Five-Year Longitudinal Follow-Up of Restorative Neurostimulation Shows Durability of Effectiveness in Patients With Refractory Chronic Low Back Pain Associated With Multifidus Muscle Dysfunction.

BACKGROUND: Adults with refractory, mechanical chronic low back pain associated with impaired neuromuscular control of the lumbar multifidus muscle have few treatment options that provide long-term clinical benefit. This study hypothesized that restorative neurostimulation, a rehabilitative treatment that activates the lumbar multifidus muscles to overcome underlying dysfunction, is safe and provides relevant and durable clinical benefit to patients with this specific etiology. MATERIALS AND METHODS: In this prospective five-year longitudinal follow-up of the ReActiv8-B pivotal trial, participants (N = 204) had activity-limiting, moderate-to-severe, refractory, mechanical chronic low back pain, a positive prone instability test result indicating impaired multifidus muscle control, and no indications for spine surgery. Low back pain intensity (10-cm visual analog scale [VAS]), disability (Oswestry Disability Index), and quality of life (EuroQol's "EQ-5D-5L" index) were compared with baseline and following the intent-to-treat principle, with a supporting mixed-effects model for repeated measures that accounted for missing data. RESULTS: At five years (n = 126), low back pain VAS had improved from 7.3 to 2.4 cm (-4.9; 95% CI, -5.3 to -4.5 cm; p < 0.0001), and 71.8% of participants had a reduction of ≥50%. The Oswestry Disability Index improved from 39.1 to 16.5 (-22.7; 95% CI, -25.4 to -20.8; p < 0.0001), and 61.1% of participants had reduction of ≥20 points. The EQ-5D-5L index improved from 0.585 to 0.807 (0.231; 95% CI, 0.195-0.267; p < 0.0001). Although the mixed-effects model attenuated completed-case results, conclusions and statistical significance were maintained. Of 52 subjects who were on opioids at baseline and had a five-year visit, 46% discontinued, and 23% decreased intake. The safety profile compared favorably with neurostimulator treatments for other types of back pain. No lead migrations were observed. CONCLUSION: Over a five-year period, restorative neurostimulation provided clinically substantial and durable benefits with a favorable safety profile in patients with refractory chronic low back pain associated with multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02577354; registration date: October 15, 2016; principal investigator: Christopher Gilligan, MD, Brigham and Women's Hospital, Boston, MA, USA. The study was conducted in Australia (Broadmeadow, New South Wales; Noosa Heads, Queensland; Welland, South Australia; Clayton, Victoria), Belgium (Sint-Niklaas; Wilrijk), The Netherlands (Rotterdam), UK (Leeds, London, Middlesbrough), and USA (La Jolla, CA; Santa Monica, CA; Aurora, CO; Carmel, IN; Indianapolis, IN; Kansas City, KS; Boston, MA; Royal Oak, MI; Durham, NC; Winston-Salem, NC; Cleveland, OH; Providence, RI; Spartanburg, SC; Spokane, WA; Charleston, WV).

Nocturnal gastro-oesophageal reflux and respiratory symptoms are increased in sleep apnoea: comparison with the general population.

AIM: To assess respiratory symptoms and nocturnal gastro-oesophageal reflux (nGER) among untreated obstructive sleep apnoea (OSA) patients, compared with the general population. Also, if nGER associates differently with respiratory symptoms among OSA patients. METHODS: 2 study cohorts were included: 822 newly diagnosed subjects with moderate-severe OSA and 738 Icelandic general population study participants. All participants answered the same questionnaires. Those reporting nGER symptoms at least once per week were defined as 'with nGER'; those without nGER symptoms and without nGER medication were defined as 'no nGER'; and other participants were defined as having 'possible nGER'. Propensity score-based weights were used to minimise confounding and selection bias and facilitate causal interpretations. RESULTS: The prevalence of nGER among OSA patients was 14.1%, compared with 5.8% in the general population. This increased prevalence in OSA was not explained by differences in age, gender, body mass index, smoking, hypertension and diabetes (adjusted OR (95% CI)=3.79 (2.24 to 6.43)). OSA patients 'with nGER' and with 'possible nGER' reported more wheezing (44% and 44% vs 25%, respectively) and productive cough (47% and 42% vs 29%, respectively), compared with OSA patients with 'no nGER'. The same pattern was seen in the general population, although with a generally lower prevalence. The effect of nGER on respiratory symptoms was similar between the two cohorts. CONCLUSION: nGER was more often reported among untreated moderate-severe OSA patients than in the general population. Participants with nGER had more wheezing and productive cough, both among untreated OSA patients and in the general population.

Long-Term Outcomes of Restorative Neurostimulation in Patients With Refractory Chronic Low Back Pain Secondary to Multifidus Dysfunction: Two-Year Results of the ReActiv8-B Pivotal Trial.

