The aim of this study was to determine the efficacy of early tocilizumab treatment for hospitalized patients with COVID-19 disease. Open-label randomized phase II clinical trial investigating ...tocilizumab in patients with proven COVID-19 admitted to the general ward and in need of supplemental oxygen. The primary endpoint of the study was 30-day mortality with a prespecified 2-sided significance level of alpha = 0.10. A post-hoc analysis was performed for a combined endpoint of mechanical ventilation or death at 30 days. Secondary objectives included comparing the duration of hospital stay, ICU admittance and duration of ICU stay and the duration of mechanical ventilation. A total of 354 patients (67% men; median age 66 years) were enrolled of whom 88% received dexamethasone. Thirty-day mortality was 19% (95% CI 14%-26%) in the standard arm versus 12% (95% CI: 8%-18%) in the tocilizumab arm, hazard ratio (HR) = 0.62 (90% CI 0.39-0.98; p = 0.086). 17% of patients were admitted to the ICU in each arm (p = 0.89). The median stay in the ICU was 14 days (IQR 9-28) in the standard arm versus 9 days (IQR 5-14) in the tocilizumab arm (p = 0.014). Mechanical ventilation or death at thirty days was 31% (95% CI 24%-38%) in the standard arm versus 21% (95% CI 16%-28%) in the tocilizumab arm, HR = 0.65 (95% CI 0.42-0.98; p = 0.042). This randomized phase II study supports efficacy for tocilizumab when given early in the disease course in hospitalized patients who need oxygen support, especially when concomitantly treated with dexamethasone.
•The Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) identifies 35% more patients at risk for malnutrition than the Short Nutritional Assessment Questionnaire.•According to the ...PG-SGA SF, high-risk patients have a 36% longer hospital length of stay than low-risk patients.•The PG-SGA SF significantly predicts length of stay in a mixed hospital population.
Malnutrition screening instruments used in hospitals mainly include criteria to identify characteristics of malnutrition. However, to tackle malnutrition in an early stage, identifying risk factors for malnutrition in addition to characteristics may be valuable.
The aim of this study was to determine the predictive validity of the Patient-Generated Subjective Global Assessment (PG-SGA SF), which addresses malnutrition characteristics and risk factors, and the Short Nutritional Assessment Questionnaire (SNAQ), which addresses mainly malnutrition characteristics, for length of stay (LOS) in a mixed hospital population.
Patients (N = 443) were screened with the PG-SGA SF and SNAQ in the first 72 h after admission to the lung, cardiology, or surgery ward. The McNemar–Bowker test was used to investigate the symmetry between the SNAQ and PG-SGA SF categorization for low, medium, and high risk. The predictive value of the PG-SGA SF and SNAQ was assessed by γ-regression before and after adjusting for several confounders.
Of the 443 patients included, 23% and 58% were categorized as being at medium/high risk for malnutrition according to the SNAQ and PG-SGA SF, respectively. The regression analysis indicated that LOS of high-risk patients according to PG-SGA SF was 36% longer than that of low-risk patients (P = 0.001). LOS in patients at high risk according to the SNAQ did not significantly differ from that of SNAQ low-risk patients.
The PG-SGA SF, as a proactive malnutrition screening instrument, predicts LOS in various hospital wards, whereas the SNAQ, as a reactive instrument, does not. Therefore, we recommend the PG-SGA SF for proactive screening for malnutrition risk.
There is a growing interest to use health status or disease control questionnaires in routine clinical practice. However, the validity of most questionnaires is established using techniques developed ...for group level validation. This study examines a new method, using patient interviews, to validate a short health status questionnaire, the Clinical COPD Questionnaire (CCQ), at the individual patient level.
Patients with COPD who visited an outpatient clinic completed the CCQ before the consultation, and the specialist physician completed it after the consultation. After the consultation all patients had a semi-structured in-depth interview. The patients' CCQ scores were compared with those of the treating clinician, and with mean scores from 5 clinicians from a pool of 20 who scored the CCQ after reading the transcript of the in-depth interviews only. Agreement was assessed using Lin's concordance correlation coefficient (CCC), and Blant and Altman plots. Interviews with patients with low agreement were reviewed for possible explanations.
A total of 44 COPD patients (32 male, mean age 66 years, FEV1 45% of predicted) participated. Agreement between the patients' CCQ scores and those of the treating clinicians (CCC = 0.87) and the mean score of the reviewing clinicians (CCC = 0.86) was very high. No systematic error was detected. No explanation for individuals with low agreement was found.
The validity of the CCQ on the individual patient level, as assessed by these methods, is good. Individual health status assessment with the CCQ is therefore sufficiently accurate to be used in routine clinical practice.
