2 Minute Medicine Rewind October 5, 2020

Early surgical intervention for symptomatic renal and ureteral stones is associated with reduced narcotic requirement relative to trial of passage

1. Among those presenting with symptomatic nephrolithiasis, patients electing for trial of passage with medical expulsion therapy were more likely to receive a prescription for an opiate compared with those electing for early surgical intervention.

Evidence Rating Level: 3 (Average)

Despite a widespread reduction in the number of prescriptions for opioids in the U.S., the number of emergency department visits for opioid overdoses continues to remain high, particularly in the Midwest. Opioids are commonly prescribed to patients with nephrolithiasis for pain control; in fact, between 2007 and 2014, opioid use among individuals with a history of nephrolithiasis was significantly higher compared with those without. This retrospective cohort study examined 135 patients with symptomatic nephrolithiasis managed with either trial of passage (TOP) with medical expulsion therapy (MET) or with surgical intervention, consisting of either primary ureteroscopy (n = 27, median [IQR] age = 51 [33-63] years, 44.4% female) or staged ureteroscopy with ureteral stenting (n = 39, median [IQR] age = 52 [35-68] years, 53.8% female). Patients electing for TOP were further grouped into successful TOP (n = 30, median [IQR] age = 36 [31-51] years, 50% female) and unsuccessful TOP requiring subsequent ureteroscopy (n = 36, median [IQR] age = 47 [36-60] years, 52.8% female) or staged ureteroscopy with ureteral stenting (n = 3, median [IQR] age = 57 [50-64] years, 0% female) cohorts. It was found that patients who elected for initial TOP were significantly more likely to receive a prescription for an opiate compared with those treated with stenting or primary ureteroscopy (60.9% vs. 35.9% vs. 33.3%, p = 0.01). Furthermore, all three TOP cohorts were significantly more likely to receive a prescription for an opiate than both primary surgical intervention cohorts (p = 0.008). In all, this study suggests that patients electing for TOP with MET were more likely to receive an opiate prescription compared with those electing for early surgical intervention. Urologists should keep these findings in mind during shared decision making with the patient, though a robust prospective study should be done to further clarify these data.


Previous preterm cesarean delivery and risk of uterine rupture in subsequent trial of labor

1. Prior preterm cesarean delivery was not associated with an increased risk of uterine rupture compared with prior term cesarean delivery during a subsequent trial of labor.

Evidence Level Rating: 2 (Good)

Uterine rupture is a feared obstetric emergency associated with substantial morbidity and mortality for both mother and fetus. It is well-established that the major risk factor for uterine rupture in high-income countries is scarring from previous uterine surgery, which became apparent after trial of labor after cesarean (TOLAC) increased in the early 1990s. The American College of Obstetricians and Gynecologists (ACOG) recommends that most women with one previous lower uterine segment cesarean can and should be offered TOLAC. That being said, there is a paucity of reliable data on the association specifically between preterm cesarean and risk of uterine rupture. This nationwide cohort study from Sweden included women with a first cesarean between 1983 and 2016 followed by a second TOLAC delivery between 1998 and 2016. In all, 9,300 women with a preterm cesarean and 57,168 women with a term cesarean had a subsequent TOLAC delivery and thus were eligible for analysis. It was found that uterine rupture occurred in 1.4% of women with a term cesarean and in 1.1% of women with a preterm cesarean, a relationship that was not significant after adjustment (aOR 0.94, 95% CI 0.74 to 1.18). These findings were consistent after stratifying preterm cesareans into subgroups based on gestational age at delivery (i.e. between 32+0 and 36+6 gestational weeks and < 32+0 gestational weeks). However, preterm cesarean was found to be associated with a significantly increased risk of placenta abruptio after adjusting for confounders like placenta abruptio during the exposure delivery and pre-eclampsia during the outcome delivery (aOR 1.40, 95% CI 1.13 to 1.93). These findings are in conflict with previously published reports; however, the large sample size and prospective study design lend credence to these data. In conclusion, this study suggests that among candidates for TOLAC, gestational age at prior cesarean need not be included in risk assessment as preterm cesarean was shown to not be associated with an increased risk of uterine rupture in subsequent TOLAC.


COVID-19 Severity and Outcomes in Patients With Cancer: A Matched Cohort Study

1. There was no significantly increased risk of ICU admission, intubation, or death among hospitalized patients with COVID-19 and active malignancy compared with a matched cohort of patients with COVID-19 and no malignancy.

Evidence Level Rating: 2 (Good)

Some institutions in the U.S. have reported higher rates of COIVD-related complications and death among patients with cancer. These studies have, in general, been limited. This has important implications, though; based on these data, the care of some patients with cancer has been altered, delayed, or even compromised. Therefore, the purpose of this matched cohort study was to examine morbidity and mortality due to COVID-19 among patients with cancer compared with those without. The primary outcome was a composite outcome consisting of ICU admission, intubation, and death. Included were a total of 585 adult patients, grouped into 117 patients with active malignancy (median [IQR] age = 72.5 [64.2-79.9] years, 54.7% male) and 468 patients without malignancy (median [IQR] age = 71.2 [62.1-79.6] years, 54.7% male). There were 29 deaths among patients in the cancer cohort compared with 100 deaths among patients in the non-cancer cohort (p = 0.894). There was no significant different in the primary outcome among patients with or without cancer. Furthermore, there was no significant difference in the primary outcome between hematologic or solid malignancies (p = 0.283). Additionally, there was no difference in outcome if patients received cytotoxic therapy within 90 days of admission (p = 0.446). In all, this study found no significant difference in the risk of ICU admission, intubation, or death among patients hospitalized for COVID-19 with and without active malignancy. This suggests that in the context of a robust, patient-centered discussion concerning risks and benefits, anticancer therapy may be able to be safely delivered or continue to be delivered to patients with COVID-19.


