Thomas J. Kufel

Comparison of potentiated and unpotentiated twitches as an index of muscle fatigue.

Recent data suggest that the potentiated twitch is a more sensitive index of contractile fatigue than is the unpotentiated twitch. We hypothesized that after a potentially fatiguing load, the fall in twitch amplitude of the potentiated twitch would be significantly greater than that of an unpotentiated twitch. We compared the response of the potentiated and unpotentiated twitches to a series of potentially fatiguing loads using magnetic stimulation of the femoral nerve in 10 healthy subjects. The baseline unpotentiated quadriceps twitch force (TwQu), potentiated quadriceps twitch force (TwQp), and maximal voluntary contraction (MVC) were 129 ± 6 N, 198 ± 6 N, and 622 ± 25 N, respectively. During a fatigue protocol that was designed to induce a spectrum of fatigue from mild to marked, the percent fall in quadriceps twitch force was significantly greater for the potentiated method than for the unpotentiated method at all levels of fatigue (P < .005). The within‐subject within‐day coefficient of variation was 7.5 ± 0.5% for TwQu and 5.6 ± 0.9% for TwQp. Thus, TwQp is reproducible and is superior to TwQu for detecting early muscle fatigue.

Interval training versus continuous training in patients with chronic obstructive pulmonary disease.

PURPOSE The purpose of this study was to compare the effects of interval training (IT) and continuous steady-pace training (CT) in patients with COPD. METHODS Patients (n = 21) (mean forced expiratory volume in 1 second ([FEV1] = 44.6% ± 13.9%) were randomized to IT, and 20 patients (mean FEV1 = 41.7% ± 12.6%) to CT. Outcome measures included 6-minute walk distance, maximal work capacity, endurance exercise time during constant workload exercise at 60% to 70% of maximal work capacity, and quality of life including fatigue and dyspnea. Participants exercised 3 times per week for 8 weeks, and total work was the same for both training regimens. RESULTS Significant improvement in mean score was observed in each variable within each of the 2 groups: 6-minute walk distance (IT = 158 ± 178 ft, CT = 106 ± 165 ft); maximal work capacity (IT = 10.0 ± 13.0 W, CT = 11.5 ± 13.1 W); endurance exercise time (IT = 15.0 ± 12.5 minutes, CT = 18.7 ± 10.6 minutes); and quality of life domains, fatigue (IT = 3.1 ± 3.0, CT = 2.8 ± 4.7), and dyspnea (IT = 4.4 ± 5.3, CT = 5.4 ± 5.1). There was no significant difference in the extent of improvement between the 2 training regimens for any of the outcome variables. CONCLUSION Compared with CT, IT was well tolerated and produced similar improvements in exercise performance and quality of life.

Diaphragmatic function after intense exercise in congestive heart failure patients

Respiratory muscle strength and endurance is reduced in patients with congestive heart failure, making these patients susceptible to diaphragmatic fatigue during exercise. In order to determine whether or not contractile fatigue of the diaphragm occurs in patients with congestive heart failure following intense exercise, twitch transdiaphragmatic pressures (twitch Ptdi) were measured during unpotentiated and potentiated cervical magnetic stimulation (CMS) of the phrenic nerves before and at intervals after cycle endurance exercise. Ten patients aged 65.7±6.0 yrs (mean±sd) with an ejection fraction of 31.2±9.8% performed a constant-load symptom-limited exercise test at 60% of their peak work capacity. Twitch Ptdi at baseline were 15.9±6.3 cmH2O (unpotentiated CMS) and 28.8±10.7 cmH2O (potentiated CMS) and at 10 min postexercise were 16.4±4.7 cmH2O (unpotentiated CMS) and 27.6±10.1 cmH2O (potentiated CMS). One patient demonstrated a sustained fall in twitch Ptdi of ≥15%, considered potentially indicative of diaphragmatic fatigue. Contractile diaphragmatic fatigue is uncommon in untrained patients with congestive heart failure following high-intensity constant-workload cycle exercise. Therefore, diaphragmatic fatigue is an unlikely cause of exercise-limitation during activities of daily living in heart failure patients.

Treatment of opioid-related central sleep apnea with positive airway pressure: a systematic review.

OBJECTIVE To systematically review the various modalities of positive airway pressure (PAP) in the treatment of opioid-related central sleep apnea (CSA). DESIGN Systematic review. INTERVENTIONS MEDLINE, the Cochrane Library, and EMBASE were screened through March 2013 to identify articles which investigated treatment of opioid related CSA with PAP. Eligible articles were identified in a staged process and were assessed by two investigators independently. The methodological quality of the reporting of eligible articles was assessed using a set of questions addressing both general and statistical methodologies. RESULTS Five articles met the inclusion criteria for a total of 127 patients. All patients had been on opioids for at least 6 months. The dose ranged from 10 mg to 450 mg daily of morphine equivalent dose. Continuous positive airway pressure (CPAP) was proven mostly ineffective in reducing central apneic events. Bi-level positive airway pressure (BiPAP) with and without supplemental oxygen achieved elimination of central apneas in 62 percent of patients. Adaptive servo ventilation (ASV) yielded conflicting results with 58 percent of participants attaining a central apnea index <10 per hour. The presence of ataxic breathing predicted poor response to PAP. CONCLUSIONS The available evidence on the efficacy of PAP in opioid-related CSA is inconclusive. With the increasing use of opioids, further studies are needed to assess optimal PAP therapy and predictors of success in this group of patients.

Omeprazole absorption from a compounded transdermal formulation in healthy volunteers.

