Abstract
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.
The effects of metformin use in PCOS pregnancies on offspring growth were examined. At 4 years of age, more children were overweight/obese in the metformin group compared with the placebo group.
Abstract
BACKGROUND
Indications and optimal timing for surgical treatment of degenerative cervical myelopathy (DCM) remain unclear, and data from daily clinical practice are warranted.
OBJECTIVE
To ...investigate clinical outcomes following decompressive surgery for DCM.
METHODS
Data were obtained from the Norwegian Registry for Spine Surgery. The primary outcome was change in the neck disability index (NDI) 1 yr after surgery. Secondary endpoints were the European myelopathy score (EMS), quality of life (EuroQoL 5D EQ-5D), numeric rating scales (NRS) for headache, neck pain, and arm pain, complications, and perceived benefit of surgery assessed by the Global Perceived Effect (GPE) scale.
RESULTS
We included 905 patients operated between January 2012 and June 2018. There were significant improvements in all patient-reported outcome measures (PROMs) including NDI (mean −10.0, 95% CI −11.5 to −8.4, P < .001), EMS (mean 1.0, 95% CI 0.8-1.1, P < .001), EQ-5D index score (mean 0.16, 95% CI 0.13-0.19, P < .001), EQ-5D visual analogue scale (mean 13.8, 95% CI 11.7-15.9, P < .001), headache NRS (mean −1.1, 95% CI −1.4 to −0.8, P < .001), neck pain NRS (mean −1.8, 95% CI −2.0 to −1.5, P < .001), and arm pain NRS (mean −1.7, 95% CI −1.9 to −1.4, P < .001). According to GPE scale assessments, 229/513 patients (44.6%) experienced “complete recovery” or felt “much better” at 1 yr. There were significant improvements in all PROMs for both mild and moderate-to-severe DCM. A total of 251 patients (27.7%) experienced adverse effects within 3 mo.
CONCLUSION
Surgery for DCM is associated with significant and clinically meaningful improvement across a wide range of PROMs.
Graphical Abstract
Graphical Abstract
Prospective pharmacoepidemiologic study.
To investigate clinical and sociodemographic factors associated with persistent opioid use in the years following spine surgery among patients with persistent ...opioid use preceding lumbar spine surgery.
It is unknown whether successful spine surgery leads to a cessation of preoperative persistent opioid use.
Data from the Norwegian Registry for Spine Surgery and the Norwegian Prescription Database were linked for patients operated for degenerative lumbar spine disorders between 2007 and 2017. The primary outcome measure was persistent opioid use in the second year after surgery. Functional disability was measured with the Oswestry Disability Index (ODI). Factors associated with persistent opioid use in the year before, and two years following, surgery were identified using multivariable logistic regression analysis. The variables included in the analysis were selected based on their demonstrated role in prior studies.
The prevalence of persistent opioid use was 8.7% in the year before surgery. Approximately two-thirds of patients also met the criteria for persistent opioid use the second year after surgery. Among patients who did not meet the criteria for persistent opioid use the year before surgery, 991 (3.3%) patients developed persistent opioid use in the second year following surgery. The strongest association was exhibited by high doses of benzodiazepines in the year preceding surgery (OR 1.7, 95% CI 1.26 to 2.19, P <0.001). Among patients without persistent opioid use, the most influential factor associated with new-onset persistent opioid use in the second year after surgery was the use of high doses of benzodiazepines (OR 1.8, 95% CI 1.26 to 2.44, P <0.001), high doses of z -hypnotics (OR 2.6, 95% CI 2.10 to 3.23, P <0.001) and previous surgery at the same lumbar level (OR 1.37, 95% CI 1.11 to 1.68, P =0.003).
A substantial proportion of patients reported sustained opioid use after surgery. Patients with persistent opioid use before surgery should be supported to taper off opioid treatment. Special efforts appear to be required to taper off opioid use in patients using high doses of benzodiazepines.
2; Prospective observational study.
Background
In endometrial cancer (EC), preoperative pelvic MRI is recommended for local staging, while final tumor stage and grade are established by surgery and pathology. MRI‐based radiomic tumor ...profiling may aid in preoperative risk‐stratification and support clinical treatment decisions in EC.
