Left Ventricular Systolic Dysfunction and Cardiovascular Outcomes in Tetralogy of Fallot: Systematic Review and Meta-analysis

BackgroundAlthough there are robust data about the pathophysiology and prognostic implications of left ventricular (LV) systolic dysfunction in patients with acquired heart disease, similar prognostic data about LV systolic dysfunction are sparse in the tetralogy of Fallot (TOF) population. The purpose of this study was to perform a meta-analysis of all studies that assessed the relationship between LV ejection fraction (LVEF) and cardiovascular adverse events (CAEs) defined as death, aborted sudden death, or sustained ventricular tachycardia.MethodsWe used random-effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsOf the 1,809 citations, 7 studies with 2,854 patients (age 28 ± 4 years) were included. During 5.6 ± 3.4 years' follow-up, there were 82 deaths, 17 aborted sudden cardiac deaths, and 56 sustained ventricular tachycardia events. Overall, CAEs occurred in 5.1% (144 patients). As a continuous variable, LVEF was a predictor of CAE (HR 1.29, 95% CI, 1.09-1.53, P = 0.001) per 5% decrease in LVEF. Similarly, LVEF < 40% was also a predictor of CAE (HR 3.22, 95% CI, 2.16-4.80, P < 0.001).ConclusionsLV systolic dysfunction was an independent predictor of CAE, and we observed a 30% increase in the risk of CAE for every 5% decrease in LVEF, and a 3-fold increase in the risk of CAE in patients with LVEF <40% compared with other patients. These findings underscore the importance of incorporating LV systolic function in clinical risk stratification of patients with TOF and the need to explore new treatment options to address this problem.     

Is intrauterine insemination a viable treatment option for women over 43 years old? An analysis by ovarian stimulation protocol and sperm source

PurposeThe aim of this study was to determine how female age at the end of the reproductive spectrum effects success of natural cycle intrauterine insemination (IUI) or IUI in combination with ovarian stimulation.MethodsWe performed a retrospective cohort study of women 43 years of age and older at the time of IUI in a single academic fertility center between January 2011 and March 2018. Primary outcomes were both pregnancies and live births per cycle of IUI. Data are presented as percentage or mean ± SD. Fisher exact and chi-squared analyses were performed.ResultsThere were 9334 IUI cycles conducted during the study period. Of these cycles, 325 IUIs (3.5%) were for women aged 43 years and over at the time of insemination (43.6 ± 0.8, range 43 to 47 years). Analysis of these 325 IUI cycles revealed 5 biochemical pregnancies (1.5%) and only 1 live birth (0.3%). The pregnancy rate did not differ between IUIs using donor sperm (N = 1/49, 2.0%) compared to IUIs with partner sperm (N = 4/276, 1.4%). The pregnancy rate did not differ between IUIs with gonadotropins (N = 2/211, 0.9%), clomiphene or letrozole (N = 2/78, 2.6%), or natural cycle (N = 1/36, 2.8%).ConclusionsThe use of intrauterine inseminations in women 43 years of age and older is an ineffective treatment strategy. This is irrespective of the use of ovarian stimulation or donor sperm. Costly gonadotropin injections did not increase the chance of pregnancy nor did oral medication when compared to natural cycle IUIs.     

Trade-offs between acquired and innate immune defenses in humans

Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology.     

Use of colony-stimulating factor primary prophylaxis and incidence of febrile neutropenia from 2010 to 2016: a longitudinal assessment

Background: Guidelines recommend primary prophylactic use of colony-stimulating factor (PP-CSF) when risk of febrile neutropenia (FN) – based on chemotherapy and patient risk factors – is high. Whether and how PP-CSF use may have changed over time (e.g. due to guideline revisions, increasing use of myelosuppressive regimens, controversy regarding inappropriate CSF use), and whether there has been a concomitant change in the incidence of FN, is unknown.

Methods: A retrospective cohort design and data from two US healthcare claims repositories were employed. The study population included patients who had non-metastatic cancer of the breast, colon/rectum, lung or ovaries, or non-Hodgkin’s lymphoma (NHL), and who received myelosuppressive chemotherapy regimens with an intermediate/high risk for FN. For each patient, the first cycle of the first course was characterized in terms of PP-CSF use and FN episodes. Crude incidence proportions for PP-CSF and FN during the first cycle were estimated by calendar quarter (2010–2016); multivariable logistic regression models were used to estimate quarter-specific adjusted mean probabilities of FN by PP-CSF use.

