Chiefs’ Inquiry Corner — 7/19/21

 The lung microbiome, and its disruption, has been described in people with idiopathic pulmonary fibrosis (IPF) and is associated with disease progression, which in turn can potentially impact acute exacerbations, hospitalizations, and mortality rate. Therefore, it has been hypothesized that the addition of antimicrobial therapy to usual care for IPF may be successful in addressing lung dysbiosis, and thus in reducing nonelective hospitalizations and mortality rates. The CleanUP-IPF Randomized Clinical Trial examined the effect of adding antimicrobial therapy with co-trimoxazole [trimethoprim/sulfamethoxazole plus folic acid) or doxycycline to usual care for IPF on time to non-elective respiratory hospital admission and all-cause mortality (primary endpoint). Results demonstrated that adding TMP/SMX or doxycycline to usual care for IPF did not significantly improve time to first elective respiratory hospitalization since trial start or death. There was no statistically significant interaction between the effect of the antimicrobial agent (TMP/SMX vs. doxycycline) on primary endpoint. Serious adverse events occurred at 5% or greater in the treatment arm as compared to usual care alone, including diarrhea and rash. Thus, these findings do not support treatment with antimicrobials in addition to usual care for IPF.

References: CleanUP-IPF Trial

As people with increasingly complex medical comorbidities undergo increasingly complex operative interventions, chronic medication optimization for a variety of types of drugs becomes ever-more important. Many studies (and thus, guidelines and consensus statements) have provided guidance for medications such as anticoagulants and blood pressure medications. Now, the Society for Perioperative Assessment and Quality Improvement (SPAQI) have released a consensus statement with recommendations for perioperative management of endocrine/hormonal and urologic medications. Continuing some spaced-repetition this week, the diabetes medication management is of particular interest. Guidelines recommend you continue intermediate- or long-acting (basal) insulin at 60-80% of the usual dose on morning of surgery or evening before surgery based on patient’s usual medication schedule. On the day of surgery, hold metformin, sulfonylureas, pioglitazone, and DPP-4 inhibitors. Thinking ahead, you will need to stop SGLT-2 inhibitors at least 3 days prior to surgery. GLP-1 agonists also require a little planning — hold on the morning of surgery if dosed daily or during the week before surgery if dosed weekly. Specific management of hormonal and urologic medications is also covered in the article linked below.

References: Peri-Operative Management

 Statin therapy is a cornerstone of cholesterol management guidelines given their demonstrated efficacy of reducing the occurrence of major vascular events. Statin-associated muscle symptoms (SAMS) remain a barrier to adherence to statin medications, potentially leading to medication discontinuation and, ultimately, worsened cardiovascular outcomes. Although most randomized controlled trials have shown small, insignificant increases in risk for SAMS, they often primarily consider adverse effects such as myopathy and rhabdomyolysis and do not necessarily account for symptoms such as myalgias, which are comparatively more benign but nevertheless may lead to discomfort significant enough to stop therapy. A recent network meta-analysis of nearly 3000 RTCs (N=152 461) aimed to estimate the relative risk of SAMS by statin therapy intensity (i.e., moderate intensity versus high intensity). Results of the NMA showed that users of moderate-intensity statins did not report significantly more overall muscle problems or myalgias, but those taking high-intensity statins did. Prior research has suggested that SAMS with moderate-intensity statin medications are at least partially attributable to patient expectation of this side effect; for example, one double-blinded study found minimal differences in SAMS when comparing statin versus placebo, but significantly more muscle symptoms when comparing placebo groups and groups taking nothing at all (unblinded). However, SAMS with high-intensity statins are likely to be the result of patient expectations as well as the intensity of the therapy. Therefore, clinicians caring for patients who are ‘statin-intolerant’ on high-intensity statins should encourage their patients to first decrease statin intensity before forgoing statin therapy altogether.

References: Statin Therapy and Muscle Symptoms