Estudio observacional prospectivo que evalúa la carga de enfermedad del HZ en Colombia / Prospective observational study evaluating the disease burden of HZ in Colombia

Resumen Introducción: el herpes zóster (HZ) es una enfermedad debilitante que afecta negativamente la calidad de vida (CV). Este estudio buscó describir la carga de la enfermedad por el HZ en Colombia. Métodos: estudio prospectivo, observacional, de cohorte única realizado en 10 centros clínicos colombianos. Para ser elegibles, los pacientes tenían que ser inmunocompetentes, ≥50 años de edad, y tener un diagnóstico confirmado de HZ en fase aguda o dolor posherpético. Los resultados del estudio incluyeron el inventario breve del dolor por zóster (ZBPI), la CV evaluada con el cuestionario EQ-5D y la utilización de recursos de atención médica (URAM) debido a HZ. El seguimiento fue de 180 días. Resultados: se incluyeron 154 pacientes con una media (DE) de la edad de 64.6 (9.6) años. La media (DE) del peor dolor agudo fue 8.2 (2.1), mientras la neuralgia posherpética (dolor por HZ ≥3 que persistió ≥90 días) fue reportado por 36.5% de los pacientes. Los predictores significativos del aumento de la carga de dolor fueron la edad avanzada y puntuaciones de peor dolor más altas desde el inicio de la erupción. El aumento en el dolor asociado a HZ estuvo acompañado con reducción significativa en CV, la cual duró aproximadamente 60 días. En términos de la URAM, medicamentos para el HZ y que fueron recetados a 98.7% de los pacientes, incluyendo aciclovir en 85.1% de los pacientes, 79.2% tuvieron un seguimiento por un médico general, 38.2% visitó una sala de emergencia y 29.2% visitó un especialista Conclusión: HZ está asociado a carga de enfermedad significativa en Colombia, incluyendo dolor, impacto en la CV y URAM. A medida que la población colombiana envejece, se deben implementar estrategias para manejar y/o prevenir de manera más efectiva la carga asociada al HZ. (Acta Med Colomb 2021; 46. DOI: https://doi.org/10.36104/amc.2021.1636).

Abstract Introduction: herpes zoster (HZ) is a debilitating disease with a negative effect on quality of life (QL). This study sought to describe the burden of disease of HZ in Colombia. Methods: this was a prospective, observational single-cohort study in 10 Colombian clinical centers. To be eligible, patients had to be immunocompetent, ≥50 years old, and have a confirmed diagnosis of acute phase HZ or postherpetic pain. The study outcomes included the Zoster Brief Pain Inventory (ZBPI), QL assessed through the EQ-5D questionnaire, and healthcare resource utilization (HCRU) due to HZ. Patients were followed for 180 days. Results: 154 patients were included with a mean (SD) age of 64.6 (9.6) years. The mean (SD) worst acute pain was 8.2 (2.1), while postherpetic neuralgia (HZ pain ≥3 which lasted for ≥90 days) was reported by 36.5% of the patients. The significant predictors of increased pain burden were advanced age and higher worst pain score from the onset of the rash. Increased HZ-related pain was associated with a significant reduction in QL, which lasted approximately 60 days. In terms of HCRU, HZ medications were prescribed for 98.7% of the patients, including acyclovir in 85.1%; 79.2% were followed by a general practitioner; 38.2% were seen in the emergency room and 29.2% consulted a specialist. Conclusion: HZ is associated with a significant burden of disease in Colombia, including pain and an impact on QL and HCRU. As the Colombian population ages, strategies should be implemented to more effectively manage and/or prevent the HZ-related burden. (Acta Med Colomb 2021; 46. DOI: https://doi.org/10.36104/amc.2021.1636).

Toward Defining Primary and Secondary Nonresponse in Rheumatoid Arthritis Patients Treated with Anti-TNF: Results from the BioTRAC and OBRI Registries.

