Effect of progestin-based contraceptives on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls.

Adolescent girls bear a disproportionate burden of both the HIV epidemic and unintended pregnancies; yet important questions remain unanswered regarding the effects of hormonal contraceptives on the vaginal immune microenvironment, which can impact HIV susceptibility in this group. Multiple studies report genital immune alterations associated with the progestin-based contraceptive Depot medroxyprogesterone acetate (DMPA) in adult women, but there is little available data in adolescents. The objective of this longitudinal cohort study was to evaluate the effects of short-term use of three progestin-based contraceptives, levonorgestrel intrauterine device (LNG-IUD), subdermal etonogestrel (ETNG), and injectable DMPA, on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls. Fifty-nine sexually active, HIV-uninfected girls aged 15-19, were recruited from the Washington DC metro area and self-selected into Control (condoms only), combined oral contraceptive pills, LNG-IUD, ETNG and DMPA groups. Vaginal swabs were collected at baseline prior to contraceptive use and at 3-month follow-up visit. Vaginal secretions were tested for pro-inflammatory (IL-1α, IL-1ß, TNF-α, IL-6, IL-8, MIP-3α, IP-10, RANTES, MIP-1α, MIP-1ß) and anti-inflammatory/anti-HIV (Serpin-A1, Elafin, Beta-Defensin-2, SLPI) immune biomarkers using ELISA and for anti-HIV activity using TZM-bl assay. Vaginal microbiome was evaluated using 16S rRNA gene sequencing. Data were analyzed using SAS Version 9. Among the 34 participants who completed both visits, no significant changes in median biomarker concentrations, HIV inhibition and microbiome composition were observed between baseline and follow-up visits for any of the contraceptive groups. IL-8 (p<0.01), MIP-3α (0.02), Elafin (p = 0.03) and RANTES (p<0.01) differed significantly by race whereas IL-6 was significantly different by age (p = 0.03). We conclude that 3-month use of LNG-IUD, ETNG and DMPA have minimal effects on adolescent vaginal immune microenvironment, and therefore unlikely to impact HIV risk. Future studies with larger sample size and longer follow-up are recommended to continue to evaluate effects of contraceptives on the lower genital tract immunity and susceptibility to sexually transmitted infections.

Increasing partner communication and understanding during pregnancy: evaluation of 'The Great Pregnancy Quiz'.

OBJECTIVE: To evaluate a Quiz designed to enhance communication and understanding in expectant parents. BACKGROUND: A supportive and understanding relationship is associated with better maternal mental health outcomes. Many services therefore advocate that couples should communicate openly with each other, particularly about worries or concerns either have. To facilitate this a quiz (The Great Pregnancy Quiz) was developed and evaluated in this project. METHOD: English-speaking women (N = 442) and men (N = 146) were recruited from antenatal clinics or classes and were given the 'Great Pregnancy Quiz' to complete at home. Approximately 2-4 weeks (T2) later they participated in either a phone interview, an online survey, or a face-face interview, still during the pregnancy, concerning the impact of the Quiz. Data were available from 90 women and 46 men. Data were analysed using a mixed-methods single group post-test only design. RESULTS: Most women (78 of the 90: 87%) and men (35 of the 46: 76%) reported that the Quiz had positively impacted either their understanding or knowledge of each other. For 30 of the 90 women (33%) and 3 of the 46 men (7%) one or other had implemented some new supportive behaviour due to the Quiz. Qualitative comments highlight the impacts of the Quiz. CONCLUSION: Most couples who did the Quiz reported positive impacts on their communication and understanding. While the issue of low T2 contact rates may have skewed the results, the benefits associated with the quiz make this resource an inexpensive and easily implemented health promotion strategy.

Sleep-disordered breathing in patients with stroke-induced dysphagia.

This study examined the nature and characteristics of sleep-disordered breathing, including obstructive sleep apnea and central sleep apnea, in patients with post-stroke dysphagia, to determine the demographic, anthropometric and clinical variables that were associated with sleep-disordered breathing. Thirty-nine patients diagnosed with acute stroke (28 males and 11 females with a mean age of 72.3 ± 10.0 years) underwent overnight polysomnography (within 3.9 ± 1.6 days after admission). Sleep-disordered breathing was described by the apnea-hypopnea index and its obstructive and central components by the obstructive apnea-hypopnea index and central apnea-hypopnea index, respectively. Severity of dysphagia was assessed using the Mann Assessment of Swallowing Ability score. Severity of stroke and functional dependence were assessed by the National Institute of Health Stroke Scale and the modified Barthel index, respectively. Most of the cohort (87%) had moderate-to-severe dysphagia (Mann Assessment of Swallowing Ability of 143.2 ± 19.9). Sleep-disordered breathing (apnea-hypopnea index ≥ 5 events/hr) was present in 38 participants (97%) with a mean apnea-hypopnea index of 37.5 ± 24.4 events/hr. Sleep-disordered breathing was predominantly obstructive in nature, with a mean obstructive apnea-hypopnea index and central apnea-hypopnea index of 19.6 ± 15.7 and 11.4 ± 17.6 events/hr, respectively. Multivariate linear regression analyses showed that the apnea-hypopnea index was associated with sex (p = .0001), body mass index (p = .029) and the modified Barthel index (p = .006); the obstructive apnea-hypopnea index was associated with the Mann Assessment of Swallowing Ability (p = .006), sex (p = .004) and body mass index (p = .015) and had a nonlinear relationship with the modified Barthel index (p = .019); and the central apnea-hypopnea index was associated with sex (p = .027) and the modified Barthel index (p = .019). The present study showed that dysphagia severity was associated with obstructive sleep apnea severity and this association was independent of sex, modified Barthel index and body mass index. However, stroke-induced dysphagia was not associated with central sleep apnea or overall sleep-disordered breathing.

