Do Common Risk Adjustment Methods Do Their Job Well if Center Effects are Correlated With the Center-Specific Mean Values of Patient Characteristics?

BACKGROUND: Direct and indirect standardization are well-established approaches to performing risk adjustment when comparing outcomes between healthcare providers. However, it is an open question whether they work well when there is an association between the center effects and the distributions of the patient characteristics in these centers. OBJECTIVES AND METHODS: We try to shed further light on the impact of such an association. We construct an artificial case study with a single covariate, in which centers can be classified as performing above, on, or below average, and the center effects correlate with center-specific mean values of a patient characteristic, as a consequence of differential quality improvement. Based on this case study, direct standardization and indirect standardization-based on marginal as well as conditional models-are compared with respect to systematic differences between their results. RESULTS: Systematic differences between the methods were observed. All methods produced results that partially reflect differences in mean age across the centers. This may mask the classification as above, on, or below average. The differences could be explained by an inspection of the parameter estimates in the models fitted. CONCLUSIONS: In case of correlations of center effects with center-specific mean values of a covariate, different risk adjustment methods can produce systematically differing results. This suggests the routine use of sensitivity analyses. Center effects in a conditional model need not reflect the position of a center above or below average, questioning its use in defining the truth. Further empirical investigations are necessary to judge the practical relevance of these findings.

Clinical effects of accreditation in general practice: a pragmatic randomized controlled study.

BACKGROUND: Accreditation has been implemented in general practice in many countries as a tool for quality improvement. Evidence of the effects of accreditation is, however, lacking. AIM: To investigate the clinical effects of accreditation in general practice. DESIGN AND SETTING: A mandatory national accreditation programme in Danish general practice was rolled out from 2016 to 2018. General practices were randomized to year of accreditation at the municipality level. METHODS: We conducted a pragmatic randomized controlled study with general practices randomized to accreditation in 2016 (intervention group) and 2018 (control group). Data on patients enlisted with these practices were collected at baseline in 2014 (before randomization) and at follow-up in 2017. We use linear and logistic regression models to compare differences in changes in outcomes from baseline to follow-up between the intervention and control groups. The primary outcome was the number of redeemed medications. Secondary outcomes were polypharmacy, nonsteroidal anti-inflammatory drugs (NSAIDs) without proton pump inhibitors, sleeping medicine, preventive home visits, annual controls, spirometry tests, and mortality. RESULTS: We found statistically significant effects of accreditation on the primary outcome, the number of redeemed medications, and the secondary outcome, polypharmacy. No other effects were detected. CONCLUSION: In this first randomized study exploring the effects of accreditation in a primary care context, accreditation was found to reduce the number of redeemed medications and polypharmacy. We conclude that accreditation can be effective in changing behaviour, but the identified effects are small and limited to certain outcomes. Evaluations on the cost-effectiveness of accreditation are therefore warranted.

The effect of exercise referral schemes and self-management strategies on use of prescription analgesics among community-dwelling older adults: registry linkage with randomised controlled trials.

BACKGROUND AND OBJECTIVE: Exercise referral schemes and self-management strategies have shown positive effects on patient-reported and objectively measured outcomes, such as increased functional capacity and physical activity level. However, the impact of these interventions on analgesic use remains uncertain. We hypothesised that exercise referral schemes, either utilised alone or in combination with self-management strategies, is more effective in reducing use of prescription analgesics compared with a self-management strategy only. SUBJECTS AND METHODS: We utilised data from two completed randomised controlled trials, namely The Welfare Innovation in Primary Prevention (n = 121) and The SITLESS project (n = 338), and information from the national Danish health registries, including the National Prescription Registry. The two trials have investigated the effectiveness of interventions, which include exercise referral schemes and self-management strategies, on various aspects such as physical function and levels of physical activity among community-dwelling older adults. The studies were conducted in the period 2015-2020 and comprised older adults aged 65+ years, living in three different Danish municipalities. Participants were recruited through nationally regulated preventive home-visits. To estimate changes in use of prescription analgesics over time, a linear fixed effects regression model was applied. The outcome measure was the mean total yearly defined daily dose of analgesics. RESULTS: All intervention groups showed a within-group increase in overall analgesic use, though not statistically significantly different from zero. There were no differences in estimated changes in mean total yearly defined daily dose when comparing the intervention groups to the group receiving the least extensive intervention (self-management strategies/control). The findings indicated that exercise referral schemes and self-management strategies, whether administrated individually or in combination, did not result in a reduction in analgesic use over time.