OBJECTIVE: Although most patients with rheumatoid arthritis (RA) respond to anti-tumor necrosis factor (anti-TNF) treatment, some present with initial nonresponse (1ry nonresponse) or lose initial responsiveness (2ry nonresponse). We compared the rate of real-world "nonresponse" to first anti-TNF as reported by treating physicians to the nonresponse rate per accepted definitions and recommended treat-to-target strategies. METHODS: Patients were included from the Biologic Treatment Registry Across Canada (BioTRAC) and Ontario Best Practices Research Initiative (OBRI) registries who were taking their first anti-TNF, with ≥ 1 followup visit. Posthoc reclassification of physician-reported nonresponse was based on prior achievement of 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA), Clinical Disease Activity Index (CDAI) LDA, or good/moderate European League Against Rheumatism (EULAR) response, and actual time of physician-reported nonresponse. RESULTS: Among 736 BioTRAC and 640 OBRI patients, 13.7% and 18%, respectively, discontinued their anti-TNF because of physician-reported nonresponse. Based on reclassification using disease activity, 65.6% (BioTRAC) and 87.2% (OBRI) of 1ry nonresponders did not achieve DAS28-ESR LDA, 65.6%/90.7% CDAI LDA, and 46.9%/61.5% good/moderate EULAR response. Among 2ry nonresponders, 50.7%/47.8% did not achieve DAS28-ESR LDA, 37.7%/52.9% CDAI LDA, and 15.9%/19.6% good/moderate EULAR response before treatment discontinuation. Regarding actual time of nonresponse, 18.8% of BioTRAC and 60.8% of OBRI 1ry nonresponders discontinued at ≤ 6 months. In both registries, a high proportion of 2ry nonresponders discontinued their anti-TNF after 12 months (87.0% BioTRAC, 60.9% OBRI). CONCLUSION: Physician-reported 1ry nonresponse was more correlated with non-achievement of DAS28-ESR LDA or CDAI LDA, whereas 2ry nonresponse with actual time of discontinuation. Further work is needed to confirm the importance of response and type of response to the initial anti-TNF in identifying patients most likely to benefit from a second biologic agent treatment.

Live birth rates remain stable in modified natural IVF despite low anti-Müllerian hormone: analysis of 638 cycles.

RESEARCH QUESTION: Do live birth rates (LBR) following modified natural IVF (mnIVF) differ according to serum anti-Müllerian hormone (AMH) concentration? DESIGN: Retrospective cohort study including 638 women aged ≤39 years starting their first mnIVF cycle at a university-affiliated private IVF centre. Patients were divided into three groups, by concentration of AMH: ≤0.5 ng/ml (25th percentile), 0.51-2.03 ng/ml (25-75th percentile, reference) and 2.04-6.56 ng/ml (75th percentile). Analyses were stratified by AMH percentile and the age of patients (<35, 35-39 years). Logistic regression assessed the impact of age and AMH percentile on outcomes. LBR was the primary outcome measure. RESULTS: LBR per started cycle were comparable across AMH percentiles (11.6%, 12.4% and 17.0% for the 25th, 25-75th and 75th percentile, respectively). No statistically significant difference was found between the three AMH groups with respect to cancellation, successful egg retrieval, embryo transfer, or biochemical and clinical pregnancy rates. Logistic regression analysis did not identify AMH percentile as a significant predictor of live birth. Compared with the reference group, the odds ratios (OR [95% confidence interval, CI]) for live birth in the <25th and >75th AMH percentile groups were 0.97 (0.54-1.76) and 1.41 (0.82-2.41), respectively. The results were the same regardless of age group (<35 years, 35-39 years). CONCLUSIONS: Serum AMH cannot be used to predict mnIVF outcomes. Patients in lower/upper AMH percentiles showed pregnancy and LBR comparable to patients with normal AMH.

The use of antibiotics in the treatment of pediatric varicella patients: real-world evidence from the multi-country MARVEL study in Latin America & Europe.