BACKGROUND: Impaired neuromuscular control and degeneration of the multifidus muscle have been linked to the development of refractory chronic low back pain (CLBP). An implantable restorative-neurostimulator system can override the underlying multifidus inhibition by eliciting episodic, isolated contractions. The ReActiv8-B randomized, active-sham-controlled trial provided effectiveness and safety evidence for this system, and all participants received therapeutic stimulation from four months onward. OBJECTIVE: This study aimed to evaluate the two-year effectiveness of this restorative neurostimulator in patients with disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery. MATERIALS AND METHODS: Open-label follow-up of 204 participants implanted with a restorative neurostimulation system (ReActiv8, Mainstay Medical, Dublin, Ireland) was performed. Pain intensity (visual analog scale [VAS]), disability (Oswestry disability index [ODI]), quality-of-life (EQ-5D-5L), and opioid intake were assessed at baseline, six months, one year, and two years after activation. RESULTS: At two years (n = 156), the proportion of participants with ≥50% CLBP relief was 71%, and 65% reported CLBP resolution (VAS ≤ 2.5 cm); 61% had a reduction in ODI of ≥20 points, 76% had improvements of ≥50% in VAS and/or ≥20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 87% of participants had continued device use during the second year for a median of 43% of the maximum duration, and 60% (34 of 57) had voluntarily discontinued (39%) or reduced (21%) opioid intake. CONCLUSIONS: At two years, 76% of participants experienced substantial, clinically meaningful improvements in pain, disability, or both. These results provide evidence of long-term effectiveness and durability of restorative neurostimulation in patients with disabling CLBP, secondary to multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The study is registered on clinicaltrials.gov with identifier NCT02577354.

Three-Year Durability of Restorative Neurostimulation Effectiveness in Patients With Chronic Low Back Pain and Multifidus Muscle Dysfunction.

BACKGROUND: Restorative neurostimulation is a rehabilitative treatment for patients with refractory chronic low back pain (CLBP) associated with dysfunction of the lumbar multifidus muscle resulting in impaired neuromuscular control. The ReActiv8-B randomized, sham-controlled trial provided evidence of the effectiveness and safety of an implanted, restorative neurostimulator. The two-year analysis previously published in this journal demonstrated accrual of clinical benefits and long-term durability. OBJECTIVE: Evaluation of three-year effectiveness and safety in patients with refractory, disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery. MATERIALS AND METHODS: Prospective, observational follow-up of the 204 implanted trial participants. Low back pain visual analog scale (VAS), Oswestry Disability Index (ODI), EuroQol quality of life survey, and opioid intake were assessed at baseline, six months, and one, two, and three years after activation. The mixed-effects model repeated measures approach was used to provide implicit imputations of missing data for continuous outcomes and multiple imputation for proportion estimates. RESULTS: Data were collected from 133 participants, and 16 patients missed their three-year follow-up because of coronavirus disease restrictions but remain available for future follow-up. A total of 62% of participants had a ≥ 70% VAS reduction, and 67% reported CLBP resolution (VAS ≤ 2.5cm); 63% had a reduction in ODI of ≥ 20 points; 83% had improvements of ≥ 50% in VAS and/or ≥ 20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 71% (36/51) participants on opioids at baseline had voluntarily discontinued (49%) or reduced (22%) opioid intake. The attenuation of effectiveness in the imputed (N = 204) analyses was relatively small and did not affect the statistical significance and clinical relevance of these results. The safety profile remains favorable, and no lead migrations have been observed to date. CONCLUSION: At three years, 83% of participants experienced clinically substantial improvements in pain, disability, or both. The results confirm the long-term effectiveness, durability, and safety of restorative neurostimulation in patients with disabling CLBP associated with multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02577354.

Resolution of organ dysfunction as a predictor of long-term survival in necrotizing soft tissue infections: Analysis of the AB103 Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections trial and a retrospective claims database-linked chart study.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) are an acute surgical condition with high morbidity and mortality. Timely identification, resuscitation, and aggressive surgical management have significantly decreased inpatient mortality. However, reduced inpatient mortality has shifted the burden of disease to long-term mortality associated with persistent organ dysfunction. METHODS: We performed a combined analysis of NSTI patients from the AB103 Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections randomized-controlled interventional trial (ATB-202) and comprehensive administrative database (ATB-204) to determine the association of persistent organ dysfunction on inpatient and long-term outcomes. Persistent organ dysfunction was defined as a modified Sequential Organ Failure Assessment (mSOFA) score of 2 or greater at Day 14 (D14) after NSTI diagnosis, and resolution of organ dysfunction defined as mSOFA score of 1 or less. RESULTS: The analysis included 506 hospitalized NSTI patients requiring surgical debridement, including 247 from ATB-202, and 259 from ATB-204. In both study cohorts, age and comorbidity burden were higher in the D14 mSOFA ≥2 group. Patients with D14 mSOFA score of 1 or less had significantly lower 90-day mortality than those with mSOFA score of 2 or higher in both ATB-202 (2.4% vs. 21.5%; p < 0.001) and ATB-204 (6% vs. 16%: p = 0.008) studies. In addition, in an adjusted covariate analysis of the combined study data sets D14 mSOFA score of 1 or lesss was an independent predictor of lower 90-day mortality (odds ratio, 0.26; 95% confidence interval, 0.13-0.53; p = 0.001). In both studies, D14 mSOFA score of 1 or less was associated with more favorable discharge status and decreased resource utilization. CONCLUSION: For patients with NSTI undergoing surgical management, persistent organ dysfunction at 14 days, strongly predicts higher resource utilization, poor discharge disposition, and higher long-term mortality. Promoting the resolution of acute organ dysfunction after NSTI should be considered as a target for investigational therapies to improve long-term outcomes after NSTI. LEVEL OF EVIDENCE: Prognostic/epidemiology study, level III.

