In this trial in patients with lumbar central stenosis and moderate-to-severe leg pain and disability, epidural injection of glucocorticoids plus lidocaine offered minimal or no short-term benefit ...over epidural injection with lidocaine alone with respect to disability and pain.
Lumbar spinal stenosis, a common cause of spine-related disability, is the leading reason for spinal surgery in older adults.
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Degenerative changes resulting in narrowing of the spinal canal and nerve-root compression can cause back and leg pain, lower-extremity paresthesias, and weakness.
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The treatment of symptomatic lumbar stenosis remains controversial.
Symptoms of lumbar stenosis are commonly treated with epidural glucocorticoid injections. These injections typically contain a glucocorticoid and an anesthetic, which are thought to relieve pain by reducing nerve-root inflammation and ischemia.
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An estimated 25% of all epidural glucocorticoid injections administered in the Medicare population and 74% of those . . .
In a randomized trial comparing antibiotic therapy with appendectomy in patients with appendicitis, antibiotics were noninferior on the basis of EQ-5D scores. In the antibiotics group, nearly 3 in 10 ...participants had undergone appendectomy by 90 days, and complications were more common, especially in those with an appendicolith.
ROC curves are a popular method for displaying sensitivity and specificity of a continuous diagnostic marker, X, for a binary disease variable, D. However, many disease outcomes are time dependent, ...D(t), and ROC curves that vary as a function of time may be more appropriate. A common example of a time-dependent variable is vital status, where D(t) = 1 if a patient has died prior to time t and zero otherwise. We propose summarizing the discrimination potential of a marker X, measured at baseline (t = 0), by calculating ROC curves for cumulative disease or death incidence by time t, which we denote as ROC(t). A typical complexity with survival data is that observations may be censored. Two ROC curve estimators are proposed that can accommodate censored data. A simple estimator is based on using the Kaplan-Meier estimator for each possible subset X > c. However, this estimator does not guarantee the necessary condition that sensitivity and specificity are monotone in X. An alternative estimator that does guarantee monotonicity is based on a nearest neighbor estimator for the bivariate distribution function of (X, T), where T represents survival time (Akritas, M. J., 1994, Annals of Statistics 22, 1299-1327). We present an example where ROC(t) is used to compare a standard and a modified flow cytometry measurement for predicting survival after detection of breast cancer and an example where the ROC(t) curve displays the impact of modifying eligibility criteria for sample size and power in HIV prevention trials.
In this multicenter, randomized trial, the administration of erythropoietin to newborns undergoing therapeutic hypothermia for hypoxic–ischemic encephalopathy did not result in a lower risk of death ...or neurodevelopmental impairment at 22 to 36 months of age than placebo and was associated with a higher rate of serious adverse events.
Stepped wedge cluster randomized controlled trials are typically analyzed using models that assume the full effect of the treatment is achieved instantaneously. We provide an analytical framework for ...scenarios in which the treatment effect varies as a function of exposure time (time since the start of treatment) and define the “effect curve” as the magnitude of the treatment effect on the linear predictor scale as a function of exposure time. The “time‐averaged treatment effect” (TATE) and “long‐term treatment effect” (LTE) are summaries of this curve. We analytically derive the expectation of the estimator δ^$$ \hat{\delta} $$ resulting from a model that assumes an immediate treatment effect and show that it can be expressed as a weighted sum of the time‐specific treatment effects corresponding to the observed exposure times. Surprisingly, although the weights sum to one, some of the weights can be negative. This implies that δ^$$ \hat{\delta} $$ may be severely misleading and can even converge to a value of the opposite sign of the true TATE or LTE. We describe several models, some of which make assumptions about the shape of the effect curve, that can be used to simultaneously estimate the entire effect curve, the TATE, and the LTE. We evaluate these models in a simulation study to examine the operating characteristics of the resulting estimators and apply them to two real datasets.
In newborns with hypoxic-ischemic encephalopathy (HIE), the correlation between neonatal neuroimaging and the degree of neurodevelopmental impairment (NDI) is unclear.
Infants with HIE enrolled in a ...randomized controlled trial underwent neonatal MRI/MR spectroscopy (MRS) using a harmonized protocol at 4-6 days of age. The severity of brain injury was measured with a validated scoring system. Using proportional odds regression, we calculated adjusted odds ratios (aOR) for the associations between MRI/MRS measures of injury and primary ordinal outcome (i.e., normal, mild NDI, moderate NDI, severe NDI, or death) at age 2 years.
Of 451 infants with MRI/MRS at a median age of 5 days (IQR 4.5-5.8), outcomes were normal (51%); mild (12%), moderate (14%), severe NDI (13%); or death (9%). MRI injury score (aOR 1.06, 95% CI 1.05, 1.07), severe brain injury (aOR 39.6, 95% CI 16.4, 95.6), and MRS lactate/n-acetylaspartate (NAA) ratio (aOR 1.6, 95% CI 1.4,1.8) were associated with worse primary outcomes. Infants with mild/moderate MRI brain injury had similar BSID-III cognitive, language, and motor scores as infants with no injury.