BACKGROUND: Varicella is a highly contagious childhood disease. Generally benign, serious complications necessitating antibiotic use may occur. The objective of this study was to characterize the rate, appropriateness and patterns of real-world antibiotic prescribing for management of varicella-associated complications, prior to universal varicella vaccination (UVV) implementation. METHODS: Pooled, post-hoc analysis of 5 international, multicenter, retrospective chart reviews studies (Argentina, Hungary, Mexico, Peru, Poland). Inpatient and outpatient primary pediatric (1-14 years) varicella cases, diagnosed between 2009 and 2016, were eligible. Outcomes, assessed descriptively, included varicella-associated complications and antibiotic use. Three antibiotic prescribing scenarios were defined based on complication profile in chart: evidence of microbiologically confirmed bacterial infection (Scenario A); insufficient evidence confirming microbiological confirmation (Scenario B); no evidence of microbiological confirmation (Scenario C). Stratification was performed by patient status (inpatient vs. outpatient) and country. RESULTS: Four hundred one outpatients and 386 inpatients were included. Mean (SD) outpatient age was 3.6 (2.8) years; inpatient age was 3.1 (2.8) years. Male gender was predominant. Overall, 12.2% outpatients reported ≥1 infectious complication, 3.7% ≥1 bacterial infection, and 0.5% ≥1 microbiologically confirmed infection; inpatient complication rates were 78.8, 33.2 and 16.6%, respectively. Antibiotics were prescribed to 12.7% of outpatients and 68.9% of inpatients. Among users, ß-lactamases (class), and clindamycin (agent), dominated prescriptions. Scenario A was assigned to 3.9% (outpatients) vs 13.2% (inpatients); Scenario B: 2.0% vs. 6.0%; Scenario C: 94.1% vs. 80.8%. CONCLUSIONS: High rates of infectious complications and antibiotic use are reported, with low rates of microbiological confirmation suggesting possible antibiotic misuse for management of varicella complications.

Autologous endometrial cell co-culture improves human embryo development to high-quality blastocysts: a randomized controlled trial.

RESEARCH QUESTION: Does autologous endometrial cell co-culture (AECC) improve the number of good-quality blastocysts obtained by IVF/intracytoplasmic sperm injection (ICSI), compared with conventional embryo culture medium in a broad group of patients referred to assisted reproductive technology (ART)? DESIGN: This interventional, randomized, double-blind study took place at Clinique Ovo from March 2013 to October 2015 and included 207 healthy patients undergoing an IVF or ICSI protocol, of which 71 were excluded before randomization. On the previous cycle, all participants underwent an endometrial biopsy at D5 to D7 post-ovulation, following which the endometrial cells were prepared for AECC. RESULTS: The data demonstrated that AECC significantly increased the incidence of good-quality blastocysts compared with culture in conventional media (42.6% vs 28.4%, P < 0.001). No significant differences were found in pregnancy and live birth rates. CONCLUSION: This study demonstrated the benefits of AECC on blastocyst quality compared with conventional embryo culture medium, in a broader category of patients referred to ART as opposed to other studies that concentrated on specific causes of infertility only. However, limitations of the study design should be taken into consideration; the analysis was performed using embryos rather than patients and a follow-up of children born following the treatments could not be conducted.

Post Hoc Analysis of the CONFIDENCE II, PROTECT I, SHAKE THE HABIT I and SHAKE THE HABIT II Observational Studies in Mild to Moderate Hypertensive Patients Treated with Perindopril and Atorvastatin Concomitantly.