A Novel Immune Modulator for Patients With Necrotizing Soft Tissue Infections (NSTI): Results of a Multicenter, Phase 3 Randomized Controlled Trial of Reltecimod (AB 103).

BACKGROUND AND OBJECTIVE: Reltecimod, a CD 28 T-lymphocyte receptor mimetic, inhibits T-cell stimulation by an array of bacterial pathogens. A previous phase 2 trial demonstrated improved resolution of organ dysfunction after NSTI. We hypothesized that early administration of reltecimod would improve outcome in severe NSTI. METHODS: Randomized, double-blind, placebo-controlled trial of single dose reltecimod (0.5 mg/kg) administered within 6 hours of NSTI diagnosis at 65 of 93 study sites. Inclusion: surgical confirmation of NSTI and organ dysfunction [modified Sequential Organ Failure Assessment Score (mSOFA) score ≥3]. Primary analysis was modified Intent-to-Treat (mITT), responder analysis using a previously validated composite endpoint, necrotizing infection clinical composite endpoint, defined as: alive at day 28, ≤3 debridements, no amputation beyond first operation, and day 14 mSOFA ≤1 with ≥3 point reduction (organ dysfunction resolution). A prespecified, per protocol (PP) analysis excluded 17 patients with major protocol violations before unblinding. RESULTS: Two hundred ninety patients were enrolled, mITT (Reltecimod 142, Placebo 148): mean age 55 ±â€Š15 years, 60% male, 42.4% diabetic, 28.6% perineal infection, screening mSOFA mean 5.5 ±â€Š2.4. Twenty-eight-day mortality was 15% in both groups. mITT necrotizing infection clinical composite endpoint success was 48.6% reltecimod versus 39.9% placebo, P = 0.135 and PP was 54.3% reltecimod versus 40.3% placebo, P = 0.021. Resolution of organ dysfunction was 65.1% reltecimod versus 52.6% placebo, P = 0.041, mITT and 70.9% versus 53.4%, P = 0.005, PP. CONCLUSION: Early administration of reltecimod in severe NSTI resulted in a significant improvement in the primary composite endpoint in the PP population but not in the mITT population. Reltecimod was associated with improved resolution of organ dysfunction and hospital discharge status.

Exploring the Negative Likelihood Ratio and How It Can Be Used to Minimize False-Positives in Breast Imaging.

OBJECTIVE: This article describes the definition and proposed utilization of negative likelihood ratios (NLRs) as statistical parameters in breast imaging. Examples with calculations are provided using BI-RADS category 4 subcategories. CONCLUSION: By auditing individual performance early and often against American College of Radiology benchmark positive predictive value ranges for the BI-RADS category 4 subcategories, and by fully understanding NLRs and their application in breast imaging, radiologists can minimize false-positive findings and unnecessary biopsies.

The obstructive sleep apnoea syndrome in adolescents.

BACKGROUND: The obstructive sleep apnoea syndrome (OSAS) results from a combination of structural and neuromotor factors; however, the relative contributions of these factors have not been studied during the important developmental phase of adolescence. We hypothesised that adenotonsillar volume (ATV), nasopharyngeal airway volume (NPAV), upper airway critical closing pressure (Pcrit) in the hypotonic and activated neuromotor states, upper airway electromyographic response to subatmospheric pressure and the ventilatory response to CO2 during sleep would be major predictors of OSAS risk. METHODS: 42 obese adolescents with OSAS and 37 weight-matched controls underwent upper airway MRI, measurements of Pcrit, genioglossal electromyography and ventilatory response to CO2 during wakefulness and sleep. RESULTS: ATV, NPAV, activated and hypotonic Pcrit, genioglossal electromyography and ventilatory response to CO2 during sleep were all associated with OSAS risk. Multivariate models adjusted for age, gender, body mass index and race indicated that ATV, NPAV and activated Pcrit each independently affected apnoea risk in adolescents; genioglossal electromyography was independently associated in a reduced sample. There was significant interaction between NPAV and activated Pcrit (p=0.021), with activated Pcrit more strongly associated with OSAS in adolescents with larger NPAVs and NPAV more strongly associated with OSAS in adolescents with more negative activated closing pressure. CONCLUSIONS: OSAS in adolescents is mediated by a combination of anatomic (ATV, NPAV) and neuromotor factors (activated Pcrit). This may have important implications for the management of OSAS in adolescents.

