Pruritus in primary biliary cholangitis is under-recorded in patient medical records.

OBJECTIVE: Cholestatic pruritus in primary biliary cholangitis (PBC) reduces patients' health-related quality of life (HRQoL). Despite this, existing research suggests that pruritus is under-recorded in patients' health records. This study assessed the extent to which pruritus was recorded in medical records of patients with PBC as compared with patient-reported pruritus, and whether patients reporting mild itch were less likely to have pruritus recorded. We also evaluated clinico-demographic characteristics and HRQoL of patients with medical record-documented and patient-reported pruritus. DESIGN: This cross-sectional study used clinical information abstracted from medical records, together with patient-reported (PBC-40) data from patients with PBC in the USA enrolled in the PicnicHealth cohort. Medical record-documented pruritus was classified as 'recent' (at, or within 12 months prior to, enrolment) or 'ever' (at, or any point prior to, enrolment). Patient-reported pruritus (4-week recall) was assessed using the first PBC-40 questionnaire completed on/after enrolment; pruritus severity was classified by itch domain score (any severity: ≥1; clinically significant itch: ≥7). Patient clinico-demographic characteristics and PBC-40 domain scores were described in patients with medical record-documented and patient-reported pruritus; overlap between groups was evaluated. Descriptive statistics were reported. RESULTS: Pruritus of any severity was self-reported by 200/225 (88.9%) patients enrolled; however, only 88/225 (39.1%) had recent medical record-documented pruritus. Clinically significant pruritus was self-reported by 120/225 (53.3%) patients; of these, 64/120 (53.3%) had recent medical record-documented pruritus. Patients reporting clinically significant pruritus appeared to have higher mean scores across PBC-40 domains (indicating reduced HRQoL), versus patients with no/mild patient-reported pruritus or medical-record documented pruritus. CONCLUSION: Compared with patient-reported measures, pruritus in PBC is under-recorded in medical records and is associated with lower HRQoL. Research based only on medical records underestimates the true burden of pruritus, meaning physicians may be unaware of the extent and impact of pruritus, leading to potential undertreatment.

A Cross-Sectional Concept Elicitation Study to Understand the Impact of Herpes Zoster on Patients' Health-Related Quality of Life.

INTRODUCTION: After a chickenpox infection, the varicella zoster virus lies dormant in nerve cells and can be reactivated in later life to cause herpes zoster (HZ), also called shingles, a painful rash that may result in persistent postherpetic neuralgia (PHN). Treatment options are limited, and HZ/PHN may have substantial negative effects on health-related quality of life (HRQoL). This qualitative cross-sectional study explored the subjective patient experience and impact on HRQoL of HZ and PHN in adults aged ≥ 50 years in Canada. METHODS: Patients were eligible for the study if they were aged at least 50 years and had been diagnosed with HZ by a healthcare practitioner 7-60 days earlier for HZ patients and 90-365 days earlier for PHN patients. Eligible patients were invited to participate in concept elicitation interviews by telephone. Data from the interviews were transcribed and analyzed to identify key concepts related to symptoms and impacts on the patients' lives. RESULTS: A total of 32 patients participated, with a mean age of 61 years. Most (72%) were female. The most common symptoms reported were rash (n = 32), pain (n = 31), fatigue (n = 26), and itchiness (n = 20). The most commonly reported HRQoL domains affected were emotional functioning (n = 31), activities of daily living (n = 31), sleep (n = 29), physical functioning (n = 25) and hobbies (n = 21). A conceptual model was developed to summarize these symptoms and impacts. CONCLUSION: HZ negatively affected many dimensions of patients' HRQoL, particularly during the acute phase of illness. This qualitative study helps to broaden understanding of the subjective patient experience of HZ.

An early look at the second dose completion of the recombinant zoster vaccine in Canadian adults: A retrospective database study.