Results: The study population totaled 142,730 patients with breast cancer (61%), colorectal cancer (14%), NHL (11%), ovarian cancer (10%) or lung cancer (5%). PP-CSF use increased from 52% in 1Q2010 to 58% in 4Q2016; pegfilgrastim was the most commonly used agent (>96% across quarters). PP-CSF administration on the same day as chemotherapy ranged from 8 to 11% until 1Q2015, and increased to 64% by 4Q2016. Adjusted incidence proportions for FN in the first chemotherapy cycle ranged from 2.7% (95% CI: 2.3–3.0) to 3.7% (95% CI: 3.1–4.3) among those who did not receive PP-CSF, and was 2.6% (95% CI: 2.5–2.7) across quarters among those who received PP-CSF.

Conclusions: Although the use of PP-CSF is commonplace in current US clinical practice, underutilization in cancer patients receiving chemotherapy regimens with an intermediate/high risk for FN may still be an issue. Use of same-day PP-CSF increased markedly from the end of 2015, although this finding reflects (at least in part) increased uptake of pegfilgrastim delivered via an on-body injector as well as the recent change in clinical practice guidelines. Overall, patients receiving PP-CSF appear to have a lower risk of FN during the first cycle of chemotherapy.     

Life on the Western Front of Israel Stressful Living Conditions and Adolescent Cannabis Use

Negative implications of exposure to violence on health and well-being of youth have been observed and studied worldwide and especially in Israel. Youth in the Western Negev of the country have been exposed to missile and terror attacks for more than a decade. However, implications of such prolonged exposure have not been fully studied. This study is aimed at the implications of exposure to such conditions on youth in the town of Ofakim in the Negev. A focus group was conducted with youth following the Israeli Defense Forces’ “Protective Edge” response to continued attacks from Gaza (July–August 2014). Focus group participants reported high stress levels during the operation that resulted in an increase of substance use including alcohol, tobacco, cannabis, and synthetic cannabis-like substances (e.g., “Nice Guy,” “Spice,” and “Black Mamba”) and changes in eating and sleeping behavior. The Ofakim resilience center served as a shelter for participants providing for them with physical and emotional comfort. Staying in the “shelter” used for protection against missile attack promoted youth resilience. Exposure to violence has a significant impact on the health and well-being of young people and others. A secure receptive facility that provides trust and support can serve as an important moderator of the negative impact of emergency conditions. From the results reported in this article, further research is needed to fully assess the long-term effects of stress conditions including the use of cannabis and synthetic cannabis-like substances among youth and other residents in the Western Negev.

     

Pediatric Teledermatology: A Survey of Usage,Perspectives, and Practice

Pediatric dermatology is one of the smallest subspecialties, and expanding the availability of care is of great interest. Teledermatology has been proposed as a way to expand access and improve care delivery, but no current assessment of pediatric teledermatology exists. The objective of the current study was to assess usage and perspectives on pediatric teledermatology. Surveys were distributed electronically to all 226 board‐certified U.S. pediatric dermatologists; 44% (100/226) responded. Nearly all respondents (89%) have experience with teledermatology. Formal teledermatology reimbursement success rates have increased to 35%. Respondents were positive about teledermatology's present and future prospects, and 41% want to use teledermatology more often, although they viewed teledermatology as somewhat inferior to in‐person care regarding accuracy of diagnosis and appropriation of management plans. Significant differences were found between formal teledermatology users and nonusers in salary structure, practice environment, sex, and region. Substantial increases in pediatric teledermatology have occurred in the last 5 to 10 years, and there remains cause for optimism for teledermatology's future. Concerns about diagnostic confidence and care quality indicate that teledermatology may be best for care of patients with characteristic clinical presentations or management of patients with established diagnoses.     

Griscelli Syndrome Type 3: Two New Cases and Review of the Literature

A 3‐year‐old Arab boy with a history of hypoplastic left heart syndrome was referred to the pediatric dermatology clinic at Sheba Medical Center for evaluation of hypomelanosis, manifested by fair skin pigmentation and silvery‐grey hair, eyebrows, and eyelashes. The child had one older brother with similar hypopigmentation and another older brother who had died of congenital heart disease. The child had no history of neurologic deficits or immunodeficiency and no additional findings on clinical evaluation.