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Adjunctive osteopathic therapy for hospitalized COVID-19 patients: A feasibility-oriented chart review study with matched controls
Abstract
Background
Osteopathic manipulative treatment (OMT) may improve outcomes during COVID-related respiratory distress – the most common cause of death from novel coronavirus (SARS-CoV-2). Outcomes from OMT treatments of respiratory distress during the COVID-19 pandemic have not been reported.
Objective
Assess adjunctive OMT in hospitalized patients with SARS-CoV-2 and respiratory distress.
Design
Feasibility oriented retrospective observational cohort study.
Setting
COVID-19 (non-ICU) ward in a tertiary academic medical center.
Methods
Inpatients received daily OMT treatments of rib raising, abdominal diaphragm doming, thoracic pump and pedal pump. Primary outcomes were procedural acceptance, satisfaction, side effects, and adverse events. Secondary outcomes were patient-reported clinical change after therapy; number of hospital days; need during hospitalization for high-flow oxygen, C-PAP/BiPAP or intensive care; need for supplementary oxygen at discharge; and discharge disposition.
Participants
Hospitalized adults with SARS-CoV-2 infection and respiratory distress.
Results
OMT (n = 27) and Control (n = 152) groups were similar in demographics and most laboratory studies. 90% of patients accepted OMT and reported high satisfaction (4.26/±0.71 (maximum 5)), few negative effects, no adverse events, and positive clinical change (5.07 ± 0.96 (maximum 7)). Although no significant differences were found in secondary outcomes, OMT patients trended towards fewer hospital days than Controls (p = 0.053; Cohen's d = 0.22), a relationship that trended towards correlation with number of co-morbidities (p = 0.068).
Conclusion
Hospitalized patients with respiratory distress and COVID-19 reported acceptance, satisfaction, and greater ease of breathing after a four-part OMT protocol, and appear to have a shorter length of hospitalization. Randomized controlled trials are needed to confirm these results.
... Indeed, past studies have demonstrated the benefits of OMT in suppressing inflammation and disease progression in patients infected with the influenza virus [54,55], and the benefits of OMT had been documented during the Spanish flu pandemic in 1917 [56]. Due to its efficacy and noninvasive nature, several clinical trials are underway to investigate whether adjunctive OMT can decrease disease progression in hospitalized COVID-19 patients as well [57,58]. Therefore, a thorough evaluation of the benefits of integrating OMT in both neonates and infants admitted to the NICU with respiratory infections is clearly needed. ...
Osteopathic manipulative treatment (OMT) is used in both inpatient and outpatient settings. Evidence suggests that OMT can reduce both patients’ recovery time and the financial cost of their acute medical treatment and rehabilitation. Multiple studies from neonatal intensive care units (NICUs) are presented in this article that demonstrate infants treated with OMT recover faster, are discharged earlier, and have lower healthcare costs than their non-OMT-treated counterparts. Data clearly show that adjunctive OMT facilitates feeding coordination in newborns, such as latching, suckling, swallowing, and breathing, and increases long-term weight gain and maintenance, which reduces hospital length of stay (LOS). Osteopathic techniques, such as soft tissue manipulation, balanced ligamentous tension, myofascial release, and osteopathic cranial manipulation (OCM), can reduce regurgitation, vomiting, milky bilious, or bloody discharge and decrease the need for constipation treatment. OMT can also be effective in reducing the complications of pneumonia in premature babies. Studies show the use of OCM and lymphatic pump technique (LPT) reduces the occurrence of both aspiration and environmentally acquired pneumonia, resulting in significantly lower morbidity and mortality in infants. Based on published findings, it is determined that OMT is clinically effective, cost efficient, a less invasive alternative to surgery, and a less toxic choice to pharmacologic drugs. Therefore, routine incorporation of OMT in the NICU can be of great benefit in infants with multiple disorders. Future OMT research should aim to initiate clinical trial designs that include randomized controlled trials with larger cohorts of infants admitted to the NICU. Furthermore, a streamlined and concerted effort to elucidate the underlying molecular mechanisms associated with the beneficial effects of OMT will aid in understanding the significant value of incorporating OMT into optimal patient care.
Physiatry and Integrative Medicine practice approaches the care of patients holistically to achieve recovery and optimal function. The current lack of knowledge on proven treatments for long COVID has resulted in a surge in both demand and use of complementary and integrative health (CIH) treatments. This overview summarizes CIH therapies using the framework of the United States National Center for Complementary and Integrative Health, divided into nutritional, psychological, physical, and combinations of these categories. Representative therapies selected based on the availability of published and ongoing research for post-COVID conditions are described.
Importance:
The efficacy of vitamin D3 supplementation in coronavirus disease 2019 (COVID-19) remains unclear.
Objective:
To investigate the effect of a single high dose of vitamin D3 on hospital length of stay in patients with COVID-19.
Design, setting, and participants:
This was a multicenter, double-blind, randomized, placebo-controlled trial conducted in 2 sites in Sao Paulo, Brazil. The study included 240 hospitalized patients with COVID-19 who were moderately to severely ill at the time of enrollment from June 2, 2020, to August 27, 2020. The final follow-up was on October 7, 2020.
Interventions:
Patients were randomly assigned to receive a single oral dose of 200 000 IU of vitamin D3 (n = 120) or placebo (n = 120).
Main outcomes and measures:
The primary outcome was length of stay, defined as the time from the date of randomization to hospital discharge. Prespecified secondary outcomes included mortality during hospitalization; the number of patients admitted to the intensive care unit; the number of patients who required mechanical ventilation and the duration of mechanical ventilation; and serum levels of 25-hydroxyvitamin D, total calcium, creatinine, and C-reactive protein.
Results:
Of 240 randomized patients, 237 were included in the primary analysis (mean [SD] age, 56.2 [14.4] years; 104 [43.9%] women; mean [SD] baseline 25-hydroxyvitamin D level, 20.9 [9.2] ng/mL). Median (interquartile range) length of stay was not significantly different between the vitamin D3 (7.0 [4.0-10.0] days) and placebo groups (7.0 [5.0-13.0] days) (log-rank P = .59; unadjusted hazard ratio for hospital discharge, 1.07 [95% CI, 0.82-1.39]; P = .62). The difference between the vitamin D3 group and the placebo group was not significant for in-hospital mortality (7.6% vs 5.1%; difference, 2.5% [95% CI, -4.1% to 9.2%]; P = .43), admission to the intensive care unit (16.0% vs 21.2%; difference, -5.2% [95% CI, -15.1% to 4.7%]; P = .30), or need for mechanical ventilation (7.6% vs 14.4%; difference, -6.8% [95% CI, -15.1% to 1.2%]; P = .09). Mean serum levels of 25-hydroxyvitamin D significantly increased after a single dose of vitamin D3 vs placebo (44.4 ng/mL vs 19.8 ng/mL; difference, 24.1 ng/mL [95% CI, 19.5-28.7]; P < .001). There were no adverse events, but an episode of vomiting was associated with the intervention.
Conclusions and relevance:
Among hospitalized patients with COVID-19, a single high dose of vitamin D3, compared with placebo, did not significantly reduce hospital length of stay. The findings do not support the use of a high dose of vitamin D3 for treatment of moderate to severe COVID-19.
Trial registration:
ClinicalTrials.gov Identifier: NCT04449718.
Background
In the current SARS-CoV-2 pandemic, there has been worldwide debate on the use of corticosteroids in COVID-19. In the recent RECOVERY trial, evaluating the effect of dexamethasone, a reduced 28-day mortality in patients requiring oxygen therapy or mechanical ventilation was shown. Their results have led to considering amendments in guidelines or actually already recommending corticosteroids in COVID-19. However, the effectiveness and safety of corticosteroids still remain uncertain, and reliable data to further shed light on the benefit and harm are needed.