The durability of previous examinations for cancer: Danish nationwide cohort study.

OBJECTIVE: Patients previously examined for cancer with a negative result may present in general practice with ongoing or new symptoms or signs suggestive of cancer. This paper explores the potential existence of a relatively safe period for cancer occurrence after receiving negative examination results for specific types of cancer, including lung (CT thorax), upper gastrointestinal (gastroscopy), colorectal (colonoscopy), bladder (cystoscopy), and breast (clinical mammography). DESIGN: Register-based time-to-event analyses. SETTING: Denmark. SUBJECTS: All 3.3 million citizens aged 30-85 years who on January first, 2017, had not previously been diagnosed with the specific type of cancer were categorized based on the time since their most recent examination. MAIN OUTCOME MEASURES: Using 1-year follow-up, we calculated the age- and sex-adjusted hazard ratios of being diagnosed with the related cancer, with non-examined individuals as reference. Negative examination results were defined as the absence of a cancer diagnosis within 6 months following the examination. RESULTS: Previous negative examination results were common, also among those diagnosed with cancer during follow-up. For 10 years after a negative colonoscopy the risk of diagnosing a colorectal cancer was nearly halved. However, already 1 year after a clinical mammography and 2 years after a CT thorax the risk of diagnosing the related cancers was significantly higher among those with a previous negative result compared to non-examined individuals. CONCLUSION: This study did not identify a post-examination period in which the cancer risk, compared to non-examined individuals, was sufficiently low to confidently rule out any of the investigated cancers.

What should one expect when considering re-examining a patient with a negative result of a previous examination for cancer? We found that previous negative examination results are common in the general population and among those subsequently diagnosed with cancer. We did not find a safe period after any of the examinations in which a negative result alone could safely rule out the presence of cancer.

Salutogenic health measures: Psychometric properties of the Danish versions of the Flourish Index and the Secure Flourish Index.

Measurement of human flourishing represents a salutogenic approach to epidemiological and behavioral research emphasizing factors contributing to "good lives" rather than pathology. The objective of this study was to translate and psychometrically test the 10-item Flourish Index (FI) and 12-item Secure Flourish Index (SFI) in a convenience sample of Danish adults. A total of 325 participants completed a cross-sectional survey, with 148 of those participants completing the survey a second time (retest). Confirmatory factor analysis in a structural equation modelling framework was used to establish structural validity by comparing four different pre-specified models of the indexes. Additionally, internal consistency, convergent and incremental validity, and retest reliability were examined. The FI models exhibited superior structural validity compared with similar models of the SFI, although all models had good fits. Internal consistencies with McDonald's omega were 0.89 and 0.87 for the FI and SFI, respectively. The five (FI) or six (SFI) domains were happiness & life satisfaction, mental & physical health, meaning & purpose, character & virtue, close social relationships, and financial & material stability (λ4 = 0.51-0.91). Convergent and incremental validity tests supported predefined hypotheses. Retest analyses with the FI and SFI showed a high degree of retest reliability. Based on the psychometric evidence reported in this study, the Danish Flourish Index and Secure Flourish Index seem suitable for use with healthy adult Danes. The authors hope that this psychometric evaluation of the FI and SFI will stimulate research on patterns, health and economic outcomes, and predictors of human flourishing in Denmark.

Quality clusters in general practice: associations between cluster organization and general practitioners' self-reported benefits.

