Impact of osteoarthritis disease severity on treatment patterns and healthcare resource use: analysis of real-world data.

OBJECTIVE: To understand treatment patterns and healthcare resource utilization (HCRU) related to osteoarthritis (OA) disease severity in patients in five European countries. METHOD: Data were drawn from the Adelphi OA Disease Specific Programme™ (2017-18). Physicians classified their patients as having mild, moderate, or severe OA, and provided details on their current prescribed therapy and HCRU, including healthcare professional (HCP) consultations, diagnostics and testing, and hospitalizations. Comparisons between disease severity groups were made using analysis of variance and chi-squared tests. RESULTS: The study included 489 physicians (primary care physicians, rheumatologists, orthopaedic surgeons) reporting on 3596 OA patients: 24% mild, 53% moderate, and 23% severe disease. Both physicians and patients reported decreasing satisfaction with treatment with greater disease severity, despite the number of classes of prescribed drugs and increased use of opioids, which were used in almost half of patients with severe OA. For patients whose treatment was not effective, physicians prescribed the same therapeutic options, which were cycled in subsequent treatment lines, with multiple treatment regimens being commonly used. Patients with greater symptom severity also had more physician consultations, while the numbers of tests/imaging, predominantly X-rays, conducted to diagnose or monitor OA increased significantly with disease severity. The type of HCP involvement in patient management also varied by OA severity. CONCLUSIONS: Across five European countries, the use of both non-pharmacological and pharmacological treatments increases with greater disease severity. Those with more severe disease place a greater demand on healthcare resources, with HCP consultations, tests, and hospital visits increasing with severity.

Patient preferences for osteoarthritis pain and chronic low back pain treatments in the United States: a discrete-choice experiment.

OBJECTIVE: To quantify preferences for attributes of potential analgesic treatments for moderate-to-severe pain associated with osteoarthritis (OA) and/or chronic low back pain (CLBP) as relevant to injectable nerve growth factor (NGF)-inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids. METHODS: We used a discrete-choice experiment (DCE) to elicit preferences for attributes of OA and CLBP pharmaceutical treatments, and a best-worst scaling (BWS) exercise to further characterize the relative importance of treatment-related side-effect risks. The survey was completed online by 602 US residents with self-reported chronic, moderate-to-severe OA pain and/or CLBP who had tried, had contraindications for, or were unwilling to take currently available pharmaceutical therapies. In the DCE, respondents repeatedly chose between two hypothetical treatments defined by six attributes (symptom control; treatment-related risks of (1) severe joint problems, (2) heart attack, and (3) physical dependence; mode/frequency of administration; and cost). In the BWS exercise, respondents evaluated ten side-effect risks. Random-parameters logit models were estimated; conditional relative attribute importance, maximum acceptable risks, and willingness to pay were calculated. RESULTS: The most important DCE attributes were improving symptom control (scaled conditional relative importance, 10.00) and reducing risk of physical dependence (6.99). The three most important BWS attributes were, in rank order, risks of stroke, physical dependence, and heart attack. Respondents were willing to accept a > 4% treatment-related risk of severe joint problems for even modest symptom improvement. CONCLUSION: A pharmaceutical treatment with a risk of severe joint problems was viewed as an acceptable alternative to other treatments with comparable efficacy but risks associated with NSAIDs or opioids.

Coexisting lower urinary tract symptoms and erectile dysfunction: a systematic review of epidemiological data.

OBJECTIVE: Assess and categorise the available prevalence data on coexistent LUTS and ED in the general population and among individuals consulting a healthcare provider for any reason or when seeking treatment for LUTS and/or ED. METHODS: Literature search of English-language articles published during the last 15 years. RESULTS: Of 23 relevant studies identified, 12 used both the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF) as assessment tools and 11 used alternative approaches. In studies using both IPSS and IIEF, overall prevalence of coexistent LUTS/ED of any severity was not assessable for men in the general population, but rates ranged from 14-37% based on alternative assessments. In the general male population, 13-29% had moderate to severe LUTS and 8-35% had moderate to severe ED. In studies using both IPSS and IIEF, overall prevalence of coexistent LUTS and ED of any severity was 71-80% among men seeking treatment for LUTS, and 74% based on alternative assessments. Among men who sought treatment for either condition, 67-100% had moderate to severe LUTS and 43-59% had moderate to severe ED. Coexistence of LUTS and ED increased with age, ranging from 59-86% among men aged 40s to 60s in primary care to 79-100% in treatment-seeking men with LUTS aged 50s to 70s. Impact on QoL varied, but health-related QoL was generally worse in treatment-seeking men compared with men in the general population. CONCLUSIONS: Although less than one-third of middle-aged and older men in the general population have coexisting LUTS and ED, most men seeking treatment for either LUTS or ED have both conditions. Symptom severity and impact on QoL in each condition increase when LUTS and ED coexist.