Objectives
The aim of this systematic review and meta-analysis was to evaluate the effectiveness and safety of corticosteroids in COVID-19.
Methods
A systematic literature search of RCTS and observational studies on adult patients was performed across Medline/PubMed, Embase and Web of Science from December 1, 2019, until October 1, 2020, according to the PRISMA guidelines. Primary outcomes were short-term mortality and viral clearance (based on RT-PCR in respiratory specimens). Secondary outcomes were: need for mechanical ventilation, need for other oxygen therapy, length of hospital stay and secondary infections.
Results
Forty-four studies were included, covering 20.197 patients. In twenty-two studies, the effect of corticosteroid use on mortality was quantified. The overall pooled estimate (observational studies and RCTs) showed a significant reduced mortality in the corticosteroid group (OR 0.72 (95%CI 0.57–0.87). Furthermore, viral clearance time ranged from 10 to 29 days in the corticosteroid group and from 8 to 24 days in the standard of care group. Fourteen studies reported a positive effect of corticosteroids on need for and duration of mechanical ventilation. A trend toward more infections and antibiotic use was present.
Conclusions
Our findings from both observational studies and RCTs confirm a beneficial effect of corticosteroids on short-term mortality and a reduction in need for mechanical ventilation. And although data in the studies were too sparse to draw any firm conclusions, there might be a signal of delayed viral clearance and an increase in secondary infections.
Background
Coronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Despite the disproportionate incidence of Covid-19 among underserved and racial and ethnic minority populations, the safety and efficacy of the anti–interleukin-6 receptor antibody tocilizumab in patients from these populations who are hospitalized with Covid-19 pneumonia are unclear.
Methods
We randomly assigned (in a 2:1 ratio) patients hospitalized with Covid-19 pneumonia who were not receiving mechanical ventilation to receive standard care plus one or two doses of either tocilizumab (8 mg per kilogram of body weight intravenously) or placebo. Site selection was focused on the inclusion of sites enrolling high-risk and minority populations. The primary outcome was mechanical ventilation or death by day 28.
Results
A total of 389 patients underwent randomization, and the modified intention-to-treat population included 249 patients in the tocilizumab group and 128 patients in the placebo group; 56.0% were Hispanic or Latino, 14.9% were Black, 12.7% were American Indian or Alaska Native, 12.7% were non-Hispanic White, and 3.7% were of other or unknown race or ethnic group. The cumulative percentage of patients who had received mechanical ventilation or who had died by day 28 was 12.0% (95% confidence interval [CI], 8.5 to 16.9) in the tocilizumab group and 19.3% (95% CI, 13.3 to 27.4) in the placebo group (hazard ratio for mechanical ventilation or death, 0.56; 95% CI, 0.33 to 0.97; P=0.04 by the log-rank test). Clinical failure as assessed in a time-to-event analysis favored tocilizumab over placebo (hazard ratio, 0.55; 95% CI, 0.33 to 0.93). Death from any cause by day 28 occurred in 10.4% of the patients in the tocilizumab group and 8.6% of those in the placebo group (weighted difference, 2.0 percentage points; 95% CI, –5.2 to 7.8). In the safety population, serious adverse events occurred in 38 of 250 patients (15.2%) in the tocilizumab group and 25 of 127 patients (19.7%) in the placebo group.
Conclusions
In hospitalized patients with Covid-19 pneumonia who were not receiving mechanical ventilation, tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival. No new safety signals were identified. (Funded by Genentech; EMPACTA ClinicalTrials.gov number, NCT04372186.)
Abstract
Objectives: Coronavirus disease 2019 (Covid-19) is an emerging, fast-spreading, and worldwide infectious disease that would be deteriorated with the precipitation of systemic or local thrombosis. The aim of the current study was to evaluate the effects of early anticoagulant treatment in hospitalized Covid-19 patients.
Method: The present retrospective and comparative cohort study investigated 413 hospitalized Covid-19 patients
treated with or without Low Molecular Weight Heparin (LMWH) (n ¼ 187 and 226, respectively) in the Covid Clinics of
Gulhane Education and Research Hospital in Ankara, Turkey, between March 18 and May 03, 2020. The treatment groups consisted of the patients evaluated before and after The Covid-19 Treatment Guide update on April 12, 2020 that included the anticoagulant treatment thereafter.
Results: The mean age of all 413 patients (204 male and 209 female) at disease onset was 50.6 16.7 years. The LMWH-treated patients had significantly higher coagulation markers such as d-dimer and platelet count than LMWHuntreated patients (p values < 0.05). The inflammatory markers, ferritin, interleukin-6, and procalcitonin were significantly increased in LMWH-untreated patients (p values < 0.05). The presence of any comorbidity was significantly more common in LMWH-treated patients compared to the LMWH-untreated group (39.6% vs 19.9%, respectively; p < 0.001).
Hypertension and diabetes mellitus were the most frequent comorbidities in both groups. The number of intensive care unit (ICU) transfers and longer length of hospital stay were more commonly observed in LMWH-untreated patients (p values <0.05).
Conclusions: Early anticoagulant treatment with relatively higher doses of LMWH may improve the clinical outcome of Covid-19 patients and shorten the length of hospital stay.
Keywords: Covid-19 disease, infectious disease, anticoagulation, heparin, thrombosis.
Although the COVID-19 pandemic affects predominantly the respiratory function, epidemiological studies show that multiple systems can be affected. The severe complications of SARS-CoV-2 infection seem to be induced by an inflammatory dysregulation (“cytokine storm”), which can also induce an immunodepression. Several studies highlight beneficial effects of osteopathic medicine on inflammation and immune regulation. A careful review of evidence-based literature brings to the fore significant improvements of osteopathic manipulative treatment (OMT) in adjunction to conventional care. OMT can improve the condition of infected patients by decreasing symptoms and boosting the efficiency of conventional care. OMT might also benefit surviving patients by reducing the long-lasting consequences of the infection as well as improving their quality of life during convalescence. This review should constitute an argument in favor of multidisciplinary care, although further biological and clinical research is essential to better assess the potential beneficial contributions of adjunct osteopathic medicine to conventional care in the fight against pandemics such as COVID-19.
i>Background: Coronavirus disease 2019 (COVID-19) is associated with diffuse lung damage. Corticosteroids may modulate inflammation-mediated lung injury, reducing progression to respiratory failure and death.
Methods: The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs. usual care alone. The primary outcome was 28-day mortality.
Results: 2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care. Overall, 482 (22.9%) patients allocated dexamethasone and 1110 (25.7%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.75 to 0.93; P<0.001). The absolute mortality rate reductions varied depending on level of respiratory support at randomization: Dexamethasone reduced deaths in patients receiving invasive mechanical ventilation (29.3% vs. 41.4%, RR 0.64 [95% CI 0.51 to 0.81]), in patients receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%, RR 0.82 [95% CI 0.72 to 0.94]), but did not reduce mortality in patients not receiving respiratory support at randomization (17.8% vs. 14.0%, RR 1.19 [95% CI 0.91 to 1.55]).
Conclusions: In patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support.
(Funded by the Medical Research Council and National Institute for Health Research; ClinicalTrials.gov NCT04381936 and ISRCTN 50189673)
COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-α agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.
