Willingness to Self-Collect a Sample for HPV-Based Cervical Cancer Screening in a Well-Screened Cohort: HPV FOCAL Survey Results

Self-collection may provide an opportunity for innovation within population-based human papillomavirus (HPV) cervical cancer screening programs by providing an alternative form of engagement for all individuals. The primary objective was to determine willingness to self-collect a vaginal sample for primary HPV screening and factors that impact willingness in individuals who participated in the Human Papillomavirus For Cervical Cancer (HPV FOCAL) screening trial, a large randomized controlled cervical screening trial. A cross-sectional online survey was distributed between 2017 and 2018 to 13,176 eligible participants exiting the FOCAL trial. Bivariate and multivariable logistic regression assessed factors that influence willingness to self-collect on 4945 respondents. Overall, 52.1% of respondents indicated willingness to self-collect an HPV sample. In multivariable analysis, the odds of willingness to self-collect were significantly higher in participants who agreed that screening with an HPV test instead of a Pap test was acceptable to them (odds ratio (OR): 1.45 (95% confidence interval (CI): 1.15, 1.82), those who indicated that collecting their own HPV sample was acceptable to them (p < 0.001), and those with higher educational ascertainment (OR: 1.31, 95% CI: 1.12, 1.54). The findings offer insight into the intentions to self-collect in those already engaged in screening, and can inform cervical cancer screening programs interested in offering alternative approaches to HPV-based screening.     

Experiences of parents whose children participated in a longitudinal follow‐up study

BackgroundLong‐term follow‐up is necessary to understand the impact of perinatal interventions. Exploring parents'' motives and experiences in consenting to their children taking part in longitudinal studies and understanding what outcomes are important to families may enhance participation and mitigate the loss to follow‐up. As existing evidence is largely based on investigators'' perspectives using Western samples, the present pilot study explored parents'' perspectives in a multicultural New Zealand context.MethodsData were generated using semi‐structured interviews with parents whose children had participated in a longitudinal study after neonatal recruitment. Parents'' experiences of being part of the study were analysed thematically using an inductive approach.ResultsParents (n = 16) were generally happy with the outcomes measured. Additionally, parents were interested in lifelong goals such as the impact of parental diabetes. We identified three themes: (1) Facilitators: Research participation was aided by motives and parent and research characteristics such as wishing to help others and straightforward recruitment; (2) Barriers: A hesitancy to participate was due to technical and clinical research aspects, participation burden and cultural barriers, such as complex wording, time commitment and nonindigenous research and (3) Benefits: Children and parents experienced advantages such as the opportunity for education.ConclusionsParents reported positive experiences and described the unexpected benefit of increasing families'' health knowledge through participation. Improvements for current follow‐up studies were identified. Different ethnicities reported different experiences and perspectives, which warrants ongoing research, particularly with indigenous research participants.Patient or Public ContributionNo active partnership with parents of patients took place.     

Sympathetic Neural Adaptation to Hypocaloric Diet With or Without Exercise Training in Obese Metabolic Syndrome Subjects

OBJECTIVE

Sympathetic nervous system (SNS) overactivity contributes to the pathogenesis and target organ complications of obesity. This study was conducted to examine the effects of lifestyle interventions (weight loss alone or together with exercise) on SNS function.

RESEARCH DESIGN AND METHODS

Untreated men and women (mean age 55 ± 1 year; BMI 32.3 ± 0.5 kg/m²) who fulfilled Adult Treatment Panel III metabolic syndrome criteria were randomly allocated to either dietary weight loss (WL, n = 20), dietary weight loss and moderate-intensity aerobic exercise (WL+EX, n = 20), or no treatment (control, n = 19). Whole-body norepinephrine kinetics, muscle sympathetic nerve activity by microneurography, baroreflex sensitivity, fitness (maximal oxygen consumption), metabolic, and anthropometric measurements were made at baseline and 12 weeks.

RESULTS

Body weight decreased by −7.1 ± 0.6 and −8.4 ± 1.0 kg in the WL and WL+EX groups, respectively (both P < 0.001). Fitness increased by 19 ± 4% (P < 0.001) in the WL+EX group only. Resting SNS activity decreased similarly in the WL and WL+EX groups: norepinephrine spillover by −96 ± 30 and −101 ± 34 ng/min (both P < 0.01) and muscle sympathetic nerve activity by −12 ± 6 and −19 ± 4 bursts/100 heart beats, respectively (both P < 0.01), but remained unchanged in control subjects. Blood pressure, baroreflex sensitivity, and metabolic parameters improved significantly and similarly in the two lifestyle intervention groups.