Content validity of the Benign Prostatic Hyperplasia Impact Index (BII); a measure of how urinary trouble and problems associated with BPH may impact the patient.

AIMS: The objective of this qualitative interview study was to assess the content validity of the Benign Prostatic Hyperplasia Impact Index (BII) in a sample of men with signs and symptoms of Benign Prostatic Obstruction believed to be caused by benign prostatic hyperplasia (BPH lower urinary tract symptoms/BPH-LUTS) using concept elicitation (CE) and cognitive interviewing (CI) methods. METHODS: Fifty men with BPH-LUTS participated in the study; 27 completed CE interviews and 23 completed cognitive interviews. RESULTS: Patient's average age was 69 years with a mean duration of BPH-LUTS of 6.5 years. IPSS scores ranged from 8 to 33 (higher scores indicating greater symptom severity). Overall, the most frequent symptoms (prevalence of ≥ 75%) reported spontaneously or after further explanation were awakening from sleep, increased daytime voiding (frequency), urgent desire to void (urgency), slow stream, and feeling of incomplete bladder emptying. Symptoms primarily recognized in response to follow up probe questions with a prevalence of ≥ 40% included terminal dribble, splitting of urinary stream, intermittent stream, straining and post-micturition dribble. Especially bothersome [> 5 on the numerical rating scale (NRS) of 0-10] and frequent symptoms included urgency and awakening at night to void. Discomfort or pain while urinating and post-micturition dribble were equally bothersome though less frequent. Five BPH symptom-related impact themes were identified: coping, daily responsibilities, emotion, lifestyle and relationships, and sleep. CONCLUSIONS: The BII was found to be easily understood, does capture clinically relevant BPH impacts related to urinary trouble and problems, and does capture most of the important symptom-related impacts as described by participants in this study.

Serotonin and noradrenaline involvement in urinary incontinence, depression and pain: scientific basis for overlapping clinical efficacy from a single drug, duloxetine.

AIMS: Serotonin (5-HT) and noradrenaline (NA) are important monoamine neurotransmitters that are ubiquitously distributed throughout the peripheral and central nervous system and modulate functions that are vital to survive. Both neurotransmitters may be involved in the pathophysiological process or the treatment of--at first glance--divergent disease areas, namely stress urinary incontinence, major depressive disorder and neuropathic pain. The present review aims at describing the neurophysiological similarities between these disease areas, focussing on the role of the neurotransmitters 5-HT and NA at synapses of the spinal and supraspinal neural circuitry. RESULTS/DISCUSSION: Recent clinical studies show convergence of symptoms (i.e. comorbidity) for incontinence, depression and pain, suggesting common biochemical imbalances. Duloxetine, a dual serotonin and noradrenaline reuptake inhibitor, has a central mechanism of action at different locations in the central nervous system and has proven to be a sound treatment of all these different diseases. Data obtained from animal model studies, randomised placebo-controlled clinical trials, as well as open label trials have provided evidence of the efficacy and safety of duloxetine as a suitable compound for the treatment of stress urinary incontinence in women as well as major depressive disorder and diabetic neuropathic pain in both men and women.

Female stress and urge incontinence in family practice: insight into the lower urinary tract.

As many as 25% of all women are affected by urinary incontinence, but only a few are treated. This frequent, often medically unrecognised, condition occurs in women of all ages. The continence mechanism is based on bladder detrusor control, intact anatomical structures in and around the urethra, correct positioning of the bladder neck and a comprehensive innervation of the lower urinary tract. Age and childbearing are established risk factors for the development of urinary incontinence, but other factors are currently suggested. The evaluation of urinary incontinence should include history, gynaecological examination, urine test, frequency-volume diary and a pad-weighing test. Female urinary incontinence can be treated in general practice by simple means, e.g. pelvic floor muscle training, bladder training, electrostimulation, drug therapy, or a combination of these approaches. This review updates the knowledge of the continence mechanism and summarises the epidemiology, risk factors, assessment and treatment of urinary incontinence in general practice.

Do fertile women remember the onset of stress incontinence? Recall bias 5 years after 1st delivery.

BACKGROUND: To evaluate fertile women's ability to recall the onset of stress incontinence. METHODS: In a prospective cohort study 305 primiparae were interviewed after 1st delivery and again 5 years later using a tested questionnaire. In 83 women with stress incontinence 5 years after 1st delivery history of onset was compared with data from the initial questionnaire by grouping women with onset before 1st pregnancy, during 1st pregnancy, during 1st puerperium or after 1st puerperium. RESULTS: Five years after 1st delivery only 26% recalled the onset of stress incontinence precisely. The statistical agreement for each of the four groups of women with different recall of onset varied with a Kappa from 0.02 to 0.38. CONCLUSION: Five years after 1st delivery stress incontinent women seem to recall the onset of the symptom imprecisely.

