary syndrome or polycystic ovarian morphology? DESIGN: Cross-sectional, case-control. SETTING: Women who delivered preterm in 1999-2006. For each index woman, a woman with a term delivery was identified. PATIENTS: Participation rate was 69%. Between 2006-2008, 262 women were included, and diagnosed to have polycystic ovary syndrome, polycystic ovarian morphology or to be normal controls. INTERVENTION(S): Blood tests, a clinical examination and vaginal ultrasound. MAIN OUTCOME MEASURE(S): Anti-Mullerian Hormone/antral follicle count-ratio, SHBG, androstenedione and insulin, to test potential influence on the Anti-Mullerian Hormone/antral follicle count -ratio. RESULTS: Mean Anti-Mullerian Hormone/antral follicle count ratio in women with polycystic ovary syndrome or polycystic ovarian morphology was similar to that of the controls (polycystic ovary syndrome: 1,2 p = 0,10 polycystic ovarian morphology: 1,2, p = 0,27 Controls 1,3). Anti-Mullerian Hormone showed a positive linear correlation to antral follicle count in all groups. Multivariate analysis did not change the results. CONCLUSIONS: We confirmed the positive correlation between AMH and follicle count. Anti-Mullerian Hormone seems to be a reliable predictor of antral follicle count, independent of polycystic ovary syndrome diagnosis or ovarian morphology.

Minimally invasive decompression versus open laminectomy for central stenosis of the lumbar spine: pragmatic comparative effectiveness study.

OBJECTIVE: To test the equivalence for clinical effectiveness between microdecompression and laminectomy in patients with central lumbar spinal stenosis. DESIGN: Multicentre observational study. SETTING: Prospective data from the Norwegian Registry for Spine Surgery. PARTICIPANTS: 885 patients with central stenosis of the lumbar spine who underwent surgery at 34 Norwegian orthopaedic or neurosurgical departments. Patients were treated from October 2006 to December 2011. INTERVENTIONS: Laminectomy and microdecompression. MAIN OUTCOME MEASURES: The primary outcome was change in Oswestry disability index score one year after surgery. Secondary endpoints were quality of life (EuroQol EQ-5D), perioperative complications, and duration of surgical procedures and hospital stays. A blinded biostatistician performed predefined statistical analyses in unmatched and propensity matched cohorts. RESULTS: The study was powered to detect a difference between the groups of eight points on the Oswestry disability index at one year. 721 patients (81%) completed the one year follow-up. Equivalence between microdecompression and laminectomy was shown for the Oswestry disability index (difference 1.3 points, 95% confidence interval -1.36 to 3.92, P<0.001 for equivalence). Equivalence was confirmed in the propensity matched cohort and full information regression analyses. No difference was found between groups in quality of life (EQ-5D) one year after surgery. The number of patients with complications was higher in the laminectomy group (15.0% v 9.8%, P=0.018), but after propensity matching for complications the groups did not differ (P=0.23). The duration of surgery for single level decompression was shorter in the microdecompression group (difference 11.2 minutes, 95% confidence interval 4.9 to 17.5, P<0.001), but after propensity matching the groups did not differ (P=0.15). Patients in the microdecompression group had shorter hospital stays, both for single level decompression (difference 1.5 days, 95% confidence interval 1.7 to 2.6, P<0.001) and two level decompression (0.8 days, 1.0 to 2.2, P=0.003). CONCLUSION: At one year the effectiveness of microdecompression is equivalent to laminectomy in the surgical treatment of central stenosis of the lumbar spine. Favourable outcomes were observed at one year in both treatment groups.Trial registration ClinicalTrials.gov NCT02006901.

Risk of intracranial hemorrhage in users of oral antithrombotic drugs: Study protocol for a nationwide study.

Background A wide range of antithrombotic medications can be used in the prevention and treatment of thrombosis. Among hemorrhagic complications of antithrombotic drugs, intracranial hemorrhage may have particularly devastating consequences with high morbidity, disability and mortality rates. The incidence and risks of intracranial hemorrhage in patients on antithrombotic treatments from regular clinical practice outside clinical trials remain largely unknown. It is not known if results from clinical trials can be extrapolated to everyday clinical practice. We will conduct a nationwide study to investigate the risks and incidence rates of intracranial hemorrhage in users oral antithrombotic drugs in Norway from 2008 through 2014.   Methods and design The aim of this nationwide study is to investigate the incidence rates of intracranial hemorrhage requiring hospitalization in users of oral antithrombotic drugs. The study will be conducted within the approximately 4.7 million inhabitants of Norway from January 1 (st), 2008, to December 31 (st), 2014. Treatment and outcome data are obtained from the Norwegian patient registry and the Norwegian prescription database.   Trial registration number Clinicaltrials.gov (NCT02481011).