Therapeutic sustainability and durability of coflex interlaminar stabilization after decompression for lumbar spinal stenosis: a four year assessment.

BACKGROUND: Approved treatment modalities for the surgical management of lumbar spinal stenosis encompass a variety of direct and indirect methods of decompression, though all have varying degrees of limitations and morbidity which potentially limit the efficacy and durability of the treatment. The coflex(®) interlaminar stabilization implant (Paradigm Spine, New York, NY), examined under a United States Food and Drug Administration (US FDA) Investigational Device Exemption (IDE) clinical trial, is shown to have durable outcomes when compared to posterolateral fusion in the setting of post-decompression stabilization for stenotic patients. Other clinical and radiographic parameters, more indicative of durability, were also evaluated. The data collected from these parameters were used to expand the FDA composite clinical success (CCS) endpoint; thus, creating a more stringent Therapeutic Sustainability Endpoint (TSE). The TSE allows more precise calculation of the durability of interlaminar stabilization (ILS) when compared to the fusion control group. METHODS: A retrospective analysis of data generated from a prospective, randomized, level-1 trial that was conducted at 21 US sites was carried out. Three hundred forty-four per-protocol subjects were enrolled and randomized to ILS or fusion after decompression for lumbar stenosis with up to grade 1 degenerative spondylolisthesis. Clinical, safety, and radiographic data were collected and analyzed in both groups. Four-year outcomes were assessed, and the TSE was calculated for both cohorts. The clinical and radiographic factors thought to be associated with therapeutic sustainability were added to the CCS endpoints which were used for premarket approval (PMA). RESULTS: Success rate, comprised of no second intervention and an ODI improvement of ≥ 15 points, was 57.6% of ILS and 46.7% of fusion patients (p = 0.095). Adding lack of fusion in the ILS cohort and successful fusion in the fusion cohort showed a CCS of 42.7% and 33.3%, respectively. Finally, adding adjacent level success to both cohorts and maintenance of foraminal height in the coflex cohort showed a CCS of 36.6% and 25.6%, respectively. With additional follow-up to five years in the U.S. PMA study, these trends are expected to continue to show the superior therapeutic sustainability of ILS compared to posterolateral fusion after decompression for spinal stenosis. CONCLUSION: There are clear differences in both therapeutic sustainability and intended clinical effect of ILS compared to posterolateral fusion with pedicle screw fixation after decompression for spinal stenosis. There are CCS differences between coflex and fusion cohorts noted at four years post-op similar to the trends revealed in the two year data used for PMA approval. When therapeutic sustainability outcomes are added to the CCS, ILS is proven to be a sustainable treatment for stabilization of the vertebral motion segment after decompression for lumbar spinal stenosis.

Effects of obesity on the association between long-term sleep apnea treatment and changes in interleukin-6 levels: the Icelandic Sleep Apnea Cohort.

The aim of this study was to evaluate changes in interleukin (IL)-6 and soluble IL-6 receptor levels in obstructive sleep apnea patients and assess the role of positive airway pressure treatment and obesity on these changes. A total of 309 newly diagnosed subjects with sleep apnea from the Icelandic Sleep Apnea Cohort were referred for treatment and reassessed at a 2-year follow-up. Full treatment was defined objectively as use ≥ 4 h day(-1) and ≥ 20 days month(-1). At the 2-year follow-up, there were 177 full users, 44 partial users and 88 non-users. The mean change in biomarker levels from baseline to the 2-year follow-up was assessed in a primary model that included adjustment for baseline biomarker levels, baseline body mass index and change in body mass index, as well as after adjustment for numerous relevant covariates. No significant overall difference in IL-6 level change was found among full, partial and non-users. However, in severely obese patients (body mass index ≥ 35), a significant increase in IL-6 levels during the 2-year period was found in partial and non-users, compared to no change in full users. Results were attenuated in a smaller propensity score matched subsample, although similar trends were observed. No differences were found in soluble IL-6 receptor levels between full users and non-users, after adjustment for confounders. In conclusion, among untreated obese sleep apnea patients, IL-6 levels increase substantially during 2 years, while adherence to positive airway pressure treatment may prevent further increases in this inflammatory biomarker.

A Novel Drug for Treatment of Necrotizing Soft-Tissue Infections: A Randomized Clinical Trial.

