Estimating excess mortality and economic burden of Clostridioides difficile infections and recurrences during 2015-2019: the RECUR Germany study.

BACKGROUND: Clostridioides difficile infections (CDIs) and recurrences (rCDIs) remain a major public health challenge due to substantial mortality and associated costs. This study aims to generate real-world evidence on the mortality and economic burden of CDI in Germany using claims data between 2015 and 2019. METHODS: A longitudinal and matched cohort study using retrospective data from Statutory Health Insurance (SHI) was conducted in Germany with the BKK database. Adults diagnosed with CDI in hospital and community settings between 2015 and 2018 were included in the study. Patients had a minimum follow-up of 12-months. All-cause mortality was described at 6-, 12-, and 24-months. Healthcare resource usage (HCRU) and associated costs were assessed at 12-months of follow-up. A cohort of non-CDI patients matched by demographic and clinical characteristics was used to assess excess mortality and incremental costs of HCRU. Up to three non-CDI patients were matched to each CDI patient. RESULTS: A total of 9,977 CDI patients were included in the longitudinal cohort. All-cause mortality was 32%, 39% and 48% at 6-, 12-, and 24-months, respectively, with minor variations by number of rCDIs. When comparing matched CDI (n = 5,618) and non-CDI patients (n = 16,845), CDI patients had an excess mortality of 2.17, 1.35, and 0.94 deaths per 100 patient-months, respectively. HCRU and associated costs were consistently higher in CDI patients compared to non-CDI patients and increased with recurrences. Total mean and median HCRU cost per patient during follow-up was €12,893.56 and €6,050 in CDI patients, respectively, with hospitalisations representing the highest proportion of costs. A total mean incremental cost per patient of €4,101 was estimated in CDI patients compared to non-CDI patients, increasing to €13,291 in patients with ≥ 3 rCDIs. CONCLUSIONS: In this real-world study conducted in Germany, CDI was associated with increased risk of death and substantial costs to health systems due to higher HCRU, especially hospitalisations. HCRU and associated costs were exacerbated by rCDIs.

Clostridioides difficile infection, recurrence and the associated healthcare consumption in Sweden between 2006 and 2019: a population-based cohort study.

BACKGROUND: Clostridioides difficile infection (CDI) causes a major burden to individuals and society, yet the impact may vary depending on age, sex, underlying comorbidities and where CDI was acquired (hospital or community). METHODS: This Swedish nationwide population-based cohort study (2006-2019) compared all 43,150 individuals with CDI to their 355,172 matched controls (first year and entire follow-up). Negative binomial regression models compared the cumulated length of stay, number of in-hospital admissions, outpatient visits and prescriptions after the first CDI episode expressed as incidence rate ratios (IRR) and 95% confidence intervals for the entire follow-up. RESULTS: Overall, 91.6% of CDI cases were hospital acquired, and 16.8% presented with recurrence(s); 74.8%of cases were ≥ 65 years and 54.2% were women. Compared to individuals without CDI, in-hospital stay rates were 18.01 times higher after CDI (95% CI 17.40-18.63, first-year: 27.4 versus 1.6 days), 9.45 times higher in-hospital admission (95% CI 9.16-9.76, first-year: 2.6 versus 1.3 hospitalisations), 3.94 times higher outpatient visit (95% CI 3.84-4.05, first-year: 4.0 versus 1.9 visits) and 3.39 times higher dispensed prescriptions rates (95% CI 3.31-3.48, first-year: 25.5 versus 13.7 prescriptions). For all outcomes, relative risks were higher among the younger (< 65 years) than the older (≥ 65 years), and in those with fewer comorbidities, but similar between sexes. Compared to those without recurrence, individuals with recurrence particularly showed a higher rate of hospital admissions (IRR = 1.18, 95% 1.12-1.24). Compared to community-acquired CDI, those with hospital-acquired CDI presented with a higher rate of hospital admissions (IRR = 7.29, 95% CI 6.68-7.96) and a longer length of stay (IRR = 7.64, 95% CI 7.07-8.26). CONCLUSION: CDI was associated with increased health consumption in all affected patient groups. The majority of the CDI burden could be contributed to hospital-acquired CDI (~ 9/10), older patients (~ 3/4) and those with multiple comorbidities (~ 6/10 Charlson score ≥ 3), with 1/5 of the total CDI burden contributed to individuals with recurrence. Yet, relatively speaking the burden was higher among the younger and those with fewer comorbidities, compared to their peers without CDI.