BACKGROUND AND OBJECTIVES: Management of hypertension and dyslipidemia is important when considering cardiovascular disease risk; however, achievement of optimal lipid and blood pressure (BP) targets in clinical practice remains inadequate. This analysis sought to estimate the frequency, effectiveness, and safety of co-administrated atorvastatin and perindopril in routine care. METHODS: We conducted a post hoc analysis of four Canadian, prospective, multi-center, observational studies assessing real-life effectiveness and safety of perindopril + atorvastatin in mild-to-moderate hypertensive patients with concomitant dyslipidemia over 16 weeks. The safety population comprised patients receiving one or more doses of free combination perindopril + atorvastatin; the full analysis set (FAS) received perindopril + atorvastatin at baseline, with one or more post-baseline systolic BP measurements while on treatment. RESULTS: A total of 3541 and 3172 patients were included in the safety population and FAS, respectively. At the last observation carried forward, significant reductions in mean systolic BP (- 18.0 mmHg; p < 0.001) and diastolic BP (- 8.9 mmHg; p < 0.001) were observed; target BP was achieved by 73.1% of patients. Emergent adverse events (AEs) were reported in 8.0% of patients, the most common being cough (4.5% of patients), headache (0.9%), and dizziness (0.8%). Four serious AEs were reported among three (0.1%) patients. No differences were observed in effectiveness or safety between studies. CONCLUSIONS: Concomitant perindopril + atorvastatin therapy demonstrated similar efficacy across all studies, with significant reductions in BP and achievement of target BP levels observed in a real-world setting. Results align with known safety profiles of atorvastatin and perindopril, with no unexpected AEs observed when compared with data from treatment with the individual drugs.

A Review of the Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: 10 Years of Clinical Experience in Canada.

Publicly funded administration of the quadrivalent HPV (qHPV) vaccine in school-aged girls was implemented for all Canadian provinces and territories between 2007 and 2009. However, the impact of female qHPV vaccination in Canada has yet to be evaluated. This systematic literature review of studies published between September 1, 2006 and September 1, 2016 looked at real-world evidence related to the effects of qHPV vaccination on prevalence of HPV infection and disease in Canada over the past decade. PubMed was searched for studies published between September 1, 2006 and September 1, 2016. Studies were eligible if one or more of the following outcomes were assessed in individuals receiving the qHPV vaccine though public immunization programs: HPV infection, anogenital warts (AGW), HPV-associated lesions of the anogenital tract. A "pre-public vaccination program" or "unvaccinated" reference group was required. Key HPV conference abstracts were also reviewed. We identified seven eligible studies representing five Canadian provinces. Results reported indicated that the prevalence of HPV types 6, 11, 16, and 18 was lower in qHPV-vaccinated than unvaccinated individuals (1.5% vs. 11.0%, respectively), whereas non-vaccine-covered genotypes were comparable across vaccination status. Risk of AGW incidence decreased by up to 45% in vaccinated cohorts; incidence of cervical intraepithelial neoplasia 2 + was significantly reduced by up to 86% in the post-vaccine era. On the basis of these findings, HPV vaccination programs constitute a successful and effective public health initiative.

Recurrence of Human Papillomavirus External Genital Wart Infection Among High-Risk Adults in Montréal, Canada.

OBJECTIVES: The incidence of recurrent genital warts is not well characterized; this is especially true in a post-human papillomavirus (HPV) vaccination era. The objectives of this study were to assess the incidence of subsequent HPV-related external genital warts (EGW) episodes in high-risk male and female adults, as well as ascertain patient profile and disease characteristics, in a real-world Canadian sexual health clinical setting. METHODS: Retrospective chart review study conducted at Clinique médicale l'Actuel, a sexual health clinic in Montréal, Québec, Canada. Eligible patients were 18 to 45 years of age with a first diagnosis of EGW associated with a HPV infection between July 1, 2006, and June 30, 2012. RESULTS: A total of 400 first-episode EGW cases were identified. Up to 6 subsequent episodes were documented, with 194 (48.5%) patients reporting at least 1 subsequent EGW episode. Median time to first subsequent EGW episode was 3.97 years, and the incidence density rate for all subsequent episodes was 0.18/100 patient-years. Over 90% of patients reported clearance of the first subsequent episode, with median time to clearance of 0.30 years. Regardless of subsequent episode number, greater than 95% of patients received treatment, primarily cryotherapy, with high-risk sexual behavior reducing as number of episodes increased. CONCLUSIONS: Overall, a high rate of subsequent EGW episodes was observed in this high-risk population, despite high treatment rates and improvement in high-risk sexual behavior. These data, assessed in a prevaccination Québec health care system, may be compared with future EGW rates to assess the impact of a governmentally-funded HPV vaccination program.

