Pieter Leffers

Strength training in patients with myotonic dystrophy and hereditary motor and sensory neuropathy: A randomized clinical trial

A randomized clinical trial on the effects of strength training was performed in myotonic dystrophy (MyD) patients and patients with hereditary motor and sensory neuropathy (HMSN). Training and most measurement tools involved the proximal lower extremity muscles. The participants trained 3 times a week for 24 weeks with weights adapted to their force. Strength was evaluated by isokinetically measured knee torque. Fatiguability was assessed by the time an isometric contraction could be sustained. Functional performance was measured by timed motor performance and by questionnaires on functional performance. Serum myoglobin (Mb) levels were determined to detect changes in muscle fiber membrane permeability. The MyD group included 33 participants, and the HMSN group included 29 participants. Within each diagnostic group, patients were individually matched and subsequently randomized for treatment allocation. In the MyD patients, none of the measurement techniques showed any training effect. Neither were there signs of deterioration caused by the training. In the HMSN group, knee torques increased. Timed motor performance did not change, although the questionnaires showed an improvement on items related to upper-leg function. Mb levels did not change significantly as a result of the training. In conclusion, the MyD group showed neither positive nor negative effects of the training protocol, whereas the training produced a moderate increase in strength and leg-related functional performance in the HMSN group.

Shoulder disability questionnaire design and responsiveness of a functional status measure

The Shoulder Disability Questionnaire (SDQ) is a measure covering 16 items designed to evaluate functional status limitation in patients with shoulder disorders. The responsiveness of the SDQ was evaluated for 180 patients with soft tissue shoulder disorders, without underlying systemic disorders. These patients participated in a randomized placebo-controlled trial, in which ultrasound and electrotherapy appeared to be ineffective as adjuvants to standardized exercise therapy. At baseline and at 6-week follow-up, patients completed the SDQ and rated severity of shoulder pain and their chief complaint, while a research physiotherapist rated severity of symptoms and restriction of mobility. At the 6-week follow-up, patients also rated overall change since baseline. According to the calibrated responsiveness ratio (CRR) and the area under the receiver-operator characteristic curve (AUC) the SDQ discriminates accurately between self-rated clinically stable and improved subjects. The presented results suggest that the SDQ is as responsive as the compared outcome measures, and therefore is ready for use in clinical trials.

No effect of bipolar interferential electrotherapy and pulsed ultrasound for soft tissue shoulder disorders: a randomised controlled trial

OBJECTIVE To assess the efficacy of bipolar interferential electrotherapy (ET) and pulsed ultrasound (US) as adjuvants to exercise therapy for soft tissue shoulder disorders (SD). METHODS Randomised placebo controlled trial with a two by two factorial design plus an additional control group in 17 primary care physiotherapy practices in the south of the Netherlands. Patients with shoulder pain and/or restricted shoulder mobility, because of a soft tissue impairment without underlying specific or generalised condition, were enrolled if they had not recovered after six sessions of exercise therapy in two weeks. They were randomised to receive (1) active ET plus active US; (2) active ET plus dummy US; (3) dummy ET plus active US; (4) dummy ET plus dummy US; or (5) no adjuvants. Additionally, they received a maximum of 12 sessions of exercise therapy in six weeks. Measurements at baseline, 6 weeks and 3, 6, 9, and 12 months later were blinded for treatment. Outcome measures: recovery, functional status, chief complaint, pain, clinical status, and range of motion. RESULTS After written informed consent 180 patients were randomised: both the active treatments were given to 73 patients, both the dummy treatments to 72 patients, and 35 patients received no adjuvants. Prognosis of groups appeared similar at baseline. Blinding was successfully maintained. At six weeks seven patients (20%) without adjuvants reported very large improvement (including complete recovery), 17 (23%) and 16 (22%) with active and dummy ET, and 19 (26%) and 14 (19%) with active and dummy US. These proportions increased to about 40% at three months, but remained virtually stable thereafter. Up to 12 months follow up the 95% CI for differences between groups for all outcomes include zero. CONCLUSION Neither ET nor US prove to be effective as adjuvants to exercise therapy for soft tissue SD.