Treating Chronic Hypoventilation With Automatic Adjustable Versus Fixed EPAP Intelligent Volume-Assured Positive Airway Pressure Support (iVAPS): A Randomized Controlled Trial.

Objectives: New noninvasive ventilation (NIV) modes can automatically adjust pressure support settings to deliver effective ventilation in response to varying ventilation demands. It is recommended that fixed expiratory positive airway pressure (FixedEPAP) is determined by attended laboratory polysomnographic (PSG) titration. This study investigated whether automatically determined EPAP (AutoEPAP) was noninferior to FixedEPAP for the control of obstructive sleep apnea (OSA) during intelligent volume-assured pressure support (iVAPS) treatment of chronic hypoventilation. Methods: In this randomized, double-blind, crossover study, patients with chronic hypoventilation and OSA used iVAPS with AutoEPAP or FixedEPAP over two separate nights of attended PSG. PSG recordings were scored by an independent scorer using American Academy of Sleep Medicine 2012 criteria. Results: Twenty-five adults (14 male) with chronic hypoventilation secondary to obesity hypoventilation syndrome (n = 11), chronic obstructive pulmonary disease (n = 9), or neuromuscular disease (n = 5), all of whom were on established home NIV therapy, were included (age 57 ± 7 years, NIV for ≥3 months, apnea-hypopnea index [AHI] >5/hour). AutoEPAP was noninferior to FixedEPAP for the primary outcome measure (median [interquartile range] AHI 2.70 [1.70-6.05]/hour vs. 2.40 [0.25-5.95]/hour; p = .86). There were no significant between-mode differences in PSG sleep breathing and sleep quality, or self-reported sleep quality, device comfort, and patient preference. Mean EPAP with the Auto and Fixed modes was 10.8 ± 2.0 and 11.8 ± 3.9 cmH2O, respectively (p = .15). Conclusions: In patients with chronic hypoventilation using iVAPS, the AutoEPAP algorithm was noninferior to FixedEPAP over a single night's therapy.

Study of a Novel APAP Algorithm for the Treatment of Obstructive Sleep Apnea in Women.

STUDY OBJECTIVES: To assess the efficacy of a novel female-specific autotitrating continuous positive airway pressure (CPAP) algorithm (AutoSet for her, AfH) in premenopausal women relative to a standard autotitrating algorithm (AutoSet, S9) (ResMed Ltd., Bella Vista, New South Wales, Australia). DESIGN: Prospective randomised crossover noninferiority trial. SETTING: Tertiary hospital sleep clinic and university research sleep laboratory. PARTICIPANTS: 20 female patients with obstructive sleep apnea (OSA) established on long-term CPAP treatment. INTERVENTIONS: Treatment with 1 night each of AfH and AutoSet while monitored with overnight laboratory-based polysomnography (PSG); order randomly allocated. MEASUREMENTS AND RESULTS: The primary outcome variables were the apnea-hypopnea index (AHI) and 3% oxygen desaturation index (ODI 3%) determined from PSG. Treatment efficacy on the AfH night was noninferior to the AutoSet night as assessed by median (IQR) AHI (1.2 [0.60-1.85]/h versus 1.15 [0.40-2.85]/h, respectively, P = 0.51) and 3% ODI (0.85 [0.25-1.5]/h versus 0.5 [0.25-2.55]/h, respectively, P = 0.83). Other PSG measures were similar, except for the percentage of the night spent in flow limitation, which was lower on the AfH (0.14%) than the AutoSet night (0.19%, P = 0.007). The device-downloaded 95th centile pressure on the AfH night was also lower than on the AutoSet night (10.6 ± 1.7 versus 11.6 ± 2.6 cmH2O, respectively; mean difference [95% confidence interval]: -1.1 [-2.13 to -0.01] cm H2O). CONCLUSION: Among premenopausal women a novel female-specific autotitrating algorithm (AfH) is as effective as the standard AutoSet algorithm in controlling obstructive sleep apnea (OSA). The new algorithm may reduce flow limitation more than the standard algorithm and achieve control of OSA at a lower (95th centile) pressure.

