The effects of childbirth on the pelvic-floor

Basically, vaginal delivery is associated with the risk of pelvic floor damage. The pelvic floor sequelae of childbirth includes anal incontinence, urinary incontinence and pelvic organ prolapse. Pathophysiology, incidence and risk factors for the development of the respective problems are reviewed. Where possible, recommendations for reducing the risk of pelvic floor damage are given

Persistent urinary incontinence and delivery mode history: a six-year longitudinal study.

Objective: To investigate the prevalence of persistent and long term postpartum urinary incontinence and associations with mode of first and subsequent delivery. Setting: Maternity units in Aberdeen (Scotland), Birmingham (England) and Dunedin (New Zealand). Design: Longitudinal study Population: 4214 women who returned postal questionnaires 3 months and 6 years after the index birth. Methods: Symptom data were obtained from both questionnaires and obstetric data from case-notes for the index birth and the second questionnaire for subsequent births. Logistic regression investigated the independent effects of mode of first delivery and delivery mode history. Main outcome measures: Urinary incontinence – persistent (at 3 months and 6 years after index birth) and long-term (at 6 years after index birth). Results: The prevalence of persistent urinary incontinence was 24%. Delivering exclusively by Caesarean section was associated with both less persistent (OR= 0.46, 95% CI 0.32 to 0.68) and long term urinary incontinence (OR=0.50, 95% CI 0.40 to 0.63). Caesarean section birth in addition to vaginal delivery however was not associated with significantly less persistent incontinence (OR 0.93, 95%CI 0.67 to 1.29). There were no significant associations between persistent or long-term urinary incontinence and forceps or vacuum extraction delivery. Other significantly associated factors were increasing number of births and older maternal age. Conclusions: The risk of persistent and long term urinary incontinence is significantly lower following Caesarean section deliveries but not if there is another vaginal birth. Even when delivering exclusively by Caesarean section, the prevalence of persistent symptoms (14%) is still high

The handling of urinary incontinence in Danish general practices after distribution of guidelines and voiding diary reimbursement: an observational study

BACKGROUND: Though urinary incontinence (UI) is a bothersome condition for the individual patient, the patients tend not to inform their physician about UI and the physician tend not to ask the patient. Recently different initiatives have been established in Danish general practices to improve the management of UI. The aim of this study was to identify the handling of urinary incontinence (UI) in Danish general practices after distribution of clinical guidelines and reimbursement for using a UI diary. METHODS: In October 2001, a questionnaire was sent to 243 general practitioners (GPs) in Frederiksborg County following distribution of clinical guidelines in July 1999 (UI in general practice) and September 2001 (UI in female, geriatric, or neurological patients). A policy for a small reimbursement to GPs for use of a fluid intake/voiding diary in the assessment of UI in general practice was implemented in October 2001. Information concerning monthly reimbursement for using a voiding diary, prescribed drugs (presumably used for treating UI), UI consultations in outpatient clinics, and patient reimbursement for pads was obtained from the National Health Service County Registry. RESULTS: Of the 132 (54%) GPs who replied, 87% had read the guidelines distributed 2 years before, but only 47% used them daily. The majority (69%) of the responding GPs had read and appreciated 1–3 other UI guidelines distributed before the study took place. Eighty-three percent of the responding GPs sometimes or often actively asked their patients about UI, and 92% sometimes or often included a voiding diary in the UI assessment. The available registry data concerning voiding diary reimbursement, prescribed UI drugs, UI consultations in outpatient clinics, and patient reimbursement for pads were insufficient or too variable to determine significant trends. CONCLUSION: GPs management of UI in a Danish county may be reasonable, but low response rate to the questionnaire and insufficient registry data made it difficult to evaluate the impact of different UI initiatives

Effect size varies based on calculation method and may affect interpretation of treatment effect: an illustration using randomised clinical trials in osteoarthritis