Purpose
To develop MRI‐based whole‐volume tumor radiomic signatures for prediction of aggressive EC disease.
Study Type
Retrospective.
Population
A total of 138 women with histologically confirmed EC, divided into training (nT = 108) and validation cohorts (nV = 30).
Field Strength/Sequence
Axial oblique T1‐weighted gradient echo volumetric interpolated breath‐hold examination (VIBE) at 1.5T (71/138 patients) and DIXON VIBE at 3T (67/138 patients) at 2 minutes postcontrast injection.
Assessment
Primary tumors were manually segmented by two radiologists with 4 and 8 years' of experience. Radiomic tumor features were computed and used for prediction of surgicopathologically‐verified deep (≥50%) myometrial invasion (DMI), lymph node metastases (LNM), advanced stage (FIGO III + IV), nonendometrioid (NE) histology, and high‐grade endometrioid tumors (E3). Corresponding analyses were also conducted using radiomics extracted from the axial oblique image slice depicting the largest tumor area.
Statistical Tests
Logistic least absolute shrinkage and selection operator (LASSO) was applied for radiomic modeling in the training cohort. The diagnostic performances of the radiomic signatures were evaluated by area under the receiver operating characteristic curve in the training (AUCT) and validation (AUCV) cohorts. Progression‐free survival was assessed using the Kaplan–Meier and Cox proportional hazard model.
Results
The whole‐tumor radiomic signatures yielded AUCT/AUCV of 0.84/0.76 for predicting DMI, 0.73/0.72 for LNM, 0.71/0.68 for FIGO III + IV, 0.68/0.74 for NE histology, and 0.79/0.63 for high‐grade (E3) tumor. Single‐slice radiomics yielded comparable AUCT but significantly lower AUCV for LNM and FIGO III + IV (both P < 0.05). Tumor volume yielded comparable AUCT to the whole‐tumor radiomic signatures for prediction of DMI, LNM, FIGO III + IV, and NE, but significantly lower AUCT for E3 tumors (P < 0.05). All of the whole‐tumor radiomic signatures significantly predicted poor progression‐free survival with hazard ratios of 4.6–9.8 (P < 0.05 for all).
Data Conclusion
MRI‐based whole‐tumor radiomic signatures yield medium‐to‐high diagnostic performance for predicting aggressive EC disease. The signatures may aid in preoperative risk assessment and hence guide personalized treatment strategies in EC.
Level of Evidence
4
Technical Efficacy Stage
2
To investigate the effect of an academic detailing intervention on the utilisation of type 2 diabetes medication among general practitioners.
We developed an academic detailing campaign based on the ...revised national treatment guideline for diabetes and the best available evidence. General practitioners were offered a 20-minute one-to-one visit by a trained academic detailer.
A total of 371 general practitioners received a visit and represented the intervention group. The control group consisted of 1282 general practitioners not receiving a visit.
Changes in prescribing from 12 months before to 12 months after the intervention. The primary endpoint was a change in metformin. Secondary endpoints were changes in other groups of Type 2 diabetes medication and of these drugs in total.
Prescribing of metformin increased by 7.4% in the intervention group and 5.2% in the control group (p = .043). Sodium-glucose cotransporter-2 inhibitors increased by 27.6% in the intervention group and 33.8% in the control group (p = .019). For sulfonylureas there was a decrease of 3.6% in the intervention group vs. 8.9% in the control group (p = .026). The total amount of prescribed medications for type 2 diabetes increased by 9.1% in the intervention group and 7.3% in the control group (p = .08).
