2 Minute Medicine Rewind April 12, 2021

Effect of high-frequency (10-kHz) spinal cord stimulation in patients with painful diabetic neuropathy

1. Pain relief and health-related quality of life was significantly improved among those undergoing 10-kHz spinal cord stimulation, compared to conventional medical management.

2. Outcomes in pain relief were sustained through the six-month follow-up.

Evidence Rating Level: 1 (Excellent)

The global prevalence of diabetes is approximately 8.5% and it is estimated that roughly 20% of this group will develop painful diabetic neuropathy (PDN). This progressive pain condition is treated with a variety of pharmacological and non-pharmacological interventions, many of which are suboptimal in effectiveness or sustained adherence. This prospective, multicenter, open-label, randomized clinical trial compared conventional medical management (CMM) with 10-kHz spinal cord stimulation (SCS) plus CMM. Participants must have had PDN for at least one year refractory to gabapentinoids and at least one other analgesic class, lower limb pain ≥5 cm on a 10-cm visual analogue scale (VAS), body mass index of ≤45, hemoglobin A1c of ≤10%, daily morphine equivalents of ≤120 mg, and were deemed appropriate candidates for SCS. A total of 216 participants (M [SD] age = 60.8 [10.7] years, 37.0% female) were randomized with a six-month follow-up and optional crossover at six months. Within this sample, the durations of diabetes (median [IQR] = 10.9 [6.3 to 16.4] years) and peripheral neuropathy (5.6 [3.0 to 10.1] years) were calculated. The primary endpoint of 50% reduction in pain on VAS without worsening neurological deficits at 3 months was achieved by 5% of the CMM group and 79% of the 10-kH SCS+CMM group (95% CI 64.2 to 83.0, p<.001). A total of 60% of the latter group achieved remission of pain (<3 m or less for 6 months) compared to only 1% in the CMM only group (p<.001). Regarding neurological examination, 6% of the CMM only group and 72% of the 10-kHz SCS+CMM group improved from baseline to 3 months (95% CI 55.4 to 76.6, p<.001). A similar difference was found at six-month follow up (difference, 58.6%, 95% CI 47.6 to 69.6, p<.001). There was no significant change in hemoglobin A1c between groups at six-month follow-up. Overall, this study found that 10-kHz SCS offers substantial pain relief over six months in refractory PND, without significant declines in neurological examination.


Association of preterm birth with long-term risk of heart failure into adulthood

1. Pre-term birth was associated with significantly increased risk of adult-onset heart failure, particularly among those 18 to 43 years of age.

Evidence Rating Level: 2 (Good)

Preterm birth is a known risk factor for early-life heart failure (HF). However, less is known about its association with adult-onset HF. This Swedish national cohort study aimed to investigate this association among all singleton live births from 1973 to 2014. HF was defined as any recorded diagnosis through 2015. A total of 4,193,069 individuals (median age = 22.5 years) were included and 4,158 (0.1%) were diagnosed with HF at some point during the study time frame (median [IQR] age at diagnosis = 15.4 [28.0] years). A gestational age of ≤37 weeks (preterm birth) aligned with previous findings and was associated with increased risk of HF at ages ≤1 year (adjusted HR = 4.49, 95% CI 3.86 to 5.22), compared with full-term birth. Among those 18 to 43 years of age, HRs were 4.72 (95% CI 2.11 to 10.52) for extremely preterm births (22 to 27 weeks), 1.92 (95% CI 1.37 to 2.71) for moderately preterm (28 to 33 weeks), 1.24 (95% CI 1.00 to 1.54) for late preterm (34 to 36 weeks), and 1.09 (95% CI 0.97 to 1.24) for early term (37 to 38 weeks). HF incidence rates for ages 18 to 43 years, across these stratified gestational ages, were 31.7, 13.8, 8.7, and 7.3, respectively, with associations persisting after removal of individuals with structural congenital cardiac anomalies. These associations, particularly among ages 18 to 43 years, were largely explained by shared familial determinants of HF and preterm birth. Overall, preterm birth was associated with a significantly increased risk of adult-onset HF. Those experiencing preterm birth may require closer follow-up as they progress into adulthood to reduce their risk for HF.


Edema index predicts cardiorespiratory fitness in patients with heart failure with reduced ejection fraction and type 2 diabetes mellitus

1. Bioelectric impedance analysis-measured edema index (EI) is a feasible, non-invasive technique for measuring fluid overload.

2. EI is an independent predictor of cardiorespiratory fitness in heart failure patients with reduced ejection fraction and type 2 diabetes mellitus.