Epidemiological and clinical burden of Clostridioides difficile infections and recurrences between 2015 - 2019: the RECUR Germany study.

BACKGROUND: This real-world study assessed the epidemiology and clinical complications of Clostridioides difficile infections (CDIs) and recurrences (rCDIs) in hospital and community settings in Germany from 2015 - 2019. METHODS: An observational retrospective cohort study was conducted among adult patients diagnosed with CDI in hospital and community settings using statutory health insurance claims data from the BKK database. A cross-sectional approach was used to estimate the annual incidence rate of CDI and rCDI episodes per 100,000 insurants. Patients' demographic and clinical characteristics were described at the time of first CDI episode. Kaplan-Meier method was used to estimate the time to rCDIs and time to complications (colonic perforation, colectomy, loop ileostomy, toxic megacolon, ulcerative colitis, peritonitis, and sepsis). A Cox model was used to assess the risk of developing complications, with the number of rCDIs as a time-dependent covariate. RESULTS: A total of 15,402 CDI episodes were recorded among 11,884 patients. The overall incidence of CDI episodes declined by 38% from 2015 to 2019. Most patients (77%) were aged ≥ 65 years. Around 19% of CDI patients experienced at least one rCDI. The median time between index CDI episode to a rCDI was 20 days. The most frequent complication within 12-months of follow-up after the index CDI episode was sepsis (7.57%), followed by colectomy (3.20%). The rate of complications increased with the number of rCDIs. The risk of any complication increased by 31% with each subsequent rCDI (adjusted hazard ratio [HR]: 1.31, 95% confidence interval: 1.17;1.46). CONCLUSIONS: CDI remains a public health concern in Germany despite a decline in the incidence over recent years. A substantial proportion of CDI patients experience rCDIs, which increase the risk of severe clinical complications. The results highlight an increasing need of improved therapeutic management of CDI, particularly efforts to prevent rCDI.

Estimating excess mortality and economic burden of Clostridioides difficile infections and recurrences during 2015-2019: The RECUR England study.

OBJECTIVES: To generate real-world evidence on all-cause mortality and economic burden of Clostridioides difficile infections (CDIs) and recurrences (rCDIs) in England. METHODS: We conducted a cohort study using retrospective data from Clinical Practice Research Datalink linked to Hospital Episode Statistics. Patients diagnosed with CDI in hospital and community settings during 2015-2018 were included and followed for ≥1 year. All-cause mortality was described at 6, 12, and 24 months. Healthcare resource usage (HCRU) and associated costs were assessed at 12 months of follow-up. A cohort of non-CDI patients, matched by demographic and clinical characteristics including Charlson Comorbidity Index score, was used to assess excess mortality and incremental costs of HCRU. RESULTS: All-cause mortality among CDI patients at 6, 12, and 24 months was 15.87%, 20.37%, and 27.03%, respectively. A higher proportion of rCDI patients died at any point during follow-up. Compared with matched non-CDI patients, excess mortality was highest at 6 months with 1.81 and 2.53 deaths per 100 patient-months among CDI and ≥1 rCDI patients. Hospitalizations were the main drivers of costs, with an incremental cost of £1209.21 per CDI patient. HCRU and costs increased with rCDIs. CONCLUSION: CDI poses a substantial mortality and economic burden, further amplified by rCDIs.

The combined effect of systemic antibiotics and proton pump inhibitors on Clostridioides difficile infection and recurrence.