Monitoring Response to Antiangiogenic Therapy in Non–Small Cell Lung Cancer Using Imaging Markers Derived from PET and Dynamic Contrast-Enhanced MRI

With antiangiogenic agents, tumor shrinkage may be absent, despite survival benefit. The present study assessed the predictive value of molecular imaging for the identification of survival benefit during antiangiogenic treatment with bevacizumab and erlotinib in patients with advanced non–small cell lung cancer. Methods: Patients were evaluated using an imaging protocol including CT, 18F-FDG PET, H215O PET, and dynamic contrast-enhanced MRI to derive measurements on tumor size, glucose metabolism, perfusion, and microvascular permeability. The percentage change in imaging parameters after 3 wk of treatment as compared with baseline was calculated and correlated with progression-free survival (PFS). Results: Forty-four patients were included, and 40 underwent CT and 18F-FDG PET at both time points. Complete datasets, containing all imaging modalities, were available for 14 patients. Bevacizumab and erlotinib treatment resulted in decreased metabolism, perfusion, and tumor size. A decrease in standardized uptake value or tumor perfusion of more than 20% at week 3 was associated with longer PFS (9.7 vs. 2.8 mo, P = 0.01, and 12.5 vs. 2.9 mo, P = 0.009, respectively). Whole-tumor Ktrans (the endothelial transfer constant) was not associated with PFS, but patients with an increase of more than 15% in the SD of tumor Ktrans values—that is, an increase in regions with low or high Ktrans values—after 3 wk had shorter PFS (2.3 vs. 7.0 mo, P = 0.008). A partial response, according to the response evaluation criteria in solid tumors (RECIST), at week 3 was also associated with prolonged PFS (4.6 vs. 2.9 mo, P = 0.017). However, 40% of patients with a partial response as their best RECIST response still had stable disease at week 3. In these cases tumor perfusion was already decreased and Ktrans heterogeneity showed no increase, indicating that the latter parameters seem to be more discriminative than RECIST at the 3-wk time point. Conclusion: PET and dynamic contrast-enhanced MRI were able to identify patients who benefit from bevacizumab and erlotinib treatment. Molecular imaging seems to allow earlier response evaluation than CT.

Botulinum toxin A and upper limb functional skills in hemiparetic cerebral palsy: a randomized trial in children receiving intensive therapy

The objective of this study was to determine whether the use of intramuscular botulinum toxin A (BTX‐A) increases upper limb function and skills in the context of a specific therapy programme in children with hemiparetic cerebral palsy. Twenty children (nine females, 11 males) aged 4 to 16 years who were thought likely to benefit from BTX‐A treatment were included. After matched pairs were made, on the basis of Zancolli grade and age, randomization took place. All patients were given structured rehabilitation (physiotherapy and occupational therapy three times a week for 6 months), and half of the patients received intramuscular BTX‐A. No placebo injections were given in the control group. Participants were assessed at baseline, at 2 and 6 weeks, and at 3, 6, and 9 months after injection. The Ash worth scale, active range of motion of arm joints, the Melbourne assessment of upper limb function, the Pediatric Evaluation of Disability Inventory, and the nine‐hole peg test were used for outcome measurement. Observers were blinded for treatment allocation only for scoring the Melbourne test. The children in the treatment group showed a clinically relevant increase in active dorsal flexion, and tone reduction of the wrist. For the functional outcome measures, no statistically significant differences between the groups could be demonstrated. Intramuscular BTX‐A added to an intensive therapy programme reduces impairment for at least 9 months; the effect on activity level is still uncertain.

Progressive resistance training in neuromuscular patients. Effects on force and surface EMG

In a randomized clinical trial the efficacy of strength training was studied in patients with myotonic dystrophy (n = 33) and in patients with Charcot-Marie-Tooth disease (n = 29). Measurements were performed at the start and after 8, 16 and 24 weeks of progressive resistance training. Surface electromyography (SEMG) of proximal leg muscles was recorded during isometric knee extension at maximum voluntary contraction (MVC) and at 20, 40, 60 and 80% of MVC. Changes in MVC, maximum electrical activity and torque-EMG ratios (TER) were calculated. Fatigue was studied by determining the changes in endurance and in the decline of the median frequency (Fmed) of the SEMG during a sustained contraction at 80% MVC. These parameters showed no significant changes after the training in either of the diagnostic groups. Only the Charcot-Marie-Tooth training group showed a gradual significant increase in mean MVC over the whole training period (21%). After 24 weeks, the increase in mean RMS was similar (25%), but this was mainly due to a sharp rise during the first 8 weeks of training (20%). The findings indicate that the initial strength increase was due to a neural factor, while the subsequent increase was mainly due to muscle hypertrophy.

Surface EMG of proximal leg muscles in neuromuscular patients and in healthy controls. Relations to force and fatigue

In an effort to find parameters to evaluate patients with neuromuscular disorders, surface electromyography (SEMG) of proximal leg muscles was performed in 33 patients with myotonic dystrophy (MyD), 29 patients with Charcot-Marie-Tooth (CMT) disease and 20 healthy controls. The root mean square (RMS) of the SEMG amplitude (microV) was calculated at different torque levels. Endurance (seconds) and median frequency (Fmed) of the SEMG power spectrum, used as parameters of fatigue, were determined at 80% of MVC. Maximum voluntary contraction (MVC) was found to be decreased in patients; the ratio between RMS values of antagonists and agonists was increased and torque-EMG ratios (Nm/microV) were decreased. These differences with respect to controls were more pronounced in MyD than in CMT. The initial Fmed value was lowest in CMT. The greatest decrease in Fmed was found in MyD. SEMG data in relation to force have not been determined before in groups of MyD or CMT patients. In both disorders, parameters differed from controls, which means that adding SEMG to strength measurements could be useful in studying the progress of the disorder and the effects of interventions.