Evidence Rating Level: 2 (Good)

One of the prominent features of heart failure (HF) is fluid overload, which is difficult to measure in a noninvasive manner. However, the edema index (EI), a surrogate for extracellular volume status, can be estimated with bioelectrical impedance analysis. This cross-sectional study investigated the relationship between EI and cardiorespiratory fitness (CRF) in patients with HF with reduced ejection fraction (EF) and type 2 diabetes mellitus. Measures included peak oxygen consumption, exercise time, serum creatinine, C-reactive protein, hemoglobin, NT-proBNP, and sodium. A quality of living measure (Minnesota Living With HF Questionnaire) was also used. A total of 72 patients (median [IQR] age = 58 [52-62] years, 69% female, 47% Black) were included in this study. Approximately 88% of this sample had hypertension and 77% had hyperlipidemia. Median body mass index (BMI) was 33.9 kg/m2 (IQR 31.2 to 37.6). Men demonstrated a higher median EI than their female counterparts (p = .013) and Black participants had significantly greater EI than White participants (p = .020). EI was positively associated with BMI (ρ = .388; p = .001) and negatively associated with age (ρ = -.239; p = .040), serum creatinine (ρ = -.296; p = .011), and hemoglobin (ρ = -.329; p = .004). Using univariate quantile regression, each 1% absolute increase in EI was associated with a decrease in median peak VO2 (β = −0.613; 95% CI −0.885 to −0.340; p<.001), and a significant decrease in median exercise time in seconds (β = −24.0; 95% CI −35.3 to −12.7; p<.001). Greater EI was also associated with worse functional capacity, as a measure of exercise time. Overall, and in spite of a relatively small sample size, this study demonstrated that bioelectrical impedance analysis, to measure EI, can be an effective tool in predicting CRF in individuals with HF and type 2 diabetes mellitus.


Initial effects of COVID-19 on patients with ESKD

1. Patients with end-stage kidney disease were at increased risk of COVID-19-related mortality, particularly among non-Hispanic Black patients.

Evidence Rating Level: 3 (Average)

End-stage kidney disease (ESKD) has been a significant contributor to COVID-19 mortality, with global fatality estimates falling between 20 to 30% of COVID-19 patients with ESKD. This retrospective cohort study identified patients with ESKD from Centers for Medicare and Medicaid Services data during epidemiologic weeks 3 through 27 of 2017 through 2020, and corresponding weeks of 2017 through 2019. These patients were then stratified by kidney replacement therapy, with primary outcomes being COVID-19 hospitalization, all-cause death, and other hospitalizations. In week 3 of 2020, a total of 568,533 (40.0% aged 45 to 64 years, 31.9% non-Hispanic Black) patients were receiving dialysis and another 237,746 (48.4% aged 45 to 64 years, 20.2% non-Hispanic Black) had a functioning transplant. Patients undergoing dialysis demonstrated a peak COVID-19 hospitalization rate between March 22 and April 25, 2020. Non-Hispanic Black and Hispanic race were associated with higher rates of COVID-19 hospitalization, compared to other racial identities. Adjusted relative risks of death in 2020, compared to 2017-2019, were 1.17 (95% CI 1.16 to 1.19) for those undergoing dialysis and 1.30 (95% CI 1.24 to 1.36) for those with a functioning transplant. Excess mortality was also higher among non-Hispanic Black, Hispanic, and Asian patients during the study period. Overall, this study of patients with ESKD suggests an increased risk of negative outcomes both in terms of all-cause mortality as well as COVID-19 mortality. Further, racial differences were readily apparent – aligning with other COVID-19 studies – and clearly demonstrate disparities within this medical population.


Mood disorders and outcomes of COVID-19 hospitalizations

1. Mood disorder diagnoses prior to hospitalization for COVID-19 was associated with increased risk of in-hospital mortality after Day 12.

2. Prior mood disorders were associated with a greater likelihood of discharge to a lower level of care, rather than home.

Evidence Rating Level: 2 (Good)

Extrapulmonary manifestations of COVID-19 have been a major area of study over the past year, particularly as they relate to morbidity and mortality. This retrospective cohort study of six hospitals in Massachusetts sought to investigate the association between prior mood disorders and hospital outcomes among those hospitalized for COVID-19 between February 15 and May 24, 2020. A total of 2,988 individuals were hospitalized for COVID-19 during this time frame, 24% of which had a prior mood disorder diagnosis. After adjusting for age, sex, and hospital, having a mood disorder prior to hospitalization was associated with greater in-hospital mortality risk after Day 12 (crude HR = 2.156, 95% CI 1.540 to 3.020; adjusted HR = 1.540, 95% CI 1.054 to 2.250). Any mood disorder diagnosis was also associated with a greater likelihood of discharge to a lower level of care rather than home, such as a rehabilitation facility (adjusted OR = 1.504, 95% CI 1.132 to 1.999). Overall, this study suggests that mood disorders confer risks in the context of hospitalization for COVID-19, including increased mortality after Day 12 and discharge to lower levels of care, rather than home.

Image: PD

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