Long-term effectiveness of eculizumab: Data from the International PNH Registry.

OBJECTIVES: Data from the International PNH Registry (NCT01374360) were used to estimate the overall survival and first occurrence of thromboembolic events/major adverse vascular events (TEs/MAVEs) for eculizumab-treated patients with paroxysmal nocturnal hemoglobinuria (PNH) compared with a contemporaneous untreated cohort. METHODS: Patients enrolled in the Registry from March 16, 2007, to February 14, 2022, were included. Treated patients received eculizumab for >35 days; untreated patients did not receive eculizumab at any time. Univariable and multivariable analyses were performed using a Cox proportional hazards regression model comparing eculizumab treatment periods to untreated periods and were adjusted for baseline covariates (e.g., high disease activity [HDA], transfusion dependency, and eculizumab treatment status). RESULTS: The analysis included 4118 patients. The univariable hazard ratio (HR) (95% CI) for mortality in eculizumab-treated time versus untreated time was 0.51 (0.41-0.64; p < 0.0001). Significant baseline covariates included age, sex, history of bone marrow failure, ≥4 erythrocyte transfusions within 12 months before baseline, and an estimated glomerular filtration rate ≤ 60 mL/min/1.73 m2 (all p < 0.0001). In the adjusted analysis, patients with baseline HDA had the greatest reduction in mortality risk (HR [95% CI], 0.51 [0.36-0.72]). Treated patients had approximately 60% reduction in TE/MAVE risk during treated versus untreated time (HR [95% CI]: TE: 0.40 [0.26-0.62], MAVE: 0.37 [0.26-0.54]; p < 0.0001). CONCLUSION: Using data from the largest Registry of patients with PNH, with ≥14 years of overall follow-up, we demonstrate that treatment with eculizumab conferred a 49% relative benefit in survival and an approximately 60% reduction in TE/MAVE risk.

Clinically important change for the FACIT-Fatigue scale in paroxysmal nocturnal hemoglobinuria: a derivation from international PNH registry patient data.

BACKGROUND: Fatigue is the most common symptom associated with paroxysmal nocturnal hemoglobinuria (PNH). The objective of this analysis was to estimate values that would suggest a clinically important change (CIC) for the functional assessment of chronic illness therapy-fatigue scale (FACIT-Fatigue) in patients with PNH. METHODS: Adults with PNH who initiated eculizumab within 28 days of enrollment in the International PNH Registry as of January 2021 with baseline FACIT-Fatigue scores were included in the analysis. Distribution-based estimates of likely difference were calculated using 0.5 × SD and SEM. Anchor-based estimates of CIC considered the European Organization for Research and Treatment of Cancer (EORTC) global health status/quality of life summary score and the EORTC Fatigue Scale score. Changes in anchors and high disease activity (HDA) shift from start of eculizumab treatment to each follow-up visit were then assessed by FACIT-Fatigue score change (≤ 1 CIC, no change, or ≥ 1 CIC). RESULTS: At baseline, 93% of 423 patients had fatigue documented in their medical history. The distribution-based estimates for FACIT-Fatigue were 6.5 using 0.5 × SD and 4.6 using SEM; internal consistency was high (α = 0.87). For anchor-based estimates, the FACIT-Fatigue CIC ranged from 2.5 to 15.5, and generally supported 5 points as a reasonable lower end of the value for meaningful individual change. The percentage of patients who changed from having HDA at baseline to no HDA at eculizumab-treated follow-up visits increased over time. CONCLUSION: These results support the use of 5 points as the CIC for FACIT-Fatigue in patients with PNH, which is within range of the CICs reported in other diseases (3-5 points).

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disease that leads to breakdown of the body's red blood cells in the blood vessels (intravascular hemolysis). Many people with PNH have fatigue, which consists of tiredness and weakness. A self-report questionnaire called the FACIT-Fatigue scale that objectively measures how fatigued a patient feels has been validated in clinical trials. Changes in the FACIT-Fatigue score help determine if a treatment is helping patients. The clinically important difference (difference between groups of people) or clinically important change (change within an individual) on the FACIT-Fatigue scale is a value that helps patients and clinicians find out if a drug helps or worsens patient fatigue. There is currently no defined clinically important difference and clinically important change on the FACIT-Fatigue scale for people with PNH. The International PNH Registry is a noninterventional, observational study collecting safety, treatment outcomes, and quality of life data from adults with PNH. This study used data from the International PNH Registry to find a clinically important difference and clinically important change in terms of improvement on the FACIT-Fatigue scale for adults with PNH who started eculizumab treatment. Different approaches were used to determine the amount of change in FACIT-Fatigue that would show that eculizumab has meaningful benefits, meaning patients are less fatigued. The authors demonstrated that a 5-point change on the FACIT-Fatigue is meaningful for people with PNH. This number is similar to the clinically important difference and clinically important change values of 3­5 points determined in other diseases.

