Superficial venous disease and combined hormonal contraceptives: a systematic review

AbstractBackgroundSuperficial venous disease, which includes superficial venous thrombosis (SVT) and varicose veins, may be associated with a higher risk of venous thromboembolism (VTE). Use of combined hormonal contraceptives (CHCs) has been associated with an increased risk of VTE compared with nonuse. Little is known about whether use of CHCs by women with superficial venous disease may further elevate the risk of VTE.ObjectivesTo investigate evidence regarding risk of VTE in women with SVT or varicose veins who use CHCs compared with non-CHC users.MethodsWe searched the PubMed database for all English-language articles published from database inception through September 2014. We included primary research studies that examined women with SVT or varicose veins who used CHCs compared to women with these conditions who did not use CHCs. Outcomes of interest included VTE (among women with SVT or varicose veins) and SVT (for those with varicose veins).ResultsTwo studies were identified that met inclusion criteria. One fair-quality case–control study reported an odds ratio (OR) for VTE of 43.0 (95% confidence interval [CI] 15.5–119.3) among women with SVT using oral contraceptives (OCs) compared with nonusers without SVT. The OR for VTE was also increased for women with SVT not using OCs (OR 5.1; 95% CI 2.8–9.5) and for women without SVT using OCs (OR 4.0; 95% CI 3.3–4.7), compared with nonusers without SVT. One fair-quality cohort study demonstrated that women with varicose veins had an increased rate of VTE with use of OCs (1.85 per 1000 women-years [WY]), compared with users without varicose veins (0.84 per 1000 WY), nonusers with varicose veins (0.31 per 1000 WY) and nonusers without varicose veins (0.19 per 1000 WY). This study also demonstrated that women with varicose veins had an increased rate of SVT with use of OCs (10.63 per 1000 WY), compared with nonusers with varicose veins (7.59 per 1000 WY), users without varicose veins (1.89 per 1000 WY) and nonusers without varicose veins (0.77 per 1000 WY).ConclusionTwo studies suggest increased risk of VTE among OC users with superficial venous disease; however, no definitive conclusions can be made due to the limited number of studies and limitations in study quality. Theoretical concerns need to be clarified with further research on whether the risk of significant sequelae from superficial venous disease among CHC users is related to clinical severity of disease and underlying factors

The rapid onset of stellar bars in the baryon-dominated centers of disk galaxies

Recent observations of high-redshift galactic disks ($z\approx 1-3$) show a strong negative trend in the dark matter fraction $f_{DM}$ with increasing baryonic surface density. For this to be true, the inner baryons must dominate over dark matter in early massive galaxies, as observed in the Milky Way today. If disks are dominant at early times, we show that stellar bars form promptly within these disks, leading to a high bar fraction at early times. New JWST observations provide the best evidence to date for mature stellar bars in this redshift range. The disk mass fraction $f_{disk}$ within $R_s=2.2 R_{disk}$ is the dominant factor in determining how rapidly a bar forms. Using 3D hydro simulations of halo-disk-bulge galaxies, we confirm the "Fujii relation" for the exponential dependence of the bar formation time $\tau_{bar}$ as a function of $f_{disk}$. For $f_{disk} > 0.3$, the bar formation time declines exponentially fast with increasing $f_{disk}$. This relation is a challenge to simulators - barred models with inadequate resolution fall off this curve. Instead of Fujii's arbitrary threshold for when a bar forms, for the first time, we exploit the exponential growth timescale associated with a positive feedback cycle as the bar emerges from the underlying disk. A modified, mass-dependent trend is observed for halos relevant to systems at cosmic noon ($10.5 < \log M_{halo} < 12$), where the bar onset is slower for higher mass halos at a fixed $f_{disk}$. If baryons dominate over dark matter within $R \approx R_s$, we predict that a high fraction of bars will be found in high-redshift disks long before $z = 1$. Due to its widespread use in simulations, we investigate the Efstathiou-Lake-Negroponte criterion for bar instability: this sub-optimal parameter is inversely related to $f_{disk}$, with a secondary dependence on $M_{halo}$.Comment: 27 pages, 8 figures, 1 table - Astrophysical Journal, accepted (9 March 2023

Erenumab in chronic migraine: Patient-reported outcomes in a randomized double-blind study.

OBJECTIVE: To determine the effect of erenumab, a human monoclonal antibody targeting the calcitonin gene-related peptide receptor, on health-related quality of life (HRQoL), headache impact, and disability in patients with chronic migraine (CM). METHODS: In this double-blind, placebo-controlled study, 667 adults with CM were randomized (3:2:2) to placebo or erenumab (70 or 140 mg monthly). Exploratory endpoints included migraine-specific HRQoL (Migraine-Specific Quality-of-Life Questionnaire [MSQ]), headache impact (Headache Impact Test-6 [HIT-6]), migraine-related disability (Migraine Disability Assessment [MIDAS] test), and pain interference (Patient-Reported Outcomes Measurement Information System [PROMIS] Pain Interference Scale short form 6b). RESULTS: Improvements were observed for all endpoints in both erenumab groups at month 3, with greater changes relative to placebo observed at month 1 for many outcomes. All 3 MSQ domains were improved from baseline with treatment differences for both doses exceeding minimally important differences established for MSQ-role function-restrictive (≥3.2) and MSQ-emotional functioning (≥7.5) and for MSQ-role function-preventive (≥4.5) for erenumab 140 mg. Changes from baseline in HIT-6 scores at month 3 were -5.6 for both doses vs -3.1 for placebo. MIDAS scores at month 3 improved by -19.4 days for 70 mg and -19.8 days for 140 mg vs -7.5 days for placebo. Individual-level minimally important difference was achieved by larger proportions of erenumab-treated participants than placebo for all MSQ domains and HIT-6. Lower proportions of erenumab-treated participants had MIDAS scores of severe (≥21) or very severe (≥41) or PROMIS scores ≥60 at month 3. CONCLUSIONS: Erenumab-treated patients with CM experienced clinically relevant improvements across a broad range of patient-reported outcomes. CLINICALTRIALSGOV IDENTIFIER: NCT02066415. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with CM, erenumab treatment improves HRQoL, headache impact, and disability

Progestogen-only contraceptive use among breastfeeding women: a systematic review.

