Illustrating risk difference and number needed to treat from a randomized controlled trial of spinal manipulation for cervicogenic headache

<p>Abstract</p> <p>Background</p> <p>The number needed to treat (NNT) for one participant to benefit is considered a useful, clinically meaningful way of reporting binary outcomes from randomized trials. Analysis of continuous data from our randomized controlled trial has previously demonstrated a significant and clinically important difference favoring spinal manipulation over a light massage control.</p> <p>Methods</p> <p>Eighty participants were randomized to receive spinal manipulation or a light massage control (n = 40/group). Improvements in cervicogenic headache pain (primary outcome), disability, and number in prior four weeks were dichotomized into binary outcomes at two thresholds: 30% representing minimal clinically important change and 50% representing clinical success. Groups were compared at 12 and 24-week follow-up using binomial regression (generalized linear models) to compute the adjusted risk difference (RD) between groups and number needed to treat (NNT) after adjusting for baseline differences between groups. Results were compared to logistic regression results.</p> <p>Results</p> <p>For headache pain, clinically important improvement (30% or 50%) was more likely for spinal manipulation: adjusted RD = 17% to 27% and NNT = 3.8 to 5.8 (p = .005 to .028). Some statistically significant results favoring manipulation were found for headache disability and number.</p> <p>Conclusion</p> <p>Spinal manipulation demonstrated a benefit in terms of a clinically important improvement of cervicogenic headache pain. The use of adjusted NNT is recommended; however, adjusted RD may be easier to interpret than NNT. The study demonstrated how results may depend on the threshold for dichotomizing variables into binary outcomes.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NLM identifier NCT00246350.</p

Are recovery stories helpful for women with eating disorders? A pilot study and commentary on future research

Background: Anecdotally it is well known that eating disorder memoirs are popular with people with anorexia nervosa and recovery stories are readily available online. However, no research to date has empirically explored whether such stories are helpful for current sufferers. The aim of the current pilot study was to explore the efficacy of recovery narratives as a means of improving motivation and self-efficacy and to qualitatively explore patient perspectives of such stories. Method: Fifty-seven women with anorexia nervosa and subclinical anorexia nervosa participated in this online study. Participants were randomised to either receive recovery stories or to a wait-list control group. After completing baseline measures, participants read five stories about recovery, and completed post-intervention measures two weeks later. Results: The quantitative results indicated that reading stories of recovery had no effect on motivation and self-efficacy over a two-week period. In contrast, the qualitative results showed that the stories generated thoughts about the possibility of recovery and the majority indicated they would recommend them to others. Conclusions: This study adds to a growing body of research exploring the integration of voices of lived experience into treatment approaches. Future research should focus on 1) identifying for whom and at which stage of illness recovery stories might be helpful; 2) the mechanism via which they might operate; and 3) the most helpful way of presenting such stories

Asymmetric Dimethylarginine, Endothelial Nitric Oxide Bioavailability and Mortality in Sepsis

Background: Plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxidesynthase, are raised in patients with chronic vascular disease, causing increased cardiovascular risk and endothelialdysfunction, but the role of ADMA in acute inflammatory states is less well defined.Methods and Results: In a prospective longitudinal study in 67 patients with acute sepsis and 31 controls, digitalmicrovascular reactivity was measured by peripheral arterial tonometry and blood was collected at baseline and 2&ndash;4 dayslater. Plasma ADMA and L-arginine concentrations were determined by high performance liquid chromatography. Baselineplasma L-arginine: ADMA ratio was significantly lower in sepsis patients (median [IQR] 63 [45&ndash;103]) than in hospital controls(143 [123&ndash;166], p,0.0001) and correlated with microvascular reactivity (r = 0.34, R2 = 0.12, p = 0.02). Baseline plasma ADMAwas independently associated with 28-day mortality (Odds ratio [95% CI] for death in those in the highest quartile($0.66 mmol/L) = 20.8 [2.2&ndash;195.0], p = 0.008), and was independently correlated with severity of organ failure. Increase inADMA over time correlated with increase in organ failure and decrease in microvascular reactivity.Conclusions: Impaired endothelial and microvascular function due to decreased endothelial NO bioavailability is a potentialmechanism linking increased plasma ADMA with organ failure and death in sepsis

