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Sep 20, 2019

Early action

The story

Type 2 diabetes is the kind of long and slow progression that only makes sense to a medical trainee. Does a strong start change the course of disease?

The background

Some clinic A1Cs pop off the page, but every patient with type 2 diabetes (T2D) starts somewhere. The disease may be less about the current state than the pace of progression. In 1998 the UK Prospective Diabetes Study found that early treatment with metformin in newly diagnosed T2D was tied to CV and mortality benefits that were present over 10 years later. So while step-up sequential therapy beginning with metformin is the current standard of care, small trials have hinted at benefits for early combinations.

The study

Pharma-backed VERIFY compared metformin monotherapy with metformin + DPP4 inhibitor vildagliptin in 2,000 patients with new onset T2D and a hemoglobin A1C between 6.5 - 7.5%. The investigators defined treatment failure as an A1C > 7% on 2 consecutive visits. Over 5-year follow-up, combo therapy patients had fewer failure events (44% vs 62%) without additional toxicity. As for pace? Monotherapy patients were more likely to have a second treatment failure after switching to combo therapy than those who were on combo all along.
Lancet

The takeaway

These results are promising, but many in the field want to see a stronger link to clinical outcomes before changing the status quo. Understanding which patients benefit most from combo therapy would help.

Say it on rounds

When you want to edit the gene for bags under your eyes

Try sleep. A new case report details the first transplant and engraftment of CRISPR edited stem cells in humans. A 27-year old patient with HIV and acute lymphoblastic leukemia underwent allogeneic transplant with cells edited to remove the HIV-entry mediator CCR5. After rigorous efforts to check against off target effects, the cells were transplanted without any unexpected adverse events. CCR5 disruption didn't cure HIV in this patient, but the approach paves the way for further human studies.
NEJM

When the ED schedules you for alternating day and night shifts

Your job doesn't always make sense, but there is some ground truth out there. A study of 300 adults with severe sepsis across 7 EDs validated the age-old dogma that blood cultures should be taken before antibiotics. When drawn from the same patient, pre-antibiotic blood cultures were positive in 31% of cases compared to 19% of cultures drawn after antibiotics were given.
Annals

When it's bedtime, and your 3rd cup of coffee has you wired

There's such a thing as too much. A post-hoc analysis of 400 women with heart failure with reduced ejection fraction within BIOSTAT-CHF found that women had optimal risk reduction at approximately 50% of guideline-recommended doses for ACE inhibitors, ARBs and β blockers. The same analysis in men found optimal risk reduction at 100% of target dose, suggesting a role for sex-specific dosing strategies.
Lancet

Brush up

Alcohol use disorders

Men are five times more likely than women to develop alcohol use disorders (AUD), though there are signs the gender gap is narrowing. The diseases are among the most common mental health disorders and have a prevalence in high income countries of 8.4%. Formal diagnosis is through operational criteria: continued alcohol use despite negative health, social, occupational, and other consequences. Only about 20% of worldwide AUD sufferers receive treatment.

Get meta

With heritability and AUD. Genes are always under scrutiny for their role in these diseases, and a 2015 meta-analysis that included 12 twin and 5 adoption studies estimated that AUD is roughly 50% heritable. Some cite measurement bias and place the estimate closer to 70%. There's a clear role for gene-environment interaction, and prevalence tends to be higher in cultures that are permissive of heavy drinking.

What your OB friends are talking about

A report from the Guttmacher Institute found that the 2017 US abortion rate declined to its lowest level since abortion became legal nationwide in 1973. Increased use of long-term contraceptives like IUDs and implants and declining birth rates are cited as contributing factors.

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