MOPSE is a registered (http://www.clinicaltrials.gov
, NCT00258661), double-blinded, randomized, controlled trial conducted from March 2004 to April 2007 with a 60-day post-admission follow-up period.
Subjects aged ≥ 60 years newly hospitalized with pneumonia were recruited for MOPSE. Ten months into the study the age criterion was lowered to ≥ 50 years to improve recruitment. Eligibility criteria included a new pulmonary infiltrate on chest x-ray and at least two of the following: new or increased cough, fever ≥ 38°C, pleuritic chest pain, new physical findings on chest examination, respiratory rate ≥ 25 breaths/min, deteriorating mental or functional status, or white blood cell count (WBC) > 12,000 cells/mm3. Exclusion criteria were nosocomial pneumonia, lung abscess, advancing pulmonary fibrosis, bronchiectasis, pulmonary tuberculosis, lung cancer, metastatic malignancy, uncontrolled metabolic bone diseases, current rib or vertebral fracture, prior pathologic fracture, previous study participation, or respiratory failure. See Figure for the MOPSE flow diagram.
Figure 1 Flow diagram of the Multicenter Osteopathic Pneumonia Study in the Elderly. ITT = intention-to-treat, PP = per-protocol, OMT = osteopathic manipulative treatment, LT = light-touch treatment, CCO = conventional care only. Data on each site are presented (more ...)
Subjects were recruited at seven community hospitals in one rural, two suburban, and two urban US communities. The respective institutional review boards approved the study protocol, and all participants gave informed consent. An independent data and safety monitoring board provided oversight for MOPSE.
Subjects were enrolled and randomized into three groups: conventional care only (CCO, standard care control), light-touch treatment (LT, sham control), or osteopathic manipulative treatment (OMT). All subjects received conventional treatment for pneumonia directed by their attending physicians. Subjects were stratified by study site and randomized from a computer-generated list using block sizes of 3 or 6. Allocation was concealed with opaque, sealed envelopes which were opened after enrollment. Subjects, personnel responsible for collecting data, attending physicians, nurses, and house staff caring for subjects were blinded to group assignment. Only the physicians giving the study treatments were unblinded to group assignment.
Participants randomized to the OMT or LT groups received protocol treatments for 15 minutes, twice daily (≥ 6 hours apart) beginning within 24 hours of admission and continuing until hospital discharge, cessation of antibiotic therapy for pneumonia, respiratory failure (ventilator dependent), death, or study withdrawal. All subjects were treated while supine in bed. The manipulation techniques of the OMT protocol were administered in the following sequence: thoracolumbar soft tissue, rib raising, doming of the diaphragm myofascial release, cervical spine soft tissue, suboccipital decompression, thoracic inlet myofascial release, thoracic lymphatic pump, and pedal lymphatic pump [15
]. Soft tissue technique consists of massage, stretching, kneading, and direct inhibitory pressure to relax the musculature. Rib raising articulates each rib for the purpose of improving rib cage motion and theoretically stimulates the sympathetic chain ganglia. Myofascial release is a method for reducing tissue tension. Doming the diaphragm and thoracic inlet myofascial release techniques are used to improve diaphragmatic movement and lymphatic drainage. Suboccipital decompression involves traction at the base of the skull, which is considered to release restrictions around the vagus nerves, theoretically improving nerve function. The thoracic lymphatic pump with activation combines rhythmical compressions to the chest wall and the rapid removal of the hands from the chest wall during deep inhalation with the intention of enhancing lymphatic circulation and triggering a sudden expansion of airways and alveoli. The pedal lymphatic pump gently rocks the patient in a superior-inferior rhythmical motion while supine, to theoretically enhance lymphatic circulation.