IMPORTANCE: Necrotizing soft-tissue infections (NSTI) have high morbidity and mortality rates despite aggressive surgical debridement and antibiotic therapy. AB103 is a peptide mimetic of the T-lymphocyte receptor, CD28. We hypothesized that AB103 will limit inflammatory responses to bacterial toxins and decrease the incidence of organ failure. OBJECTIVES: To establish the safety of AB103 in patients with NSTI and evaluate the potential effects on clinically meaningful parameters related to the disease. DESIGN, SETTING, AND PARTICIPANTS: A prospective, randomized, placebo-controlled, double-blinded study was performed in 6 academic medical centers in the United States. Participants included adults with NSTI. Of 345 patients screened, 43 were enrolled for the intent-to-treat analysis, and 40 met criteria for the modified intent-to-treat analysis; 15 patients each were included in the high-dose and low-dose treatment arms, and 10 in the placebo arm. INTERVENTION: Single intravenous dose of AB103 (0.5 or 0.25 mg/kg) within 6 hours after diagnosis of NSTI. MAIN OUTCOMES AND MEASURES: Change in the Sequential Organ Failure Assessment score within 28 days, intensive care unit-free and ventilator-free days, number and timing of debridements, plasma and tissue cytokine levels at 0 to 72 hours, and adverse events. RESULTS: Baseline characteristics were comparable in the treatment groups. The Sequential Organ Failure Assessment score improved from baseline in both treatment groups compared with the placebo group at 14 days (change from baseline score, -2.8 in the high-dose, -2 in the low-dose, and +1.3 in the placebo groups; P = .04). AB103-treated patients had a similar number of debridements (mean [SD], 2.2 [1.1] for the high-dose, 2.3 [1.2] for the low-dose, and 2.8 [2.1] for the placebo groups; P = .56). There were no statistically significant differences in intensive care unit-free and ventilator-free days or in plasma and tissue cytokine levels. No drug-related adverse events were detected. CONCLUSIONS AND RELEVANCE: AB103 is a safe, promising new agent for modulation of inflammation after NSTI. Further study is warranted to establish efficacy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01417780.

Mitigating adverse event reporting bias in spine surgery.

BACKGROUND: Recent articles in the lay press and literature have raised concerns about the ability to report honest adverse event data from industry-sponsored spine surgery studies. To address this, clinical trials may utilize an independent Clinical Events Committee (CEC) to review adverse events and readjudicate the severity and relatedness accordingly. We are aware of no prior study that has quantified either the degree to which investigator bias is present in adverse event reporting or the effect that an independent CEC has on mitigating this potential bias. METHODS: The coflex Investigational Device Exemption study is a prospective randomized controlled trial comparing coflex (Paradigm Spine) stabilization with lumbar spinal fusion to treat spinal stenosis and spondylolisthesis. Investigators classified the severity of adverse events (mild, moderate, or severe) and their relationship to the surgery and device (unrelated, unlikely, possibly, probably, or definitely). An independent CEC, composed of three spine surgeons without affiliation to the study sponsor, reviewed and reclassified all adverse event reports submitted by the investigators. RESULTS: The CEC reclassified the level of severity, relation to the surgery, and/or relation to the device in 394 (37.3%) of 1055 reported adverse events. The proportion of adverse events that underwent reclassification was similar in the coflex and fusion groups (37.9% compared with 36.0%, p = 0.56). The CEC was 5.3 (95% confidence interval [CI], 2.6 to 10.7) times more likely to upgrade than downgrade the adverse event. The CEC was 7.3 (95% CI, 5.1 to 10.6) times more likely to upgrade than downgrade the relationship to the surgery and 11.6 (95% CI, 7.5 to 18.8) times more likely to upgrade than downgrade the relationship to the device. The status of the investigator's financial interest in the company had little effect on the reclassification of adverse events. CONCLUSIONS: Thirty-seven percent of adverse events were reclassified by the CEC; the large majority of the reclassifications were an upgrade in the level of severity or a designation of greater relatedness to the surgery or device. CLINICAL RELEVANCE: An independent CEC can identify and mitigate potential inherent investigator bias and facilitate an accurate assessment of the safety profile of an investigational device, and a CEC should be considered a requisite component of future clinical trials.

Hits and misses: screening commercial drivers for obstructive sleep apnea using guidelines recommended by a joint task force.

OBJECTIVE: To evaluate joint task force criteria-based screening for severe obstructive sleep apnea (s-OSA) in commercial drivers. METHODS: Among a community-based cohort of licensed commercial vehicle drivers, we assessed utility of the joint task force criteria. We conducted full, 14-channel overnight polysomnography in all drivers, defining s-OSA as an apnea-hypopnea index of 30 or more per hour. RESULTS: One hundred of 104 drivers with successful polysomnography studies were predominantly obese (median body mass index = 32.8 kg/m; interquartile range = 26.8 to 37.4) and had a median apnea-hypopnea index of 20.6 per hour (interquartile range = 10.0 to 34.2). Examination-based criteria were more effective (sensitivity = 80%; negative posttest probability [nPTP] = 17%) than symptom-based criteria (sensitivity = 63%; nPTP = 23%). Examination and symptom-based criteria combined had high sensitivity (97%) and low nPTP (7%), but poor specificity (19%). CONCLUSIONS: Examination-based criteria missed 20% of s-OSA cases. Combining examination with confidentially reported symptoms improved sensitivity but required confirmatory polysomnography in 86%, supporting universal screening of all drivers.