The employment of physician assistants (PAs) is a strategy to improve access to care. Since the new millennium, a handful of countries have turned to PAs as a means to bridge the growing gap between ...the supply and demand of medical services. However, little is known about this new workforce entity from the patient's perspective. The objective of this study was to assess the willingness of Dutch patients to be treated by a PA or a medical doctor (MD) under various time constraints and semi-urgent medical scenarios.
A total of 450 Dutch adults were recruited to act as surrogate patients. A convenience sample was drawn from patients in a medical office waiting room in a general hospital awaiting their appointments. Each participant was screened to be naive as to what a PA and a nurse practitioner are and then read a definition of a PA and an MD. One of three medical scenarios was assigned to the participants in a patterned 1-2-3 strategy. Patients were required to make a trade-off decision of being seen after 1 hour by a PA or after 4 hours by a doctor. This forced-choice method continued with the same patient two more times with 30 minutes and 4 hours and another one of 2 hours versus 4 hours for the PA and MD, respectively.
Surrogate patients chose the PA over the MD 96 % to 98 % of the time (depending on the scenario). No differences emerged when analysed by gender, age, or parenthood status.
Willingness to be seen by a PA was tested a priori to determine whether surrogate Dutch patients would welcome this new health-care provider. The findings suggest that employing PAs, at least in concept, may be an acceptable strategy for improving access to care with this population.
In this study, the effects of a 12-week hospital-based outpatient pulmonary rehabilitation program (HRP) are compared with those of a 12-week home-care rehabilitation program (HCRP) in COPD patients. ...A control group received no rehabilitation therapy.
After randomization and stratification, effects on lung function, exercise performance (4-min walking test and cycle ergometer test), dyspnea, and leg effort during exercise, and well-being were assessed in 45 COPD patients with moderate to severe airflow limitation (mean SD FEV1 percent predicted, 42.8 8.4).
After HRP and HCRP, at 3 to 6 months after the start of the study, equal improvements were detected in exercise capacity and in Borg dyspnea and leg effort scores at similar work levels during the cycle test. However, whereas after HRP at longer term values tended to return to baseline outcome, after HCRP a further ongoing significant improvement in exercise capacity was observed, while Borg dyspnea scores remained significantly improved over 18 months. Improvements in cycle workload and dyspnea score were significantly better maintained after HCRP as compared with HRP. Lung function, arterial oxygen saturation, and heart frequency during exercise did not change. A significant improvement in well-being was maintained over 18 months in both rehabilitation groups.
Beneficial effects are achieved both after a HRP and a HCRP in COPD patients with moderate to severe airflow limitation. Yet we recommend to initiate HCRPs as improvements are maintained longer and are even further strengthened in this setting.
In this study, the effects of a 12-week hospital-based outpatient pulmonary rehabilitation program (HRP) are compared with those of a 12-week home-care rehabilitation program (HCRP) in COPD patients. ...A control group received no rehabilitation therapy.
After randomization and stratification, effects on lung function, exercise performance (4-min walking test and cycle ergometer test), dyspnea, and leg effort during exercise, and well-being were assessed in 45 COPD patients with moderate to severe airflow limitation (mean SD FEV1 percent predicted, 42.8 8.4).
After HRP and HCRP, at 3 to 6 months after the start of the study, equal improvements were detected in exercise capacity and in Borg dyspnea and leg effort scores at similar work levels during the cycle test. However, whereas after HRP at longer term values tended to return to baseline outcome, after HCRP a further ongoing significant improvement in exercise capacity was observed, while Borg dyspnea scores remained significantly improved over 18 months. Improvements in cycle workload and dyspnea score were significantly better maintained after HCRP as compared with HRP. Lung function, arterial oxygen saturation, and heart frequency during exercise did not change. A significant improvement in well-being was maintained over 18 months in both rehabilitation groups.
Beneficial effects are achieved both after a HRP and a HCRP in COPD patients with moderate to severe airflow limitation. Yet we recommend to initiate HCRPs as improvements are maintained longer and are even further strengthened in this setting.
•Prospective placebo-controlled study on influenza vaccination in myasthenia gravis.•The immune response is effective irrespectively of immunosuppressive medication.•No immunological nor clinical ...exacerbations were observed.
To investigate the efficacy and safety of an influenza vaccination in patients with myasthenia gravis with acetylcholine receptor antibodies (AChR MG).