Non-thrust techniques were used to treat areas unaddressed by the above techniques, limited to ≤ 5 minutes of the 15-minute session. The LT protocol, designed as a sham control treatment, applied light touch to the same body regions, in the same sequence, and for the same duration as the OMT protocol. A more detailed description of the OMT and LT protocols has been published [15
Twenty osteopathic neuromusculoskeletal (OMT) specialists and 64 resident physicians from 12 specialties administered the protocols. An OMT specialist at each site administered one of the first two OMT or LT treatments and 3 treatments per week thereafter. Using a standardized patient, treatment skills and protocol adherence were evaluated by the principal investigator and an OMT specialist at 9 training sessions at each site during the study. A pressure mapping system (Sensor Products LLC, East Hanover, NJ) was used to standardize three OMT techniques: rib raising, suboccipital decompression, and thoracic lymphatic pump. Presentation of the pressure mapping data is beyond the scope of this manuscript.
Primary outcomes were LOS, time to clinical stability [19
], and a symptomatic and functional recovery score [20
]. LOS was defined by the date and time of the admission and discharge orders. Based on data recorded daily, time to clinical stability was defined as the hospital calendar day when all seven clinical parameters first met criteria for stability (ie, lowest systolic blood pressure ≥ 90 mmHg, highest heart rate ≤ 100 beats/min, highest respiratory rate ≤ 24 breaths/min, highest temperature ≤ 38°C, lowest oxygen saturation ≥ 90%, ability to eat food by mouth or by a feeding tube, and mental status back to pre-pneumonia baseline) [19
]. The symptomatic and functional recovery score was calculated from a pneumonia-specific, validated questionnaire addressing five symptoms: cough, dyspnea, sputum production, pleuritic chest pain, and fatigue [20
]. Higher scores indicate more symptoms. This questionnaire was administered at admission and via telephone on post-admission days 14, 30, and 60.
Secondary outcomes were duration of intravenous and oral antibiotics; treatment endpoint, including death and respiratory failure; 60-day hospital readmission rate; highest daily temperature; highest daily respiratory rate; and WBC. Baseline severity of illness was assessed using the pneumonia severity index [21
]. Adverse events, whether related to the study treatments or not, were monitored daily while subjects were in the hospital. Treatment side effects were evaluated 24 hours post-discharge; subjects were asked to report the severity and character of muscle soreness, worsening of breathing, or other side effects. The success of subject blinding was assessed via questionnaire within 24 hours of hospital discharge.
Using pilot data [18
] to estimate the median LOS for the OMT and CCO groups, a log-rank test for survival has 80% power to detect a difference in median LOS of 6 versus 9 days when the sample size in each group is 96 subjects discharged from the hospital. MOPSE was designed to enroll 120 subjects per group with censored values (death, respiratory failure, or study withdrawal) estimated at ≤ 20% of the subjects.
Data were entered in duplicate at the study site and the central coordinating center, and checked for agreement. Data were analyzed by intention-to-treat (ITT) analysis and by per-protocol (PP) analysis of subjects receiving 100% of prescribed treatments. Data were analyzed for all subjects (≥ 50 years) and then separately for subjects who met the original age criterion (≥ 60 years). To test the hypotheses regarding group differences, we used three statistical analysis methods that stratify by study site to account for clustering. Groups were compared on LOS, time to clinical stability, and duration of in-hospital antibiotics using stratified Cox proportional hazards models in order to include incomplete data from subjects who withdrew from the study, died, or were placed on a ventilator. Hazard ratios for LOS greater than 1 correspond to earlier discharge from the hospital for the treatment group compared to the control group. Differences in the three groups on continuous outcome measures were assessed using general linear mixed-effects models with subjects and study sites treated as random effects and group assignment, time, and the interaction of group and time as fixed effects. The Cochran-Mantel-Haenszel test for general association was used to analyze categorical outcome measures and compare the incidence of adverse events and serious adverse events between the groups. P values ≤ 0.05 were considered statistically significant. The statistical analyses were performed using SAS© version 9.1 (SAS Institute, Inc., Cary, NC).