Screening for severe obstructive sleep apnea syndrome in hypertensive outpatients.

The authors attempted to validate a 2-stage strategy to screen for severe obstructive sleep apnea syndrome (s-OSAS) among hypertensive outpatients, with polysomnography (PSG) as the gold standard. Using a prospective design, outpatients with hypertension were recruited from medical outpatient clinics. Interventions included (1) assessment of clinical data; (2) home sleep testing (HST); and (3) 12-channnel, in-laboratory PSG. The authors developed models using clinical or HST data alone (single-stage models) or clinical data in tandem with HST (2-stage models) to predict s-OSAS. For each model, area under receiver operating characteristic curves (AUCs), sensitivity, specificity, negative likelihood ratio, and negative post-test probability (NPTP) were computed. Models were then rank-ordered based on AUC values and NPTP. HST used alone had limited accuracy (AUC=0.727, NPTP=2.9%). However, models that used clinical data in tandem with HST were more accurate in identifying s-OSAS, with lower NPTP: (1) facial morphometrics (AUC=0.816, NPTP=0.6%); (2) neck circumference (AUC=0.803, NPTP=1.7%); and Multivariable Apnea Prediction Score (AUC=0.799, NPTP=1.5%) where sensitivity, specificity, and NPTP were evaluated at optimal thresholds. Therefore, HST combined with clinical data can be useful in identifying s-OSAS in hypertensive outpatients, without incurring greater cost and patient burden associated with in-laboratory PSG. These models were less useful in identifying obstructive sleep apnea syndrome of any severity.

Heritability of performance deficit accumulation during acute sleep deprivation in twins.

STUDY OBJECTIVES: To determine if the large and highly reproducible interindividual differences in rates of performance deficit accumulation during sleep deprivation, as determined by the number of lapses on a sustained reaction time test, the Psychomotor Vigilance Task (PVT), arise from a heritable trait. DESIGN: Prospective, observational cohort study. SETTING: Academic medical center. PARTICIPANTS: There were 59 monozygotic (mean age 29.2 ± 6.8 [SD] yr; 15 male and 44 female pairs) and 41 dizygotic (mean age 26.6 ± 7.6 yr; 15 male and 26 female pairs) same-sex twin pairs with a normal polysomnogram. INTERVENTIONS: Thirty-eight hr of monitored, continuous sleep deprivation. MEASUREMENTS AND RESULTS: Patients performed the 10-min PVT every 2 hr during the sleep deprivation protocol. The primary outcome was change from baseline in square root transformed total lapses (response time ≥ 500 ms) per trial. Patient-specific linear rates of performance deficit accumulation were separated from circadian effects using multiple linear regression. Using the classic approach to assess heritability, the intraclass correlation coefficients for accumulating deficits resulted in a broad sense heritability (h(2)) estimate of 0.834. The mean within-pair and among-pair heritability estimates determined by analysis of variance-based methods was 0.715. When variance components of mixed-effect multilevel models were estimated by maximum likelihood estimation and used to determine the proportions of phenotypic variance explained by genetic and nongenetic factors, 51.1% (standard error = 8.4%, P < 0.0001) of twin variance was attributed to combined additive and dominance genetic effects. CONCLUSION: Genetic factors explain a large fraction of interindividual variance among rates of performance deficit accumulations on PVT during sleep deprivation.

The interaction of obstructive sleep apnea and obesity on the inflammatory markers C-reactive protein and interleukin-6: the Icelandic Sleep Apnea Cohort.

STUDY OBJECTIVES: To assess the relative roles and interaction of obstructive sleep apnea (OSA) severity and obesity on interleukin-6 (IL-6) and C-reactive protein (CRP) levels. DESIGN: Cross-sectional cohort. SETTING: The Icelandic Sleep Apnea Cohort. PARTICIPANTS: 454 untreated OSA patients (380 males and 74 females), mean ± standard deviation age 54.4 ± 10.6 yr. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Participants underwent a sleep study, abdominal magnetic resonance imaging to measure total abdominal and visceral fat volume, and had fasting morning IL-6 and CRP levels measured in serum. A significantly higher correlation was found for BMI than visceral fat volume with CRP and IL-6 levels. Oxygen desaturation index, hypoxia time, and minimum oxygen saturation (SaO2) significantly correlated with IL-6 and CRP levels, but apnea-hypopnea index did not. When stratified by body mass index (BMI) category, OSA severity was associated with IL-6 levels in obese participants only (BMI > 30 kg/m²). A multiple linear regression model with interaction terms showed an independent association of OSA severity with IL-6 levels and an interaction between OSA severity and BMI, i.e., degree of obesity altered the relationship between OSA and IL-6 levels. An independent association of OSA severity with CRP levels was found for minimum SaO2 only. A similar interaction of OSA severity and BMI on CRP levels was found for males and postmenopausal women. CONCLUSIONS: OSA severity is an independent predictor of levels of IL-6 and CRP but interacts with obesity such that this association is found only in obese patients.

