Reducing short-acting beta-agonist use in asthma: Impact of national incentives on prescribing practices in England and the findings from SENTINEL Plus early adopter sites.

Short-acting beta-agonist (SABA) over-use in asthma is harmful for patients and the environment. The Investment and Impact Fund (IIF) 2022/2023 financially rewarded English primary care networks that achieved specific targets, including reducing SABA over-use (RESP-02) and lowering the mean carbon footprint per salbutamol inhaler prescribed (ES-02). SENTINEL Plus is a co-designed quality improvement package that aims to improve asthma outcomes and reduce asthma's environmental impact by addressing SABA over-use. We investigated the impact of (i) the IIF incentives and (ii) SENTINEL Plus implementation on asthma prescribing. Using Openprescribing.net data, we demonstrate that IIF 2022-2023 had no significant impact on the total number of SABA prescribed in England (25,927,252 during 12-months pre- and 25,885,213 12-months post-IIF; 0.16% decrease; p=NS), but lower carbon footprint SABA inhaler use increased (Salamol™ prescribing increased from 5.1% to 19% of SABA prescriptions, p < 0.01). In contrast, SENTINEL Plus sites significantly reduced SABA prescribing post-implementation (5.43% decrease, p < 0.05).

Multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis.

A serious adverse clinical effect of glucocorticoid steroid treatment is secondary osteoporosis, enhancing fracture risk in bone. This rapid increase in bone fracture risk is largely independent of bone loss (quantity), and must therefore arise from degradation of the quality of the bone matrix at the micro- and nanoscale. However, we lack an understanding of both the specific alterations in bone quality n steroid-induced osteoporosis as well as the mechanistic effects of these changes. Here we demonstrate alterations in the nanostructural parameters of the mineralized fibrillar collagen matrix, which affect bone quality, and develop a model linking these to increased fracture risk in glucocorticoid induced osteoporosis. Using a mouse model with an N-ethyl-N-nitrosourea (ENU)-induced corticotrophin releasing hormone promoter mutation (Crh(-120/+)) that developed hypercorticosteronaemia and osteoporosis, we utilized in situ mechanical testing with small angle X-ray diffraction, synchrotron micro-computed tomography and quantitative backscattered electron imaging to link altered nano- and microscale deformation mechanisms in the bone matrix to abnormal macroscopic mechanics. We measure the deformation of the mineralized collagen fibrils, and the nano-mechanical parameters including effective fibril modulus and fibril to tissue strain ratio. A significant reduction (51%) of fibril modulus was found in Crh(-120/+) mice. We also find a much larger fibril strain/tissue strain ratio in Crh(-120/+) mice (~1.5) compared to the wild-type mice (~0.5), indicative of a lowered mechanical competence at the nanoscale. Synchrotron microCT show a disruption of intracortical architecture, possibly linked to osteocytic osteolysis. These findings provide a clear quantitative demonstration of how bone quality changes increase macroscopic fragility in secondary osteoporosis.

Microfluidics enables multiplex evaluation of the same cells for further studies.

OBJECTIVE: The continuous discovery of biomarkers and their evolving use for the diagnosis and guidance of therapy for patients with cancer has increased awareness of the need to triage biospecimens properly. On occasion, cytology samples are the only type of biospecimen available for analysis. Often, the current approach for these latter specimens is cytopathology-centric, with cells limited to examination by bright field microscopy. When specimens are paucicellular, there is often insufficient material for ancillary testing. Therefore, a need exists to develop an alternative approach that allows for the multiplexed analysis of cells when they are limited in number. In recent previous publications, we demonstrated that clinically derived cells from tissue are suitable for evaluation in a microfluidic device. In our current endeavour, we seek to expand upon those findings and determine if those same cells can be recovered for further analysis. METHODS: A microfluidic channel was designed, fabricated and tested using cytology specimens generated from tissue specimens. The cytological features of the cells tested were examined prior to entering the channel; they were then compared to similar cells while in the channel, and upon recovery from the channel. Recovery of DNA and proteins were also tested. RESULTS: The morphology of the tested cells was not compromised in either the channel or upon recovery. More importantly, the integrity of the cells remained intact, with the recovery of proteins and high molecular weight DNA possible. CONCLUSIONS: We developed and tested an alternative approach to the processing of cytopathology specimens that enables multiplexed evaluation. Using microfluidics, cytological examination of biopecimens can be performed, but in contrast to existing approaches, the same cells examined can be recovered for downstream analysis.