CONCLUSIONS

The addition of moderate-intensity aerobic exercise training to a weight loss program does not confer additional benefits on resting SNS activity. This suggests that weight loss is the prime mover in sympathetic neural adaptation to a hypocaloric diet.The metabolic syndrome (MetS) is an increasingly prevalent multidimensional risk factor for cardiovascular disease and type 2 diabetes (1). Its etiology is complex and incompletely understood, but thought to involve the interplay between metabolic susceptibility, lifestyle factors, and the acquisition of excess visceral adiposity (2). Scientific studies performed over the last 2 decades strongly support the relevance of the sympathetic nervous system (SNS) in both the pathogenesis and target organ complications of MetS obesity (3).Several indexes of SNS activity, such as urinary norepinephrine excretion, norepinephrine spillover from sympathetic nerves, and postganglionic muscle sympathetic nerve activity (MSNA) are increased in subjects with MetS, even in the absence of hypertension (4–7). Among the adiposity indexes, abdominal visceral fat is most strongly associated with elevated MSNA (8). Because of the bidirectional relationship between sympathetic activation and insulin resistance, much debate has focused on their chronology. Prospective studies with 10–20 years follow-up indicate that elevated plasma norepinephrine concentration (9) and sympathetic reactivity (10) precede and predict future rise in BMI and development of insulin resistance. Although seemingly counterintuitive, sympathetic activation may be causally linked to obesity via β-adrenoceptor desensitization (11) and insulin resistance (12,13). In established obesity, metabolic, cardiovascular (baroreflex impairment), and medical conditions (obstructive sleep apnea) contribute significantly to sympathetic neural drive and further aggravate insulin resistance, hence establishing a vicious cycle (3,7). Chronic sympathetic activation is associated with an increased prevalence of preclinical cardiovascular and renal changes that are recognized predictors of adverse clinical prognosis (3,14,15).Weight loss and exercise are recommended as first-line treatments for MetS. The Diabetes Prevention Program and the Oslo Diet and Exercise Study have shown the marked clinical benefits of intensive lifestyle intervention on the resolution of the MetS (16,17). Individually, both weight loss (5) and exercise training (18,19) cause sympathoinhibition and improvement in MetS components. We have previously reported that moderate weight loss (7% of body weight) by diet alone is accompanied by reductions in whole-body norepinephrine spillover and MSNA and improvement in spontaneous cardiac baroreflex function in middle-aged MetS subjects (5). Because exercise is often added to energy restriction in the treatment of obesity, it is pertinent to clarify its additive benefits. Augmented improvements in metabolic, anthropometric, and cardiovascular parameters have been observed after combined exercise training and dietary weight loss in some (17,20,21), but not other studies (22), and there are limited data regarding their combined effect on sympathetic activity (23). Exercise training may potentially augment weight loss induced sympathoinhibition by promoting a greater loss of fat relative to lean mass (20,21), by further improvement in insulin sensitivity (24) and reduction in plasma leptin concentration (21), and by potentiation of baroreceptor sensitivity (18).The present study was conducted to 1) test the hypothesis that weight loss by combined hypocaloric diet and aerobic exercise training would be associated with greater sympathoinhibition and improvement in MetS components than hypocaloric diet alone and 2) to examine the interrelationships between reduction in sympathetic tone and concurrent changes in anthropometric, metabolic (insulin sensitivity, plasma leptin concentration), and cardiovascular parameters. A moderate-intensity bicycle riding protocol was chosen as the exercise intervention, based on an earlier study that demonstrated attenuation in whole-body and renal norepinephrine spillover rates with this regimen in healthy men (19).     

CNS 7056: A Novel Ultra-short-acting Benzodiazepine

Background: A new benzodiazepine derivative, CNS 7056, has been developed to permit a superior sedative profile to current agents, i.e., more predictable fast onset, short duration of sedative action, and rapid recovery profile. This goal has been achieved by rendering the compound susceptible to metabolism via esterases. The authors now report on the profile of CNS 7056 in vitro and in vivo.

Methods: The affinity of CNS 7056 and its carboxylic acid metabolite, CNS 7054, for benzodiazepine receptors and their selectivity profiles were evaluated using radioligand binding. The activity of CNS 7056 and midazolam at subtypes ([alpha]1[beta]2[gamma]2, [alpha]2[beta]2[gamma]2, [alpha]3[beta]2[gamma]2, [alpha]5[beta]2[gamma]2) of the [gamma]-aminobutyric acid type A (GABAA) receptor was evaluated using the whole cell patch clamp technique. The activity of CNS 7056 at brain benzodiazepine receptors in vivo was measured in rats using extracellular electrophysiology in the substantia nigra pars reticulata. The sedative profile was measured in rodents using the loss of righting reflex test.

Results: CNS 7056 bound to brain benzodiazepine sites with high affinity. The carboxylic acid metabolite, CNS 7054, showed around 300 times lower affinity. CNS 7056 and CNS 7054 (10 [mu]m) showed no affinity for a range of other receptors. CNS 7056 enhanced GABA currents in cells stably transfected with subtypes of the GABAA receptor. CNS 7056, like midazolam and other classic benzodiazepines, did not show clear selectivity between subtypes of the GABAA receptor. CNS 7056 (intravenous) caused a dose-dependent inhibition of substantia nigra pars reticulata neuronal firing and recovery to baseline firing rates was reached rapidly. CNS 7056 (intravenous) induced loss of the righting reflex in rodents. The duration of loss of righting reflex was short (< 10 min) and was inhibited by pretreatment with flumazenil.