The effects of psychoeducation and telephone counseling on the adjustment of women with early-stage breast cancer.

BACKGROUND: Throughout the illness trajectory, women with breast cancer experience issues that are related to physical, emotional, and social adjustment. Despite a general consensus that state-of-the-art treatment for breast cancer should include educational and counseling interventions to reduce illness or treatment-related symptoms, there are few prospective, theoretically based, phase-specific randomized, controlled trials that have evaluated the effectiveness of such interventions in promoting adjustment. PURPOSE: The aim of this study is to examine the physical, emotional, and social adjustment of women with early-stage breast cancer who received psychoeducation by videotapes, telephone counseling, or psychoeducation plus telephone counseling as interventions that address the specific needs of women during the diagnostic, postsurgery, adjuvant therapy, and ongoing recovery phases of breast cancer. DESIGN: Primary data from a randomized controlled clinical trial. SETTING: Three major medical centers and one community hospital in New York City. METHODS: A total of 249 patients were randomly assigned to either the control group receiving usual care or to one of the three intervention groups. The interventions were administered at the diagnostic, postsurgery, adjuvant therapy, and ongoing recovery phases. Analyses were based on a mixed model analysis of variance. MAIN RESEARCH VARIABLES AND MEASUREMENT: Physical adjustment was measured by the side effects incidence and severity subscales of the Breast Cancer Treatment Response Inventory (BCTRI) and the overall health status score of the Self-Rated Health Subscale of the Multilevel Assessment Instrument. Emotional adjustment was measured using the psychological well-being subscale of the Profile of Adaptation to Life Clinical Scale and the side effect distress subscale of BCTRI. Social adjustment was measured by the domestic, vocational, and social environments subscales of the Psychosocial Adjustment to Illness Scale. FINDINGS: Patients in all groups showed improvement over time in overall health, psychological well-being, and social adjustment. There were no significant group differences in physical adjustment, as measured by side effect incidence, severity, or overall health. There was poorer emotional adjustment over time in the usual care (control) group as compared to the intervention groups on the measure of side effect distress. For the telephone counseling group, there was a marked decline in psychological well-being from the adjuvant therapy phase through the ongoing recovery phase. There were no significant group differences in the dimensions of social adjustment. CONCLUSION: The longitudinal design of this study has captured the dynamic process of adjustment to breast cancer, which in some aspects and at various phases has been different for the control and intervention groups. Although patients who received the study interventions improved in adjustment, the overall conclusion regarding physical, emotional, and social adjustment is that usual care, which was the standard of care for women in both the usual care (control) and intervention groups, supported their adjustment to breast cancer, with or without additional interventions. IMPLICATIONS FOR NURSING: The results are important to evidence-based practice and the determination of the efficacy and cost-effectiveness of interventions in improving patient outcomes. There is a need to further examine adjustment issues that continue during the ongoing recovery phase. KEY POINTS: Psychoeducation by videotapes and telephone counseling decreased side effect distress and side effect severity and increased psychological well-being during the adjuvant therapy phase. All patients in the control and intervention groups improved in adjustment. Adjustment issues are still present in the ongoing recovery phase.

Obstructive sleep apnea in patients undergoing bariatric surgery--a tertiary center experience.