Galectin-1 suppresses methamphetamine induced neuroinflammation in human brain microvascular endothelial cells: Neuroprotective role in maintaining blood brain barrier integrity.

Methamphetamine (Meth) abuse can lead to the breakdown of the blood-brain barrier (BBB) integrity leading to compromised CNS function. The role of Galectins in the angiogenesis process in tumor-associated endothelial cells (EC) is well established; however no data are available on the expression of Galectins in normal human brain microvascular endothelial cells and their potential role in maintaining BBB integrity. We evaluated the basal gene/protein expression levels of Galectin-1, -3 and -9 in normal primary human brain microvascular endothelial cells (BMVEC) that constitute the BBB and examined whether Meth altered Galectin expression in these cells, and if Galectin-1 treatment impacted the integrity of an in-vitro BBB. Our results showed that BMVEC expressed significantly higher levels of Galectin-1 as compared to Galectin-3 and -9. Meth treatment increased Galectin-1 expression in BMVEC. Meth induced decrease in TJ proteins ZO-1, Claudin-3 and adhesion molecule ICAM-1 was reversed by Galectin-1. Our data suggests that Galectin-1 is involved in BBB remodeling and can increase levels of TJ proteins ZO-1 and Claudin-3 and adhesion molecule ICAM-1 which helps maintain BBB tightness thus playing a neuroprotective role. Galectin-1 is thus an important regulator of immune balance from neurodegeneration to neuroprotection, which makes it an important therapeutic agent/target in the treatment of drug addiction and other neurological conditions.

Simulating the influence of plasma protein on measured receptor affinity in biochemical assays reveals the utility of Schild analysis for estimating compound affinity for plasma proteins.

BACKGROUND AND PURPOSE: Plasma protein binding (PPB) influences the free fraction of drug available to bind to its target and is therefore an important consideration in drug discovery. While traditional methods for assessing PPB (e.g. rapid equilibrium dialysis) are suitable for comparing compounds with relatively weak PPB, they are not able to accurately discriminate between highly bound compounds (typically >99.5%). The aim of the present work was to use mathematical modelling to explore the potential utility of receptor binding and cellular functional assays to estimate the affinity of compounds for plasma proteins. Plasma proteins are routinely added to in vitro assays, so a secondary goal was to investigate the effect of plasma proteins on observed ligand-receptor interactions. EXPERIMENTAL APPROACH: Using the principle of conservation of mass and the law of mass action, a cubic equation was derived describing the ligand-receptor complex [LR] in the presence of plasma protein at equilibrium. KEY RESULTS: The model demonstrates the profound influence of PPB on in vitro assays and identifies the utility of Schild analysis, which is usually applied to determine receptor-antagonist affinities, for calculating affinity at plasma proteins (termed KP ). We have also extended this analysis to functional effects using operational modelling and demonstrate that these approaches can also be applied to cell-based assay systems. CONCLUSIONS AND IMPLICATIONS: These mathematical models can potentially be used in conjunction with experimental data to estimate drug-plasma protein affinities in the earliest phases of drug discovery programmes.

Nanotherapeutic approach for opiate addiction using DARPP-32 gene silencing in an animal model of opiate addiction.

Opiates act on the dopaminergic system of the brain and perturb 32 kDa dopamine and adenosine 3', 5'-monophosphate-regulated phosphoprotein (DARPP-32) function. The DARPP-32 mediated inhibition of protein phosphatase-1 (PP-1) and modulation of transcriptional factor CREB is critical to the changes in neuronal plasticity that result in behavioral responses during drug abuse. To investigate the role of DARPP-32 mediated signaling on withdrawal behavior in a rat model of opiate addiction, we used intracerebral administration of gold nanorods (GNR) complexed to DARPP-32 siRNA to silence DARPP-32 gene expression and measure its effects on the opiate withdrawal syndrome. We hypothesized that DARPP-32 siRNA will suppress the neurochemical changes underlying the withdrawal syndrome and therefore prevent conditioned place aversion by suppressing or removing the constellation of negative effects associated with withdrawal, during the conditioning procedure. Our results showed that opiate addicted animals treated with GNR-DARPP-32 siRNA nanoplex showed lack of condition place aversive behavior consequent to the downregulation of secondary effectors such as PP-1 and CREB which modify transcriptional gene regulation and consequently neuronal plasticity. Thus, nanotechnology based delivery systems could allow sustained knockdown of DARPP-32 gene expression which could be developed into a therapeutic intervention for treating drug addiction by altering reward and motivational systems and interfere with conditioned responses.