The risk of stress incontinence 5 years after first delivery.

OBJECTIVES: We aimed to evaluate the impact of a first pregnancy and delivery on the prevalence of stress incontinence 5 years afterward. STUDY DESIGN: This longitudinal cohort study included 278 women who were questioned after their first delivery and again 5 years later. RESULTS: The prevalence of stress incontinence 5 years after a first delivery was 30%, and the 5-year incidence was 19%. The risk of stress incontinence 5 years after a first delivery was related to the onset and duration of symptoms after the first pregnancy and delivery in a "dose-response-like" manner. The use of vacuum extraction or episiotomy during the first delivery increased the risk. CONCLUSIONS: First pregnancy and delivery may result in stress incontinence 5 years later. Women with incontinence 3 months after a first delivery have a particularly high risk of long-lasting symptoms. Obstetric risk factors are vacuum extraction and episiotomy.

Lower urinary tract symptoms 5 years after the first delivery.

The aim of the study was to estimate the prevalence and 5-year incidence of lower urinary tract symptoms after the first delivery. A total of 278 primiparae were questioned about lower urinary tract symptoms after their first pregnancy and puerperium, and again 5 years later. The prevalence of such symptoms in the study population increased significantly during the 5 years of observation. The prevalence of stress or urge incontinence 5 years after first delivery was significantly higher in women with onset during the first pregnancy or 1st puerperium than in those without incontinence before or during that period. The prevalence of urgency or frequent voiding 5 years after first delivery was not increased in the women with onset during that time compared to those without such symptoms. Stress or urge incontinence during the first pregnancy and puerperium predicts an increased risk of having the symptom 5 years later. Urgency and diurnal frequent voiding cannot be predicted from onset during that period.

The diagnosis of appendicitis during pregnancy and maternal and fetal outcome after appendectomy.

OBJECTIVE: A review of the literature reveals contradictive conclusions regarding appendicitis during pregnancy due to the few patients included in previous reports. METHODS: From 1980 to 1985, the Danish National Patient Registry identified the patients having the WHO codes Y60 (pregnancy), 54000 (acute appendicitis) and the operation code 43 000 (appendectomy). Each patient's file was reviewed by the authors. RESULTS: The ratio of appendicitis (n = 58) to appendectomy (n = 117) was 50%. The appendicitis group was significantly older (26.2 years) than the normal appendix group (23.8 years). Second trimester had the highest incidence of appendicitis, perforated appendicitis and normal appendix. No effect of tocolytic agents could be demonstrated. No maternal mortality. Obstetrical complications were few and appeared only in the group having a normal appendix and first after discharge. CONCLUSIONS: Pregnant women suspected of having appendicitis should be evaluated as non-pregnant women. Use of tocolytic agents is a matter of choice. Obstetrical complications are few and not related to the surgical trauma.

Fertility and long-term complications four to nine years after appendectomy during pregnancy.

BACKGROUND: The purpose of this study was to determine the long-term outcome after an appendectomy during pregnancy, especially focusing on fertility. METHODS: The Danish National Registry of Patients identified 117 pregnant women who had had an appendectomy during the period 1980 to 1985. One hundred-and-one of these women answered a questionnaire designed to focus on long-term complications, including infertility, during a 4 to 9 year period after the appendectomy. More than a 2-year attempt to conceive was defined as infertility. RESULTS: Of the 101 women 15 with a normal appendix had a new intraperitoneal operation due to different indications. Three of these women had intraperitoneal adhesions. In one patient, adhesions were located on the Fallopian Tube but the location did not influence fertility. Five of the 101 women complained of infertility as defined; all had a normal appendix and none had intraperitoneal surgery during the observation period. Two of these five women conceived later during the observation period; one had confounding female and male infertility factors and two were not examined. CONCLUSIONS: Appendectomy during pregnancy of a normal, inflamed or perforated appendix does not seem to cause clinically significant intraperitoneal adhesions or infertility later in life.

Delayed onset of fatal basilar thrombotic embolus after whiplash injury.