BACKGROUND: Antibiotics and proton pump inhibitors (PPI) are recognized risk factors for acquisition and recurrence of Clostridioides difficile infection (CDI), yet combined effects remain unclear. OBJECTIVES: To assess the short- and long-term effects of antibiotics and PPIs on CDI risk and recurrence. METHODS: Population-based study including all 43 152 patients diagnosed with CDI in Sweden (2006-2019), and 355 172 matched population controls without CDI. The impact of antibiotics and PPIs on CDI risk and recurrence was explored for recent (0-30 days) and preceding (31-180 days) use prior to their first CDI diagnosis, using multivariable conditional logistic regression presented as odds ratios (ORs) and 95% confidence interval, adjusted for demographics, comorbidities and other drugs. RESULTS: Compared to controls, the combined effect of recent PPIs and antibiotics [ORAB+PPI = 17.51 (17.48-17.53)] on CDI risk was stronger than the individual effects [ORAB = 15.37 (14.83-15.93); ORPPI = 2.65 (2.54-2.76)]. Results were less pronounced for exposure during the preceding months. Dose-response analyses showed increasing exposure correlated with CDI risk [recent use: ORAB = 6.32 (6.15-6.49); ORPPI = 1.65 (1.62-1.68) per prescription increase].Compared to individuals without recurrence (rCDI), recent [ORAB = 1.30 (1.23-1.38)] and preceding [ORAB = 1.23 (1.16-1.31); ORPPI = 1.12 (1.03-1.21)] use also affected the risk of recurrence yet without significant interaction between both. Recent macrolides/lincosamides/streptogramins; other antibacterials including nitroimidazole derivates; non-penicillin beta lactams and quinolones showed the strongest association with CDI risk and recurrence, particularly for recent use. PPI use, both recent and preceding, further increased the CDI risk associated with almost all antibiotic classes. CONCLUSION: Recent and less recent use of PPIs and systemic antibiotics was associated with an increased risk of CDI, particularly in combination.

Clostridioides difficile infections, recurrences, and clinical outcomes in real-world settings from 2015 to 2019: The RECUR England study.

OBJECTIVE: To estimate the epidemiological and clinical burden of Clostridioides difficile infections (CDIs) and recurrences (rCDIs) in England. METHODS: This retrospective study included adult patients diagnosed with CDI (community or hospital settings) over 2015-2019 from Clinical Practice Research Datalink and Hospital Episode Statistics databases. Incidences of CDI and rCDI were determined annually. Time to subsequent rCDI was estimated by Kaplan-Meier method. Rates of complications were assessed within 12 months from index episode. Association of risk factors with complications was evaluated using a Cox regression model. RESULTS: A total of 52,443 CDI episodes were recorded among 36,913 patients. Of these, 75% were aged ≥65 years, 59% were women; 73% were treated in community settings. CDI incidence remained stable (111 episodes per 100,000 patients in 2019). Around 21% of patients had ≥1 rCDI. Sepsis (12%) was the most common complication, followed by colectomy and ulcerative colitis. Age, gender, comorbidities, rCDI, preindex medical procedures, hospitalizations and consultations, and CDI treatment in hospital, were found to increase the risk of complication. CONCLUSIONS: CDI remains a concern in England. The study highlights the importance of managing primary and rCDI episodes via effective and improved therapies to prevent fatal complications.

Clostridioides difficile infection-associated cause-specific and all-cause mortality: a population-based cohort study.

OBJECTIVES: Clostridioides difficile infection (CDI) is a common healthcare-associated infection and leading cause of gastroenteritis-related mortality worldwide. However, data on CDI-associated mortality are scarce. We aimed to examine the association between CDI and all-cause and cause-specific mortality. We additionally explored contributing causes of mortality, including recurrent CDI, hospital- or community-acquired CDI, chronic comorbidities, and age. METHODS: This nationwide population-based cohort study (from 2006 to 2019) compared individuals with CDI with the entire Swedish background population using standardized mortality ratios. In addition, a matched-cohort design (1:10), utilizing multivariable Poisson-regression models, provided incidence rate ratios (IRRs) with 95% CIs. RESULTS: This study included 43 150 individuals with CDI and 355 172 controls. In total, 69.7% were ≥65 years, and 54.9% were female. CDI was associated with a 3- to 7-fold increased mortality rate (IRR = 3.5, 95% CI: 3.3-3.6; standardized mortality ratio = 6.8, 95% CI: 6.7-6.9) compared with the matched controls and Swedish background population, respectively. Mortality rates were highest for hospital-acquired CDI (IRR = 2.4, 95% CI: 1.9-3.2) and during the first CDI episode (IRR = 0.2, 95% CI: 0.2-0.3 for recurrent versus first CDI). Individuals with CDI had more chronic comorbidities than controls, yet mortality remained higher among CDI cases even after adjustment and stratification for comorbidity; CDI was associated with increased mortality (IRR = 6.1, 95% CI: 5.5-6.8), particularly among those without any chronic comorbidities. DISCUSSION: CDI was associated with elevated all-cause and cause-specific mortality, despite possible confounding by ill health. Mortality rates were consistently increased across sexes, all age groups, and comorbidity groups.