By Feb 27th, 2020, the outbreak of COVID‐19 caused 82623 confirmed cases and 2858 deaths globally, more than Severe Acute Respiratory Syndrome (SARS) (8273 cases, 775 deaths) and Middle East Respiratory Syndrome (MERS) (1139 cases, 431 deaths) caused in 2003 and 2013 respectively. COVID‐19 has spread to 46 countries internationally. Total fatality rate of COVID‐19 is estimated at 3.46% by far based on published data from Chinese Center for Disease Control and Prevention (China CDC). Average incubation period of COVID‐19 is around 6.4 days, ranges from 0‐24 days. The basic reproductive number (R0) of COVID‐19 ranges from 2‐3.5 at the early phase regardless of different prediction models, which is higher than SARS and MERS. A study from China CDC showed majority of patients (80.9%) were considered asymptomatic or mild pneumonia but released large amounts of viruses at the early phase of infection, which posed enormous challenges for containing the spread of COVID‐19. Nosocomial transmission was another severe problem. 3019 health workers were infected by Feb 12, 2020, which accounted for 3.83% of total number of infections, and extremely burdened the health system, especially in Wuhan. Limited epidemiological and clinical data suggest that the disease spectrum of COVID‐19 may differ from SARS or MERS. We summarize latest literatures on genetic, epidemiological, and clinical features of COVID‐19 in comparison to SARS and MERS and emphasize special measures on diagnosis and potential interventions. This review will improve our understanding of the unique features of COVID‐19 and enhance our control measures in the future.
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Context:
By promoting the recirculation of tissue fluid, the lymphatic system preserves tissue health, aids in the absorption of gastrointestinal lipids, and supports immune surveillance. Failure of the lymphatic system has been implicated in the pathogenesis of several infectious and inflammatory diseases. Thus, interventions that enhance lymphatic circulation, such as osteopathic lymphatic pump treatment (LPT), should aid in the management of these diseases.
Objective:
To determine whether thoracic duct lymph (TDL) mobilized during LPT would alter the function of macrophages in vitro.
Methods:
The thoracic ducts of 6 mongrel dogs were cannulated, and TDL samples were collected before (baseline), during, and 10 minutes after LPT. Thoracic duct lymph flow was measured, and TDL samples were analyzed for protein concentration. To measure the effect of TDL on macrophage activity, RAW 264.7 macrophages were cultured for 1 hour to acclimate. After 1 hour, cell-free TDL collected at baseline, during LPT, and after TDL was added at 5% total volume per well and co-cultured with or without 500 ng per well of lipopolysaccharide (LPS) for 24 hours. As a control for the addition of 5% TDL, macrophages were cultured with phosphate-buffered saline (PBS) at 5% total volume per well and co-cultured with or without 500 ng per well of LPS for 24 hours. After culture, cell-free supernatants were assayed for nitrite (NO2-), tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10). Macrophage viability was measured using flow cytometry.
Results:
Lymphatic pump treatment significantly increased TDL flow and the flux of protein in TDL (P<.001). After culture, macrophage viability was approximately 90%. During activation with LPS, baseline TDL, TDL during LPT, and TDL after LPT significantly decreased the production of NO2-, TNF-α, and IL-10 by macrophages (P<.05). However, no significant differences were found in viability or the production of NO2-, TNF-α, or IL-10 between macrophages cultured with LPS plus TDL taken before, during, and after LPT (P>.05).
Conclusion:
The redistribution of protective lymph during LPT may provide scientific rationale for the clinical use of LPT to reduce inflammation and manage edema.
The purpose of the present case study was to explore the efficacy of osteopathic manipulative treatment (OMT) in patient with pulmonary fibrosis (PF) in the critical care outpatient department. Here, we present a 48‑year‑old male case with breathlessness, increased frequency of defecation, and pain in and around the nape of neck with diagnosed pulmonary fibrosis. He scored 3 on a patient‑reported modified Medical Research Council (mMRC) dyspnea scale. Osteopathic examination reveals multiple somatic findings across the chest and abdominal region and treated by OMT. Pre‑ and post‑intervention changes were assessed by the 13‑item shortness of breath with daily activities (13iSOBDA). 27.2, 22, 16.4, and 11.8 were noted at the end of 1st, 2nd, 3rd, and 4th week of intervention, respectively, on 13iSOBDA while mMRC decreased from 3 to 1. OMT may be a feasible option in decreasing the symptoms of the PPF in the critical care outpatient department.
The Consolidated Standards of Reporting Trials (CONSORT) statement is a guideline designed to improve the transparency and quality of the reporting of randomised controlled trials (RCTs). In this article we present an extension to that statement for randomised pilot and feasibility trials conducted in advance of a future definitive RCT. The checklist applies to any randomised study in which a future definitive RCT, or part of it, is conducted on a smaller scale, regardless of its design (eg, cluster, factorial, crossover) or the terms used by authors to describe the study (eg, pilot, feasibility, trial, study). The extension does not directly apply to internal pilot studies built into the design of a main trial, non-randomised pilot and feasibility studies, or phase II studies, but these studies all have some similarities to randomised pilot and feasibility studies and so many of the principles might also apply. The development of the extension was motivated by the growing number of studies described as feasibility or pilot studies and by research that has identified weaknesses in their reporting and conduct. We followed recommended good practice to develop the extension, including carrying out a Delphi survey, holding a consensus meeting and research team meetings, and piloting the checklist. The aims and objectives of pilot and feasibility randomised studies differ from those of other randomised trials. Consequently, although much of the information to be reported in these trials is similar to those in randomised controlled trials (RCTs) assessing effectiveness and efficacy, there are some key differences in the type of information and in the appropriate interpretation of standard CONSORT reporting items. We have retained some of the original CONSORT statement items, but most have been adapted, some removed, and new items added. The new items cover how participants were identified and consent obtained; if applicable, the prespecified criteria used to judge whether or how to proceed with a future definitive RCT; if relevant, other important unintended consequences; implications for progression from pilot to future definitive RCT, including any proposed amendments; and ethical approval or approval by a research review committee confirmed with a reference number. This article includes the 26 item checklist, a separate checklist for the abstract, a template for a CONSORT flowchart for these studies, and an explanation of the changes made and supporting examples. We believe that routine use of this proposed extension to the CONSORT statement will result in improve
Context:
Osteopathic manipulative treatment (OMT) is a promising adjunctive treatment for older adults hospitalized for pneumonia.
Objective:
To report subgroup analyses from the Multicenter Osteopathic Pneumonia Study in the Elderly (MOPSE) relating to hospital length of stay (LOS), ventilator-dependent respiratory failure rate, and in-hospital mortality rate.
Design:
Multicenter randomized controlled trial.
Setting:
Seven community hospitals.
Participants:
Three hundred eighty-seven patients aged 50 years or older who met specific criteria for pneumonia on hospital admission.
Interventions:
Participants were randomly assigned to 1 of 3 groups that received an adjunctive OMT protocol (n=130), a light touch (LT) protocol (n=124), or conventional care only (CCO) (n=133).
Main outcome measures:
Outcomes for subgroup analyses were LOS, ventilator-dependent respiratory failure rate, and in-hospital mortality rate. Subgroups were age (50-74 years or ≥75 years), Pneumonia Severity Index (PSI) class (I-II, III, IV, or V), and type of pneumonia (community-acquired or nursing-home acquired). Data were analyzed by intention-to-treat and per-protocol analyses using stratified Cox proportional hazards models and Cochran-Mantel-Haenszel tests for general association.