OBJECTIVE To evaluate the plasma concentration versus time profile of omeprazole following the administration of a compounded transdermal gel formulation in healthy volunteers. DESIGN Single-dose transdermal pharmacokinetic (PK) study including a comparison with historical data from an oral PK study. SETTING Academic clinical research center. PARTICIPANTS Eight healthy volunteers between 18 and 50 years of age. INTERVENTIONS Omeprazole gel 40 mg (0.8 mL) was applied to the ventral surface of the forearm covering an area of 7 x 15 cm without an occlusive dressing. Blood samples were collected just before application and then at 1, 2, 3, 4, 6, and 8 hours. Plasma concentrations of omeprazole were determined using a validated liquid chromatography tandem mass spectrometry method. MAIN OUTCOME MEASURES PK parameters (maximal plasma concentration [C(max)], the time of C(max), [T(max)], the area under the omeprazole concentration versus time curve from 0 to 8 hours, the elimination rate constant, and the half-life of the elimination phase) following transdermal administration, compared with historical controls who had received an oral omeprazole 40 mg dose during a previous study. RESULTS Of the eight volunteers, five had undetectable plasma omeprazole concentrations throughout the 8-hour study, precluding a complete PK analysis. For the three volunteers with detectable plasma omeprazole concentrations, the values ranged from 0.204 to 0.552 ng/mL. Including values of 0 for the patients with undetectable levels, the mean (+/- SD) C(max) was 0.153 +/- 0.241 ng/mL, and the T(max) in patients with detectable levels occurred at approximately 6 hours. The plasma concentrations following transdermal administration were approximately 1,000-fold lower than those observed with oral dosing. CONCLUSION Transdermal absorption from a single dose of the omeprazole gel formulation used in this study was poor. This transdermal gel formulation is clearly not bioequivalent to the oral capsule.

A Randomized Crossover Trial Evaluating Continuous Positive Airway Pressure Versus Mandibular Advancement Device on Health Outcomes in Veterans With Posttraumatic Stress Disorder

STUDY OBJECTIVES Despite the overall improvement in posttraumatic stress disorder (PTSD) symptomatology with continuous positive airway pressure (CPAP) therapy, adherence to CPAP is far worse in veterans with PTSD compared to the general population with obstructive sleep apnea (OSA). The aim of this study was to compare the efficacy, adherence, and preference of CPAP versus mandibular advancement device (MAD) and the effect of these treatments on health outcomes in veterans with PTSD. METHODS Forty-two subjects with PTSD and newly diagnosed OSA by polysomnography were treated in a randomized, crossover trial of 12 weeks with CPAP alternating with MAD separated by a 2-week washout period. The primary outcome was the difference in titration residual apnea-hypopnea index (AHI) between CPAP and MAD. Secondary outcome measures included PTSD Checklist and health-related quality of life (Medical Outcomes Study 36-Item Short Form and Pittsburgh Sleep Quality Index). RESULTS Analyses were limited to the 35 subjects (mean age 52.7 ± 11.6 years) who completed the trial, regardless of compliance with their assigned treatment. CPAP was more efficacious in reducing AHI and improving nocturnal oxygenation than MAD (P < .001 and P = .04, respectively). Both treatments reduced PTSD severity and ameliorated scores of the Medical Outcomes Study Short Form 36 and Pittsburgh Sleep Quality Index, although no differences were detected between the CPAP and MAD arms. The reported adherence to MAD was significantly higher than CPAP (P < .001), with 58% preferring MAD to CPAP. CONCLUSIONS Although CPAP is more efficacious than MAD at improving sleep apnea, both treatment modalities imparted comparable benefits for veterans with PTSD in relation to PTSD severity and health-related quality of life. MAD offers a viable alternative for veterans with OSA and PTSD who are nonadherent to CPAP. CLINICAL TRIAL REGISTRATION Title: A Randomized Cross Over Trial of Two Treatments for Sleep Apnea in Veterans With Post-Traumatic Stress Disorder; URL: https://www.clinicaltrials.gov/ct/show/NCT01569022; Identifier: NCT01569022.

ENDURANCE AND STRENGTH TRAINING IN PATIENTS WITH COPD

STUDY OBJECTIVES The purpose of this study was to compare the effects of endurance training only to endurance plus strength (combined) training in a randomized trial of patients with COPD. METHODS Twenty-four patients completed the study: 11 patients in the combined training group (FEV(1) 45 +/- 5% predicted), and 13 patients in the endurance training group (FEV(1) 40 +/- 4% predicted) [mean +/- SE]. Muscle strength, quality of life, exercise performance, and quadriceps fatigability were measured before and after rehabilitation. RESULTS Combined training led to significant improvements in quadriceps (23.6%), hamstring (26.7), pectoralis major (17.5%), and latissimus dorsi (20%) muscle strength. Endurance training alone did not produce significant improvements in muscle strength: quadriceps (1.1% decrease), hamstring (12.2% increase), pectoralis major (7.8% increase), and latissimus dorsi (2.8% decrease). The increase in strength after training was significantly greater in the combined group compared to the endurance group for the quadriceps and latissimus dorsi muscles but not for the hamstring and pectoralis major muscles. Six-minute walk distance, endurance exercise time, and quality of life (as measured by the Chronic Respiratory Questionnaire) significantly increased in both groups after rehabilitation with no significant differences in the extent of improvement between groups. The extent of improvement in quadriceps fatigability after training (assessed by quadriceps twitch force before and after exercise) was not significantly different between groups. CONCLUSION Strength training can lead to significant improvement in muscle strength in elderly patients with COPD. However, this improvement in muscle strength does not translate into additional improvement in quality of life, exercise performance or quadriceps fatigability compared to that achieved by endurance exercise alone.