Unmet Parenthood Goals, Health-Related Quality of Life and Apparent Irrationality: Understanding the Value of Treatments for Infertility.

An increasing number of prospective parents are experiencing infertility along with associated negative impacts on mental health and life satisfaction that can extend across a network of individuals and family members. Assistive reproductive technologies (ART) can help prospective parents achieve their parenthood goals but, like any health technology, they must demonstrate acceptable 'value for money' to qualify for public funding. We argue that current approaches to understanding the value of ART, including quality-adjusted life-year (QALY) gains based on changes in health-related quality of life (HRQOL) and, more often, cost per live birth, are too narrow to capture the full impact of unmet parenthood goals and ART. We see a fundamental disconnect between measures of HRQOL and broader measures of wellbeing associated with met and unmet parenthood goals. We also suggest that simple concepts such as 'patient' and 'carer' are of limited applicability in the context of ART, where 'spillovers' extend across a wide network of individuals, and the person receiving treatment is often not the infertile individual. Consideration of individual and societal wellbeing beyond HRQOL is necessary to understand the full range of negative impacts associated with unmet parenthood goals and the corresponding positive impacts of successful ART. We suggest moving towards a wellbeing perspective on value to achieve a fuller understanding of value and promote cross-sector allocative efficiency.

Nocturnal polyuria in women: results from the EpiNP study.

INTRODUCTION AND HYPOTHESIS: Data from a large US population-based, cross-sectional, epidemiological study (the EpiNP Study) were used to assess the symptoms and bother experienced by women with nocturnal polyuria (NP). METHODS: Consenting participants recruited from an online panel completed the baseline EpiNP survey online (Lower Urinary Tract Symptoms Tool and urological comorbidities). All reporting ≥2 voids/night and a random sample of 100 respondents, each reporting 0 or 1 void/night were asked to complete a 3-day web-based bladder diary recording time, volume, and urgency rating of each void. NP was calculated by the proportion of urine production that occurred during nocturnal hours using a Nocturnal Polyuria Index (NPI33) threshold of >0.33 or nocturnal urine production of >90 ml/h (NUP90). The frequency of participants reporting LUTS and bother was determined by age and NP: idiopathic NP, NP associated with overactive bladder (NPOAB), NP associated with comorbidities (NPCom), and no NP (did not meet NP criteria). RESULTS: A total of 5,290 women completed the baseline survey. Mean age (range) was 54.9 (30-95) years; 1,841 (34.8%) reported ≥2 nocturnal voids. The prevalence of LUTS increased across the lifespan; however, bother associated with each LUTS decreased with increasing age. The percentage of women rating bother by nocturia episodes ≥2 "> somewhat" ranged from 40.3% to 68.3%, with bother ratings highest in the NPOAB and No NP groups. CONCLUSIONS: NP is prevalent in women with considerable bother and is often associated with other urinary symptoms. Multifactorial causes and potential treatments of NP should be considered, particularly at a later age.

The patient burden of nocturnal polyuria in the United States: Results from the epidemiology of nocturnal polyuria (EpiNP) study.

OBJECTIVES: To explore the impact of nocturnal polyuria (NP) on health-related quality of life (HRQoL), work productivity, mental health, fatigue, bother, and daytime sleepiness. MATERIALS AND METHODS: This large-scale, US population-representative epidemiologic study was conducted in two parts: a web-based survey and 3-day bladder diary. Consenting participants completed the baseline Epidemiology of NP (EpiNP) survey online (Lower Urinary Tract Symptoms [LUTS] Tool, comorbidities, burden, and multiple HRQoL measures). Participants who reported ≥2 voids/night, and a random sample of 100 respondents each reporting 0 or 1 void/night, were sent urine measurement containers and asked to complete the 3-day bladder diary. NP was defined as Nocturnal Polyuria Index >0.33 (NPI33) or nocturnal urine production >90 ml/h (NUP90). Five subgroups were created: Idiopathic NP (NP with no underlying cause), NP associated with symptoms of overactive bladder (NPOAB) or bladder outlet obstruction (NPBOO; men only), NP associated with other comorbidities (NPCOM; e.g., diabetes, hypertension, heart disease, sleep apnea), and no NP (did not meet NP criteria). RESULTS: A total of 4893 men and 5297 women completed the EpiNP survey; mean age was 54.4 (SD = 14.7). Significantly greater patient burden (p < 0.0001) was evidenced in the nocturia group (≥2 voids/night) versus no nocturia group (0-1 void/night) on daily impact of nocturia, LUTS Bother, prostate symptoms (men only), work productivity, physical and mental health component scores, depression, fatigue, and daytime sleepiness. NP subgroup analyses showed men in the NPBOO group and women in the NPOAB group reported the greatest impact on LUTS bother, fatigue, physical health, work productivity impairment, daytime sleepiness, and depression (women only). CONCLUSION: This was the first large-scale, epidemiologic study to explore the impact of different forms of NP on patients' HRQoL. Findings demonstrate that NP associated with other urologic or comorbid conditions appears to have greater patient burden than idiopathic NP, in particular for women.