An Observational Cohort Study of the Kynurenine to Tryptophan Ratio in Sepsis: Association with Impaired Immune and Microvascular Function

Both endothelial and immune dysfunction contribute to the high mortality rate in human sepsis, but the underlying mechanisms are unclear. In response to infection, interferon-γ activates indoleamine 2,3-dioxygenase (IDO) which metabolizes the essential amino acid tryptophan to the toxic metabolite kynurenine. IDO can be expressed in endothelial cells, hepatocytes and mononuclear leukocytes, all of which contribute to sepsis pathophysiology. Increased IDO activity (measured by the kynurenine to tryptophan [KT] ratio in plasma) causes T-cell apoptosis, vasodilation and nitric oxide synthase inhibition. We hypothesized that IDO activity in sepsis would be related to plasma interferon-γ, interleukin-10, T cell lymphopenia and impairment of microvascular reactivity, a measure of endothelial nitric oxide bioavailability. In an observational cohort study of 80 sepsis patients (50 severe and 30 non-severe) and 40 hospital controls, we determined the relationship between IDO activity (plasma KT ratio) and selected plasma cytokines, sepsis severity, nitric oxide-dependent microvascular reactivity and lymphocyte subsets in sepsis. Plasma amino acids were measured by high performance liquid chromatography and microvascular reactivity by peripheral arterial tonometry. The plasma KT ratio was increased in sepsis (median 141 [IQR 64–235]) compared to controls (36 [28–52]); p<0.0001), and correlated with plasma interferon-γ and interleukin-10, and inversely with total lymphocyte count, CD8+ and CD4+ T-lymphocytes, systolic blood pressure and microvascular reactivity. In response to treatment of severe sepsis, the median KT ratio decreased from 162 [IQR 100–286] on day 0 to 89 [65–139] by day 7; p = 0.0006) and this decrease in KT ratio correlated with a decrease in the Sequential Organ Failure Assessment score (p<0.0001). IDO-mediated tryptophan catabolism is associated with dysregulated immune responses and impaired microvascular reactivity in sepsis and may link these two fundamental processes in sepsis pathophysiology

Initial assessment of recharge areas for large karst springs: a case study from the central Zagros Mountains, Iran

Sousan Spring emerges from the Keyno Anticline, Zagros Mountains (Iran), and the mean annual discharge is ~24 m3 /s. Geological and hydrochemical evaluations suggest that the spring recharge is from the limestone Ilam-Sarvak Formation (Cretaceous) but the Mafaroon Fault, a major thrust feature, influences the regional groundwater flow path by juxtaposing other strata. Geological, geochemical, stable isotope and water balance studies were employed to interpret this behavior. Using the isotope data, the sources and elevations of the recharge area were found. Temporal variations of the isotopic data were compared with variations of electrical conductivity (EC). Unexpectedly, high EC was associated with a relative increase of discharge and depletion of δ18O. Several hypotheses were investigated and approximate water balance studies employed for validation. It was found that an elongated catchment on the Keyno Anticline plus a lesser catchment on a pair of parallel anticlines recharge the aquifer. While the long groundwater flow path along the Keyno Anticline plus guidance by Mafaroon Fault and the adjacent Garou shaly strata lead to increased EC in the Sousan Spring at the end of the dry season, a flow pulse from two adjoining anticlines (Mahalbakh and Shirgoon) arrives at the same time to increase the discharge and deplete the δ18O signal. Apparently the spring did not experience true base flow conditions during the recorded hydrological year. Although the spring response to specific precipitation events was similar to typical karst aquifers, standard interpretation of recession curves and related coefficients will not be practical at Sousan