Casting methods and plantar pressure: effects of custom-made foot orthoses on dynamic plantar pressure distribution.

Foot orthoses are widely used to treat various foot problems. A literature search revealed no publications on differences in plantar pressure distribution resulting from casting methods for foot orthoses. Four casting methods were used for construction of orthoses. Two foam box techniques were used: accommodative full weightbearing method (A) and functional semiweightbearing method (B). Also, two suspension plaster casting techniques were used: accommodative casting (C) and functional subtalar joint neutral position (Root) method (D). Their effects on contact area, plantar pressure, and walking convenience were evaluated. All orthoses increased the total contact area (mean, 17.4%) compared with shoes without orthoses. Differences in contact areas between orthoses for total plantar surface were statistically significant. Peak pressures for the total plantar surface were lower with orthoses than without orthoses (mean, 22.8%). Among orthoses, only the difference between orthoses A and B was statistically significant. Differences between orthoses for the forefoot were small and not statistically significant. The gait lines of the shoe without an insole and of the accommodative orthoses are more medially located than those of functional orthoses. Walking convenience in the shoe was better rated than that with orthoses. There were no differences in perception of walking convenience between orthoses A, B, and C. Orthosis D had the lowest convenience rating. The four casting methods resulted in differences between orthoses with respect to contact areas and walking convenience but only slight differences in peak pressures.

The impact of delirium on the prediction of in-hospital mortality in intensive care patients

IntroductionPredictive models, such as acute physiology and chronic health evaluation II (APACHE-II), are widely used in intensive care units (ICUs) to estimate mortality. Although the presence of delirium is associated with a higher mortality in ICU patients, delirium is not part of the APACHE-II model. The aim of the current study was to evaluate whether delirium, present within 24 hours after ICU admission, improves the predictive value of the APACHE-II score.MethodsIn a prospective cohort study 2116 adult patients admitted between February 2008 and February 2009 were screened for delirium with the confusion assessment method-ICU (CAM-ICU). Exclusion criteria were sustained coma and unable to understand Dutch. Logistic regression analysis was used to estimate the predicted probabilities in the model with and without delirium. Calibration plots and the Hosmer-Lemeshow test (HL-test) were used to assess calibration. The discriminatory power of the models was analyzed by the area under the receiver operating characteristics curve (AUC) and AUCs were compared using the Z-test.Results1740 patients met the inclusion criteria, of which 332 (19%) were delirious at the time of ICU admission or within 24 hours after admission. Delirium was associated with in-hospital mortality in unadjusted models, odds ratio (OR): 3.22 (95% confidence interval [CI]: 2.23 - 4.66). The OR between the APACHE-II and in-hospital mortality was 1.15 (95% CI 1.12 - 1.19) per point. The predictive accuracy of the APACHE-II did not improve after adding delirium, both in the total group as well as in the subgroup without cardiac surgery patients. The AUC of the APACHE model without delirium was 0.77 (0.73 - 0.81) and 0.78 (0.74 - 0.82) when delirium was added to the model. The z-value was 0.92 indicating no improvement in discriminative power, and the HL-test and calibration plots indicated no improvement in calibration.ConclusionsAlthough delirium is a significant predictor of mortality in ICU patients, adding delirium as an additional variable to the APACHE-II model does not result in an improvement in its predictive estimates.

Does alcohol protect against the formation of gallstones ? a demonstration of protopathic bias

Previous studies have found an inverse relation between alcohol use and clinical gallstone disease, suggestive of a protective effect of alcohol use. However, such an inverse relation may (at least partly) be explained by a reduction of alcohol use because of symptoms related to clinical gallstone disease (protopathic bias). We empirically evaluated the consequences of different designs for the avoidance of such bias in a series of case-control studies. A first study deliberately used a design that is commonly seen in the literature. Cases of clinical gallstone disease, referred to hospital because of symptoms, were contrasted with general population controls. The results suggested an inverse relation between alcohol use and gallstones. Next, three alternative case-control studies were performed using designs that safeguard against protopathic bias. In none of these studies was an association between alcohol use and gallstones found. This demonstrates the probable existence of protopathic bias in case-control studies on alcohol use and gallstones. It is argued that earlier non-experimental studies on this topic were susceptible to such bias. This has most likely led to an overestimation of the protective effect.