Reassessment of the pharmacology of Sphingosine-1-phosphate S1P3 receptor ligands using the DiscoveRx PathHunter™ and Ca2+ release functional assays.

BACKGROUND AND PURPOSE: DiscoverRx's PathHunter™ assay measures GPCR agonist potency, via the recruitment of ß-arrestin, independent of the subtype of G(α) protein activated. This assay is frequently used in drug discovery although little is known about the agonist pharmacology generated. Here we have compared agonist potency, efficacy and affinity values obtained in PathHunter™ assays with those from more established radioligand binding and functional techniques. EXPERIMENTAL APPROACH: Using cells expressing the human sphingosine-1-phosphate S1P(3) receptor at four different densities, we compared pharmacological affinity and efficacy values of four structurally distinct ligands - FTY720-P, VPC24191, CYM5442 and the endogenous agonist S1P - obtained from competition binding, functional Ca(2+) release and PathHunter™ assays. KEY RESULTS: The pK(i) values for S1P were significantly different (9.34 ± 0.10 and 8.92 ± 0.15) in clones expressing different receptor levels using the binding assay. In the PathHunter™ and Ca(2+) assays, S1P and CYM5442 were full agonists, FTY720-P was a partial agonist, while the efficacy of VPC24191 could not be detected in PathHunter™ assays. VPC23019, previously described as a S1P(1/3) receptor antagonist, behaved as an S1P(3) receptor partial agonist in the Ca(2+) release assay. CONCLUSIONS AND IMPLICATIONS: Comparison of data from the PathHunter™ assay with binding and functional Ca(2+) assays suggest that PathHunter™ assays measured a different agonist-bound receptor conformation. While this assay has great utility in drug discovery, care must be taken as high-efficacy, low-affinity agonist compounds would not be detected. Therefore highly amplified, more traditional assays are necessary to identify agonists with low efficacy.

The use of digital infrared thermal imaging to detect estrus in gilts.

Yorkshire/Landrace crossbred gilts (N = 32) were evaluated using digital infrared thermal imaging (DITI) to discriminate between estrus and diestrus phases of the porcine estrous cycle. Gilts (N = 32) were part of an ongoing reproductive efficiency study involving the use of raw soybean (RSB; N = 15) versus soybean meal (SBM; N = 17) as a source of dietary protein. Gilts were monitored daily for signs of estrus using a teaser boar. Thermal images of vulva surface temperatures (TEMP) were recorded at standing estrus and diestrus. Measurements for analysis included minimum (MIN), maximum (MAX), mean (AVG), and standard deviation (SD) of temperature gradients. At imaging, ambient (AMB) and rectal temperatures (RT) were recorded, and blood samples taken for serum progesterone (P(4)) concentration analysis (by RIA) to confirm stage of cycle. Mean serum progesterone values at estrus and diestrus were (mean ± SD) 1.0 ± 0.1 and 10.9 ± 0.8 ng/mL, respectively. Vulva MIN, MAX, and AVG thermal images were positively correlated with one another (P < 0.01), and were positively correlated with ambient temperature (P < 0.01). Vulva MAX and AVG thermal temperatures were greater (P < 0.05) at estrus than at diestrus (36.6 ± 0.2 °C and 33.4 ± 0.3 °C vs. 35.6 ± 0.3 °C and 31.8 ± 0.6 °C, respectively), whereas MIN and SD had no differences (P > 0.05) between stages of the cycle. No differences (P > 0.05) in RT were detected between stages and RT was not significantly correlated with vulva thermal images. Diet had no significant effect on RT or vulva temperature.

A systematic review of treatment guidelines for metastatic colorectal cancer.