Background: Postpartum women need effective contraception. Concerns have been raised that use of progestogen-only contraceptives (POCs) may affect breastfeeding performance and infant health outcomes. Objectives: We investigated the clinical outcomes of breastfeeding duration, initiation of supplemental feeding and weaning, as well as infant outcomes including infant growth, health and development among breastfeeding women using POCs compared with breastfeeding women not using POCs. Search strategy: We searched the PubMed database for all articles published from database inception through December 2014. Selection criteria: We included primary research studies of breastfeeding women of any age or parity who received POCs, including progestogen-only pills, injectables, implants or hormonal intrauterine devices (IUDs). The main outcomes were breastfeeding performance (as measured by initiation, continuation, frequency and exclusivity of breastfeeding) and infant health (as measured by growth, development or adverse health effects). Results: Forty-nine articles reporting on 47 different studies were identified that investigated the use of POCs in breastfeeding women and reported clinically relevant outcomes of infant growth, health or breastfeeding performance. Studies ranged from poor to fair methodological quality and generally failed to show negative effects of the use of POCs on breastfeeding outcomes or on infant growth or development. One randomized controlled trial (RCT) raises concerns that immediate insertion of the levonorgestrel IUD postpartum may be associated with poorer breastfeeding performance when compared with delayed insertion, although two other RCTs evaluating early etonogestrel implants compared with delayed initiation of implants or depot medroxyprogesterone acetate failed to find such an association. Conclusion: The preponderance of evidence fails to demonstrate adverse breastfeeding outcomes or negative health outcomes in infants such as restricted growth, health problems or impaired development. Evidence newly added to this review was largely consistent with previous evidence

Cumulative Effects of Neonatal Hyperoxia on Murine Alveolar Structure and Function

Background Bronchopulmonary dysplasia (BPD) results from alveolar simplification and abnormal development of alveolar and capillary structure. Survivors of BPD display persistent deficits in airflow and membrane and vascular components of alveolar gas diffusion. Despite being the defining feature of BPD, various neonatal hyperoxia models of BPD have not routinely assessed pulmonary gas diffusion. Methods To simulate the most commonly-utilized neonatal hyperoxia models, we exposed neonatal mice to room air or ≥90% hyperoxia during key stages of distal lung development: through the first 4 (saccular), 7 (early alveolar), or 14 (bulk alveolar) postnatal days, followed by a period of recovery in room air until 8 weeks of age when alveolar septation is essentially complete. We systematically assessed and correlated the effects of neonatal hyperoxia on the degree of alveolar–capillary structural and functional impairment. We hypothesized that the degree of alveolar–capillary simplification would correlate strongly with worsening diffusion impairment. Results Neonatal hyperoxia exposure, of any duration, resulted in alveolar simplification and impaired pulmonary gas diffusion. Mean Linear Intercept increased in proportion to the length of hyperoxia exposure while alveolar and total lung volume increased markedly only with prolonged exposure. Surprisingly, despite having a similar effect on alveolar surface area, only prolonged hyperoxia for 14 days resulted in reduced pulmonary microvascular volume. Estimates of alveolar and capillary structure, in general, correlated poorly with assessment of gas diffusion. Conclusion Our results help define the physiological and structural consequences of commonly-employed neonatal hyperoxia models of BPD and informtheir clinical utility

Increased Ipsilateral M1 Activation after Incomplete Spinal Cord Injury Facilitates Motor Performance

Incomplete spinal cord injury (SCI) may result in muscle weakness and difficulties with force gradation. Although these impairments arise from the injury and subsequent changes at spinal levels, changes have also been demonstrated in the brain. Blood-oxygen-level dependent (BOLD) imaging was used to investigate these changes in brain activation in the context of unimanual contractions with the first dorsal interosseous muscle. BOLD- and force data were obtained in 19 individuals with SCI (AISA Impairment Scale [AIS] C/D, level C4-C8) and 24 able-bodied controls during maximal voluntary contractions (MVCs). To assess force modulation, participants performed 12 submaximal contractions with each hand (at 10, 30, 50, and 70% MVC) by matching their force level to a visual target. MVCs were weaker in the SCI group (both hands p < 0.001), but BOLD activation did not differ between SCI and control groups. For the submaximal contractions, force (as %MVC) was similar across groups. However, SCI participants showed increased activity of the ipsilateral motor cortex and contralateral cerebellum across all contractions, with no differential effect of force level. Activity of ipsilateral M1 was best explained by force of the target hand (vs. the non-target hand). In conclusion, the data suggest that after incomplete cervical SCI, individuals remain capable of producing maximal supraspinal drive and are able to modulate this drive adequately. Activity of the ipsilateral motor network appears to be task related, although it remains uncertain how this activity contributes to task performance and whether this effect could potentially be harnessed to improve motor functioning