Academic detailing initiated a small but statistically significant increase in the prescription of metformin. For a complex subject like type 2 diabetes, we recommend reserving more time in the visit than the 20 min our campaign aimed for.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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
Preoperative MR imaging in endometrial cancer patients provides valuable information on local tumor extent, which routinely guides choice of surgical procedure and adjuvant therapy. Furthermore, ...whole-volume tumor analyses of MR images may provide radiomic tumor signatures potentially relevant for better individualization and optimization of treatment. We apply a convolutional neural network for automatic tumor segmentation in endometrial cancer patients, enabling automated extraction of tumor texture parameters and tumor volume. The network was trained, validated and tested on a cohort of 139 endometrial cancer patients based on preoperative pelvic imaging. The algorithm was able to retrieve tumor volumes comparable to human expert level (likelihood-ratio test, Formula: see text). The network was also able to provide a set of segmentation masks with human agreement not different from inter-rater agreement of human experts (Wilcoxon signed rank test, Formula: see text, Formula: see text, and Formula: see text). An automatic tool for tumor segmentation in endometrial cancer patients enables automated extraction of tumor volume and whole-volume tumor texture features. This approach represents a promising method for automatic radiomic tumor profiling with potential relevance for better prognostication and individualization of therapeutic strategy in endometrial cancer.
Purpose
Previous studies on the effect of tumor location on overall survival in glioblastoma have found conflicting results. Based on statistical maps, we sought to explore the effect of tumor ...location on overall survival in a population-based cohort of patients with glioblastoma and
IDH
wild-type astrocytoma WHO grade II–III with radiological necrosis.
Methods
Patients were divided into three groups based on overall survival: < 6 months, 6–24 months, and > 24 months. Statistical maps exploring differences in tumor location between these three groups were calculated from pre-treatment magnetic resonance imaging scans. Based on the results, multivariable Cox regression analyses were performed to explore the possible independent effect of centrally located tumors compared to known prognostic factors by use of distance from center of the third ventricle to contrast-enhancing tumor border in centimeters as a continuous variable.
Results
A total of 215 patients were included in the statistical maps. Central tumor location (corpus callosum, basal ganglia) was associated with overall survival < 6 months. There was also a reduced overall survival in patients with tumors in the left temporal lobe pole. Tumors in the dorsomedial right temporal lobe and the white matter region involving the left anterior paracentral gyrus/dorsal supplementary motor area/medial precentral gyrus were associated with overall survival > 24 months. Increased distance from center of the third ventricle to contrast-enhancing tumor border was a positive prognostic factor for survival in elderly patients, but less so in younger patients.
Conclusions
Central tumor location was associated with worse prognosis. Distance from center of the third ventricle to contrast-enhancing tumor border may be a pragmatic prognostic factor in elderly patients.
STUDY DESIGN.Observational multicenter study.
OBJECTIVE.The aim of this study was to evaluate changes in pain during sexual activity after surgery for lumbar disc herniation (LDH).
SUMMARY OF ...BACKGROUND DATA.There are limited data available on sexual function in patients undergoing surgery for LDH.
METHODS.Data were retrieved from the Norwegian Registry for Spine Surgery. The primary outcome was change in pain during sexual activity at one year, assessed by item number eight of the Oswestry disability index (ODI) questionnaire. Secondary outcome measures included ODI, EuroQol-5D (EQ-5D), and numeric rating scale (NRS) scores for back and leg pain.
RESULTS.Among the 18,529 patients included, 12,103 (64.8%) completed 1-year follow-up. At baseline, 16,729 patients (90.3%) provided information about pain during sexual activity, whereas 11,130 (92.0%) among those with complete follow-up completed this item. Preoperatively 2586 of 16,729 patients (15.5%) reported that pain did not affect sexual activity and at 1 year, 7251 of 11,130 patients (65.1%) reported a normal sex-life without pain. Preoperatively, 2483 (14.8%) patients reported that pain prevented any sex-life, compared to 190 patients (1.7%) at 1 year. At baseline, 14,143 of 16,729 patients (84.5%) reported that sexual activity caused pain, and among these 7232 of 10,509 responders (68.8%) reported an improvement at 1 year. A multivariable regression analysis showed that having a life partner, college education, working until time of surgery, undergoing emergency surgery, and increasing ODI score were predictors of improvement in pain during sexual activity. Increasing age, tobacco smoking, increasing body mass index, comorbidity, back pain >12 months, previous spine surgery, surgery in two or more lumbar levels, and complications occurring within 3 months were negative predictors.
CONCLUSION.This study clearly demonstrates that a large proportion of patients undergoing surgery for LDH experienced an improvement in pain during sexual activity at 1 year.Level of Evidence2
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