Background: To illustrate how (standardised) effect sizes (ES) vary based on calculation method and to provide considerations for improved reporting. Methods: Data from three trials of tanezumab in subjects with osteoarthritis were analyzed. ES of tanezumab versus comparator for WOMAC Pain (outcome) was defined as least squares difference between means (mixed model for repeated measures analysis) divided by a pooled standard deviation (SD) of outcome scores. Three approaches to computing the SD were evaluated: Baseline (the pooled SD of WOMAC Pain values at baseline [pooled across treatments]); Endpoint (the pooled SD of these values at the time primary endpoints were assessed); and Median (the median pooled SD of these values based on the pooled SDs across available timepoints). Bootstrap analyses were used to compute 95% confidence intervals (CI). Results: ES (95% CI) of tanezumab 2.5 mg based on Baseline, Endpoint, and Median SDs in one study were − 0.416 (− 0.796, − 0.060), − 0.195 (− 0.371, − 0.028), and − 0.196 (− 0.373, − 0.028), respectively; negative values indicate pain improvement. This pattern of ES differences (largest with Baseline SD, smallest with Endpoint SD, Median SD similar to Endpoint SD) was consistent across all studies and doses of tanezumab. Conclusion: Differences in ES affect interpretation of treatment effect. Therefore, we advocate clearly reporting individual elements of ES in addition to its overall calculation. This is particularly important when ES estimates are used to determine sample sizes for clinical trials, as larger ES will lead to smaller sample sizes and potentially underpowered studies. Trial Registration: Clinicaltrials.gov NCT02697773, NCT02709486, and NCT02528188

Patient Preferences for Episodic Migraine Medications: A Discrete Choice Experiment of Self-Injectable Versus Oral Treatments Targeting Calcitonin Gene-Related Peptide Pathway

Chiara Whichello,1 Lars Viktrup,2 Oralee J Varnado,2 Matthew Quaife,1 Myrto Trapali,1 Antje Tockhorn-Heidenreich3 1Evidera, London, UK; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Eli Lilly and Company, Bracknell, UKCorrespondence: Antje Tockhorn-Heidenreich, Eli Lilly and Company Ltd, 8 Arlington Square West, Downshire Way, Bracknell, RG12 1PU 0044, UK, Tel +44 7901 92 76 75, Email [email protected]: To understand the trade-offs that patients with episodic migraine are willing to make between attributes of self-injectable calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and oral small-molecule calcitonin gene-related peptide receptor antagonists (gepants).Patients and Methods: This was an online discrete choice experiment survey among adults with episodic migraine (≥ 4 and < 15 migraine headache days and < 15 headache days per month over 3 months) in the United States. Hypothetical treatments were characterized by five attributes: chance of ≥ 50% migraine reduction, impact on daily activities, onset of treatment effect, reduction in number of acute medications, and treatment administration. The attributes were selected based on insights gained from a previously conducted literature review and focus group study and aligned with the primary and secondary outcome measures in the double-blind Phase IV head-to-head clinical trial of a CGRP mAb versus gepant.Results: 601 patients (mean age: 44.8 years) completed the survey. Treatment preferences differed significantly between patients. However, for all patients, the most important driver of treatment preferences was the chance of a ≥ 50% reduction in monthly migraine headache days (relative attribute importance: 38.3%), followed by the impact on daily activities (23.5%), the onset of treatment effect (19.5%), the reduction in need for acute medication (15.4%), and finally the route of administration (3.4%). Patients were willing to consider a one-week delayed onset of treatment effect or one-day increased need for acute medication for a higher chance (by 2.06% and 2.65% respectively) of a ≥ 50% reduction in monthly migraine headache days. Patients would trade a reduction of migraine’s impact on daily activities from “extreme” to “moderate” or “minimal” with a lower chance (17.09%, 12.06% respectively) of halving the number of monthly migraine headache days.Conclusion: A ≥ 50% reduction in monthly migraine headache days was the most important treatment attribute for which participants were willing to trade against other attributes. The variation in treatment preferences between patients emphasizes the importance to align decision-making with individual patients’ preferences.Plain Language Summary: Patients seeking care for migraine have varying levels of migraine severity, disability, and different experience with prior treatment. In this study, we researched patients’ preferences for different preventive treatments, by having 601 patients complete an online survey. The survey presented a ‘discrete choice experiment’ where hypothetical migraine treatments described by five treatment characteristics, including whether the treatment was an oral pill or an injection, and asked patients to choose between them. Our results suggested that the chance of reducing the number of migraine days each month by half was the most important therapeutic characteristic, for which patients were willing to exchange other treatment characteristics in order to have a greater chance of achieving this improvement. Patients also valued if treatments worked quickly or reduced the impact of migraine on everyday activities. Whether a treatment was given as an injection or oral pill did not affect preferences.Keywords: gepants, self-injectable treatment, treatment preferences, preventive treatment, United State