Results:
By per-protocol analysis of the younger age subgroup, LOS was shorter for the OMT group (median, 2.9 days; n=43) than the LT (median, 3.7 days; n=45) and CCO (median, 4.0 days; n=65) groups (P=.006). By intention-to-treat analysis of the older age subgroup, in-hospital mortality rates were lower for the OMT (1 of 66 [2%]) and LT (2 of 68 [3%]) groups than the CCO group (9 of 67 [13%]) (P=.005). By per-protocol analysis of the PSI class IV subgroup, the OMT group had a shorter LOS than the CCO group (median, 3.8 days [n=40] vs 5.0 days [n=50]; P=.01) and a lower ventilator-dependent respiratory failure rate than the CCO group (0 of 40 [0%] vs 5 of 50 [10%]; P=.05). By intention-to-treat analysis, in-hospital mortality rates in the PSI class V subgroup were lower (P=.05) for the OMT group (1 of 22 [5%]) than the CCO group (6 of 19 [32%]) but not the LT group (2 of 15 [13%]).
Conclusion:
Subgroup analyses suggested adjunctive OMT for pneumonia reduced LOS in adults aged 50 to 74 years and lowered in-hospital mortality rates in adults aged 75 years or older. Adjunctive OMT may also reduce LOS and in-hospital mortality rates in older adults with more severe pneumonia. Interestingly, LT also reduced in-hospital mortality rates in adults aged 75 years or older relative to CCO. (ClinicalTrials.gov number NCT00258661).
Background
Feasibility and pilot studies are essential components of planning or preparing for a larger randomized controlled trial (RCT). They are intended to provide useful information about the feasibility of the main RCT—with the goal of reducing uncertainty and thereby increasing the chance of successfully conducting the main RCT. However, research has shown that there are serious inadequacies in the reporting of pilot and feasibility studies. Reasons for this include a lack of explicit publication policies for pilot and feasibility studies in many journals, unclear definitions of what constitutes a pilot or feasibility RCT/study, and a lack of clarity in the objectives and methodological focus. All these suggest that there is an urgent need for new guidelines for reporting pilot and feasibility studies.
Objectives
The aim of this paper is to describe the methods and processes in our development of an extension to the Consolidated Standards of Reporting Trials (CONSORT) Statement for reporting pilot and feasibility RCTs, that are executed in preparation for a future, more definitive RCT.
Methods/design
There were five overlapping parts to the project: (i) the project launch—which involved establishing a working group and conducting a review of the literature; (ii) stakeholder engagement—which entailed consultation with the CONSORT group, journal editors and publishers, the clinical trials community, and funders; (iii) a Delphi process—used to assess the agreement of experts on initial definitions and to generate a reporting checklist for pilot RCTs, based on the 2010 CONSORT statement extension applicable to reporting pilot studies; (iv) a consensus meeting—to discuss, add, remove, or modify checklist items, with input from experts in the field; and (v) write-up and implementation—which included a guideline document which gives an explanation and elaboration (E&E) and which will provide advice for each item, together with examples of good reporting practice. This final part also included a plan for dissemination and publication of the guideline.
Conclusions
We anticipate that implementation of our guideline will improve the reporting completeness, transparency, and quality of pilot RCTs, and hence benefit several constituencies, including authors of journal manuscripts, funding agencies, educators, researchers, and end-users.
Lymphatic pump treatment (LPT) is a technique used by osteopathic physicians as an adjunct to antibiotics for patients with respiratory tract infections, and previous studies have demonstrated that LPT reduces bacterial load in the lungs of rats with pneumonia. Currently, it is unknown whether LPT affects drug effcacy.
To determine whether the combination of antibiotics and LPT would reduce bacterial load in the lungs of rats with acute pneumonia.
Rats were infected intranasally with 5×107 colony-forming units (CFU) of Streptococcus pneumoniae. At 24, 48, and 72 hours after infection, the rats received no therapy (control), 4 minutes of sham therapy, or 4 minutes of LPT, followed by subcutaneous injection of 40 mg/kg of levofoxacin or sterile phosphate-buffered saline. At 48, 72, and 96 hours after infection, the spleens and lungs were collected, and S pneumoniae CFU were enumerated. Blood was analyzed for a complete blood cell count and leukocyte differential count.
At 48 and 72 hours after infection, no statistically significant differences in pulmonary CFU were found between control, sham therapy, or LPT when phosphate-buffered saline was administered; however, the reduction in CFU was statistically significant in all rats given levofoxacin. The combination of sham therapy and levofoxacin decreased bacterial load at 72 and 96 hours after infection, and LPT and levofoxacin significantly reduced CFU compared with sham therapy and levofoxacin at both time points (P<.05). Colony-forming units were not detected in the spleens at any time. No statistically significant differences in hematologic findings between any treatment groups were found at any time point measured.
The results suggest that 3 applications of LPT induces an additional protective mechanism when combined with levofoxacin and support its use as an adjunctive therapy for the management of pneumonia; however, the mechanism responsible for this protection is unclear.
Pneumonia, the inflammatory state of lung tissue primarily due to microbial infection, claimed 52,306 lives in the United States in 20071 and resulted in the hospitalization of 1.1 million patients2. With an average length of in-patient hospital stay of five days2, pneumonia and influenza comprise significant financial burden costing the United States $40.2 billion in 20053. Under the current Infectious Disease Society of America/American Thoracic Society guidelines, standard-of-care recommendations include the rapid administration of an appropriate antibiotic regiment, fluid replacement, and ventilation (if necessary). Non-standard therapies include the use of corticosteroids and statins; however, these therapies lack conclusive supporting evidence4. (Figure 1)
Osteopathic Manipulative Treatment (OMT) is a cost-effective adjunctive treatment of pneumonia that has been shown to reduce patients’ length of hospital stay, duration of intravenous antibiotics, and incidence of respiratory failure or death when compared to subjects who received conventional care alone5. The use of manual manipulation techniques for pneumonia was first recorded as early as the Spanish influenza pandemic of 1918, when patients treated with standard medical care had an estimated mortality rate of 33%, compared to a 10% mortality rate in patients treated by osteopathic physicians6. When applied to the management of pneumonia, manual manipulation techniques bolster lymphatic flow, respiratory function, and immunological defense by targeting anatomical structures involved in the these systems7,8, 9, 10.
The objective of this review video-article is three-fold: a) summarize the findings of randomized controlled studies on the efficacy of OMT in adult patients with diagnosed pneumonia, b) demonstrate established protocols utilized by osteopathic physicians treating pneumonia, c) elucidate the physiological mechanisms behind manual manipulation of the respiratory and lymphatic systems. Specifically, we will discuss and demonstrate four routine techniques that address autonomics, lymph drainage, and rib cage mobility: 1) Rib Raising, 2) Thoracic Pump, 3) Doming of the Thoracic Diaphragm, and 4) Muscle Energy for Rib 1.5,11
The 2012-2013 influenza epidemic arrived approximately 4 weeks early, augmented by an unusual variant type-A ("swine flu") strain that caused greater-than-normal illness and a lack of efficacy in vaccination against it. Tens of thousands of people die of influenza or related complications during a nonepidemic influenza season. Osteopathic medicine can substantially help to address the complications that result from influenza. For example, during the deadly 1918-1919 Spanish influenza pandemic, osteopaths reduced patient mortality and morbidity by using lymphatic treatment techniques. Use of osteopathic manipulative treatment with vaccination, antiviral therapy, and chemoprophylaxis has potential to save lives and reduce complications. The present article describes the role of osteopathic manipulative treatment in the management of influenza and highlights current issues surrounding the use of antiviral therapy.
Background
Chronic Non Specific Low Back Pain (CNSLBP) is a common, complex and disabling condition that has been present for longer than three months and is not caused by a serious pathology. Osteopaths are health practitioners who commonly diagnose and treat CNSLBP patients using a complex set of interventions that includes manual therapy. The study aimed to complete a Systematic Review of clinical research into osteopathic intervention in CNSLBP using a rigorous assessment of study quality.