Non-invasive monitoring and treat-to-target approach are cost-effective in patients with mild-moderate ulcerative colitis.

BACKGROUND: There are no data to assess the value associated with a treat-to-target (T2T) strategy based on tight control of mild-moderate ulcerative colitis (UC). AIM: To assess the cost-effectiveness of a T2T approach based on the normalisation of clinical signs and faecal calprotectin (FC) METHODS: A decision analytical Markov model was developed to compare T2T algorithm combining clinical symptoms and FC levels to define treatment response and the possible switch to the next treatment line (T2T-FC), and the reference strategy based only on symptoms. The model included five treatment lines and was conducted from the Italian national health service (NHS) perspective using a 3-year time horizon. The model calculated the incremental cost-effectiveness ratio as € per relapse avoided. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: The cost-effectiveness analysis produced an increased time spent by a patient in clinical remission and FC ≤ 100 level (+0.177 years; about 2 months) and a decreasing number of relapses (-0.1937; -20.9%) per patient using a T2T-FC approach compared to only symptoms. Furthermore, the T2T-FC was associated with higher cost (+€1795). The ICER estimated was €9263 per relapse avoided. These results were confirmed by sensitivity analyses. CONCLUSIONS: T2T-FC approach resulted in a higher benefit for mild-moderate UC patients in terms of time in remission and incidence of relapse but was associated with higher costs. Clinical trials and real-world clinical studies are needed to provide additional data on the cost-benefit of this approach.

Partially different? The importance of general equilibrium in health economic evaluations: An application to nocturia.

Both the human capital approach and the friction cost approach are frequently used to quantify the productivity costs associated with illness, disability or death in health economic evaluations. In this paper we argue that these approaches have one major, but common shortcoming: they only capture partial equilibrium (PE) effects and therefore underestimate the true potential productivity costs associated with health conditions. They neglect the sizable, indirect, ripple effects in the economy captured by general equilibrium (GE) models. To demonstrate our point, we compare a traditional PE with a GE approach for the application to nocturia, a condition characterized by the need to frequently wake up at night to urinate. Nocturia is associated with substantial impairment of daytime functioning and work productivity. We employ large-scale United Kingdom (UK) employer-employee survey data to estimate the prevalence and productivity loss. These estimates are then used as shared inputs to drive both approaches. We find that the traditional PE approach underestimates the annual productivity cost of clinically relevant nocturia by around 16%. We propose a generalized GE/PE multiplier to approximate the GE effect for other health conditions. Our findings stress the importance of accounting for sizable GE effects when conducting health economic evaluations.

Differences in the Prevalence of Nocturnal Polyuria in the U.S. by Definition: Results from the Epidemiology of Nocturnal Polyuria Study.