BACKGROUND: Quality clusters were introduced as a quality improvement concept in Danish general practice in 2018. This new concept anchored quality improvement in local clusters managed by general practitioners (GPs). OBJECTIVES: To describe the cluster organization and GPs' self-reported benefits of participating in them and explore the associations between cluster organization and self-reported benefits. METHODS: A national survey in Danish general practice gathering information about cluster organization (cluster size, cluster meetings, participants, and content) and GPs' self-reported benefits (overall benefit, internal changes in the clinic, and improved external collaboration). RESULTS: One hundred and eight (95%) clusters and 1,219 GPs (36%) were included. Cluster size varied from 10 to 68 GPs (34 GPs on average). Approximately 70% of GPs reported moderate to very high overall benefit from cluster participation. Most GPs experienced changes in their clinic organization (68%), drug prescriptions (78%), and patient care (77%). Collaboration was reported improved between the GPs (86%), municipality (50%), and hospital (36.2%). GPs in clusters with 3-6 planned meetings per year (odds ratio [OR] 1.9; confidence interval [CI] 1.3-2.9), mixed meeting types (OR 1.7; CI 1.2-2.4), group work (OR 1.7; CI 1.1-2.5), and use of guidelines in their meetings (OR 1.8; CI 1.3-2.4) had statistically significantly higher odds for reporting overall benefit of participating in clusters compared with GPs in clusters without these characteristics. CONCLUSIONS: Frequent and active meetings with a relevant meeting content are positively related to GPs' perceived benefits and with improved collaboration between GPs in the clusters. There seems to be a potential for developing collaboration with other healthcare providers.

A cross-sectional study of student empathy across four medical schools in Denmark-associations between empathy level and age, sex, specialty preferences and motivation.

BACKGROUND: Professional empathy has been associated with a range of positive patient- and clinician outcomes and is therefore considered important to develop for future physicians. Measuring changes in empathy scores among medical students by using the Jefferson Scale of Empathy (Student version) (JSE-S) has led to mixed results. So far, no investigation of Danish medical students' empathy development has been conducted. The aim of this study was therefore to examine the associations between empathy scores among Danish medical students and medical school, year of curriculum, age, sex, co-habitation, and parental status, specialty preferences and motivations for choosing medicine as a future profession. METHODS: This was a cross-sectional questionnaire study. All medical students from four medical schools in Denmark in their first, third and sixth year (N = 4,178) were invited to participate in the study in October 2020. The associations between JSE-S sum score and the above explanatory factors were analysed by uni- and multivariable linear regression models. RESULTS: The JSE-S was completed by 672 medical students. The overall mean score was 112.7. There were no statistically significant differences in empathy between medical schools, first, third- and sixth- year medical students, age groups or parental status. Female students and students living with a spouse or partner scored higher on JSE-S than male students or students living alone, and the sex difference remained statistically significant in the multivariable regression. In both the univariable and multivariable setting, preference for future medical specialty was statistically significant, with a decrease in scores for students choosing surgery-specialties. Motivational factors were not statistically significantly associated with empathy, although there was a slight upwards trend for one of the motivational categories, named "personal experiences". CONCLUSIONS: Overall, our results showed neither decrease nor increase but instead rather stable empathy scores across years of curriculum of medical students in Denmark, adding to the mixed picture of empathy development among medical students. Our findings are consistent with positive associations found in international studies between empathy scores and higher age, female sex, specialty preferences for psychiatry and general practice and altruistic motivations for choosing to enroll. Although specialty preferences are changing during medical education, they may be used meaningfully as predictors of individual student empathy levels.

The Association Between Individualised Religiosity and Health Behaviour in Denmark: Are Social Networks a Mediating Factor?

The present study investigates whether social networks mediate the well-established positive association between religiosity and health behaviour. Most research has focused on traditional public religiosity (e.g. regular church attendance). This study, however, focuses on the Danish population in which non-traditional and private religiosity is common. We utilise data from the Danish population-based project, Early Detection and Prevention. Our results suggest that religiosity is linked to health behaviour; however, this association is not mediated by social network.

Measuring Spiritual Needs in a Secular Society: Validation and Clinimetric Properties of the Danish 20-Item Spiritual Needs Questionnaire.

In secular cultures, such as Denmark, tools to measure spiritual needs are warranted to guide existential and spiritual care. We examined the clinimetric properties of the Danish version of the Spiritual Needs Questionnaire (DA-SpNQ-20) based on a digital survey in a test-retest setup. A convenience sample was reached via social media and student platforms. A total of 325 (148 for retest) respondents were included in the analysis. The sample was randomly split into two groups (A and B) and used for exploratory (EFA) and confirmatory factor analysis (CFA) by structural equation modeling, respectively. SpNQ dimensions had an internal consistency with Cronbach's alpha between 0.73 and 0.93. The four factors of the SpNQ were supported by both EFA and CFA as follows: religious needs, existential needs, inner peace needs, and generativity needs. The instrument showed good internal consistency, good test-retest reliability, and acceptable structural validity in the sample of relatively young and healthy persons.