BACKGROUND: In 2017, the two-dose recombinant zoster vaccine (RZV) was authorized for use in Canada for the prevention of herpes zoster (HZ) in adults ≥ 50 years of age (YOA), which is administered 2-6 months apart. The National Advisory Committee on Immunization (NACI) states that a 0, 12-month schedule may be considered if flexibility in the timing of the second dose is needed to improve coverage. This retrospective database study evaluated the second-dose completion of RZV in Canada from January 2018 to May 2019. METHODS: Data were obtained from the IQVIA LRx Longitudinal Prescription Database which tracks retail prescriptions of anonymized patients. Patients were followed for 6- or 12-months to evaluate the second dose completion aligned with the licensed RZV dosing schedule and NACI's option for greater flexibility. The primary outcomes were time from first to second dose and the proportion of patients who received the second dose. RESULTS: In the 6-month (155,747 patients) and 12-month (55,524 patients) analytic cohorts, 65.0% and 74.9% received the second RZV dose within 2-6 months and 2-12 months after the first dose with a truncated mean time of 97.8 days and 109.8 days between doses, respectively. Variation in completion rates was observed across age and geography, but sex, rurality, and pharmacy type did not impact results. CONCLUSION: Second dose completion of RZV in Canada is high but suboptimal. Further research to understand the factors influencing second dose timing and completion will be an important next step to improve series completion.

The health and economic burden of pertussis in Canada: A microsimulation study.

BACKGROUND: Despite excellent vaccine coverage, pertussis persists in Canada, with high incidence during recent outbreaks and non-negligible incidence in non-outbreak years. While Canadian pertussis incidence is well-characterized, the full health and economic impact of pertussis have not been examined in Canada. We estimated age-specific life years (LYs) and quality-adjusted life years (QALYs) lost, and costs due to pertussis in Ontario, Canada, using a model-based approach. METHODS: We developed a microsimulation model to simulate pertussis natural history. Daily probabilities of pertussis complications, hospitalizations, and disease sequelae as well as utilities and costs for health states were literature-derived. A healthcare payer perspective was used with a lifetime time horizon. Model outcomes were compared to those from a model with no pertussis health states. Probabilistic sensitivity analyses were used to generate distributions for estimates. Economic burden was estimated by multiplying case cost estimates by annual age-specific incidence. RESULTS: Overall, LYs lost per pertussis case was low, with negligible LYs lost in those aged >4 years. Infants (<6 months) had the greatest mean QALY loss per case (0.58), while adults lost only 0.05 QALYs per case. Infants experienced the greatest mean cost per case of $22,768 (95% CI: 21,144-23,406). Case costs generally declined with age, but increased in seniors (aged 65+) with mean cost of $1920 (95% CI: 1800-2033). Based on historic age-specific incidence, pertussis costs the Ontario healthcare system approximately $7.6-$21.5 M annually. In total economic cost estimates with QALYs valued at 1xGDP (3xGDP) per capita, the net impact of pertussis in Ontario was estimated at $21.7-$66.5 M annually ($50.0-$156.3 M). For all of Canada, total economic costs were estimated at $79.6-$241.3 M ($187.5-$580.5 M) annually. CONCLUSION: The health and economic consequences of pertussis persistence are substantial and highlight the need for improved control strategies.

Public Health Impact and Cost-Effectiveness of Non-live Adjuvanted Recombinant Zoster Vaccine in Canadian Adults.

OBJECTIVES: In Canada, incidences of herpes zoster (HZ) and postherpetic neuralgia (PHN) are increasing, posing a significant burden on the healthcare system. This study aimed to determine the public health impact and cost effectiveness of an adjuvanted recombinant zoster vaccine (RZV) compared to no vaccination and to the live attenuated vaccine (ZVL) in Canadians aged 60 years and older. METHODS: A multi-cohort Markov model has been adapted to the Canadian context using recent demographic and epidemiologic data. Simulations consisted of age-cohorts annually transitioning between health states. Health outcomes and costs were discounted at 1.5% per year. The perspective of the Canadian healthcare payer was adopted. A coverage of 80% for the first RZV and ZVL dose and a compliance of 75% for the second RZV dose were assumed. RESULTS: RZV was estimated to be cost effective compared with no vaccination with an incremental cost-effectiveness ratio (ICER) of $28,360 (Canadian dollars) per quality-adjusted life-year (QALY) in persons aged ≥ 60 years, avoiding 554,504 HZ and 166,196 PHN cases. Compared with ZVL, RZV accrued more QALYs through the remaining lifetime and an increase in costs of approximately $50 million resulting in an average ICER of $2396. Results were robust under deterministic and probabilistic sensitivity analyses. HZ incidence rate and persistence of vaccine efficacy had the largest impact on cost effectiveness. CONCLUSIONS: The cost-utility analysis suggested that RZV would be cost effective in the Canadian population compared with no vaccination and vaccination with ZVL at a willingness-to-pay threshold of $50,000.