PURPOSE: Prevalence data on nocturnal polyuria (NP), nocturia caused by overproduction of urine during sleep, is primarily limited to men and varies by NP definition. This U.S.-representative epidemiological study of men and women ≥30 years old assessed the prevalence of NP. MATERIALS AND METHODS: Consenting participants completed the baseline EpiNP (Epidemiology of Nocturnal Polyuria) survey (eg Lower Urinary Tract Symptoms Tool, comorbidities). All reporting ≥2 voids/night and a target of 100 random respondents reporting 0 or 1 void/night were asked to complete 3-day bladder diaries. NP was defined as nocturnal polyuria index (NPI) >0.33 (NPI33) and nocturnal urine production >90 ml/hour (NUP90). Extrapolated prevalence was stratified by sex and subgroups: idiopathic (without underlying causes), associated with overactive bladder (NPOAB), bladder outlet obstruction (NPBOO; men) and comorbidities. Voided volumes and timing, including first uninterrupted sleep period, were assessed by subgroup. RESULTS: A total of 10,190 individuals completed the baseline survey; mean age (range) was 54.4 (30-95). A total of 3,938 individuals were invited to complete the diary; 1,763 (49.3%) completed 3-day bladder diaries. Urine production (maximum nighttime volume, total volume, nocturnal urine production, nocturia index) was higher in both men and women with idiopathic NP and comorbidities. The median number of nighttime voids was greatest for NPBOO in men and NPOAB in women. Bother associated with nighttime voiding differed by NP subgroup but was highest in NPBOO for men (NPI33: 69.6%; NUP90: 71.1%) and NPOAB for women (NPI33: 67.5%; NUP90: 66.0%). CONCLUSIONS: This population-based NP prevalence study including men and women characterizes NP subgroups and provides insights into nocturia treatment by emphasizing factors influencing urine production versus factors influencing bladder capacity.

The Prevalence of Nocturnal Polyuria in the United States: Results from the Epidemiology of Nocturnal Polyuria Study.

BACKGROUND: The prevalence of nocturnal polyuria (NP), which is passing large volumes of urine during the main sleep period, has been investigated primarily in middle-aged to older men. There is thus a gap in the NP evidence base for women and for younger individuals. OBJECTIVE: To estimate the prevalence of nocturia due to NP in the USA. DESIGN, SETTING, AND PARTICIPANTS: This large epidemiologic study used a US population-representative sample of men and women aged ≥30 yr to assess the prevalence of NP (NCT04125186). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Consenting participants completed an online survey (Lower Urinary Tract Symptoms Tool and comorbidities). All who reported two or more voids per night and 100 random respondents each reporting no or one void per night were asked to complete a 3-d bladder diary. Two NP definitions were used: nocturnal urine production >90 ml/h (NUP90) and Nocturnal Polyuria Index >0.33 (NPI33). Crude and population-adjusted prevalence results were calculated from completed diaries for the following subgroups by sex and age: idiopathic NP; NP with overactive bladder (NP-OAB) or bladder outlet obstruction (NP-BOO; men only); NP associated with other comorbidities; and no NP (did not meet the NPI33 or NUP90 definition). RESULTS AND LIMITATIONS: Among the 10,190 respondents who completed the survey, the mean age was 54.4 yr (range 30-95); 3,339 reported two or more nocturnal voids and 1,763 completed the 3-d diary (response rate 49.3%). The adjusted overall NP prevalence was 31.5% among men and 38.5% among women using the NPI33 definition, and 23.8% among men and 18.1% among women using NUP90. The adjusted idiopathic NP prevalence was lower among men (NPI33: 5.2%; NUP90: 1.4%) than among women (NPI33: 9.8%; NUP90: 4.0%). The prevalence of idiopathic NP decreased with age as NP associated with other possible causes increased with age in men (most common, BOO) and women (most common, OAB). CONCLUSIONS: This is the first population-based study of NP prevalence to include men, women, and young adults. NP is common; a multifactorial etiology should be considered, particularly as age increases. PATIENT SUMMARY: In this population-based US study, we examined the frequency of nighttime urination among men and women aged ≥30 y and older. We found that nighttime urination is common among men and women. Many conditions can lead to increased nighttime urination as people age.

Cost-effectiveness analysis of carbetocin versus oxytocin for the prevention of postpartum hemorrhage following vaginal birth in the United Kingdom.