Predictors of health-related quality of life in patients with Crohn's disease receiving biological therapy.

BACKGROUND AND AIM: Health-related quality of life (HRQoL) is impaired in patients with Crohn's disease (CD). This study aimed to identify the impact of clinical disease activity on HRQoL in CD patients treated with biological agents. METHODS: Patients with moderate to severe active CD treated with biological agents in Denmark were included from 2016-2018. Disease related symptoms were assessed via the Harvey Bradshaw Index. HRQoL was measured on the Short Health Scale (SHS). Multivariable linear regression models were conducted separately for each SHS item and average SHS score stratified for sex, adjusting for clinical manifestation and age. RESULTS: In total, 1,181 CD patients were included. The mean age was 33 years and 56% were women. Abdominal pain (range of regression coefficients 1.18-1.42), number of liquid stools (0.33-0.58), and the appearance of a new rectal fistula (0.91-1.32) affected all domains in the SHS negatively for men and women. Arthralgia (0.47-0.67) and abdominal mass (0.54-0.62) affected 4 out of 5 items on SHS negatively for women and men, respectively. Female sex was found a predictor of lower HRQoL across all SHS items, whereas age and fistulizing disease, as phenotype, were not associated with lower HRQoL. CONCLUSIONS: Abdominal pain, number of liquid stools, a new rectal fistula, arthralgia for women, clinically assessed abdominal mass for men as well as female sex, were all found to be predictors of decreased HRQoL.

Socioeconomic position and mental health care use before and after first redeemed antidepressant and time until subsequent contact to psychologist or psychiatrists: a nationwide Danish follow-up study.

PURPOSE: The purpose was to investigate inequalities in access to care among people with possible depression. METHOD: In this nationwide register-based cohort study of 30,593 persons, we observed the association between socioeconomic position (SEP, education/income) and mental health care use (MHCU) four months before the date of first redeemed antidepressant (Index Date/ID) and 12 months afterwards-and time to contact to psychologist/psychiatrist (PP). Logistic, Poisson, and Cox regression models were used, adjusted for sex, age, cohabitation, and psychiatric comorbidity. RESULTS: Before ID, high SEP was associated with less GP contact (general practitioner), higher odds ratios for GP-Mental Health Counseling (GP-MHC), psychologist contact, and admissions to hospital. This disparity decreased the following 12 months for GP-MHC but increased for contact to psychologist; same pattern was seen for rate of visits. However, the low-income group had more contact to private psychiatrist. For the 25,217 individuals with no MHCU before ID, higher educational level was associated with almost twice the rate of contact to PP the following 12 months; for the high-income group, the rate was 40% higher. 10% had contact to PP within 40 days after ID in the group with higher education; whereas, 10% of those with a short education would reach PP by day 120. High-income group had faster access as well. CONCLUSION: Being in high SEP was positively associated with MHCU, before and after ID, and more rapid PP contact, most explicit when measured by education. Co-payment for psychologist may divert care towards private psychiatrist for low-income groups.

Prescribing antibiotics: the use of diagnostic tests in general practice. A register-based study.