Assessment of applied epidemiology competencies among the Virginia Department of Health workforce.

OBJECTIVES: Epidemiologists play critical roles in public health. However, until recently, no formal standards existed for epidemiology practice. In 2005, the Centers for Disease Control and Prevention and Council of State and Territorial Epidemiologists drafted Competencies for Applied Epidemiologists in Governmental Public Health Agencies (AECs) that provide a foundation for expectations and training programs for three tiers of practice. We characterized the Virginia Department of Health (VDH) epidemiology workforce and assessed its baseline applied epidemiology competency by using these competencies. METHODS: Epidemiologists representing multiple divisions developed an Internet survey based on the AECs. Staff who met the definition of an epidemiologist were requested to complete the survey. Within eight skill domains, specific competencies were listed. For each competency, frequency and confidence in performing and need for training were measured by using Likert scales. Differences among tier levels were assessed using analysis of variance. RESULTS: Eighty-eight people from 10 program areas responded and were included in the analysis. Median epidemiology experience was four years, with 52% having completed formal training. Respondents self-identified as Tier 1/entry-level (38%), Tier 2/mid-level (47%), or Tier 3/senior-level (15%) epidemiologists. Compared with lower tiers, Tier 3 epidemiologists more frequently performed financial or operational planning and management (p=0.023) and communication activities (p=0.018) and had higher confidence in assessment and analysis (p<0.001). Overall, training needs were highest for assessment/ analysis and basic public health sciences skills. CONCLUSIONS: VDH has a robust epidemiology workforce with varying levels of experience. Frequency and confidence in performing competencies varied by tier of practice. VDH plans to use these results and the AECs to target staff training activities.

Elevated pulse wave velocity increases the odds of coronary calcification in overweight postmenopausal women.

BACKGROUND: Aortic stiffness, assessed using carotid-femoral pulse wave velocity (cfPWV), predicts all-cause and cardiovascular mortality. Brachial-ankle pulse wave velocity index (baPVI) is a newer measure of arterial stiffness obtained using an automated system. Our aim is to evaluate the association between both these measures of arterial stiffness and coronary calcification (CAC), in overweight/obese postmenopausal women, without apparent cardiovascular disease. METHODS: The CAC was assessed using electron beam tomography in 504 postmenopausal women, aged 52 to 62 years (88.2% white) with mean body mass index (BMI) 30.8 kg/m(2). The CAC scores were analyzed as CAC >0 and CAC >100 versus CAC = 0, or as ln (CAC + 1). RESULTS: The cfPWV was available in 476 women (mean [SD]: 900 (255) cm/sec) and baPVI was available in 441 women (mean [SD]: 1434 (231) cm/sec. Any CAC (CAC >0) was present in approximately 51% of the cohort. Both high cfPWV (RR = 1.5, 1.6, and 1.7 for quartiles 2, 3, and 4 v 1) and baPVI (RR = 2.9, 3.7. and 4.0 for quartiles 2, 3, and 4 v 1) were associated with the presence of calcification (CAC >0). The association was attenuated but remained significant only for baPVI after adjusting for age, systolic blood pressure, average waist circumference, BMI, fasting glucose, insulin, lipids, hormone replacement therapy, and smoking status. High odds of severe calcification (CAC >100) was seen with the highest quartile of the cfPWV (RR = 5.3) and baPVI (RR = 7.8), and these associations remained significant in multivariable analysis. CONCLUSIONS: Both cfPWV and baPVI are associated with presence and severity of coronary calcification in overweight postmenopausal women.

Cardiovascular risk factors associated with enlarged diameter of the abdominal aortic and iliac arteries in healthy women.