AIMS: To assess the cost-effectiveness of carbetocin versus oxytocin for the prevention of postpartum hemorrhage (PPH) following vaginal birth from the perspective of the UK National Health Service (NHS). MATERIALS AND METHODS: A decision tree model was designed to analyze the cost per PPH event avoided associated with utilizing carbetocin versus oxytocin for prophylactic treatment of PPH in women following vaginal birth from a UK perspective. It modelled the potential for women to require an additional uterotonic after prophylaxis, and to still experience a PPH event and receive associated treatment. Inpatient recovery and follow-up periods post-PPH were also included in the model. Costs associated with drug acquisition and administration, PPH management (i.e. additional staffing and possible operating theater and high dependency unit utilization), inpatient hospitalization, and follow-up visits were all considered. Adverse event management costs were not included. Resource utilization varied depending on the severity of the PPH event (as defined by the amount of blood lost). PPH events avoided were estimated. In an exploratory analysis, quality adjusted life years (QALYs) were estimated as well. RESULTS: In the deterministic base case, costs were £55 lower and PPH events were 0.0342 lower per woman with carbetocin use compared to oxytocin use. Across the cohort of 100 women the reduction in PPH events led to the largest cost savings (£4,233 saved) out of all cost categories, with total cost savings of £5,495. Carbetocin utilization amongst the entire cohort led to 3.42 avoided PPH events compared to oxytocin utilization, comprised of 3.03 fewer mild/moderate PPH events and 0.39 fewer severe PPH events. Carbetocin utilization led to 0.0001 additional QALYs per woman. CONCLUSION: Carbetocin utilization leads to lower prophylactic treatment costs and less PPH events versus oxytocin when utilized for the prevention of PPH following vaginal birth in the UK.

Psychometric validation and interpretation of the Nocturia Impact Diary in a clinical trial setting.

PURPOSE: Psychometric evaluation of the Nocturia Impact (NI) Diary was conducted to support its use as a trial endpoint. METHODS: As part of a randomized, controlled Phase 2 clinical trial investigating a novel drug candidate for nocturnal polyuria, adult nocturia patients completed the NI Diary and a voiding diary for three nights preceding their clinic visit at Baseline and Weeks 1, 4, 8, and 12 (end of treatment). Exit interviews were conducted to obtain patient impressions of the NI Diary. RESULTS: A total of N = 302 participants were included. Confirmatory factor analysis (CFA) indicated that the 11-item measure is unidimensional with values of CFI, TLI, and RMSEA meeting relevant thresholds. Good internal consistency (Cronbach's α 0.941) and test-retest reliability (intra-class correlation coefficients 0.730-0.880). Convergent validity with two reference measures was demonstrated with strong correlations of 0.573-0.730 were shown. Significant differences (P = 0.0018, standardized effect size = 0.372) between groups defined by number of night-time voids supported known-groups validity. Exit interviews in 66 patients indicated all participants experienced improvement in at least 1 NI Diary item and that a 1-point improvement on the item response scale and 1-void reduction per night (associated with an average best cut point on ROC analysis of - 11.6) constituted meaningful improvement. Anchor and distribution-based analyses identified a meaningful change threshold of - 15 to - 18 points on the NI Diary. CONCLUSION: The NI Diary is a reliable and valid patient-reported psychometric instrument which is fit-for-purpose to evaluate the impact of nocturia on patient quality of life in the clinical trial setting. Trial registration number and registration date NCT03201419; June 28, 2017.

Burden of Clostridioides difficile infection (CDI) - a systematic review of the epidemiology of primary and recurrent CDI.

BACKGROUND: Clostridioides difficile is a Gram-positive anaerobic bacterium, which causes Clostridioides difficile infection (CDI). It has been recognised as a leading cause of healthcare-associated infections and a considerable threat to public health globally. This systematic literature review (SLR) summarises the current evidence on the epidemiology and clinical burden of CDI. METHODS: A SLR was conducted to identify CDI and recurrent CDI (rCDI) epidemiology studies, to evaluate patient and disease characteristics, incidence rates, epidemiological findings and risk factors. Embase, MEDLINE and the Cochrane Library databases were searched for English articles from 2009 to 2019. Included territories were the United Kingdom, France, Germany, Italy, Spain, Poland, US, Canada, Australia, Japan and China. RESULTS: Of 11,243 studies identified, 165 fulfilled the selection criteria. An additional 20 studies were identified through targeted review of grey literature. The most widely reported findings were incidence and risk factors for CDI and rCDI. Among key studies reporting both healthcare-associated (HA-CDI) and community-associated CDI (CA-CDI) incidence rates for each country of interest, incidence rates per 10,000 patient days in the US were 8.00 and 2.00 for HA-CDI and CA-CDI, respectively. The highest incidence in Europe was reported in Poland (HA-CDI: 6.18 per 10,000 patient days, CA-CDI: 1.4 per 10,000 patient days), the lowest from the UK, at 1.99 per 10,000 patient days and 0.56 per 10,000 patient days for HA-CDI and CA-CDI, respectively. No clear trend for incidence over time emerged, with most countries reporting stable rates but some either a decrease or increase. Rates of recurrent CDI varied based on geographical setting. The rate of recurrence was lower in community-associated disease compared to healthcare-associated disease. Independent CDI risk factors identified common to both initial CDI and recurrent CDI included increasing age, antibiotic use, recent hospitalisation, and proton pump inhibitor (PPI) use. In addition, leukocyte count, length of hospital stays, and Charlson comorbidity index score featured as statistically significant risk factors for recurrent CDI, but these are not reported among the most common statistically significant risk factors for initial CDI. CONCLUSIONS: Despite considerable heterogeneity, evidence suggests substantial incidence of recurrent and primary CDI, even after considerable efforts in the last decade.