Gestational diabetes mellitus among Nordic Caucasian women: prevalence and risk factors according to WHO and simplified IADPSG criteria.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with both maternal and offspring adverse effects. The World Health Organization (WHO) has recently adopted novel GDM criteria. The aim of this study was to evaluate the former WHO and a simplified version of the new International Association for Diabetes in Pregnancy Study Group (IADPSG) criteria as to prevalence of and risk factors for GDM in a Nordic Caucasian population. METHODS: A 75 g oral glucose tolerance test was performed in 687 women at 18-22 and 32-36 pregnancy weeks. GDM was defined according to the WHO criteria as fasting plasma glucose ≥ 7.0 mmol/L and/or 2-hour plasma glucose ≥ 7.8 mmol/L and by a simplified version of the IADPSG criteria as either fasting glucose ≥ 5.1 mmol/L and/or 2-h plasma glucose ≥ 8.5 mmol/L. One-hour glucose values were not available and were thus not included in the diagnosis of GDM by IADPSG. Prevalence of GDM during pregnancy and risk factors for GDM at 18-22 weeks were studied in retrospect according to each of the two criteria. RESULTS: The total prevalence of GDM during pregnancy was 6.1% (42/687) for the WHO criteria and 7.4% (51/687) for the simplified IADPSG criteria. High maternal age and short stature were independently associated with WHO GDM. Maternal age, fasting insulin and no regular exercise at 18-22 pregnancy weeks associated with simplified IADPSG GDM. CONCLUSIONS: Simplified IADPSG criteria moderately increase GDM prevalence compared with the WHO criteria. Risk factors for GDM differ with the diagnostic criteria used.

Comparative effectiveness of microdecompression and laminectomy for central lumbar spinal stenosis: study protocol for an observational study.

INTRODUCTION: This observational study is designed to test the equivalence between the clinical effectiveness of microdecompression and laminectomy in the surgical treatment of central lumbar spinal stenosis. Lumbar spinal stenosis is the most frequent indication for spinal surgery in the elderly, and as the oldest segment of the population continues to grow its prevalence is likely to increase. However, data on surgical outcomes are limited. Open or wide decompressive laminectomy, often combined with medial facetectomy and foraminotomy, was formerly the standard treatment. In recent years a growing tendency towards less invasive decompressive procedures has emerged. At present, many spine surgeons perform microdecompression for central lumbar spinal stenosis. METHODS AND ANALYSIS: Prospectively registered treatment and outcome data are obtained from the Norwegian Registry for Spine Surgery. The primary outcome measure is change in Oswestry disability index between baseline and 12-month follow-up. Secondary outcome measures are changes in health-related quality of life measured by the Euro-Qol-5D between baseline and 12-month follow-up, perioperative complications, and duration of surgical procedures and length of hospital stay. ETHICS AND DISSEMINATION: The study has been evaluated and approved by the regional committee for medical research in central Norway and all participants provided written informed consent. The findings of this study will be disseminated through peer-reviewed publications. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov (NCT02006901).

Maternal and fetal insulin levels at birth in women with polycystic ovary syndrome: data from a randomized controlled study on metformin.

CONTEXT: Metformin is suggested to reduce pregnancy complications in women with polycystic ovary syndrome (PCOS). Metformin crosses the placenta and therapeutic concentrations are measured in the fetal circulation. Whether metformin treatment in pregnant PCOS women affects maternal and fetal insulin concentrations at birth is not clarified. OBJECTIVES: To investigate the possible effect of metformin on insulin concentrations in umbilical cord blood and the possible association between maternal and fetal insulin concentrations. DESIGN: Post-hoc analysis of a subgroup of PCOS women participating in a double-blind randomized controlled trial. SETTING: University hospital setting. PARTICIPANTS: Women with PCOS (n=118), aged 19-39 years. MAIN OUTCOME MEASURES: Maternal and umbilical cord insulin concentrations immediately after birth. RESULTS: At delivery women randomized to metformin had lower insulin concentrations than those randomized to placebo (259±209 vs 361±261 pmol/l; P=0.020). No difference was found in insulin concentrations in umbilical venous (P=0.95) and arterial (P=0.39) blood between the metformin and placebo groups. The arteriovenous difference was also equal between the groups (P=0.38). Insulin concentrations were higher in the umbilical vein than in the umbilical artery independent of randomization (70±51 vs 45±48 pmol/l; P<0.0005). CONCLUSIONS: In PCOS, metformin treatment during pregnancy resulted in lower maternal insulin concentrations at delivery. Metformin treatment did not affect fetal insulin concentrations. Higher insulin concentrations in the umbilical vein indicate that the placenta somehow secretes insulin to the fetus. The possibility of placental insulin secretion to the fetus deserves further investigations.