Methods
The literature was searched to August 2011 using the following databases: AMED, CINAHL Plus, Cochrane Central Register of Clinical Trials, MEDLINE Plus, EMBASE, MANTIS, OSTMED, PEDro, ScienceDirect. Multiple search terms were used in various combinations: osteopathy/osteopathic, osteopathic manipulative technique, OMT, Spinal Manipulative Therapy, SMT, clinical trial, back pain, chronic back pain. The inclusion criteria were papers that: reported clinical trials; had adult participants; tested the effectiveness and/or efficacy of osteopathic manual therapy intervention applied by osteopaths, and had a study condition of CNSLBP. The quality of the papers was assessed using the Cochrane Back Review Risk of Bias criteria. A meta-analysis would proceed if the studies had adequate clinical and methodological homogeneity.
Results
Initial searches revealed 809 papers, 772 of which were excluded on the basis of abstract alone. The remaining 37 trial papers were subjected to a more detailed analysis of the full text, which resulted in 35 being excluded. The two remaining trials had a lack of methodological and clinical homogeneity, precluding a meta-analysis. The trials used different comparators with regards to the primary outcomes, the number of treatments, the duration of treatment and the duration of follow-up.
Conclusion
There are only two studies assessing the effect of the manual therapy intervention applied by osteopathic clinicians in adults with CNSLBP. One trial concluded that the osteopathic intervention was similar in effect to a sham intervention, and the other suggests similarity of effect between osteopathic intervention, exercise and physiotherapy. Further clinical trials into this subject are required that have consistent and rigorous methods. These trials need to include an appropriate control and utilise an intervention that reflects actual practice.
Lymph stasis can result in edema and the accumulation of particulate matter, exudates, toxins and bacteria in tissue interstitial fluid, leading to inflammation, impaired immune cell trafficking, tissue hypoxia, tissue fibrosis and a variety of diseases. Previously, we demonstrated that osteopathic lymphatic pump techniques (LPTs) significantly increased thoracic and intestinal duct lymph flow. The purpose of this study was to determine if LPT would mobilize inflammatory mediators into the lymphatic circulation. Under anesthesia, thoracic or intestinal lymph of dogs was collected at resting (pre-LPT), during four minutes of LPT, and for 10 min following LPT (post-LPT), and the lymphatic concentrations of interleukin-2 (IL-2), IL-4, IL-6, IL-10, interferon-γ, tissue necrosis factor α, monocyte chemotactic protein-1 (MCP-1), keratinocyte chemoattractant, superoxide dismutase (SOD) and nitrotyrosine (NT) were measured. LPT significantly increased MCP-1 concentrations in thoracic duct lymph. Further, LPT increased both thoracic and intestinal duct lymph flux of cytokines and chemokines as compared with their respective pre-LPT flux. In addition, LPT increased lymphatic flux of SOD and NT. Ten minutes following cessation of LPT, thoracic and intestinal lymph flux of cytokines, chemokines, NT and SOD were similar to pre-LPT, demonstrating that their flux was transient and a response to LPT. This re-distribution of inflammatory mediators during LPT may provide scientific rationale for the clinical use of LPT to enhance immunity and treat infection.
Lymphatic pump techniques (LPT) are used clinically by osteopathic practitioners for the treatment of edema and infection; however, the mechanisms by which LPT enhances lymphatic circulation and provides protection during infection are not understood. Rhythmic compressions on the abdomen during LPT compress the abdominal area, including the gut-associated lymphoid tissues (GALT), which may facilitate the release of leukocytes from these tissues into the lymphatic circulation. This study is the first to document LPT-induced mobilization of leukocytes from the GALT into the lymphatic circulation.
Catheters were inserted into either the thoracic or mesenteric lymph ducts of dogs. To determine if LPT enhanced the release of leukocytes from the mesenteric lymph nodes (MLN) into lymph, the MLN were fluorescently labeled in situ. Lymph was collected during 4 min pre-LPT, 4 min LPT, and 10 min following cessation of LPT. LPT significantly increased lymph flow and leukocytes in both mesenteric and thoracic duct lymph. LPT had no preferential effect on any specific leukocyte population, since neutrophil, monocyte, CD4+ T cell, CD8+ T cell, IgG+B cell, and IgA+B cell numbers were similarly increased. In addition, LPT significantly increased the mobilization of leukocytes from the MLN into lymph. Lymph flow and leukocyte counts fell following LPT treatment, indicating that the effects of LPT are transient.
LPT mobilizes leukocytes from GALT, and these leukocytes are transported by the lymphatic circulation. This enhanced release of leukocytes from GALT may provide scientific rationale for the clinical use of LPT to improve immune function.
The Multicenter Osteopathic Pneumonia Study in the Elderly (MOPSE) is a registered, double-blinded, randomized, controlled trial designed to assess the efficacy of osteopathic manipulative treatment (OMT) as an adjunctive treatment in elderly patients with pneumonia.
406 subjects aged >/= 50 years hospitalized with pneumonia at 7 community hospitals were randomized using concealed allocation to conventional care only (CCO), light-touch treatment (LT), or OMT groups. All subjects received conventional treatment for pneumonia. OMT and LT groups received group-specific protocols for 15 minutes, twice daily until discharge, cessation of antibiotics, respiratory failure, death, or withdrawal from the study. The primary outcomes were hospital length of stay (LOS), time to clinical stability, and a symptomatic and functional recovery score.
Intention-to-treat (ITT) analysis (n = 387) found no significant differences between groups. Per-protocol (PP) analysis (n = 318) found a significant difference between groups (P = 0.01) in LOS. Multiple comparisons indicated a reduction in median LOS (95% confidence interval) for the OMT group (3.5 [3.2-4.0] days) versus the CCO group (4.5 [3.9-4.9] days), but not versus the LT group (3.9 [3.5-4.8] days). Secondary outcomes of duration of intravenous antibiotics and treatment endpoint were also significantly different between groups (P = 0.05 and 0.006, respectively). Duration of intravenous antibiotics and death or respiratory failure were lower for the OMT group versus the CCO group, but not versus the LT group.
ITT analysis found no differences between groups. PP analysis found significant reductions in LOS, duration of intravenous antibiotics, and respiratory failure or death when OMT was compared to CCO. Given the prevalence of pneumonia, adjunctive OMT merits further study.
The thoracic pump and the abdominal pump are osteopathic manipulative (OM) lymphatic pump techniques frequently used by osteopathic physicians to treat patients with infections (eg, pneumonia, otitis media). Although there is a widely accepted belief among the osteopathic medical profession that increasing lymphatic flow is beneficial, no measurements of lymph flow during osteopathic manipulative treatment have been reported. The authors surgically instrumented five mongrel dogs to record lymphatic flow in the thoracic duct (TDF) and cardiac variables during three intervention protocols. After recovery from surgery, canine subjects were placed in a standing-support sling, and TDF, cardiac output, mean aortic blood pressure, and heart rate were recorded during two randomized 30-second sessions of manipulative intervention using the osteopathic thoracic pump and abdominal pump techniques on two successive days. Lymph flow in the thoracic duct increased from 1.57+/-0.20 mL x min(-1) to a peak TDF of 4.80+/-1.73 mL x min(-1) during abdominal pump, and from 1.20+/-0.41 mL x min(-1) to 3.45+/-1.61 mL x min(-1) during thoracic pump. Lymph flow in the thoracic duct and cardiac variables were also recorded for canine subjects during physical activity (ie, treadmill exercise at 3 miles per hour at 0% incline). During physical activity, TDF increased from 1.47+/-0.33 mL x min(-1) to 5.81+/-1.30 mL x min(-1). Although cardiac variables did not change significantly during manipulative intervention with lymphatic pump techniques, cardiac output and heart rate did increase during physical activity. The authors conclude that physical activity and manipulative intervention using thoracic pump and abdominal pump techniques produced net increases in TDF (P<.05).
