The influence of knee rigidity on balance corrections: a comparison with responses of cerebellar ataxia patients

Knee rigidity due to aging or disease is associated with falls. A causal relationship between instability and knee rigidity has not been established. Here, we examined whether insufficient knee movement due to knee rigidity could underlie poor balance control in patients. We addressed this by examining the effect of artificially "locking” the knees on balance control in 18 healthy subjects, tested with and without individually fitted knee casts on both legs. Subjects were exposed to sudden rotations of a support surface in six different directions. The primary outcome measure was body centre of mass (COM) movement, and secondary outcome measures included biomechanical responses of the legs, pelvis and trunk. Knee casts caused increased backward COM movement for backward perturbations and decreased vertical COM movement for forward perturbations, and caused little change in lateral COM movement. At the ankles, dorsiflexion was reduced for backward perturbations. With knee casts, there was less uphill hip flexion and more downhill hip flexion. A major difference with knee casts was a reversed pelvis pitch movement and an increased forward trunk motion. These alterations in pitch movement strategies and COM displacements were similar to those we have observed previously in patients with knee rigidity, specifically those with spinocerebellar ataxia (SCA). Pelvis roll and uphill arm abduction were also increased with the casts. This roll movement strategy and minor changes in lateral COM movement were not similar to observations in patients. We conclude that artificial knee rigidity increases instability, as reflected by greater posterior COM displacement following support surface tilts. Healthy controls with knee casts used a pitch movement strategy similar to that of SCA patients to offset their lack of knee movement in regaining balance following multidirectional perturbations. This similarity suggests that reduced knee movements due to knee rigidity may contribute to sagittal plane postural instability in SCA patients and possibly in other patient groups. However in the roll plane, healthy controls rapidly compensate by adjusting arm movements and hip flexion to offset the effects of knee rigidit

Improving Community Healthcare for Patients with Parkinson's Disease: The Dutch Model

Because of the complex nature of Parkinson's disease, a wide variety of health professionals are involved in care. Stepwise, we have addressed the challenges in the provision of multidisciplinary care for this patient group. As a starting point, we have gained detailed insight into the current delivery of allied healthcare, as well as the barriers and facilitators for optimal care. To overcome the identified barriers, a tertiary referral centre was founded; evidence-based guidelines were developed and cost-effectively implemented within regional community networks of specifically trained allied health professionals (the ParkinsonNet concept). We increasingly use ICT to bind these professional networks together and also to empower and engage patients in making decisions about their health. This comprehensive approach is likely to be feasible for other countries as well, so we currently collaborate in a European collaboration to improve community care for persons with Parkinson's disease

Systematic review and meta-analysis of the value of initial biomarkers in predicting adverse outcome in febrile neutropenic episodes in children and young people with cancer

Background: Febrile neutropenia is a frequently occurring and occasionally life-threatening complication of treatment for childhood cancer. Many biomarkers have been proposed as predictors of adverse events. We aimed to undertake a systematic review and meta-analysis to summarize evidence on the discriminatory ability of initial serum biomarkers of febrile neutropenic episodes in children and young people. Methods: This review was conducted in accordance with the Center for Reviews and Dissemination Methods, using three random effects models to undertake meta-analysis. It was registered with the HTA Registry of systematic reviews, CRD32009100485. Results: We found that 25 studies exploring 14 different biomarkers were assessed in 3,585 episodes of febrile neutropenia. C-reactive protein (CRP), pro-calcitonin (PCT), and interleukin-6 (IL6) were subject to quantitative meta-analysis, and revealed huge inconsistencies and heterogeneity in the studies included in this review. Only CRP has been evaluated in assessing its value over the predictive value of simple clinical decision rules. Conclusions: The limited data available describing the predictive value of biomarkers in the setting of pediatric febrile neutropenia mean firm conclusions cannot yet be reached, although the use of IL6, IL8 and procalcitonin warrant further study

Predicting infectious complications in neutropenic children and young people with cancer (IPD protocol)

<p>Abstract</p> <p>Background</p> <p>A common and potentially life-threatening complication of the treatment of childhood cancer is infection, which frequently presents as fever with neutropenia. The standard management of such episodes is the extensive use of intravenous antibiotics, and though it produces excellent survival rates of over 95%, it greatly inconveniences the three-fourths of patients who do not require such aggressive treatment. There have been a number of studies which have aimed to develop risk prediction models to stratify treatment. Individual participant data (IPD) meta-analysis in therapeutic studies has been developed to improve the precision and reliability of answers to questions of treatment effect and recently have been suggested to be used to answer questions regarding prognosis and diagnosis to gain greater power from the frequently small individual studies.</p> <p>Design</p> <p>In the IPD protocol, we will collect and synthesise IPD from multiple studies and examine the outcomes of episodes of febrile neutropenia as a consequence of their treatment for malignant disease. We will develop and evaluate a risk stratification model using hierarchical regression models to stratify patients by their risk of experiencing adverse outcomes during an episode. We will also explore specific practical and methodological issues regarding adaptation of established techniques of IPD meta-analysis of interventions for use in synthesising evidence derived from IPD from multiple studies for use in predictive modelling contexts.</p> <p>Discussion</p> <p>Our aim in using this model is to define a group of individuals at low risk for febrile neutropenia who might be treated with reduced intensity or duration of antibiotic therapy and so reduce the inconvenience and cost of these episodes, as well as to define a group of patients at very high risk of complications who could be subject to more intensive therapies. The project will also help develop methods of IPD predictive modelling for use in future studies of risk prediction.</p