More than 95% of adults aged 50 are infected with varicella-zoster virus and are at risk of developing herpes zoster, also known as shingles. This risk is higher in older people and in people with a reduced immune system. Shingles causes a painful rash and may trigger persistent pain and other complications that greatly reduce quality of life. In Canada, Zostavax is the only existing approved vaccine against shingles. It has been offered in a publicly funded program in Ontario to those aged 65­70 years since September 2016. Shingrix, is a new shingles vaccine that has recently been approved by Health Canada for adults aged ≥ 50 years. The present model suggests that Shingrix confers higher protection against shingles compared to Zostavax, with a greater reduction in shingles episodes. The increase in vaccination costs would be partially offset by reduced healthcare visit and medication expenses. For these reasons, provincial health plans may consider offering Shingrix to people aged ≥ 50 years.

A systematic literature review and network meta-analysis feasibility study to assess the comparative efficacy and comparative effectiveness of pneumococcal conjugate vaccines.

Background: No head-to-head studies are currently available comparing pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with 13-valent pneumococcal conjugate vaccine (PCV-13). This study explored the feasibility of using network meta-analysis (NMA) to conduct an indirect comparison of the relative efficacy or effectiveness of the two vaccines.Methods: A systematic literature search was conducted for published randomized controlled trials (RCTs) and non-RCT studies reporting data on vaccine efficacy or effectiveness against invasive pneumococcal disease in children aged <5 years receiving 7-valent pneumococcal conjugate vaccine (PCV-7), PHiD-CV or PCV-13. Study quality was evaluated using published scales. NMA feasibility was assessed by considering whether a connected network could be constructed by examining published studies for differences in study or patient characteristics that could act as potential treatment effect modifiers or confounding variables.Results: A total of 26 publications were included; 2 RCTs (4 publications), 7 indirect cohort studies, and 14 case-control studies (15 publications). Study quality was generally good. The RCTs could not be connected in a network as there was no common comparator. The studies differed considerably in design, dose number, administration schedules, and subgroups analyzed. Reporting of exposure status and subject characteristics was inconsistent.Conclusion: NMA to compare the relative efficacy or effectiveness of PHiD-CV and PCV-13 is not feasible on the current evidence base, due to the absence of a connected network across the two RCTs and major heterogeneity between studies. NMA may be possible in future if sufficient RCTs become available to construct a connected network.

The comparative efficacy and safety of herpes zoster vaccines: A network meta-analysis.

BACKGROUND: We estimated the relative efficacy and safety of vaccines for prevention of herpes zoster (HZ) using network meta-analysis (NMA) based on evidence from randomized controlled trials. METHODS: A systematic literature review evaluated two different HZ vaccines: adjuvanted recombinant zoster vaccine (RZV) and zoster vaccine live (ZVL), with different formulations assessed. Detailed feasibility assessment indicated that a NMA was feasible for efficacy (incidence of HZ and postherpetic neuralgia [PHN]) and safety (serious adverse events [SAE] and reactogenicity [injection-site reactions, systemic reaction]) outcomes. Primary analyses included frequentist NMAs with fixed effects for efficacy outcomes, due to limited data availability, and both fixed and random effects for safety and reactogenicity outcomes. As age is a known effect modifier of vaccine efficacy (VE), VE analyses were stratified by age. RESULTS: RZV demonstrated significantly higher HZ efficacy than ZVL in adults ≥60 years of age (YOA) (VERZV = 0.92 (95% confidence interval [95%CI]: 0.88, 0.94), VEZVL = 0.51 (95%CI: 0.44, 0.57)) and adults ≥70 YOA (VERZV = 0.91 (95%CI: 0.87, 0.94), VEZVL = 0.37 (95%CI: 0.25, 0.48)). Similarly, RZV demonstrated significantly higher PHN efficacy than ZVL in adults ≥60 YOA (VERZV = 0.89 (95%CI: 0.70, 0.96), VEZVL = 0.66 (95%CI: 0.48, 0.78)) and adults ≥70 YOA (VERZV = 0.89 (95%CI: 0.69, 0.96), VEZVL = 0.67 (95%CI: 0.44, 0.80)). RZV was associated with significantly more injection-site and systemic reactions compared to most formulations of ZVL and placebo, however definitions and data collection procedures differed across the included studies. There were no statistically significant differences found between RZV and any formulation of ZVL or placebo for SAEs. CONCLUSION: RZV is significantly more effective in reducing HZ and PHN incidence in adults ≥60 YOA, compared with ZVL. As anticipated with an adjuvanted vaccine, RZV results in more reactogenicity following immunization. No differences in SAEs were found between RZV and ZVL.

