2 Minute Medicine Rewind April 19, 2021

Effects of a self-directed web-based strengthening exercise and physical activity program supported by automated text messages for people with knee osteoarthritis: A randomized clinical trial

1. Among a cohort of patients with knee osteoarthritis, a web-based intervention of self-directed strengthening exercises and activity guidance supported with automated text messaging improved both pain and functional capacity at 24 weeks.

Evidence Rating Level: 1 (Excellent)

Osteoarthritis (OA) of the knee is highly prevalent and has no known cure; symptoms are often managed with strengthening exercises. This randomized trial evaluated the efficacy of a 24-week self-directed intervention consisting of a website and automated text messages to support home exercise therapy using behavioral change theory. 103 patients (mean [SD] age = 60.3 [8.2] years, 58% female) were randomized to the intervention cohort – consisting of website access, guidance to increase physical activity, automated text messaging support, and home exercise programming – and 103 (mean [SD] age = 59.0 [8.5] years, 64% female) to the control cohort – consisting only of website access. The primary outcomes were pain using the 11-point Numeric Rating Scale and limitations with functional capacity using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). At 24 weeks, there was evidence that adherence to knee exercises favored the intervention cohort. With regards to the primary outcomes, there was evidence of both greater improvement in overall pain (mean difference 1.6 units, 95% CI 0.9 to 2.2 units, p < 0.001) and in functional capacity (mean difference 5.2 units, 95% CI 1.9 to 8.5 units, p = 0.002) favoring the intervention cohort. The use of pain medications and other treatments for the knee was similar across the two groups, except that more participants in the control cohort used massage, heat or cold, and topical anti-inflammatory drugs. Overall, this study provides robust evidence that a self-directed exercise regimen augmented by automated text messaging support significantly improves both pain and functional capacity for patients with knee OA. This easily scalable intervention may have a significant impact on population health and aid to reduce the burden of disease associated with knee OA.

Comparative outcomes between COVID-19 and influenza patients placed on veno-venous extracorporeal membrane oxygenation for severe ARDS

1. COVID-19 patients with severe ARDS on veno-venous extracorporeal membrane oxygenation were nearly three times as likely to experience in-hospital death compared with influenza patients.

Evidence Level Rating: 3 (Average)

Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is an established supportive therapy for patients with severe acute respiratory distress syndrome (ARDS) refractory to more conventional therapies. As the COVID-19 pandemic continues to place stress on the healthcare system, providers may have to triage the use of V-V ECMO among patients with ARDS secondary to COVID-19 or to influenza, which peaks during winter months and will again impose a dual burden on healthcare workers. There are very little data highlighting the differences between using V-V ECMO to manage ARDS in these two patient populations, and this study evaluated the differences in patient characteristics and clinical outcomes. Using data from a large quaternary medical center, the first 32 adult COVID-19 patients with severe ARDS placed on V-V ECMO were compared with the last 28 adult influenza patients with severe ARDS placed on V-V ECMO. The primary outcome was survival to hospital discharge. Secondary outcomes included ECMO-related complications, such as bleeding events, air emergencies, and organ failure. COVID-19 patients were significantly older (47.8±10.3 vs. 41.2±12.8 years, p = 0.033). Furthermore, there were significantly more Hispanic patients in the COVID-19 group and the prevalence of diabetes was significantly higher. The duration of V-V ECMO was significantly longer in the COVID-19 cohort with a mean of 12.4 days compared with 7.7 days in the influenza cohort (p = 0.002); additionally, the time to canulation from symptom onset and ICU admission was longer. The need for a circuit change due to oxygenation failure was also higher among COVID-19 patients. Finally, crude in-hospital mortality was significantly higher in the COVID-19 cohort compared with the influenza cohort (65.6% vs. 36.3%). Cox regression modeling adjusted for age, race, organ failure while on ECMO, and Charles Comorbidity Index (CCI) revealed an adjusted hazard ratio over sixty days for COVID-19 patients compared to influenza patients of 2.81 (95% CI 1.07 to 7.35). In all, this retrospective analysis revealed that COVID-19 patients with severe ARDS on V-V ECMO had a nearly threefold increased risk of in-hospital death compared with influenza patients. The limitations of this study were myriad, including a single center perspective, but suggest that more robust data are needed to define critical care management of COVID-19 patients with ARDS on V-V ECMO.

Percutaneous peripheral nerve stimulation (neuromodulation) for postoperative pain: A randomized, sham-controlled pilot study

1. Among patients undergoing ambulatory orthopedic surgical procedures, percutaneous peripheral nerve stimulation reduced pain and the use of opiates in the first 7 postoperative days.