Effects on upper airway collapsibility of presence of a pharyngeal catheter.

Catheters that traverse the pharynx are often in place during clinical or research evaluations of upper airway function. The purpose of this study was to determine whether the presence of such catheters affects measures of upper airway collapsibility itself. To do so, pharyngeal critical closing pressure (Pcrit) and resistance upstream of the site of collapse Rus) were assessed in 24 propofol-anaesthetized subjects (14 men) with and without a multi-sensor oesophageal catheter (external diameter 2.7 mm) in place. Anaesthetic depth and posture were maintained constant throughout each study. Six subjects had polysomnography(PSG)-defined obstructive sleep apnea (OSA) and 18 either did not have or were at low risk of OSA. Airway patency was maintained with positive airway pressure. At intervals, pressure was reduced by varying amounts to induce varying degrees of inspiratory flow limitation. The slope of the pressure flow relationship for flow-limited breaths defined Rus. Pcrit was similar with the catheter in and out (-1.5 ± 5.4 cmH2 O and -2.1 ± 5.6 cmH2O, respectively, P = 0.14, n = 24). This remained the case both for those with PSG-defined OSA (3.9 ± 2.2 cmH2O and 2.6 ± 1.4 cmH2O, n = 6) and those at low risk/without OSA (-3.3 ± 4.9 cmH2O and -3.7 ± 5.6 cmH2O, respectively, n = 18). Rus was similar with the catheter in and out (20.0 ± 12.3 cmH2O mL(-1) s(-1) and 16.8 ± 10.1 cmH2O mL(-1) s(-1), P = 0.22, n = 24). In conclusion, the presence of a small catheter traversing the pharynx had no significant effect on upper airway collapsibility in these anaesthestized subjects, providing reassurance that such measures can be made reliably in their presence.

Elastic properties of the central airways in obstructive lung diseases measured using anatomical optical coherence tomography.

RATIONALE: Our understanding of how airway remodeling affects regional airway elastic properties is limited due to technical difficulties in quantitatively measuring dynamic, in vivo airway dimensions. Such knowledge could help elucidate mechanisms of excessive airway narrowing. OBJECTIVES: To use anatomical optical coherence tomography (aOCT) to compare central airway elastic properties in control subjects and those with obstructive lung diseases. METHODS: After bronchodilation, airway lumen area (Ai) was measured using aOCT during bronchoscopy in control subjects (n = 10) and those with asthma (n = 16), chronic obstructive pulmonary disease (COPD) (n = 9), and bronchiectasis (n = 8). Ai was measured in each of generations 0 to 5 while airway pressure was increased from -10 to 20 cm H(2)O. Airway compliance (Caw) and specific compliance (sCaw) were derived from the transpulmonary pressure (Pl) versus Ai curves. MEASUREMENTS AND MAIN RESULTS: Caw decreased progressively as airway generation increased, but sCaw did not differ appreciably across the generations. In subjects with asthma and bronchiectasis, Caw and sCaw were similar to control subjects and the Pl-Ai curves were left-shifted. No significant differences were observed between control and COPD groups. CONCLUSIONS: Proximal airway elastic properties are altered in obstructive lung diseases. Although central airway compliance does not differ from control subjects in asthma, bronchiectasis, or COPD, Ai is lower in asthma and the Pl-Ai relationship is left-shifted in both asthma and bronchiectasis, suggesting that airways are maximally distended at lower inflating pressures. Such changes reflect alteration in the balance between airway wall distensibility and radial traction exerted on airways by surrounding lung parenchyma favoring airway narrowing. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN12607000624482).

Abnormal knee joint position sense in individuals with patellofemoral pain syndrome.

The purpose of this cross-sectional study was to compare knee joint position sense (JPS) in 20 individuals with and 20 without patellofemoral pain syndrome (PFPS). Five active tests with ipsilateral limb matching responses were performed at 20 degrees and 60 degrees flexion under non-weightbearing conditions, and at 40 degrees flexion under uni- and bi-lateral weightbearing conditions. The response errors were calculated as the difference between each target and response position (accuracy) and the standard deviation of these differences (reliability). JPS was: (i) significantly less accurate and less consistent in the knees with PFPS during both the non-weightbearing and weightbearing tests when compared to the control subject knees; (ii) less accurate when the symptomatic and asymptomatic knees of the 12 uni-lateral PFPS subjects were compared and (iii) less accurate in the asymptomatic knees of the uni-lateral PFPS subjects and knees of the control subjects. The maximum intensity of pain experienced during each knee JPS test was not correlated to any of the JPS test results. The results confirm abnormal knee joint proprioception in individuals with PFPS. Although it cannot be determined whether the abnormality precedes or follows the development of PFPS, the results support including proprioceptive reeducation in management of PFPS.