Treatment Patterns and Healthcare Resource Utilization by Gender and Migraine Frequency in Adult Patients Receiving Galcanezumab Versus Standard of Care Preventive Medications Over 24&nbsp;months: A United States Retrospective Claims Study

Oralee J Varnado,1 Michelle Vu,2 Erin K Buysman,2 Gilwan Kim,1 Gayle Allenback,2 Margaret Hoyt,1 Helen Trenz,2 Feng Cao,2 Lars Viktrup1 1Eli Lilly and Company, Indianapolis, IN, USA; 2Optum Life Sciences, HEOR, Eden Prairie, MN, USACorrespondence: Oralee J Varnado, Value, Evidence, and Outcomes, Eli Lilly and Company, Lilly Corporate Center, 893 Delaware Street, Indianapolis, IN, 46285, USA, Tel +1  317-277-0599, Email [email protected]: To describe 24-month treatment patterns, healthcare resource utilization (HCRU), and direct costs of patients initiating galcanezumab (GMB) versus standard of care migraine preventive medications (SOC), stratified by gender and migraine type.Methods: This retrospective cohort study used Optum’s® de-identified Market Clarity database (September 2018−March 2020) and included adults with migraine with ≥ 1 claim for GMB or SOC. Patients in the GMB cohort were stratified by gender (female/male) and migraine type (CM/EM), and propensity score matched 1:1 to patients in the SOC cohort. Treatment patterns, all-cause and migraine-related HCRU, and direct costs for GMB versus SOC cohorts were compared using a Z-test and reported over 24 months.Results: Following stratification and matching, the GMB and SOC cohorts included the following patient pairs: 2015-female, 292-male, 1024-CM, and 1282-EM. Treatment adherence, measured by proportion of days covered, and median time to treatment discontinuation were significantly greater in those initiating GMB compared with SOC in females, males, patients with CM, and patients with EM (all p < 0.001). Over 24 months, reduction in migraine-related ambulatory visits, office visits, and medical costs were significantly higher in GMB versus SOC cohorts in females and patients with CM. Increases in HCRU associated with preventive migraine medication counts and migraine-related total and pharmacy costs were significantly higher in GMB versus SOC cohorts in all subgroups.Conclusion: While direct costs over 24 months were higher in patients initiating GMB for migraine prevention, better adherence and longer treatment duration with GMB regardless of gender or migraine type support the use of GMB compared with SOC.Plain Language Summary: What was known before?The risk of migraine is about two to three times higher for women than for men.Migraine is broadly classified into episodic migraine (EM, 14 or fewer migraine headache days per month) and chronic migraine (CM, at least 15 migraine headache days per month for at least 3 months) based on frequency of monthly migraine headache days. Individuals with CM appear to have higher rates of comorbid conditions than those with EM.Traditional standard of care migraine preventive medications (SOC) were not specifically developed for migraine treatment, and more than half of patients stop using oral medications prematurely.Calcitonin gene-related peptide monoclonal antibodies such as galcanezumab (GMB), fremanezumab, erenumab, and eptinezumab provide migraine-specific preventive treatment.Previous studies with 6-, 12-, and 24-month follow-ups have described the treatment patterns and healthcare resource utilization (HCRU) after initiation of GMB versus SOC.What does this study add?In this 24-month study, we divided a population of patients starting GMB or SOC for migraine prevention 1) based on their gender (female or male) and 2) based on the type of migraine they reported (CM or EM), and compared treatment patterns, HCRU, and direct costs.Irrespective of gender and migraine type, patients who started GMB used their medicine as prescribed for a longer period of time than those who started SOC.Irrespective of gender and migraine type, following initiation of GMB, all-cause and migraine-related total costs increased, with the increase primarily driven by increased pharmacy costs.InterpretationPatients with migraine initiating GMB as their preventive treatment are more likely to continue using it for a longer duration compared with those initiating SOC, based on better adherence and persistence rates. While total costs were higher in patients initiating GMB compared with those initiating SOC, some reductions were observed in HCRU.Treatment patterns, HCRU, and direct costs were generally consistent between females and males as well as those with CM and EM.Keywords: CGRP mAbs, treatment patterns, direct costs, healthcare resource utilization, migraine preventio