Avian influenza is an infection caused by the H5N1 virus. The infection is highly contagious among birds, and only a few known cases of human avian influenza have been documented. However, healthcare experts around the world are concerned that mutation or genetic exchange with more commonly transmitted human influenza viruses could result in a pandemic of avian influenza. Their concern remains in spite of the fact that the first United States vaccine against the H5N1 virus was recently approved. Under these circumstances the fear is that a pandemic of avian influenza could result in the kind of mortality that was seen with the Spanish influenza pandemic of 1918–1919, where the number of deaths was estimated to be as high as 40 million people.
Retrospective data gathered by the American Osteopathic Association shortly after the 1918–1919 influenza pandemic have suggested that osteopathic physicians (DOs), using their distinctive osteopathic manipulative treatment (OMT) methods, observed significantly lower morbidity and mortality among their patients as compared to those treated by allopathic physicians (MDs) with standard medical care available at the time. In light of the limited prevention and treatment options available, it seems logical that a preparedness plan for the treatment of avian influenza should include these OMT procedures, provided by DOs and other healthcare workers capable of being trained to perform these therapeutic interventions. The purpose of this paper is to discuss the characteristics of avian influenza, describe the success of DOs during the 1918–1919 Spanish influenza pandemic, describe the evidence base for the inclusion of OMT as part of the preparedness plan for the treatment of avian influenza, and describe some of the specific OMT procedures that could be utilized as part of the treatment protocol for avian influenza patients.
Previous studies suggest that rhythmic compression of the abdomen (abdominal lymphatic pump techniques, LPT) enhances immunity and resistance to infectious disease, but direct evidence of this has not been documented. In this study, the thoracic duct of eight anesthetized mongrel dogs was catheterized, so the immediate effects of LPT on lymph flow and leukocyte output could be measured.
Lymph flow was measured by timed collection or ultrasonic flowmeter, and lymph was collected over ice under 1) resting (baseline) conditions, and 2) during application of LPT. The baseline leukocyte count was 4.8 +/- 1.7 x 10(6) cells/ml of lymph, and LPT significantly increased leukocytes to 11.8 +/- 3.6 x 10(6) cells/ml. Flow cytometry and differential cell staining revealed that numbers of macrophages, neutrophils, total lymphocytes, T cells and B cells were similarly increased during LPT. Furthermore, LPT significantly enhanced lymph flow from 1.13 +/- 0.44 ml/min to 4.14 +/- 1.29 ml/min. Leukocyte flux, computed from the product of lymph flow and cell count, was increased by LPT from 8.2 +/- 4.1 x 10(6) to 60 +/- 25 x 10(6) total cells/min. Similar trends were observed in macrophages, neutrophils, total lymphocytes, T cells and B cells during LPT.
LPT significantly increased both thoracic duct lymph flow and leukocyte count, so lymph leukocyte flux was markedly enhanced. Increased mobilization of immune cells is likely and important mechanism responsible for the enhanced immunity and recovery from infection of patients treated with LPT.
Importance
Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed.
Objective
To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19.
Design, Setting, and Participants
This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients.
Interventions
Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237).
Main Outcomes and Measures
The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality.
Results
Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, −0.2% [95% CI, −5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]).
Conclusions and Relevance
Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults.
Trial Registration
ClinicalTrials.gov: NCT04332991
This coronavirus is here for the long haul — here’s what scientists predict for the next months and years. This coronavirus is here for the long haul — here’s what scientists predict for the next months and years.
Since Dec. 2019 the new coronavirus (SARS-CoV-2) has infected millions and claimed life of several hundred thousand worldwide. However, so far no approved vaccine or drug therapy is available for treatment of virus infection. Convalescent plasma has been considered a potential modality for COVID-19 infection. One hundred eighty-nine COVID-19 positive patients including 115 patients in plasma therapy group and 74 patients in control group, registered in the hospitals with confirmed COVID-19 infection, entered this multi-center clinical study. Comparison of outcomes including all-cause mortality, total hospitalization days and patients’ need for intubation between the two patient groups shows that total of 98 (98.2%) of patients who received convalescent plasma were discharged from hospital which is substantially higher compared to 56 (78.7%) patients in control group. Length of hospitalization days was significantly lower (9.54 days) in convalescent plasma group compared with that of control group (12.88 days). Only 8 patients (7%) in convalescent plasma group required intubation while that was 20% in control group. This clinical study provides strong evidence to support the efficacy of convalescent plasma therapy in COVID-19 patients and recommends this treatment for management of these patients. Clinical efficacy, immediate availability and potential cost effectiveness could be considered as main advantages of convalescent plasma therapy.
Background
Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious.
Methods
We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.
Results
A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%).
Conclusions
Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACCT-1 ClinicalTrials.gov number, NCT04280705.)
Importance
Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. However, information on cardiac injury in patients affected by COVID-19 is limited.
Objective
To explore the association between cardiac injury and mortality in patients with COVID-19.
Design, Setting, and Participants
This cohort study was conducted from January 20, 2020, to February 10, 2020, in a single center at Renmin Hospital of Wuhan University, Wuhan, China; the final date of follow-up was February 15, 2020. All consecutive inpatients with laboratory-confirmed COVID-19 were included in this study.
Main Outcomes and Measures
Clinical laboratory, radiological, and treatment data were collected and analyzed. Outcomes of patients with and without cardiac injury were compared. The association between cardiac injury and mortality was analyzed.
Results
A total of 416 hospitalized patients with COVID-19 were included in the final analysis; the median age was 64 years (range, 21-95 years), and 211 (50.7%) were female. Common symptoms included fever (334 patients [80.3%]), cough (144 [34.6%]), and shortness of breath (117 [28.1%]). A total of 82 patients (19.7%) had cardiac injury, and compared with patients without cardiac injury, these patients were older (median [range] age, 74 [34-95] vs 60 [21-90] years; P < .001); had more comorbidities (eg, hypertension in 49 of 82 [59.8%] vs 78 of 334 [23.4%]; P < .001); had higher leukocyte counts (median [interquartile range (IQR)], 9400 [6900-13 800] vs 5500 [4200-7400] cells/μL) and levels of C-reactive protein (median [IQR], 10.2 [6.4-17.0] vs 3.7 [1.0-7.3] mg/dL), procalcitonin (median [IQR], 0.27 [0.10-1.22] vs 0.06 [0.03-0.10] ng/mL), creatinine kinase–myocardial band (median [IQR], 3.2 [1.8-6.2] vs 0.9 [0.6-1.3] ng/mL), myohemoglobin (median [IQR], 128 [68-305] vs 39 [27-65] μg/L), high-sensitivity troponin I (median [IQR], 0.19 [0.08-1.12] vs <0.006 [<0.006-0.009] μg/L), N-terminal pro-B-type natriuretic peptide (median [IQR], 1689 [698-3327] vs 139 [51-335] pg/mL), aspartate aminotransferase (median [IQR], 40 [27-60] vs 29 [21-40] U/L), and creatinine (median [IQR], 1.15 [0.72-1.92] vs 0.64 [0.54-0.78] mg/dL); and had a higher proportion of multiple mottling and ground-glass opacity in radiographic findings (53 of 82 patients [64.6%] vs 15 of 334 patients [4.5%]). Greater proportions of patients with cardiac injury required noninvasive mechanical ventilation (38 of 82 [46.3%] vs 13 of 334 [3.9%]; P < .001) or invasive mechanical ventilation (18 of 82 [22.0%] vs 14 of 334 [4.2%]; P < .001) than those without cardiac injury. Complications were more common in patients with cardiac injury than those without cardiac injury and included acute respiratory distress syndrome (48 of 82 [58.5%] vs 49 of 334 [14.7%]; P < .001), acute kidney injury (7 of 82 [8.5%] vs 1 of 334 [0.3%]; P < .001), electrolyte disturbances (13 of 82 [15.9%] vs 17 of 334 [5.1%]; P = .003), hypoproteinemia (11 of 82 [13.4%] vs 16 of 334 [4.8%]; P = .01), and coagulation disorders (6 of 82 [7.3%] vs 6 of 334 [1.8%]; P = .02). Patients with cardiac injury had higher mortality than those without cardiac injury (42 of 82 [51.2%] vs 15 of 334 [4.5%]; P < .001). In a Cox regression model, patients with vs those without cardiac injury were at a higher risk of death, both during the time from symptom onset (hazard ratio, 4.26 [95% CI, 1.92-9.49]) and from admission to end point (hazard ratio, 3.41 [95% CI, 1.62-7.16]).
