May 3, 2019

Replacement level

The story

If you thought your hospital's move from pagers to HIPAA-proof iPhones was sexy, wait 'til you see what else science has in store. Gene therapy is making waves in X-linked severe combined immunodeficiency (SCID-X1).

The background

The best science is simple, and when it comes to SCID-X1 – the rare immunodeficiency disorder of 1970's bubble boy fame – the way to correct for absent gene function is to add back what's missing. Affected patients can't manufacture lymphocytes due to mutations in culprit-gene ILR2G and accordingly suffer early and frequent opportunistic infections. Researchers have tinkered for years with an HIV-like retrovirus vector designed to insert a normal copy of IL2RG into stem cells, but prior attempts failed to find the right balance between safety and efficacy.

The study

The current approach to SCID-X1 gene therapy harvests stem cells from the blood and transfects them with IL2RG cDNA, then uses chemotherapy to clear immunodeficient lymphocytes before re-introducing the new cells. A phase 1-2 study of the technique in 8 infants with SCID-X1 found that 7 participants had signs of robust immune system recovery after 3 - 4 months following treatment, and the 8th patient did well after a second infusion of reengineered cells. All infants continued to grow normally and previous infections cleared. Four patients were taken off IVIG and 3 were successfully vaccinated.

The takeaway

The hope here is that all of these patients will go on to develop normal, healthy immune systems. Long-term results will be watched closely and larger, confirmatory trials await.  

Say it on rounds

When the hospital cafeteria is off its game

Imagine how patients feel. A Swiss trial of 2,100 inpatients at risk for malnutrition assigned participants to individualized nutritional support – a step-up plan with patient-specific nutrition targets and the option to escalate to enteral and parenteral nutrition if caloric goals were not met – or standard hospital food. The intervention group saw lower 30-day mortality (7% vs. 10%) and reported a higher quality of life. Patients with chronic kidney disease were especially likely to benefit.

When you hit your step count, but it took a few codes

Two birds, one stone. AUGUSTUS randomized 4,600 patients with a-fib who underwent PCI to the direct oral anticoagulant (DOAC) apixaban or warfarin and to aspirin or placebo in a 2 x 2 factorial trial. All patients were also on a P2Y12 inhibitor. In line with prior studies, DOAC patients had a lower incidence of death or hospitalization than those on warfarin (24% vs. 27%) at 6 months. The aspirin results were less clear, as treatment patients had higher rates of bleeding while the placebo group had more ischemic events in a trend that did not meet significance.

When the EMR crashes without saving your note

Take a deep breath. Emotion dysregulation is known to hinder treatment outcomes for women with substance use disorder (SUD). A RCT of 190 women in intensive treatment for SUD evaluated Mindful Awareness in Body-oriented Therapy (MABT), an approach designed to teach interoceptive awareness and skills for emotion regulation, as an adjunct to standard treatment. MABT patients were abstinent from substance use an average of 22 more days than controls over 1 year despite imperfect participation. They also reported improvements in emotion regulation and cravings.
Drug Alcohol Depend

Brush up

Depression in primary care

Eighty percent of antidepressant scripts are written by non-mental health providers. Your job? Be ready to recognize depression and know the basics of initial treatment. Rule out underlying medical conditions like dementia, identify contributing substances like prescribed meds and illicits, and perform a laboratory work up including TSH, folate, and B12. For mild depression, first-line treatment is psychotherapy and symptom monitoring. Consider antidepressants for moderate-to-severe depression, and screen for symptoms of mania before starting treatment.   

What's the evidence

For Patient Health Questionnaires (PHQ) 2 and PHQ 9? The screening forms that are passed around to all of your clinic patients were evaluated in a 2010 analysis of 2,600 consecutive adult patients in New Zealand. A PHQ-2 score of ≥ 2 was 86% sensitive and 78% specific for major depression compared to the CIDI reference standard, while a PHQ-9 score ≥ 10 was 74% sensitive and 91% specific. The USPSTF recommends universal screening for depression in all adult primary care patients.

What your health policy friends are talking about

Get a little lost when the discussion turns to single-payer and Medicare-for-all? This week the Congressional Budget Office released a long-awaited report on the logistics of single-payer healthcare in the US.

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