BACKGROUND: The patient population that is evaluated for bariatric surgery is characterized by a very high body mass index (BMI). Since obesity is the most important risk factor for obstructive sleep apnea (OSA), sleep disordered breathing is highly prevalent in this population. If undiagnosed before bariatric surgery, untreated OSA can lead to perioperative and postoperative complications. Debate exists whether all patients that are considered for bariatric surgery should undergo polysomnography (PSG) evaluation and screening for OSA as opposed to only those patients with clinical history or examination concerning sleep disordered breathing. We examined the prevalence and severity of OSA in all patients that were considered for bariatric surgery. We hypothesized that, by utilizing preoperative questionnaires (regarding sleepiness and OSA respiratory symptoms) in combination with menopausal status and BMI data, we would be able to predict which subjects did not have sleep apnea without the use of polysomnography. In addition, we hypothesized that we would be able to predict which subjects had severe OSA (apnea-hypopnea index (AHI) > 30). METHODS: Three hundred forty-two consecutive subjects, evaluated for bariatric surgery from November 1, 2005 to January 31, 2007 underwent overnight polysomnography and completed questionnaires regarding sleepiness, menopausal status, and respiratory symptoms related to OSA. Apneas and hypopneas were classified as follows: mild apnea 5 ≤ AHI ≤ 15, moderate apnea 15 < AHI ≤ 30, and severe apnea AHI > 30. RESULTS: The overall sample prevalence of OSA was 77.2%. Of these, 30.7% had mild OSA; 19.3% had moderate OSA, and 27.2% had severe OSA. Among men, the prevalence of OSA was 93.6% and 73.5% among women. The mean AHI (events per hour) for men with OSA was 49.2 ± 35.5 and 26.3 ± 28.3 for women with OSA. Separate logistic regression models were developed for the following three outcomes: AHI ≥ 5 events per hour, AHI > 15 events per hour, and AHI > 30 events per hour. When predicting these three levels of OSA severity, the area under the curve (AUC) values were: 0.8, 0.72, and 0.8, respectively. The negative predictive value for the presence of sleep apnea (AHI ≥ 5) was 75% when using the most stringent possible cutoff for the prediction model. CONCLUSIONS: The prevalence of OSA in all patients considered for bariatric surgery was greater than 77%, irrespective of OSA symptoms, gender, menopausal status, age, or BMI. The prediction model that we developed for the presence of OSA (AHI ≥ 5 events per hour) has excellent discriminative ability (evidenced by an AUC value of 0.8). However, the negative prediction values for the presence of OSA were too low to be clinically useful due to the high prevalence of OSA in this high-risk group. We demonstrated that, by utilizing even the most stringent possible cutoff values for the prediction model, OSA cannot be predicted with enough certainty. Therefore, we advocate routine PSG testing for all patients that are considered for bariatric surgery.

Factors influencing decisions to admit patients to veterans affairs specialized rehabilitation units after lower-extremity amputation.

UNLABELLED: Bates BE, Kwong PL, Kurichi JE, Bidelspach DE, Reker DM, Maislin G, Xie D, Stineman M. Factors influencing decisions to admit patients to Veterans Affairs specialized rehabilitation units after lower-extremity amputation. OBJECTIVE: To understand patient- and facility-level characteristics that influence decisions to admit veterans to a specialized rehabilitation unit (SRU) after a lower-extremity amputation. DESIGN: Database study. SETTING: All Veterans Affairs Medical Centers (VAMCs). PARTICIPANTS: Veterans with lower-extremity amputation discharged from VAMCs between October 1, 2002, and September 30, 2004. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Admission to an SRU. RESULTS: There were a total of 2922 veterans with lower-extremity amputations; 616 patients were admitted to an SRU, whereas 2306 received consultative rehabilitation services only. Patients admitted to an SRU waited longer to have their first rehabilitation assessment after surgery and had middle-range physical and cognitive disabilities. Patients who received consultative rehabilitation services only tended to have greater illness burden. They were more likely to have previous amputation complication, paralysis, or renal failure and either very severe or minimal physical and cognitive disabilities. CONCLUSIONS: The selection of veterans with new lower-extremity amputations for admission to an SRU appears clinically reasonable and based on the likelihood of successful outcomes.

Differences in physical, emotional, and social adjustment of intimate, family, and nonfamily patient-partner dyads based on a breast cancer intervention study.

PURPOSE/OBJECTIVES: To assess the degree to which postsurgical adjustment in patients with breast cancer and their partners depends on the nature of the patient-partner dyad relationship. DESIGN: Secondary data analysis from a randomized controlled trial. SETTING: Three cancer centers and one suburban community hospital in New York. SAMPLE: 205 patient-partner dyads (112 intimate-partner, 58 family-member, and 35 nonfamily-member dyads). METHODS: Mann-Whitney nonparametric comparisons and chi-square tests were used to assess dyad types on continuous and categorical variables, and a mixed model for repeated measures compared postsurgical adjustment among dyad types. MAIN RESEARCH VARIABLES: Type of patient-partner dyads and physical, emotional, and social adjustment. FINDINGS: Patients in intimate-partner dyads were younger, had greater incomes, and discovered the lump by routine mammogram as compared to family- or nonfamily-member dyads. No significant differences were observed in patients' physical or emotional adjustment. Patients with intimate partners had greater difficulty in their social and domestic environments. Partners in intimate-partner dyads had lower scores on psychological well-being, more problems in social and domestic adjustment, and less social support to promote social adjustment. CONCLUSIONS: Women with breast cancer experience successful physical and emotional adjustment whether they have intimate-partner, family-member, or nonfamily-member partners. Intimate partners are at greater risk for emotional and social adjustment issues. IMPLICATIONS FOR NURSING: When designing interventions, consideration must be given to the type of patient-partner dyad involved.