Effects of carrying a pregnancy and of method of delivery on urinary incontinence: a prospective cohort study

BACKGROUND: This study was carried out to identify risk factors associated with urinary incontinence in women three months after giving birth. METHODS: Urinary incontinence before and during pregnancy was assessed at study enrolment early in the third trimester. Incontinence was re-assessed three months postpartum. Logistic regression analysis was used to assess the role of maternal and obstetric factors in causing postpartum urinary incontinence. This prospective cohort study in 949 pregnant women in Quebec, Canada was nested within a randomised controlled trial of prenatal perineal massage. RESULTS: Postpartum urinary incontinence was increased with prepregnancy incontinence (adjusted odds ratio [adj0R] 6.44, 95% CI 4.15, 9.98), incontinence beginning during pregnancy (adjOR 1.93, 95% CI 1.32, 2.83), and higher prepregnancy body mass index (adjOR 1.07/unit of BMI, 95% CI 1.03,1.11). Caesarean section was highly protective (adjOR 0.27, 95% CI 0.14, 0.50). While there was a trend towards increasing incontinence with forceps delivery (adjOR 1.73, 95% CI 0.96, 3.13) this was not statistically significant. The weight of the baby, episiotomy, the length of the second stage of labour, and epidural analgesia were not predictive of urinary incontinence. Nor was prenatal perineal massage, the randomised controlled trial intervention. When the analysis was limited to women having their first vaginal birth, the same risk factors were important, with similar adjusted odds ratios. CONCLUSIONS: Urinary incontinence during pregnancy is extremely common, affecting over half of pregnant women. Urinary incontinence beginning during pregnancy roughly doubles the likelihood of urinary incontinence at 3 months postpartum, regardless whether delivery is vaginal or by Caesarean section

Is there an association between depressive and urinary symptoms during and after pregnancy?

Depressive symptoms and urinary symptoms are both highly prevalent in pregnancy. In the general population, an association is reported between urinary symptoms and depressive symptoms. The association of depressive and urinary symptoms has not yet been assessed in pregnancy. In this study, we assessed (1) the prevalence of depressive symptoms, over-active bladder (OAB) syndrome, urge urinary incontinence (UUI) and stress urinary incontinence (SUI) during and after pregnancy using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Urogenital Distress Inventory (UDI) and (2) the association of depressive symptoms with urinary incontinence and over-active bladder syndrome during and after pregnancy, controlling for confounding socioeconomic, psychosocial, behavioural and biomedical factors in a cohort of healthy nulliparous women. Our data show a significant increase in prevalence of depressive symptoms, UUI, SUI and OAB during pregnancy and a significant reduction in prevalence of depressive symptoms, SUI and OAB after childbirth. UUI prevalence did not significantly decrease after childbirth. In univariate analysis, urinary incontinence and the OAB syndrome were significantly associated with a CES-D score indicative of a possible clinical depression at 36 weeks gestation. However, after adjusting for possible confounding factors, only the OAB syndrome remained significantly associated (OR 4.4 [1.8–10.5]). No association was found between depressive and urinary symptoms at 1 year post-partum. Only OAB was independently associated with depressive symptoms during pregnancy. Possible explanations for this association are discussed