AIM: A systematic review of treatment guidelines for metastatic colorectal cancer (mCRC) was performed to assess recommendations for monoclonal antibody therapy in these guidelines. METHOD: Relevant papers were identified through electronic searches of MEDLINE, MEDLINE In Process, EMBASE and the Cochrane Library; through manual searches of reference lists; and by searching the Internet. RESULTS: A total of 57 relevant guidelines were identified, 32 through electronic database searches and 25 through the website searches. The majority of guidelines were published between 2004 and 2010. The country publishing the most guidelines was the USA (12), followed by the UK (10), Canada (eight), France (eight), Germany (three), Australia (two), Spain (two) and Italy (one). In addition, eight European and three international guidelines were identified. As monoclonal antibody therapy for mCRC was not introduced until 2004, no firm recommendations for monoclonal antibody therapy were made in guidelines published between 2004 and 2006. Recommendations for monoclonal antibody therapy first appeared in 2007 and evolved as more data became available. The most recent international, European and US guidelines recommend combination chemotherapy with the addition of a monoclonal antibody for the first-line treatment of mCRC. Second-line treatment depends on the first-line regimen used. For chemoresistant mCRC, cetuximab or panitumumab are recommended as monotherapy in patients with wild-type KRAS tumours. CONCLUSION: The study indicates that recent treatment guidelines have recognized the role of monoclonal antibodies in the management of mCRC, and that treatment guidelines should be updated in a timely manner to reflect the most recently available data.

Genomic and proteomic analysis of the effects of cannabinoids on normal human astrocytes.

Delta-9-tetrahydrocannabinol (Delta(9)-THC), the main psychoactive component of marijuana, is known to dysregulate various immune responses. Cannabinoid (CB)-1 and -2 receptors are expressed mainly on cells of the central nervous system (CNS) and the immune system. The CNS is the primary target of cannabinoids and astrocytes are known to play a role in various immune responses. Thus we undertook this investigation to determine the global molecular effects of cannabinoids on normal human astrocytes (NHA) using genomic and proteomic analyses. NHA were treated with Delta(9)-THC and assayed using gene microarrays and two-dimensional (2D) difference gel electrophoresis (DIGE) coupled with mass spectrometry (MS) to elucidate their genomic and proteomic profiles respectively. Our results show that the expression of more than 20 translated protein gene products from NHA was differentially dysregulated by treatment with Delta(9)-THC compared to untreated, control NHA.

Spray characterization of thermal fogging equipment typically used in vector control.

Droplet size spectra from different sprayers used to generate insecticide-laden fogs for controlling flying insects were measured by a laser diffraction instrument and Teflon-coated slides. The objectives of this work were to present not only information on spray-system droplet size generated by different sprayers, but to compare methodologies by which other similar systems can be evaluated and give applicators sprayer-system performance data. Data from 45 replicated spray tests, comprising 11 sprayers and 5 pesticides, showed a wide range in the droplet size spectra produced. The volume median diameter measurements ranged from 2.6 to 75.5 microm for diesel-diluted sprays and from 27.9 to 59.9 microm for water-diluted sprays. Similarly, the percent volume <20 microm ranged between 12.0-100% and 8.5-30.7%, for diesel- and water-diluted sprays, respectively. The droplet sizes measured by the swinging slide and laser diffraction methods were not consistent. The information presented aids users in sprayer selection and operation to produce the specific droplet size spectra required for a particular application.

Characterization of patients with an inadequate clinical outcome from osteoporosis therapy: the Observational Study of Severe Osteoporosis (OSSO).

BACKGROUND: Osteoporotic fractures remain a major public health problem. Currently available osteoporosis therapies significantly reduce the risk of fractures, but up to 50% of patients have an inadequate clinical outcome to therapy. AIM: To describe the clinical and quality of life (QOL) of a study population meeting a proposed definition of inadequate clinical outcome to osteoporosis therapy, recruited for the Observational Study of Severe Osteoporosis (OSSO). DESIGN: Cross-sectional, observational study. METHODS: Post-menopausal women with osteoporosis (n = 2314) were divided into Group 1 (those who had previously experienced a fragility fracture despite osteoporosis drug therapy for at least 12 months) (n = 1309, 57%), or Group 2 (those who had previously discontinued osteoporosis drug therapy due to non-compliance or side-effects) (n = 1005; 43%). Baseline clinical characteristics, quality of life (QOL) and osteoporosis/falls risk factors were analysed. RESULTS: The overall population had low BMD (mean +/- SD T-score at lumbar spine -3.1 +/- 1.1), and risk factors for fracture such as previous fractures (67.8%), family history (15.1%), and prolonged glucocorticoid use (17.5%). QOL was poor: total QUALEFFO and EQ-5D scores were 46.8 +/- 18.7, and 0.50 +/- 0.33, respectively. Patients in Group 1 had higher age and body mass index, fewer hours of exercise, more previous fragility fractures and falls, and poorer QOL scores. DISCUSSION: Our definition of inadequate clinical outcome from osteoporosis drug therapy identifies a severe osteoporosis cohort with poor QOL and increased fracture risk. Using such a definition may lead to earlier recognition of inadequate clinical outcome to osteoporosis therapy, and improved interventions and results.