Achieving clinically meaningful quality of life benefits in nocturia takes time: Results from a long-term, multicenter phase 3 study of desmopressin in Japanese patients.

OBJECTIVES: To investigate the long-term efficacy, quality of life (QoL), and safety of desmopressin orally disintegrating tablets (ODTs) in Japanese patients with nocturia. METHODS: A long-term, multicenter phase 3 study was conducted that enrolled Japanese male and female patients with nocturia (NCT03051009). Male patients received desmopressin 25- or 50-µg ODTs, and female patients received desmopressin 25-µg ODTs for up to 1 year. The primary endpoint was safety. Secondary endpoints included change from baseline in number of nocturnal voids, time to first awakening to void, and QoL assessments (nocturia-specific zQoL [N-QoL], Insomnia Severity Index [ISI], and Hsu bother score). RESULTS: Overall, 503 patients were enrolled. Reductions from baseline in mean number of nocturnal voids were observed in all treatment groups from week 1 (-0.62 to -1.00), with improvements continuing through week 52 (-1.39 to -1.71). Changes from baseline above or approximating a clinically meaningful improvement were seen by week 52 in the disease-specific N-QoL total score (improved by 11.5-22.6), ISI (improved by -3.9 to -7.1), and Hsu bother scores (improved by -1.5 to -2.0). Adverse events (AEs) were reported in 54.9% of desmopressin-treated patients. Most AEs were mild or moderate in severity. CONCLUSIONS: Desmopressin ODTs (25 and 50 µg) demonstrated long-term efficacy, improved QoL, and were well tolerated in Japanese male and female patients with nocturia treated for up to 1 year. Clinically meaningful improvements in patients' QoL, assessed by N-QoL, sleep quality, and bother, occur later than objective symptom improvements, such as voids.

Psychometric evaluation of the Nocturia Sleep Quality Scale based on data from a prospective observational study.

STUDY OBJECTIVES: The Nocturia Sleep Quality Scale (NSQS), a novel patient-reported outcomes measure, was developed to assess the impact of sleep disturbance from nocturia. The objective of this study was to assess the psychometric properties of the NSQS, including its structure, reliability, and validity. METHODS: Data were collected in the context of a web-based, prospective, longitudinal, observational study. Participants with nocturia were randomized 1:1 to either a group that received sleep hygiene instructions, including instructions to limit liquids at nighttime and empty bladder prior to bedtime, or one that did not receive sleep instructions. All participants were asked to provide responses to the web-based questionnaires from day 1 to day 10. Psychometric analyses, aligned with current regulatory guidance, were conducted to evaluate the daily scores and 3-day average scores of NSQS items and potential composites. Item-level analyses were conducted first, followed by composite-level analyses. RESULTS: The NSQS items and supporting measures demonstrated very slight improvement in patient-perceived sleep disturbance from nocturia over the course of the study. NSQS test-retest reliabilities were generally satisfactory. Correlations between NSQS items and related patient-reported measures tended to support the construct validity of the NSQS, and the known-groups analyses supplied evidence of its discriminating ability. NSQS responsiveness statistics were small. CONCLUSIONS: The NSQS is a reliable and valid measure of the impact of nocturia on patients' sleep. The present analyses lay the psychometric groundwork for the use of the NSQS in future clinical trials to support product approval and labeling claims.