Early Change in Albuminuria with Canagliflozin Predicts Kidney and Cardiovascular Outcomes: A Post Hoc Analysis from the CREDENCE Trial

1. Among patients with type 2 diabetes mellitus and chronic kidney disease being treated with canagliflozin, earlier reductions in albuminuria were associated with a decreased risk of adverse renal and cardiovascular outcomes.

Evidence Level Rating: 2 (Good)

In the past, post hoc analyses from clinical trials of RAAS inhibitors have shown that the magnitude of reduction of albuminuria – a strong, independent risk marker of cardiovascular and kidney disease – is associated with the degree of risk reduction. The 2019 Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial demonstrated that the SGLT2 inhibitor canagliflozin, originally developed a glucose-lowering agent, results in a sustained reduction in albuminuria and confers a reduced risk of kidney failure and poor cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). This post hoc analysis of the CREDENCE trial sought to answer whether early reductions in albuminuria are associated with the magnitude of risk reduction, similar to what has been observed in RAAS-modulated drugs. Briefly, CREDENCE was a double-blind, placebo-controlled randomized trial involving 4,401 patients randomized to receive 100 mg of canagliflozin daily, or matching placebo. The cohort in this analysis included 3,836 participants from CREDENCE. The primary kidney outcome was a composite of ESRD (defined as dialysis for at least 30 days, kidney transplantation, or an eGFR of < 15 mL/min/1.73 m2 sustained for at least 30 days), doubling of the serum creatinine level from baseline sustained for at least 30 days, or kidney death. The primary cardiovascular outcomes were major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, as well as a composite of hospitalization for heart failure or cardiovascular death. Overall, it was found that an early reduction in urine albumin-to-creatinine ratio (UACR) was associated favorably with kidney and cardiovascular outcomes. Indeed, each 30% decrease in UACR over the first 26 weeks of treatment was associated with significant hazard reductions for the kidney (HR 0.71, 95% CI 0.67 to 0.76, p < 0.001), MACE (HR 0.92, 95% CI 0.88 to 0.96, p < 0.001), and hospitalizations for heart failure or cardiovascular death (HR 0.86, 95% CI 0.81 to 0.90, p < 0.001) outcomes. Furthermore, the association between early reduction in UACR and the kidney outcome was stronger among patient with a lower eGFR and higher UACR; in contrast, the associations were consistent for the cardiovascular outcomes. In all, this post hoc analysis suggests that an early reduction in UACR during treatment with canagliflozin is associated with a reduced risk of adverse kidney and cardiovascular outcomes among patients with T2DM and CKD, highlighting the importance of tracking albuminuria to both guide treatment and assess prognosis.


Early Gluten Introduction and Celiac Disease in the EAT Study: A Prespecified Analysis of the EAT Randomized Clinical Trial

1. The early introduction of the gluten into the diet of infants was associated with a lower incidence of celiac disease at age 3 years.

Evidence Level Rating: 2 (Good)

The Enquiring About Tolerance (EAT) Study, a randomized controlled trial published in 2016, assessed whether introducing allergenic foods to infants’ diet from age 4 months alongside breastfeeding (early introduction group [EIG]) compared with continuation of exclusive breastfeeding and avoidance of allergenic foods until age 6 months (standard introduction group [SIG]) had any impact on food allergy prevention. This study represents a prespecified analysis of EAT, evaluating whether early introduction of gluten is associated with a reduced prevalence of celiac disease at age 3 years. A total of 1,303 infants were enrolled in EAT. One of the six allergenic foods introduced to the EIG was wheat; the minimum recommended gluten dose was 3.2 g/wk or 500 mg/d, corresponding to 4 g of wheat protein given as two wheat-based cereal biscuits throughout the week. Serum anti-transglutaminase type 2 (anti-TG2) antibodies were tested at three years to assess for the development of celiac disease. For this analysis, a total of 1,004 infants were tested for anti-TG2 antibodies, 488 in the EIG and 516 in the SIG. At three years, nine children, seven in the SIG and 2 in the EIG, had sufficiently elevated anti-TG2 antibodies and were referred for further investigation. Ultimately, all seven infants in the SIG received a diagnosis of celiac disease, confirmed by a pediatric gastroenterologist; in contrast, none of the infants in the EIG received a diagnosis (p = 0.02). These findings are in contrast to several other similar studies, which found no association between the timing of gluten introduction and celiac disease. Overall, it is clear that dedicated randomized controlled trials are needed to further investigate these data. However, this study suggests that early dietary introduction of gluten may have a role in the primary prevention of celiac disease among children.

Image: PD

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