In the absence of severe injury, brain MRI/MRS does not accurately discriminate the degree of NDI. Given diagnostic uncertainty, families need to be counseled regarding a range of possible neurodevelopmental outcomes.
Half of all infants with hypoxic-ischemic encephalopathy (HIE) enrolled in a large clinical trial either died or had neurodevelopmental impairment at age 2 years despite receiving therapeutic hypothermia. Severe brain injury and a global pattern of brain injury on MRI were both strongly associated with death or neurodevelopmental impairment. Infants with mild or moderate brain injury had similar mean BSID-III cognitive, language, and motor scores as infants with no brain injury on MRI. Given the prognostic uncertainty of brain MRI among infants with less severe degrees of brain injury, families should be counseled regarding a range of possible neurodevelopmental outcomes.
Stepped wedge designed trials are a type of cluster‐randomized study in which the intervention is introduced to each cluster in a random order over time. This design is often used to assess the ...effect of a new intervention as it is rolled out across a series of clinics or communities. Based on a permutation argument, we derive a closed‐form expression for an estimate of the intervention effect, along with its standard error, for a stepped wedge design trial. We show that these estimates are robust to misspecification of both the mean and covariance structure of the underlying data‐generating mechanism, thereby providing a robust approach to inference for the intervention effect in stepped wedge designs. We use simulations to evaluate the type 1 error and power of the proposed estimate and to compare the performance of the proposed estimate to the optimal estimate when the correct model specification is known. The limitations, possible extensions, and open problems regarding the method are discussed.
Summary Background A previous randomised controlled trial reported greater efficacy of surgery than of splinting for patients with carpal tunnel syndrome. Our aim was to compare surgical versus ...multi-modality, non-surgical treatment for patients with carpal tunnel syndrome without denervation. We hypothesised that surgery would result in improved functional and symptom outcomes. Methods In this parallel-group randomised controlled trial, we randomly assigned 116 patients from eight academic and private practice centres, using computer-generated random allocation stratified by site, to carpal tunnel surgery (n=57) or to a well-defined, non-surgical treatment (including hand therapy and ultrasound; n=59). The primary outcome was hand function measured by the Carpal Tunnel Syndrome Assessment Questionnaire (CTSAQ) at 12 months assessed by research personnel unaware of group assignment. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00032227. Findings 44 (77%) patients assigned to surgery underwent surgery. At 12 months, 101 (87%) completed follow-up and were analysed (49 of 57 assigned to surgery and 52 of 59 assigned to non-surgical treatment). Analyses showed a significant 12-month adjusted advantage for surgery in function (CTSAQ function score: Δ −0·40, 95% CI 0·11–0·70, p=0·0081) and symptoms (CTSAQ symptom score: 0·34, 0·02–0·65, p=0·0357). There were no clinically important adverse events and no surgical complications. Interpretation Symptoms in both groups improved, but surgical treatment led to better outcome than did non-surgical treatment. However, the clinical relevance of this difference was modest. Overall, our study confirms that surgery is useful for patients with carpal tunnel syndrome without denervation. Funding NIH/NIAMS 5P60AR048093 and the Intramural Research Program of the NIH Clinical Center.
Chronic insomnia is common in patients undergoing in-center hemodialysis, yet there is limited evidence on effective treatments for this population.
To compare the effectiveness of cognitive ...behavioral therapy for insomnia (CBT-I), trazodone, and placebo for insomnia in patients undergoing long-term hemodialysis.
Randomized, multicenter, double-blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT03534284).
26 dialysis units in Albuquerque, New Mexico, and Seattle, Washington.
Patients with Insomnia Severity Index (ISI) score of 10 or greater, with sleep disturbances on 3 or more nights per week for 3 or more months.
Participants were randomly assigned to 6 weeks of CBT-I, trazodone, or placebo.
The primary outcome was the ISI score at 7 and 25 weeks from randomization.
A total of 923 patients were prescreened, and of the 411 patients with chronic insomnia, 126 were randomly assigned to CBT-I (
= 43), trazodone (
= 42), or placebo (
= 41). The change in ISI scores from baseline to 7 weeks with CBT-I or trazodone was no different from placebo: CBT-I, -3.7 (95% CI, -5.5 to -1.9); trazodone, -4.2 (CI, -5.9 to -2.4); and placebo, -3.1 (CI, -4.9 to -1.3). There was no meaningful change in ISI scores from baseline to 25 weeks: CBT-I, -4.8 (CI, -7.0 to -2.7); trazodone, -4.0 (CI, -6.0 to -1.9); and placebo, -4.3 (CI, -6.4 to -2.2). Serious adverse events (SAEs), particularly serious cardiovascular events, were more frequent with trazodone (annualized cardiovascular SAE incidence rates: CBT-I, 0.05 CI, 0.00 to 0.29; trazodone, 0.64 CI, 0.34 to 1.10; and placebo, 0.21 CI, 0.06 to 0.53).
Modest sample size and most participants had mild or moderate insomnia.
In patients undergoing hemodialysis with mild or moderate chronic insomnia, there was no difference in the effectiveness of 6 weeks of CBT-I or trazodone compared with placebo. The incidence of SAEs was higher with trazodone.
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases.
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