Conclusions and Relevance
Cardiac injury is a common condition among hospitalized patients with COVID-19 in Wuhan, China, and it is associated with higher risk of in-hospital mortality.
In recent years, evidence has emerged regarding the effectiveness of osteopathic manipulative treatments (OMT). Despite growing evidence in this field, there is need for appropriate research designs that effectively reflect the person-centred system of care promoted in osteopathy and provide data which can inform policy decisions within the healthcare system. The purpose of this systematic review is to identify, appraise and synthesise the evidence from comparative effectiveness and economic evaluation research involving OMT. A database search was conducted using CINAHL, PubMed, PEDro, AMED, SCOPUS and OSTMED.DR, from their inception to May 2015. Two separate searches were undertaken to identify original research articles encompassing the economic evaluation and comparative effectiveness of OMT. Identified comparative effectives studies were evaluated using the Cochrane risk of bias tool and appraised using the Good Reporting of Comparative Effectiveness (GRACE) principles. Identified economic studies were assessed with the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guidelines. Sixteen studies reporting the findings of comparative effectiveness (n = 9) and economic evaluation (n = 7) research were included. The comparative effectiveness studies reported outcomes for varied health conditions and the majority (n = 6) demonstrated a high risk of bias. The economic evaluations included a range of analyses and considerable differences in the quality of reporting were evident. Despite some positive findings, published comparative effectiveness and health economic studies in OMT are of insufficient quality and quantity to inform policy and practice. High quality, well-designed, research that aligns with international best practice is greatly needed to build a pragmatic evidence base for OMT.
Introduction:
Placebo and nocebo represent complex and distinct psychoneurobiological phenomena in which behavioural and neurophysiological modifications occur together with the application of a treatment. Despite a better understanding of this topic in the medical field, little is known about their role in physiotherapy.
Purpose:
The aim of this review is: a) to elucidate the neurobiology behind placebo and nocebo effects, b) to describe the role of the contextual factors as modulators of the clinical outcomes in rehabilitation and c) to provide clinical and research guidelines on their uses.
Implications:
The physiotherapist's features, the patient's features, the patient-physiotherapist relationship, the characteristics of the treatment and the overall healthcare setting are all contextual factors influencing clinical outcomes. Since every physiotherapy treatment determines a specific and a contextual effect, physiotherapists should manage the contextual factors as a boosting element of any manual therapy to improve placebo effects and avoid detrimental nocebo effects.
Background:
Manipulation and mobilisation are commonly used to treat neck pain. This is an update of a Cochrane review first published in 2003, and previously updated in 2010.
Objectives:
To assess the effects of manipulation or mobilisation alone compared wiith those of an inactive control or another active treatment on pain, function, disability, patient satisfaction, quality of life and global perceived effect in adults experiencing neck pain with or without radicular symptoms and cervicogenic headache (CGH) at immediate- to long-term follow-up. When appropriate, to assess the influence of treatment characteristics (i.e. technique, dosage), methodological quality, symptom duration and subtypes of neck disorder on treatment outcomes.
Search methods:
Review authors searched the following computerised databases to November 2014 to identify additional studies: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We also searched ClinicalTrials.gov, checked references, searched citations and contacted study authors to find relevant studies. We updated this search in June 2015, but these results have not yet been incorporated.
Selection criteria:
Randomised controlled trials (RCTs) undertaken to assess whether manipulation or mobilisation improves clinical outcomes for adults with acute/subacute/chronic neck pain.
Data collection and analysis:
Two review authors independently selected studies, abstracted data, assessed risk of bias and applied Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methods (very low, low, moderate, high quality). We calculated pooled risk ratios (RRs) and standardised mean differences (SMDs).
Main results:
We included 51 trials (2920 participants, 18 trials of manipulation/mobilisation versus control; 34 trials of manipulation/mobilisation versus another treatment, 1 trial had two comparisons). Cervical manipulation versus inactive control: For subacute and chronic neck pain, a single manipulation (three trials, no meta-analysis, 154 participants, ranged from very low to low quality) relieved pain at immediate- but not short-term follow-up. Cervical manipulation versus another active treatment: For acute and chronic neck pain, multiple sessions of cervical manipulation (two trials, 446 participants, ranged from moderate to high quality) produced similar changes in pain, function, quality of life (QoL), global perceived effect (GPE) and patient satisfaction when compared with multiple sessions of cervical mobilisation at immediate-, short- and intermediate-term follow-up. For acute and subacute neck pain, multiple sessions of cervical manipulation were more effective than certain medications in improving pain and function at immediate- (one trial, 182 participants, moderate quality) and long-term follow-up (one trial, 181 participants, moderate quality). These findings are consistent for function at intermediate-term follow-up (one trial, 182 participants, moderate quality). For chronic CGH, multiple sessions of cervical manipulation (two trials, 125 participants, low quality) may be more effective than massage in improving pain and function at short/intermediate-term follow-up. Multiple sessions of cervical manipulation (one trial, 65 participants, very low quality) may be favoured over transcutaneous electrical nerve stimulation (TENS) for pain reduction at short-term follow-up. For acute neck pain, multiple sessions of cervical manipulation (one trial, 20 participants, very low quality) may be more effective than thoracic manipulation in improving pain and function at short/intermediate-term follow-up. Thoracic manipulation versus inactive control: Three trials (150 participants) using a single session were assessed at immediate-, short- and intermediate-term follow-up. At short-term follow-up, manipulation improved pain in participants with acute and subacute neck pain (five trials, 346 participants, moderate quality, pooled SMD -1.26, 95% confidence interval (CI) -1.86 to -0.66) and improved function (four trials, 258 participants, moderate quality, pooled SMD -1.40, 95% CI -2.24 to -0.55) in participants with acute and chronic neck pain. A funnel plot of these data suggests publication bias. These findings were consistent at intermediate follow-up for pain/function/quality of life (one trial, 111 participants, low quality). Thoracic manipulation versus another active treatment: No studies provided sufficient data for statistical analyses. A single session of thoracic manipulation (one trial, 100 participants, moderate quality) was comparable with thoracic mobilisation for pain relief at immediate-term follow-up for chronic neck pain. Mobilisation versus inactive control: Mobilisation as a stand-alone intervention (two trials, 57 participants, ranged from very low to low quality) may not reduce pain more than an inactive control. Mobilisation versus another active treatment: For acute and subacute neck pain, anterior-posterior mobilisation (one trial, 95 participants, very low quality) may favour pain reduction over rotatory or transverse mobilisations at immediate-term follow-up. For chronic CGH with temporomandibular joint (TMJ) dysfunction, multiple sessions of TMJ manual therapy (one trial, 38 participants, very low quality) may be more effective than cervical mobilisation in improving pain/function at immediate- and intermediate-term follow-up. For subacute and chronic neck pain, cervical mobilisation alone (four trials, 165 participants, ranged from low to very low quality) may not be different from ultrasound, TENS, acupuncture and massage in improving pain, function, QoL and participant satisfaction at immediate- and intermediate-term follow-up. Additionally, combining laser with manipulation may be superior to using manipulation or laser alone (one trial, 56 participants, very low quality).