The cost-effectiveness of palivizumab in infants with cystic fibrosis in the Canadian setting: A decision analysis model.

BACKGROUND: Children with cystic fibrosis (CF) are at higher risk of severe respiratory syncytial virus (RSV) infection, which can lead to a decline in lung function. A monoclonal antibody, palivizumab (PMB), effectively prevents RSV hospitalizations; however, the high cost of PMB, approximately C$10,000 per patient per RSV season, limits its widespread use. We assess the cost-effectiveness of PMB prophylaxis in CF children less than 2 y of age from the Canadian healthcare payer's perspective. METHODS: In 2014, a Markov cohort model of CF disease and infant RSV infections in the Canadian setting was developed based on literature data. Infants were treated with monthly PMB injections over the 5-month RSV season. Lifetime health outcomes, quality-adjusted life years (QALYs) and 2013 $CAD costs, discounted at 5%, were estimated. Findings are summarized as incremental cost-effectiveness ratios (ICERs) and budget impact. Deterministic sensitivity analysis was conducted to assess parameter uncertainty. RESULTS: Implementation of a hypothetical Canadian RSV prophylaxis program resulted in ICERs of C$652,560 (all CF infants) and C$157,332 (high-risk CF infants) per QALY gained and an annual budget impact of C$1,400,000 (all CF infants) and C$285,000 (high-risk CF infants). The analysis was highly sensitive to the probability of severe RSV, the degree of lung deterioration following infection, and the cost of PMB. CONCLUSIONS: Our results suggest PMB is not cost-effective in Canada by commonly used thresholds. However, given the rarity of CF and relatively small budget impact, consideration may be given for the selective use of PMB for immunoprophylaxis of RSV in high-risk CF infants on a case-by-case scenario basis.

Duration of pertussis immunity after DTaP immunization: a meta-analysis.

BACKGROUND AND OBJECTIVES: Pertussis incidence is increasing, possibly due to the introduction of acellular vaccines, which may have decreased the durability of immune response. We sought to evaluate and compare the duration of protective immunity conferred by a childhood immunization series with 3 or 5 doses of diphtheria-tetanus-acellular pertussis (DTaP). METHODS: We searched Medline and Embase for articles published before October 10, 2013. Included studies contained a measure of long-term immunity to pertussis after 3 or 5 doses of DTaP. Twelve articles were eligible for inclusion; 11 of these were included in the meta-analysis. We assessed study quality and used meta-regression models to evaluate the relationship between the odds of pertussis and time since last dose of DTaP and to estimate the probability of vaccine failure through time. RESULTS: We found no significant difference between the annual odds of pertussis for the 3- versus 5-dose DTaP regimens. For every additional year after the last dose of DTaP, the odds of pertussis increased by 1.33 times (95% confidence interval: 1.23-1.43). Assuming 85% vaccine efficacy, we estimated that 10% of children vaccinated with DTaP would be immune to pertussis 8.5 years after the last dose. Limitations included the statistical model extrapolated from data and the different study designs included, most of which were observational study designs. CONCLUSIONS: Although acellular pertussis vaccines are considered safer, the adoption of these vaccines may necessitate earlier booster vaccination and repeated boosting strategies to achieve necessary "herd effects" to control the spread of pertussis.

Estimation of the underlying burden of pertussis in adolescents and adults in Southern Ontario, Canada.

Despite highly successful vaccination programs and high vaccine uptake, both endemic pertussis and periodic pertussis outbreaks continue to occur. The under-recognized role of adolescents and adults in disease transmission, due to waning immunity following natural infection and vaccination, and reduced likelihood of correct diagnosis, may contribute to pertussis persistence. We constructed a mathematical model to describe the transmission of pertussis in Southern Ontario in both pre-vaccine and vaccine eras, to estimate the underlying burden of pertussis in the population. The model was well calibrated using the best available data on pertussis in the pre-vaccination (1880-1929) and vaccination (1993-2004) eras in Ontario. Pertussis under-reporting by age group was estimated by comparing model-projected incidence to reported laboratory-confirmed cases for Greater Toronto. Best-fit model estimates gave a basic reproductive number of approximately 10.6, (seasonal range 9.9 to 11.5). Under-reporting increased with age, and approximately >95% of infections in children were caused by infections in persons with waning immunity to pertussis following prior infection or vaccination. A well-calibrated model suggests that under-recognized cases of pertussis in older individuals are likely to be an important driver of ongoing pertussis outbreaks in children. Model projections strongly support enhancement of booster vaccination efforts in adults.