The Burden of Illness Related to Chronic Obstructive Pulmonary Disease Exacerbations in Québec, Canada.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) prevalence in Canada has risen over time. COPD-related exacerbations contribute to the increased health care utilization (HCU) in this population. This study investigated the impact of exacerbations on COPD-related HCU. METHODS: This retrospective observational cohort study used patient data from the Québec provincial health insurance databases. Eligible patients with a new HCU claim with a diagnostic billing for COPD during 2001-2010 were followed until March 31, 2011. Exacerbation rates and time to first exacerbation were assessed. Unadjusted analyses and multivariable models compared the rate of HCU by exacerbation classification (any [moderate/severe], moderate, or severe). RESULTS: The exacerbation event rate in patients with an exacerbation was 34.3 events/100 patient-years (22.7 for moderate exacerbations and 11.6 for severe exacerbations). Median time to first exacerbation of any classification was 37 months. In unadjusted analyses, COPD-related HCU significantly increased with exacerbation severity. In the multivariable, HCU rates were significantly higher after exacerbation versus before exacerbation (p < 0.01) for patients with an exacerbation or moderate exacerbations. For severe exacerbations, general practitioner, respiratory specialist, emergency room, and hospital visits were significantly higher after exacerbation versus before exacerbation (p < 0.001). CONCLUSIONS: Exacerbations were associated with increased HCU, which was more pronounced for patients with severe exacerbations. Interventions to reduce the risk of exacerbations in patients with COPD may reduce disease burden.

Association between work time loss and quality of life in patients with Herpes Zoster: a pooled analysis of the MASTER studies.

BACKGROUND: Herpes zoster (HZ) has a significant negative effect on the productive work life of individuals, and has been shown to be responsible for cases of absenteeism, presenteeism and decreased work effectiveness. The aim of this study was to evaluate health utility scores and associated predictors in an actively employed population of Herpes Zoster (HZ) patients with and without work time loss (WTL). METHODS: This was a pooled analysis of the prospective, observational MASTER cohort studies, conducted in 8 countries across North America, Latin America and Asia. A total of 428 HZ patients engaged in full or part time work were included. WTL, defined as missing ≥ 1 partial or full work day, and work effectiveness, reported on a scale of 0-100%, were evaluated with the Work and Productivity Questionnaire (WPQ). The Pearson product-moment correlation was used to assess the correlation between work effectiveness and HRQoL. Mixed models with repeated measures assessed the relationship between HZ-related WTL over a 6-month follow-up period, and HRQoL, as evaluated by the EQ-5D. Additional predictors of HRQoL were also identified. RESULTS: Overall, 57.7% of respondents reported WTL. Mean (SD) percent work effectiveness of patients in the WTL group was significantly lower compared to non-WTL (NWTL) patients at baseline [50.3 (31.6) vs. 71.4 (27.8); p < 0.001]. Patients in the WTL group also reported lower health utility scores at baseline and overall than their NWTL counterparts, with WTL identified as an independent negative predictor of both the EQ-5D summary scores and the EQ-5D VAS (p < 0.001). Decrease in work effectiveness was negatively associated with HRQoL overall (p < 0.001). Predictors of lower HRQoL were worst Zoster Brief Pain Inventory (ZBPI) pain score, the presence of HZ complications and country income (predictor of EQ-5D VAS only). CONCLUSIONS: HZ adversely impacts the work and productive life of actively employed individuals. In turn, HZ-related reductions in work effectiveness and work time are associated with a negative effect on HRQoL.