Authors' conclusions:
Although support can be found for use of thoracic manipulation versus control for neck pain, function and QoL, results for cervical manipulation and mobilisation versus control are few and diverse. Publication bias cannot be ruled out. Research designed to protect against various biases is needed. Findings suggest that manipulation and mobilisation present similar results for every outcome at immediate/short/intermediate-term follow-up. Multiple cervical manipulation sessions may provide better pain relief and functional improvement than certain medications at immediate/intermediate/long-term follow-up. Since the risk of rare but serious adverse events for manipulation exists, further high-quality research focusing on mobilisation and comparing mobilisation or manipulation versus other treatment options is needed to guide clinicians in their optimal treatment choices.
To assess the effectiveness of OMT on chronic migraineurs using HIT-6 questionnaire, drug consumption, days of migraine, pain intensity and functional disability.
3-Armed randomized controlled trial setting: all patients admitted in the Department of Neurology of Ancona's United Hospitals, Italy, with a diagnosis of migraine and without chronic illness, were considered eligible for the study.
Patients were randomly divided into three groups: (1) OMT+medication therapy, (2) sham+medication therapy and (3) medication therapy only. Patients received 8 treatments in a study period of 6 months.
Changing from baseline HIT-6 score.
105 subjects were included. At the end of the study, ANOVA showed that OMT significantly reduced HIT-6 score (mean change scores OMT-conventional care: -8.74; 95% confidence interval (CI) -12.96 to -4.52; p<0.001 and OMT-sham: -6.62; 95% CI -10.85 to -2.41; p<0.001), drug consumption (OMT-sham: RR=0.22, 95% CI 0.11-0.40; OMT-control: RR=0.20, 95% CI 0.10-0.36), days of migraine (OMT-conventional care: M=-21.06; 95% CI -23.19 to -18.92; p<0.001 and OMT-sham: -17.43; 95% CI -19.57 to -15.29; p<0.001), pain intensity (OMT-sham: RR=0.42, 95% CI 0.24-0.69; OMT-control: RR=0.31, 95% CI 0.19-0.49) and functional disability (p<0.001).
These findings suggest that OMT may be considered a valid procedure for the management of migraineurs. The present trial was registered on www.ClinicalTrials.gov (identifier: NCT01851148).
Copyright © 2015 Elsevier Ltd. All rights reserved.
Background:
Osteopathic practitioners utilize manual therapies called lymphatic pump techniques (LPT) to treat edema and infectious diseases. While previous studies examined the effect of a single LPT treatment on the lymphatic system, the effect of repeated applications of LPT on lymphatic output and immunity has not been investigated. Therefore, the purpose of this study was to measure the effects of repeated LPT on lymphatic flow, lymph leukocyte numbers, and inflammatory mediator concentrations in thoracic duct lymph (TDL).
Methods and results:
The thoracic ducts of five mongrel dogs were cannulated, and lymph samples were collected during pre-LPT, 4 min of LPT, and 2 hours post-LPT. A second LPT (LPT-2) was applied after a 2 hour rest period. TDL flow was measured, and TDL were analyzed for the concentration of leukocytes and inflammatory mediators. Both LPT treatments significantly increased TDL flow, leukocyte count, total leukocyte flux, and the flux of interleukin-8 (IL-8), keratinocyte-derived chemoattractant (KC), nitrite (NO2(-)), and superoxide dismutase (SOD). The concentration of IL-6 increased in lymph over time in all experimental groups; therefore, it was not LPT dependent.
Conclusion:
Clinically, it can be inferred that LPT at a rate of 1 pump per sec for a total of 4 min can be applied every 2 h, thus providing scientific rationale for the use of LPT to repeatedly enhance the lymphatic and immune system.
IntroductionThe treatment of ileus has been estimated to cost the United States $750 million to $1 billion in a year. In a study by Bennett-Guerrero et al. on 1056 patients who had major non-cardiac surgery, the most frequent problem that delayed discharge was persistent postoperative GI tract dysfunction in 42% of patients. Despite its huge cost to our society, there have been very few advances in our approach to treatment of ileus. Upon reviewing osteopathic literature for treatment of postoperative ileus it seemed that OMT may be of benefit to patients being treated for ileus in the hospital setting.
Patients with pneumonia often remain hospitalized after becoming clinically stable, without demonstrated benefits on outcome. The purposes of this study were to assess the relation between length of hospital stay and daily medical care costs and to estimate the potential cost savings associated with a reduced length of stay for patients with pneumonia.
As part of a prospective study of adults hospitalized with community-acquired pneumonia at a community hospital and two university teaching hospitals, daily medical care costs were estimated by multiplying individual charges by department-specific cost-to-charge ratios obtained from each hospital's Medicare cost reports.
The median total cost of hospitalization for all 982 inpatients was $5, 942, with a median daily cost of $836, including $491 (59%) for room and $345 (41%) for non-room costs. Average daily non-room costs were 282% greater on the first hospital day, 59% greater on the second day, and 19% greater on the third day than the average daily cost throughout the hospitalization (all P <0.05), and were 14% to 72% lower on the last 3 days of hospitalization. Average daily room costs remained relatively constant throughout the hospital stay, with the exception of the day of discharge. A projected mean savings of $680 was associated with a 1-day reduction in length of stay.
Despite institutional differences in total costs, patterns of daily resource use throughout hospitalization were similar at all institutions. A 1-day reduction in length of stay might yield substantial cost-savings.
Mesenteric lymph may provide the mechanistic link between gut ischemia and acute lung injury after hemorrhagic shock (HS). Studies have focused on the toxic mediators that develop in the post-shock mesenteric lymph (PSML). However, a complementary possibility is that there is loss of protective mediators found in pre-shock normal mesenteric lymph (NML) after HS. We hypothesize that NML protects against inflammatory insults to the pulmonary endothelium and that this effect is lost in PSML.
Primary human pulmonary endothelial cells (HMVECs) were incubated with NML or PSML collected from rats subjected to HS and resuscitation and then stimulated with 20 ng/mL LPS. ICAM-1 surface expression was measured by flow cytometry. In subsequent experiments, lipoproteins were extracted from NML before incubation and LPS-induced ICAM-1 expression determined.
Mean fluorescent intensity (MFI) of LPS-induced ICAM-1 in NML and PSML treated HMVECs were 10.1 +/- 2.3 versus 27.7 +/- 0.83, respectively (P < 0.05). This represented at 71% decrease in ICAM-1 expression by NML compared to ICAM-1 expression in LPS-induced controls (MFI: 34.6 +/- 6.9). Lipoprotein extraction from NML abolished this protective effect (MFI: 31.2 +/- 5.3 versus Control + LPS: 33.5 +/- 3.6, P > 0.05). Baseline ICAM-1 levels were not significantly different among control, NML, and PSML groups.
Lipoproteins in NML contain anti-inflammatory properties that decrease ICAM-1 expression induced by LPS in pulmonary endothelium. Decreased protective lipoproteins after HS and resuscitation may contribute to the toxicity associated with PSML from the ischemic gut.
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