The abdominal aorta is known to be more susceptible to arterial dilation than to occlusion primarily due to the effects of vascular aging. Few studies have considered the effects of cardiovascular risk factors on arterial diameter, particularly within a population of healthy women at mid-life. This study seeks to examine associations between cardiovascular risk factors and abdominal aortic and iliac adventitial diameter. Abdominal aortic ultrasound was performed in 260 post-menopausal women aged 53.9+/-2.5 years at time of scan as a component of the Healthy Women Study. Risk factors were evaluated at premenopause and post-menopausal clinic visits closest in date to the abdominal ultrasound scan. Post-menopausal weight and change of weight from pre- to post-menopause were among the strongest correlates of larger adventitial diameter after controlling for age, systolic blood pressure, and body size using height. Other post-menopausal risk factors significantly correlated with both abdominal aortic and iliac diameter were BMI, waist circumference, HDL, and insulin (p<0.05). These data suggest that weight is a key risk factor in the promotion of vascular aging as indexed by enlarged arterial diameter. Women at mid-life should continue to be targeted for weight interventions to reduce their risk for more serious cardiovascular complications.

Risk of cancer as a result of community exposure to gasoline vapors.

The Tranguch Gasoline Spill leaked 50,000-900,000 gallons of gasoline from underground storage tanks, potentially exposing an area of Hazle Township and Hazleton, Pennsylvania, to chronic low levels of benzene since at least 1990. A retrospective cohort study of 663 individuals representing 275 households assessed whether affected residents were at increased risk for cancer from 1990-2000 compared with the Pennsylvania populace. Age-adjusted standard incidence ratios (SIRs) were calculated using Pennsylvania rates to determine expected numbers. The age-adjusted SIR for the gasoline-affected area was 4.40 (95% confidence interval: 1.09-10.24) for leukemia. These results suggest an association between living within the area affected by the Tranguch Gasoline Spill and increased risk for leukemia.

Hearing sensitivity in older adults: associations with cardiovascular risk factors in the health, aging and body composition study.

OBJECTIVES: To examine the association between cardiovascular disease (CVD) and its risk factors and age-associated hearing loss in a cohort of older black and white adults. DESIGN: Cross-sectional cohort study. SETTING: The Health, Aging, and Body Composition (Health ABC) Study, a community-based cohort study of older adults from Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Two thousand forty-nine well-functioning adults (mean age 77.5; 37% black). MEASUREMENTS: Pure-tone audiometry measurement and history of clinical CVD were obtained at the fourth annual follow-up visit. Pure-tone averages in decibels reflecting low (250, 500, and 1,000 Hz), middle (500, 1,000, and 2,000 Hz), and high (2,000, 4,000, and 8,000 Hz) frequencies were calculated for each ear. CVD risk factors, aortic pulse-wave velocity (PWV), and ankle-arm index (AAI) were obtained at study baseline. RESULTS: In sex-stratified models, after adjustment for age, race, study site, and occupational noise exposure, risk factors associated with poorer hearing sensitivity in men included high triglyceride levels, high resting heart rate, and history of smoking. In women, poor hearing sensitivity was associated with high body mass index, high resting heart rate, fast PWV, and low AAI. CONCLUSION: Modifiable risk factors for CVD may play a role in the development of age-related hearing loss.

Infection control practices in assisted living facilities: a response to hepatitis B virus infection outbreaks.

BACKGROUND: The medical needs of the approximately 1 million persons residing in assisted living facilities (ALFs) continually become more demanding. Moreover, the number of ALF residents is expected to double by 2030. ALFs are not subject to federal oversight; state regulations that govern ALF infection control are variable. In 2005, two outbreaks of acute hepatitis B virus (HBV) infection in ALFs in Virginia were associated with sharing fingerstick devices used in blood glucose monitoring. OBJECTIVE: To characterize infection control practices, determine compliance with guidelines, and identify educational and policy needs in ALFs in Virginia. METHODS: Following the outbreaks of HBV infection, educational packets were sent to ALFs in Virginia to inform them of infection control guidelines and recommendations regarding glucose monitoring. A follow-up survey consisting of on-site interviews was conducted in a random sample of ALFs. Differences among infection control practices, according to the size and ownership of the ALFs, were assessed. RESULTS: Fifty of 155 ALFs in central Virginia were surveyed. Of the 45 ALFs that had used fingerstick devices, 7 (16%) had shared these devices (without cleaning) between residents. Sharing practices for glucose monitoring equipment did not differ by facility size or ownership. Of all 50 ALFs, 17 (34%) did not offer employees HBV vaccine. HBV vaccine was less frequently offered at ALFs that had fewer than 50 residents, compared with ALFs with at least 50 residents (P<.01), and HBV vaccine was less frequently offered at ALFs that were individually owned, compared with those that were not individually owned (P=.02). CONCLUSIONS: Despite outreach and long-standing recommendations, approximately 1 in 6 facilities shared fingerstick devices, and more than one-third of ALFs surveyed were considered noncompliant with federal guidelines (Occupational Safety and Health Administration Bloodborne Pathogens Standard). Public health and licensing agencies should work with ALFs to implement infection control measures and prevent disease transmission.