Economic evaluation of parathyroid hormone (PTH) in the treatment of osteoporosis in postmenopausal women.

Parathyroid hormone (PTH) is a new treatment for osteoporosis and has been shown to reduce the risks of vertebral and non-vertebral fractures in postmenopausal women in clinical trials. The objective of this study was to estimate the cost-effectiveness of teriparatide in addition to calcium and vitamin D, using a simulation model. The base case analysis was conducted for a cohort of 69-year-old women in Sweden who had at least one previous vertebral fracture and low bone mineral density. The model simulated the course of events in 6-month cycles in individual patients until death or 100 years of age. During each cycle the patients were at risk of experiencing clinical vertebral, hip or wrist fractures, or death. Total accumulated life-time costs and quality-adjusted life years (QALYs) were estimated. Swedish data on fracture costs, utility reductions after fracture, fracture risks and mortality rates were used. The model incorporated new epidemiological evidence that indicates fracture risks and mortality rates are higher in the subsequent years post-fracture. The results showed that the cost-effectiveness of the treatment is highly dependant on the risk profile of the treated patients and the timing of starting treatment relative to previous fractures. The cost per QALY gained for treatment of a population of 69-year-olds with a T-score at the femoral neck of -3 was in the base case estimated to be between EUR (euro) 20,000 and 64,000 for patients with a recent or historic vertebral fracture respectively. The study provides further evidence of the benefit and cost-effectiveness of starting osteoporotic treatments early in patients with a new fracture, and also that teriparatide may provide valuable clinical benefits for these patients and may be considered a cost-effective intervention when targeted to the appropriate patients.

Contributions of depressive mood and circulating inflammatory markers to coronary heart disease in healthy European men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME).

BACKGROUND: Data on the possible association between depressive disorders and inflammatory markers are scarce and inconsistent. We investigated whether subjects with depressive mood had higher levels of a wide range of inflammatory markers involved in coronary heart disease (CHD) incidence and examined the contribution of these inflammatory markers and depressive mood to CHD outcome. METHODS AND RESULTS: We built a nested case-referent study within the Prospective Epidemiological Study of Myocardial Infarction (PRIME) study of healthy middle-aged men from Belfast and France. We considered the baseline plasma sample from 335 future cases (angina pectoris, nonfatal myocardial infarction, coronary death) and 670 matched controls (2 controls per case). Depressive mood characterized men whose baseline depression score (13-item modification of the Welsh depression subscale) was in the fourth quartile (mean score, 5.75; range, 4 to 12). On average, men with depressive mood had 46%, 16%, and 10% higher C-reactive protein, interleukin-6, and intercellular adhesion molecule-1 levels, respectively, independently of case-control status, social characteristics, and classic cardiovascular risk factors; no statistical difference was found for fibrinogen. The odds ratios of depressive mood for CHD were 1.35 (95% CI, 1.05 to 1.73) in univariate analysis and 1.50 (95% CI, 1.04 to 2.15) after adjustment for social characteristics and classic cardiovascular risk factors. The latter odds ratio remained unchanged when each inflammatory marker was added separately, and in this analysis, each inflammatory marker contributed significantly to CHD event risk. CONCLUSIONS: These data support an association of depressive mood with inflammatory markers and suggest that depressive mood is related to CHD even after adjustment for these inflammatory markers.

Help-seeking behaviour and associated factors among women with urinary incontinence in France, Germany, Spain and the United Kingdom.