OBJECTIVE: To assess (i) the pattern of antibiotic prescribing in Danish general practice, (ii) the use of diagnostic tests [point-of-care (POC) and tests analysed at the hospital laboratory (laboratory tests)], and (iii) the frequency of diagnostic testing in relation to antibiotic prescriptions. DESIGN: Retrospective cross-sectional register-based study. SETTING: General practice in a geographical area of Denmark covering 455,956 inhabitants. SUBJECTS: We studied redeemed antibiotic prescriptions and performed diagnostic tests in general practice from 2013 to 2017 among inhabitants in nine selected municipalities. MAIN OUTCOME MEASURES: Frequency of antibiotic courses. Frequency and type of diagnostic testing performed in relation to types of antibiotics. RESULTS: A total of 783,252 antibiotic courses were redeemed from general practice with an overall decrease of 19% during 2013-2017. Diagnostic testing increased by 6% during this period. POC tests comprised the majority of performed diagnostic tests (83%) with C-reactive protein (CRP) as the most frequently used test. A 27% increase in the use of laboratory tests was observed. Tests were performed in relation to 43% of all antibiotic courses; most in relation to prescriptions for sulphonamide and trimethoprim (57%) and rarely when prescribing tetracyclines (10%). Conflicting with national guidelines, Danish GPs prescribed fluoroquinolones without performing any kind of diagnostic testing in 48% of the cases. CONCLUSIONS: This study provides an overview of the use of diagnostic tests in relation to antibiotics and creates basis for further research into the variability between types of antibiotics. The study indicates that there is room for improvement to use diagnostic tests as an aid to promote prudent antibiotic use.KEY POINTSDiagnostic tests (point-of-care or tests analysed at the hospital laboratory), can increase diagnostic certainty and lead to a reduction in antibiotic use in general practice.A decrease in antibiotic courses in general practice in Denmark was observed during 2013-2017, while the use of diagnostic tests increased.A diagnostic test was performed in relation to 43% of antibiotic courses.Only 52% of prescribed fluoroquinolones was related to a diagnostic test, conflicting with national guidelines.

Age-stratified validation of the functional assessment of chronic illness therapy-spiritual well-being based on a large cohort of Danish cancer survivors.

OBJECTIVE: Previous research indicates that the FACIT-Sp instrument is susceptible to bias when measuring spiritual well-being in older patients. Our first focus was to evaluate the two-factor vs the three-factor model of the FACIT-Sp and our second focus was to explore how these models behave for different age groups. METHODS: We used a large national cohort of Danish cancer patients (N = 3439) which included a significant number of patients aged at least 70 years (N = 1033). Item-test correlations and factor analyses were conducted on complete cases (N = 2820). Additionally, a reliability analysis was performed using Cronbach's alpha and Guttman's lower-bound estimate. RESULTS: Factor analysis revealed a loading pattern for the oldest age group (70+) showing items on peace and meaning loading into a single factor, as originally proposed in the two-factor model. The loading estimates for the patients younger than 70 matched the three-factor model. Furthermore, item-test correlations changed as age increased. Based on Cronbach's alpha and Guttman's estimate of .83 and .89, respectively, total scores proved reliable. Items 4, 8, and 12 are discussed separately concerning their problematic influence on instrument validity in their current formulation. CONCLUSION: Overall, the three-factor model had a good fit; however, for the eldest patients a two-factor solution proved even better. Interpretation of FACIT-Sp subscale scores of older cancer patients must therefore be done with caution.

Predictors of health-related quality of life in patients with moderate to severely active ulcerative colitis receiving biological therapy.

Background and aims: Patients with ulcerative colitis have reduced health-related quality of life compared to the general population. Current treatment strategy aims to reduce patients' symptoms and increase health-related quality of life. We investigated which symptoms of ulcerative colitis correlate to decreased health-related quality of life.Methods: Among 743 patients with moderate to severely active ulcerative colitis receiving biological therapy in a cross-sectional national study, we determined which disease-related symptoms, as measured by the Simple Clinical Colitis Activity Index, worsened health-related quality of life scores across the Short Health Scale dimensions, while adjusting for treatment, age, and clinical manifestation, and stratifying for sex, by means of multiple linear regression.Results: Patients with active disease had decreased health-related quality of life compared to those with inactive disease (median 5.8 (range 4.5-7.5) vs. 2 (0.8-3.3)). Both sexes had decreased health-related quality of life in all dimensions for the symptoms: bowel frequency during daytime (0.37-0.86 and 0.46-0.84), urgency of defecation (0.54-0.79 and 0.49-0.65) and blood in stool (0.50-0.75 and 0.36-0.54) for men and women respectively. Women were more often negatively affected by bowel frequency during night-time (4 domains vs. 1) and arthritis (5 domains vs. 3). In non-stratified analysis female sex is an independent predictor of lower health-related quality of life for 3 domains (0.38-0.53).Conclusions: Health-related quality of life was most prominently associated with bowel frequency during daytime, urgency of defecation, and blood in stool. Other symptoms associated for some health-related quality of life dimensions, and appear to vary between the sexes.