Evidence Level Rating: 1 (Excellent)

Poor pain control following surgery is very common and is associated with excessive reliance on opiates for analgesia. Percutaneous peripheral nerve stimulation – which involves the implantation of a lead followed by delivery of an electrical current using an external pulse generator – has been used extensively for chronic pain, but use for acute, postoperative pain may also improve analgesia and decrease reliance on opiates. This randomized, sham-controlled trial evaluated this strategy among patients undergoing ambulatory orthopedic surgical procedures. All patients randomized in the trial underwent implantation of a lead and pulse generator prior to surgery, with 31 patients ultimately analyzed from the intervention cohort (mean [SD] age = 56.8 [15.8] years, 48% female) and 34 from the sham cohort (mean [SD] age = 55.4 [15.9] years, 50% female), where the implanted leads did not generate any pulses. The primary outcomes were cumulative oral opiate consumption in morphine equivalents and the mean values of the daily pain scores as measured by the Numeric Rating Scale within the initial 7-day postoperative period. During the first 7 postoperative days, opiate consumption in oral morphine equivalents was a median of 5 mg in the intervention cohort compared with 48 mg in the sham cohort (p < 0.001). Furthermore, the average pain intensity among the intervention cohort was 1.1±1.1 compared with 3.1±1.7 in the sham cohort (p < 0.001). The significance of both outcomes did not vary as a function of sex or specific type of surgical procedure. Superiority was found on both primary outcomes, and active stimulation was concluded to be better than sham treatment. In all, this pilot study demonstrated that percutaneous peripheral nerve stimulation reduces pain scores and demonstrated opiate sparing effects free from systemic side effects during the first week following ambulatory orthopedic surgery. Further prospective studies are needed to clarify these findings and evaluate whether this strategy is effective on a larger scale.

Real-world experience of bamlanivimab for COVID-19: A case-control study

1. Patients from a large academic medical center with mild to moderate COVID-19 in receipt of the monoclonal antibody bamlanivimab had a lower 30-day rate of hospitalization.

Evidence Level Rating: 2 (Good)

Despite the extent to which SARS-CoV-2 has impacted the world and the delivery of medicine and pharmacotherapeutics, remdesivir, an RNA-dependent RNA polymerase, remains the only drug approved by the U.S. Food and Drug Administration (FDA) expressly for the treatment of COVID-19. Neutralizing monoclonal antibodies, such as bamlanivimab, bind to the virus’s spike protein and prevent attachment to human surface ACE2 receptors and have shown promise in some clinical trials. This study described the impact on hospitalization rate of bamlanivimab as monotherapy for mild to moderate COVID-19 infection among high-risk ambulatory patients. 218 patients who received bamlanivimab (median [IQR] age = 66 [57-74] years, 52.8% male) were matched with 185 patients who were referred for but ultimately did not receive bamlanivimab (median [IQR] age = 62 [50-72] years, 51.4% male). Of note, patients in receipt of bamlanivimab were more likely to be older, immunosuppressed, or have a chronic lung disease. Patient who were white and spoke English were also significantly more likely to receive bamlanivimab. The 30-day hospitalization rate, the primary outcome, was 7.3% in the bamlanivimab cohort and 20.0% in the control cohort (RR 0.37, 95% CI 0.21 to 0.64, p < 0.001), yielding a number needed to treat of 8 to prevent one hospitalization. In a multivariate analysis, not receiving bamlanivimab and a high total number of comorbidities were associated with a 4.19- and 1.68-times increased risk of hospitalization. The study was not sufficiently powered to assess the significance of ICU admission, intubation, or mortality at 30 days. In all, this study suggests that patients with mild to moderate COVID-19 who received bamlanivimab had a lower 30-day rate of hospitalization.

Continued versus discontinued oxytocin stimulation in the active phase of labour (CONDISOX): double blind randomised controlled trial

1. Among pregnant women, discontinuing the administration of oxytocin during the active phase of labor is associated with a small, absolute increase in the risk of cesarean delivery but significantly reduces the risk of uterine hyperstimulation and abnormal fetal heart rate.

Evidence Level Rating: 1 (Excellent)

About a quarter of all term pregnancies are induced, often with oxytocin stimulation. The use of oxytocin, however, carries with it a risk of hyperstimulation, which may lead to emergent cesarean for fetal indications secondary to uterine hyperstimulation. Recent evidence suggests that once a woman is in active labor, the labor will continue even if oxytocin is stopped; little of this evidence, though, is supported by randomized trials. As such, the aim of this double-blind, randomized controlled trial was to test whether discontinuation of oxytocin stimulation once the active phase of labor is reached reduces the overall cesarean rate. 607 women were randomized to the discontinued cohort (mean [SD] age = 31.0 [4.9] years) and 591 to the continued cohort (mean [SD] age = 31.3 [4.9] years). There was no significant difference in the rate of cesarean delivery between the discontinued (16.6%) and continued cohorts (14.2%) (RR 1.17 95% CI 0.90 to 1.53). The prespecified noninferiority testing was inconclusive (p = 0.70). Among parous women without prior cesarean, however, the risk of cesarean was substantially higher in the discontinued cohort (7.5%) compared with the continued cohort (0.6%) (RR 11.6, 95% CI 1.15 to 88.7). When reviewing secondary outcomes, it was found that the discontinuation of oxytocin was associated with a longer duration of labor, a reduced risk of uterine hyperstimulation, and a reduced risk of fetal heart rate abnormalities. There were similar rates of other adverse maternal and neonatal outcomes between the two groups. In all, this study suggests that the discontinuation of oxytocin stimulation during the active phase of labor is associated with a small, absolute increase in the risk of cesarean delivery but significantly reduces the risk of uterine hyperstimulation and abnormal fetal heart rate.

Image: PD

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