OBJECTIVES: To assess the proportion of women who consult their doctor about urinary incontinence (UI), and explore factors associated with help-seeking in France, Germany, Spain and the UK. METHODS: A representative sample of 29,500 women received a 13 item postal questionnaire to identify those with UI. A randomly selected sub-sample of 2953 women with UI received a more detailed follow-up questionnaire. RESULTS: There was a response rate of 58% in the initial survey and 53% in the second. Thirty-one percent of all women had consulted a doctor about their UI symptoms with more women consulting in France and Germany than in the UK and Spain. A number of factors relating to general health care, UI and women's attitudes were found to be associated with help-seeking after adjusting for women's age, UI duration and frequency, and 'bothersomeness' of UI; factors traditionally associated with help-seeking. After adjusting for these factors, willingness to take long-term medication and having spoken to others about UI were found to be strong predictors of help-seeking in all four countries.

Cost-effectiveness of raloxifene in the UK: an economic evaluation based on the MORE study.

Raloxifene treatment has been shown to reduce the risk of vertebral fractures and breast cancer in postmenopausal women. The long-term economic implications of treatment with raloxifene have not yet been investigated. The aim of this study was to assess the cost-effectiveness of treating postmenopausal women in the UK with raloxifene. A previously developed computer simulation model was used to estimate the cost-effectiveness of osteoporotic treatments with extra skeletal benefits. The model was populated with epidemiological data and cost data relevant for a UK female population. Data on the effect of treatment were taken from the Multiple Outcomes of Raloxifene (MORE) study, which recruited women with low bone mineral density or with a prior vertebral fracture. Cost-effectiveness was estimated using Quality Adjusted Life Years (QALYs) and life years gained as primary outcome measures. The cost per QALY gained of treating postmenopausal women without prior vertebral fractures was 18,000 pounds, 23,000 pounds , 18,000 pounds and 21,000 pounds at 50, 60, 70 and 80 years of age. Corresponding estimates for women with prior vertebral fractures were 10,000 pounds, 24,000 pounds, 18,000 pounds and 20,000 pounds. In relation to threshold values that are recommended in the UK, the analysis suggests that raloxifene is cost-effective in the treatment of postmenopausal women at an increased risk of vertebral fractures.

Pharmaceutical treatment of symptomatic vertebral fractures in primary care.

BACKGROUND: Vertebral fractures are associated with a reduction in quality of life and are an important predictor of other non-spine fractures. Previous work has shown that up to 60% of patients with a vertebral fracture identified in primary care remain untreated. OBJECTIVE: To examine the prevalence of pharmaceutical treatment and predictors of treatment in a primary care setting. METHODS: Case-control study using the general practice research database (GPRD). All women aged 50 years and over with a first diagnosis of a vertebral fracture since 1990 were identified and matched with a control by age and practice. Appropriate use of a pharmaceutical agent was defined as a prescription occurring within 30 days of the diagnosis being recorded. RESULTS: We identified 2719 women with the same number of controls. Within 30 days of diagnosis 61% of women were prescribed treatment, compared with only 3% of the controls. Bisphosphonate was the single most important treatment prescribed. Predictors of any drug treatment included: year of fracture (most recent year increased the likelihood of treatment); age (younger patients were more likely to receive treatment); history of back pain; low body weight; history of steroid use. CONCLUSIONS: Treatment of diagnosed vertebral fractures is becoming more common. Treated patients tend to be younger but to have a higher prevalence of clinical risk factors than untreated patients. There remain significant numbers of patients who are not offered treatment.

The prevalence of urinary incontinence in women in four European countries.

OBJECTIVE: To determine the prevalence, type and treatment behaviour of women with urinary incontinence in four European countries. SUBJECTS AND METHODS: Data were collected using a postal survey which was sent to 29,500 community-dwelling women aged > or = 18 years in France, Germany, Spain and the UK. Subjects were asked about the type of urinary incontinence they had experienced and their treatment behaviour. RESULTS: Of the women who responded, 35% reported involuntary loss of urine in the preceding 30 days; stress urinary incontinence was the most prevalent type. The lowest prevalence was in Spain (23%), while the prevalence was 44%, 41% and 42% for France, Germany and the UK, respectively. About a quarter of women with urinary incontinence in Spain (24%) and the UK (25%) had consulted a doctor about it; in France (33%) and Germany (40%) the percentages were higher. Overall, <5% of the women had ever undergone surgery for their condition. While pads were used by half of the women, there were some differences among the countries. CONCLUSIONS: Millions of women in Europe have urinary incontinence; the consultation and treatment rates were low in the European countries included in this study.