Weight change is associated with change in arterial stiffness among healthy young adults.

Risk factors for arterial stiffness progression have not been well characterized. We examined the relationship between arterial stiffness progression and body weight and weight gain in a group of healthy young adults. Aortic pulse-wave velocity was assessed at 2 time points approximately 2 years apart in 152 white and black adults aged 20 to 40 years, and was standardized by the time between visits to obtain annualized pulse-wave velocity changes. Blacks had 15.5 cm/s per year larger annual pulse-wave velocity increases compared with whites (P=0.02), even after multivariable adjustment for weight and blood pressure changes. Larger annual pulse-wave velocity increases were also associated with larger baseline body weight (P=0.02), waist girth (P=0.003), and body mass index (P<0.001), and greater annual weight gain (P=0.02), after adjustment for baseline pulse-wave velocity. After multivariable adjustment that included blood pressure changes, larger baseline waist girth (P=0.009), baseline body mass index (P=0.001), body mass index increase (P=0.037), and weight gain (P=0.017) remained significantly associated with larger annual pulse-wave velocity progression. Weight change showed a direct relationship with pulse-wave velocity change; mean annual pulse-wave velocity changes were -29.9 cm/s per year (regression) for those with >or=4.5 kg annual weight loss and 18.2 cm/s per year (progression) for those with >or=4.5 kg annual weight gain. These data show strong associations between weight gain and arterial stiffness progression, as well as between weight loss and arterial stiffness regression. These data greatly underscore the vascular benefit of weight loss. Successful weight loss programs in young adults, particularly blacks, are needed.

Ethnic variation in hypertension among premenopausal and perimenopausal women: Study of Women's Health Across the Nation.

Data are sparse regarding hypertension prevalence, treatment, and control among some ethnic groups of American women. Furthermore, the effects of ethnicity on hypertension, independent of other factors that vary with ethnicity, are poorly understood. We examined the prevalence of hypertension (defined as systolic > or =140 or diastolic > or =90 mm Hg or receiving treatment), treatment, and control (to <140/<90 mm Hg) in a multiethnic study of premenopausal and perimenopausal women. Stepwise multivariable logistic regression was used to select covariates associated with hypertension. Among 3292 women, 46.9% were white, 28.3% were black, 8.7% were Hispanic, 7.6% were Chinese, and 8.5% were Japanese. Among these 5 ethnic groups, respectively, there was substantial variation in prevalence of normal blood pressure levels (<120/<80 mm Hg; 59.9%, 35.4%, 16.8%, 67.2%, and 63.7%) and hypertension (14.5%, 38.1%, 27.6%, 12.8%, and 11.0%). After multivariable adjustment, hypertension prevalence was 2 to 3x higher among black and Hispanic women but similar among Chinese and Japanese women compared with white women. Among hypertensive participants, prevalence of antihypertensive treatment was highest among blacks (58.9%) and whites (55.2%) and lowest among Chinese (34.4%). Prevalence of control to goal blood pressure levels was highest among whites (43.0%) and Japanese (38.7%) and markedly lower among Hispanic women (11.4%). Compared with whites, black and Hispanic women have significantly higher prevalence of hypertension independent of other factors, whereas Chinese and Japanese women have similar prevalence. Treatment and control rates vary considerably across ethnicities. Greater efforts must be made to improve hypertension awareness, treatment, and control in all middle-aged women, particularly those in ethnic minority groups.