BACKGROUND: Whiplash injuries are generally seen after rear-end rather than frontal car collisions. Previous reports have documented death up to 8 days after serious whiplash injury. We report a case of lethal basilar thrombotic embolus that occurred 2 months after the patient's injury in a collision. CASE DESCRIPTION: After whiplash trauma in a car accident, a 50-year-old taxi driver suffered from headache and episodic visual disturbances. Two months after the accident he suddenly lost consciousness and was admitted to the hospital. A CT scan performed at that time was indicative of basilar thrombosis. The patient died 3 days later. The autopsy revealed a thrombosis in the right vertebral artery and a thrombotic embolus in the basilar artery. Microscopically, a lesion of the right vertebral artery was found at the level of the atlantoaxial joint. CONCLUSIONS: We conclude that the whiplash injury caused a lesion of the right vertebral artery, leading to repeated transient ischemic attacks and finally to a fatal basilar thrombotic embolus. We suggest that in patients with disturbances of the vertebrobasilar circulation, attention should be paid to occurrence of neck trauma in the preceding 3 months. Further, anticoagulant therapy should particularly be considered in patients who after suffering neck injuries develop signs of transient ischemic attacks with origin from the posterior cerebral circulation.

Epidural anesthesia during labor and stress incontinence after delivery.

OBJECTIVE: To test the hypothesis that epidural anesthesia during labor prevents the development of stress incontinence after vaginal birth. METHODS: We interviewed 208 primiparas about stress incontinence 3 months postpartum. The women who developed stress incontinence after delivery were interviewed again 1 year postpartum. RESULTS: Twelve of 45 women (27%) who had epidural anesthesia developed stress incontinence de novo after vaginal delivery, versus 21 of 163 (13%) who did not receive epidural anesthesia, a marginally significant difference (P = .05). Those who had epidural anesthesia also had a significantly longer first stage of labor. One year after delivery, three of 42 (7%) in the epidural anesthesia group had stress incontinence, compared with five of 163 (3%) in the control group. CONCLUSION: Our results do not support the hypothesis that epidural anesthesia protects against the development of stress incontinence after vaginal delivery.

[Bronchial asthma treated with long-acting beta 2 agonist. Comparison between formoterol (12 mu/g) inhaled twice daily and salbutamol (200 mu/g) inhaled 4 times daily]. / Asthma bronchiale behandlet med langtidsvirkende beta 2-agonist. En sammenligning mellem formoterol (12 micrograms) inhaleret to gange daglig og salbutamol (200 micrograms) inhaleret fire gange daglig.

Forty patients with stable asthma and daily need for inhaled beta 2-agonist, were included in a randomized double-blind study. They were treated for six weeks with inhaled beta 2-agonist, either salbutamol, 4 x 200 micrograms daily, of formoterol, 2 x 12 micrograms and 2 x placebo daily. This was preceded by a run-in period, where all patients received terbutalin-inhalation, 4 x 500 micrograms daily. Twenty patients were given formoterol and 18 salbutamol. One patient in the salbutamol-treated group discontinued treatment after three weeks, because of deterioration of asthma. On a diary card, patients recorded peak expiratory flow rate (PEFR) morning and evening before medication, score of asthma symptoms (scale 0-3; 0 = no symptoms, and 3 = severe symptoms) and use of additional doses of beta 2-agonist. Forced expiratory volume in 1 sec. (FEV1), forced vital capacity (FVC) and PEFR were obtained after 0, three and six weeks of treatment. Blinded global assessment of the treatment was performed by both patient and physician at the end of the study. During run-in the two groups of patients were different. The group subsequently treated with salbutamol had a statistical significant (ss) higher morning-PEFR, ss fewer asthma-symptom scores than one during night and ss less need for additional puffs of beta 2-agonist. During treatment, the formoterol-treated group showed an ss increase in morning-PEFR, as compared to run-in. Furthermore this group had ss fewer nocturnal symptom scores than one and ss less need for extra beta 2-agonist during night, than the salbutamol-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

The symptom of stress incontinence caused by pregnancy or delivery in primiparas.

Three hundred five primiparas were interviewed repeatedly about stress incontinence before and during pregnancy and after delivery. Eleven (4%) had stress incontinence before pregnancy and 98 (32%) during pregnancy, whereas 21 (7%) developed it after delivery. According to the International Continence Society definition, the corresponding frequencies were one (0.3%), three (1%), and one (0.3%), respectively. Obstetric factors such as length of the second stage of labor, head circumference, birth weight, and episiotomy seemed to be associated with, whereas cesarean delivery seemed to protect against, the development of stress incontinence after delivery. Three months after delivery, the statistically significant influence of the obstetric factors had vanished, as stress incontinence had disappeared in most women. However, 1 year after delivery eight of 292 women (3%) had stress incontinence, three with onset during pregnancy and five with onset after delivery. Three of these eight had stress incontinence according to International Continence Society criteria; four women wanted treatment. The symptom of stress incontinence occurs as a natural consequence of pregnancy and delivery and generally resolves in the puerperium. However, pregnancy and delivery carry a small risk (1% or less) of initiating persistent stress incontinence. The importance of various obstetric factors seems transient and their etiologic role remains unclear.