Anxiety and depression symptoms in Danish patients with an implantable cardioverter-defibrillator: prevalence and association with indication and sex up to 2 years of follow-up (data from the national DEFIB-WOMEN study).

AIMS: To investigate (i) the prevalence of anxiety and depression and (ii) the association between indication for implantable cardioverter-defibrillator (ICD) implantation and sex in relation to anxiety and depression up to 24 months' follow-up. METHODS AND RESULTS: Patients with a first-time ICD, participating in the national, multi-centre, prospective DEFIB-WOMEN study (n = 1496; 18% women) completed the Hospital Anxiety and Depression Scale at baseline, 3, 6, 12, and 24 months. Data were analysed using linear mixed modelling for longitudinal data. Patients with a secondary prophylactic indication (SPI) had higher mean anxiety scores than patients with a primary prophylactic indication (PPI) at baseline, 3, and 12 months and higher mean depression scores at all-time points, except at 24 months. Women had higher mean anxiety scores as compared to men at all-time points; however, only higher mean depression scores at baseline. Overall, women with SPI had higher anxiety and depression symptom scores than men with SPI. Symptoms decreased over time in both women and men. From baseline to follow-up, the prevalence of anxiety (score ≥8) was highest in patients with SPI (13.3-20.2%) as compared to patients with PPI (range 10.0-14.7%). The prevalence of depression was stable over the follow-up period in both groups (range 8.5-11.1%). CONCLUSION: Patients with a SPI reported higher anxiety and depression scores as compared to patients with PPI. Women reported higher anxiety scores than men, but only higher depression scores at baseline. Women with SPI reported the highest anxiety and depression scores overall.

Correction to: Neurodevelopmental outcomes after moderate to severe neonatal hypoglycemia.

The family name of the co-author of the article mentioned above was incorrectly presented. The correct name should have been "Annett Helleskov Rasmussen" instead of "Annett Rasmussen Helleskov".

Neurodevelopmental outcomes after moderate to severe neonatal hypoglycemia.

The long-term consequences of transient neonatal hypoglycemia are sparsely studied. We performed a follow-up of a cohort of neonates with blood glucose recordings < 1.7 mmol/L (< 30 mg/dL), treated with > 2.5 mmol/L (> 45 mg/dL), compared with healthy siblings. Exclusion criteria were gestational age < 35 weeks, severe asphyxia, head injury, and other cerebral diseases. In 71 children with neonatal hypoglycemia and 32 control siblings, Wechsler IV cognitive test, Movement ABC-2 test, and Child Behavior Checklist were performed at mean age 7.75 and 9.17 years, respectively. No significant changes were detected for cognitive function by using Wechsler IV or for behavior by using Child Behavior Checklist. In univariate analysis, the hypoglycemia group had lower age-adjusted fine motor scores by using the Movement ABC-2 test compared with control siblings, 42.6 ± 31.2 vs. 57.2 ± 30.8 percentile (p = 0.03). In the sibling-paired analysis, the decrease in total motor score was highly significant, p = 0.009, driven by a decrease in fine motor score, p = 0.008. In the hypoglycemia group, adjusted analysis showed a lower fine motor function for boys, ß = - 16.4, p = 0.048.Conclusion: Neonatal hypoglycemia treated with > 2.5 mmol/L was associated with lower fine motor scores within the normal range, particularly in boys. No associations with cognitive function or behavior were detected. What is Known: • Transient neonatal hypoglycemia is associated with acute neurologic dysfunction and long-term neurodevelopment impairment in 18 months of age. What is New: • Neonatal hypoglycemia treated with > 2.5 mmol/L is associated with lower fine motor function within the normal range, particularly in boys, but not to changes in cognitive function or behavior.

