Loss of function,missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts

Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes.     

Age-specific trends in health-related quality of life among US adults: findings from National Health and Nutrition Examination Survey, 2001–2016

Quality of Life Research - Health-related quality of life (HRQoL) is an important indicator of population health, yet no age-specific trend analyses in HRQoL have been conducted with a nationally...     

Chronic urticaria and osteoporosis: a longitudinal,community-based cohort study of 11 944 patients

Osteoporosis is a condition in which the bones are thinner and more liable to fracture. It is commoner in women and in people over 50. It cannot be cured so the focus is on prevention, which means identifying and addressing risk factors such as obesity, low vitamin D, chronic inflammation and prolonged steroid medication. Chronic urticaria (hives, CU) is an inflammatory condition, so one might expect it to be linked with osteoporosis, but that has never been investigated. If people with CU are indeed more likely to develop osteoporosis, they could be advised about preventative measures. To study this, doctors from Israel identified 11,944 patients diagnosed with CU in a large medical database covering 4.5 million people. A potential difficulty was that people with CU are more likely to be female, obese and to have been treated with systemic steroids, all of which also increase the risk of osteoporosis. Therefore for each CU patient they studied 5 age- and sex-matched control patients (people of the same age and sex but without CU) and their analyses took into account other known risk factors for osteoporosis. During a 16 year period 8.7% of the patients with CU were diagnosed with osteoporosis compared with 6.8% of the controls. They concluded that CU is a small but significant additional risk factor for osteoporosis. An accompanying editorial cautions against basing conclusions on routine health records which may not have all the information required. Nonetheless, doctors treating chronic urticaria might bear in mind the risk of osteoporosis in their patients, and counsel accordingly.     

Tinea faciei starting at day two of life

Dermatophyte infections are exceedingly rare in neonates, possibly due to the thin stratum corneum and high sebum content of neonatal skin. Only a handful of cases of tinea faciei have been reported in neonates, with the majority of reports occuring in India. Here, we report what to our knowledge is the earliest reported presentation of tinea faciei in the United States. We also provide a brief literature review of other reported cases of tinea faciei in neonates less than 30 days of age.     

‘Ammonia,lactate and blood gases – A user's guide’

Basic biochemical tests are frequently obtained in acutely unwell neonates and children, as well as in some elective situations. Correct interpretation can be invaluable in identifying rare inherited primary metabolic disorders, but secondary causes of hyperammonaemia, elevated blood lactate or blood gas derangement are more common and require appropriate treatment of the underlying cause. This Personal Practice guide provides an overview of these tests and their interpretation.     

Intimate partner violence as a mechanism of traumatic ocular injury in women

ObjectiveDetermine the prevalence of intimate partner violence (IPV) as a mechanism of traumatic ocular injury in women, typical injury patterns, and the clinical course of affected patients. Encourage IPV screening and safety assessment in patients presenting with characteristic ocular trauma.MethodsMedical records of 211 female patients with traumatic ocular injuries evaluated at the University of Iowa Hospitals and Clinics between January 1995 and January 2015 were reviewed to determine the rate of IPV as a mechanism of ocular trauma. Twenty-one patients were excluded due to no documented trauma.ResultsLeading causes of traumatic ocular injuries in the 190 female patients included were accidental trauma with an inanimate object (n = 70/190, 36.8%), falls (n = 52/190, 27.4%), motor vehicle collisions (n = 21/190, 11.1%), and assault (n = 16/190, 8.4%). In 2.1% of cases (n = 4/190), no mechanism of traumatic injury was documented. Assault was the fourth leading mechanism of injury accounting for 8.4% of cases (n = 16/190), with IPV accounting for more than one third of cases with a documented perpetrator (n = 5/13). No perpetrator was documented in 18.8% (n = 3/16). All 5 patients with IPV-related injuries sustained scleral laceration or rupture; 4 out of 5 patients had no light perception vision and ultimately required enucleation.ConclusionIPV is an important mechanism of traumatic ocular injury. IPV-associated injuries tend to be severe in nature, as demonstrated by the high rate of globe laceration or rupture and subsequent enucleation in the study population. By appropriate screening and referral, ophthalmologists have an opportunity to redirect a potentially devastating course.     

A Burnout Reduction and Wellness Strategy: Personal Financial Health for the Medical Trainee and Early Career Radiation Oncologist

PurposePhysician burnout is reported in more than one out of every 2 practicing clinicians and is just as prevalent in training physicians. Burnout severity is also associated with increasing levels of financial debt. Medical professionals are notable for their high and increasing levels of debt; despite this, financial literacy is poor among physicians, and financial education is largely absent from medical education. Radiation oncologists (ROs) are no different in this regard, with 33% of residents reporting high levels of burnout symptoms, 33% carrying >$200,000 of educational debt, and 75% reporting being unprepared to handle future financial decisions. To fill this gap, we reviewed the basic tenets of personal financial health for the early career RO.Methods and materialsThe core concept of financial independence (FI) is introduced, and we review 4 basic tenets of personal financial health for the young medical professional: debt, behavior, investment, and asset protection strategies.ResultsFI is achieved by saving until the desired quality of life can be maintained, independent of employment income. Debt strategy involves minimizing debt accrual, understanding student loans, and having a debt management plan. Behavioral strategy involves setting financial goals, calculating worth and a savings rate, budgeting, and frugal living. The basics of investing include asset allocation, diversification, rebalancing, and minimizing expenses. Finally, asset protection includes insuring against catastrophic events with disability, life, health, liability, and property insurance.ConclusionsHealthy financial practices can lead to FI and may facilitate professional and personal freedoms with the goal of mitigating burnout-associated stressors. The tenets of strong financial health for ROs in the early stages of their career include sound debt, behavioral, investment, and asset protection strategies. Furthermore, initial and continuing financial education is an overlooked but important curriculum component. ROs with their financial houses in order can devote more resources to learning and practicing good medicine while living healthy, rewarding lives.