An influenza vaccination or placebo was administered to 47 AChR MG patients. Before and 4 weeks after administration blood samples and clinical outcome scores were obtained. Antibodies to the vaccine strains A/California/7/2009 (H1N1)pdm09, A/Hong Kong/4801/14 (H3N2) and B/Brisbane/060/08 were measured using the hemagglutination-inhibition (HI) assay and disease-specific AChR antibody titers were measured with a radio-immunoprecipitation assay. Forty-seven healthy controls (HC) were vaccinated with the same influenza vaccine to compare antibody titers.
A post-vaccination, seroprotective titer (HI ≥ 1:40) was achieved in 89.4% of MG patients vs. 93.6% in healthy controls for the H3N2 strain, 95.7% vs 97.9% for the H1N1 strain and 46.8 vs 51% for the B-strain. A seroprotective titer for all three strains of the seasonal influenza vaccine was reached in 40.4% (19/47) of the MG group and in 51% (24/47) of the HC group. Immunosuppressive medication did not significantly influence post geomean titers (GMT). The titers of disease-specific AChR antibodies were unchanged 4 weeks after vaccination. The clinical outcome scores showed no exacerbation of MG symptoms.
The antibody response to an influenza vaccination in patients with AChR MG was not different from that in healthy subjects, even in AChR MG patients using immunosuppressive medication. Influenza vaccination does not induce an immunological or clinical exacerbation of AChR MG.
The influenza trial is listed on clinicaltrialsregister.eu under 2016-003138-26.
Muscle-specific kinase (MuSK) myasthenia gravis (MG) is a neuromuscular autoimmune disease belonging to a growing group of IgG4 autoimmune diseases (IgG4-AIDs), in which the majority of pathogenic ...autoantibodies are of the IgG4 subclass. The more prevalent form of MG with acetylcholine receptor (AChR) antibodies is caused by IgG1–3 autoantibodies. A dominant role for IgG4 in autoimmune disease is intriguing due to its anti-inflammatory characteristics. It is unclear why MuSK autoantibodies are predominantly IgG4. We hypothesized that MuSK MG patients have a general predisposition to generate IgG4 responses, therefore resulting in high levels of circulating IgG4. To investigate this, we quantified serum Ig isotypes and IgG subclasses using nephelometric and turbidimetric assays in MuSK MG and AChR MG patients not under influence of immunosuppressive treatment. Absolute serum IgG1 was increased in both MuSK and AChR MG patients compared to healthy donors. In addition, only MuSK MG patients on average had significantly increased and enriched serum IgG4. Although more MuSK MG patients had elevated serum IgG4, for most the IgG4 serum levels fell within the normal range. Correlation analyses suggest MuSK-specific antibodies do not solely explain the variation in IgG4 levels. In conclusion, although serum IgG4 levels are slightly increased, the levels do not support ubiquitous IgG4 responses in MuSK MG patients as the underlying cause of dominant IgG4 MuSK antibodies.
•Enrichment of serum IgG4 in MuSK myasthenia gravis•MG patients have a mild increase in multiple immunoglobulins•Increased IgG4 serum levels appear to be a general phenomenon in IgG4 autoimmune disease
Pulmonary rehabilitation programs often show beneficial effects in patients with chronic obstructive pulmonary disease (COPD). These programs are usually hospital-based. This study assesses the ...feasibility and application of a 12-week Home-Care Rehabilitation Program (HCRP), carried out by general practitioners, physiotherapists, and home-care nurses.
Effects of the HCRP are assessed in 15 COPD patients with moderate to severe airflow limitation (inspiratory vital capacity IVC: mean, 75.4 SD, 13.7 percent predicted, mean FEV1: 45.5 6.9 percent predicted) and are compared with a stratified and randomized control group (n = 15).
All participating disciplines judged the program to be useful and feasible. Patient compliance with the rehabilitation exercises was high. No major problems concerning the rehabilitation program were reported. After the HCRP, 4-minute walking distance improved significantly from 274 m 61 to 301 m 72 and maximal work load (W max), as measured during an incremental cycle test, increased from 75.3 W 24 to 85.3 W 28. At equal work levels (W submax) during the cycle test both Borg dyspnea and leg effort scores decreased significantly after the HCRP (6.7 1.3 versus 4.9 1.7 and 4.2 2.0 versus 1.7 2.5, respectively). Changes in walking distance, dyspnea, and leg effort scores at W submax were significantly different between the two groups. IVC and FEV1 did not change significantly. In the control group, no significant changes in any parameter were observed.
It was possible to design and perform successfully a home-care rehabilitation program, providing both objective and subjective improvements in a group of patients with COPD. A home-care rehabilitation program appears to be a valuable component in the management of COPD patients with a moderate to severe airflow limitation.
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