Therapeutic Use of the Human Papillomavirus Vaccine on Recurrent Respiratory Papillomatosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Recurrent respiratory papillomatosis is a benign condition caused by human papillomavirus (HPV). Surgery is the mainstay of treatment, but numerous adjuvant therapies have been applied to improve surgical outcome. Recently, HPV vaccination has been introduced, but only smaller studies of its effect have been published. The present meta-analysis is intended as a possible substitute for a proposed but not yet realized multicenter randomized controlled trial. METHODS: A systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. PubMed, Embase, and Cochrane were systematically searched. All retrieved studies (n = 593) were reviewed and qualitatively assessed. In addition, 2 previously unpublished data sets were included. The systematic review included 11 studies, comprising 133 patients, of whom 63 patients from 5 studies were eligible for meta-analysis. A random-effects meta-analysis was conducted for the mean difference in number of surgical procedures per month before and after vaccination. RESULTS: The number of surgical procedures per month was significantly reduced after HPV vaccination compared with before vaccination (estimated mean, 0.06 vs 0.35). The mean intersurgical interval increased from 7.02 months (range, 0.30-45 months) before to 34.45 months (2.71-82 months) after HPV vaccination. CONCLUSION: The present study supports the continued use of the HPV vaccine as an adjuvant treatment for recurrent respiratory papillomatosis.

Risk of Ectopic Pregnancy in Women With Inflammatory Bowel Disease: A 22-Year Nationwide Cohort Study.

BACKGROUND & AIMS: Few data are available on adverse events of pregnancy in women with inflammatory bowel diseases (IBD), such as ectopic pregnancy. We assessed the risk of ectopic pregnancy in pregnancies of women in Denmark with IBD compared with those without IBD over a 22-year period. We also examined the disease-specific risks of ectopic pregnancies in pregnancies of women with ulcerative colitis (UC) or Crohn's disease (CD) who underwent IBD-related surgical procedures. METHODS: We performed a retrospective study of all women of child-bearing age (ages, 15-50 y) registered in the Danish National Patient Registry with at least 1 pregnancy during the period from January 1994 through December 31, 2015. We collected data on all women with an ectopic pregnancy, hydatidiform mole, miscarriages (spontaneous and other abortions, including abnormal pregnancy products, missed abortion, and pregnancy without a fetus), induced abortions, and births in women with and without IBD. Our study population included 7548 pregnancies in women with UC, 6731 pregnancies in women with CD, and 1,832,732 pregnancies in women without IBD. We controlled for multiple covariates, including pelvic and abdominal surgery. RESULTS: Women with CD had a greater risk of ectopic pregnancy, per pregnancy, than women without IBD (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.01-1.49), whereas women with UC did not (OR, 0.98; 95% CI, 0.80-1.20). In pregnancies of women with CD and UC who underwent IBD-related surgery before pregnancy, there was a nonsignificant increase in risk of ectopic pregnancy compared with pregnancies in women with IBD who did not have surgery (OR, 1.49; 95% CI, 0.91-2.44 for CD, and OR, 1.17; 95% CI, 0.54-2.52 for UC). CONCLUSIONS: We found a statistically significant increased risk of ectopic pregnancy in pregnancies of women with CD compared with pregnancies of women without IBD. Surgery for IBD before pregnancy increased the risk of ectopic pregnancy, although this increase was not statistically significant.

Causes of death among full term stillbirths and early neonatal deaths in the Region of Southern Denmark.

OBJECTIVE: We examined the causes of death amongst full term stillbirths and early neonatal deaths. METHODS: Our cohort includes women in the Region of Southern Denmark, who gave birth at full term to a stillborn infant or a neonate who died within the first 7 days from 2010 through 2014. Demographic, biometric and clinical variables were analyzed to assess the causes of death using two classification systems: causes of death and associated conditions (CODAC) and a Danish system based on initial causes of fetal death (INCODE). RESULTS: A total of 95 maternal-infant cases were included. Using the CODAC and INCODE classification systems, we found that the causes of death were unknown in 59/95 (62.1%). The second most common cause of death in CODAC was congenital anomalies in 10/95 (10.5%), similar to INCODE with fetal, genetic, structural and karyotypic anomalies in 11/95 (11.6%). The majority of the mothers were healthy, primiparous, non-smokers, aged 20-34 years and with a normal body mass index (BMI). CONCLUSION: Based on an unselected cohort from an entire region in Denmark, the cause of stillbirth and early neonatal deaths among full term infants remained unknown for the vast majority.