Differences in coding provided by proprioceptive and vestibular sensory signals may contribute to lateral instability in vestibular loss subjects

One of the signatures of balance deficits observed in vestibular loss subjects is the greater instability in the roll compared to pitch planes. Directional differences in the timing and strengths of vestibular and proprioceptive sensory signals between roll and pitch may lead to a greater miscalculation of roll than pitch motion of the body in space when vestibular input is absent. For this reason, we compared the timing and amplitude of vestibular information, (observable in stimulus-induced head accelerations when subjects are tilted in different directions), with that of proprioceptive information caused by stimulus induced rotations of ankle and hip joints [observable as short latency (SL) stretch responses in leg and trunk muscle EMG activity]. We attempted to link the possible mode of sensory interaction with the deficits in balance control. Six subjects with bilaterally absent vestibular function and 12 age-matched controls were perturbed, while standing, in 8 directions of pitch and roll support surface rotation in random order. Body segment movements were recorded with a motion analysis system, head accelerations with accelerometers, and muscle activity with surface EMG. Information on stimulus pitch motion was available sequentially. Pitch movements of the support surface were best coded in amplitude by ankle rotation velocity, and by head vertical linear acceleration, which started at 13 ms after the onset of ankle rotation. EMG SL reflex responses in soleus with onsets at 46 ms provided a distal proprioceptive correlate to the pitch motion. Roll information on the stimulus was available simultaneously. Hip adduction and lumbo-sacral angular velocity were represented neurally as directionally specific short latency stretch and unloading reflexes in the bilateral gluteus medius muscles and paraspinal muscles with onsets at 28 ms. Roll angular accelerations of the head coded roll amplitude and direction at the same time (31 ms). Significant differences in amplitude coding between vestibular loss subjects and controls were only observed as a weaker coding between stimulus motion and head roll and head lateral linear accelerations. The absence of vestibular inputs in vestibular loss subjects led to characteristic larger trunk in motion in roll in the direction of tilt compared to pitch with respect to controls. This was preceded by less uphill flexion and no downhill extension of the legs in vestibular loss subjects. Downhill arm abduction responses were also greater. These results suggest that in man vestibular inputs provide critical information necessary for the appropriate modulation of roll balance-correcting responses in the form of stabilising knee and arm movements. The simultaneous arrival of roll sensory information in controls may indicate that proprioceptive and vestibular signals can only be interpreted correctly when both are present. Thus, roll proprioceptive information may be interpreted inaccurately in vestibular loss subjects, leading to an incorrect perception of body tilt and insufficient uphill knee flexion, especially as cervico-collic signals appear less reliable in these subjects as an alternative sensory input

Prevalence and associated factors of worry for cancer in patients with a Barrett’s esophagus

Abstract Although the risk of cancer progression in a Barrett’s esophagus (BE) is very low, worrying about cancer is known as an important factor affecting HRQoL. The aim of this study was to determine the proportion of BE patients with high levels of worry for cancer, to compare outcomes of patients endoscopically treated for BE neoplasia (DBE), non-dysplastic BE patients (NDBE) and patients with reflux symptoms, and to examine associated factors. We performed a cross sectional, exploratory, self-administered questionnaire study using the cancer worry scale, and the reflux disease questionnaire. A total of 192 DBE patients, 213 NDBE patients and 111 refractory reflux symptom patients were included from October 2019 until July 2021, 76.8% of BE participants were male and aged 66.9 years. High cancer worry was reported in 40.6% of the DBE patients and 36.2% of NDBE patient. Reflux patients scored statistically significant worse with 56.6% stated high cancer worry. Positive correlations were found between reflux symptoms and cancer worry in NDBE patients and reflux patients. In DBE patients’ negative correlations were found between higher cancer worry and younger age as well as a family history of esophageal carcinoma. A clinically significant group of BE patients reported high cancer worry, which was associated with reflux symptoms in NDBE patients and a younger age and a (family) history of esophageal carcinoma diagnosis in BE patients treated for (early) neoplasia. Physicians should communicate about the actual cancer risk, which leads to greater patient understanding and therefore may have a positive impact on health outcomes

Highly Divergent SARS-CoV-2 Alpha Variant in Chronically Infected Immunocompromised Person

We detected a highly divergent SARS-CoV-2 Alpha variant in an immunocompromised person several months after the latest detection of the Alpha variant in the Netherlands. The patient was infected for 42 weeks despite several treatment regimens and disappearance of most clinical symptoms. We identified several potential immune escape mutations in the spike protein

Utility of Routine Esophageal Biopsies in Patients With Refractory Reflux Symptoms

INTRODUCTION: This study aimed to assess the diagnostic yield of routine esophageal biopsies in patients with refractory reflux symptoms. METHODS: We prospectively enrolled consecutive patients referred for upper endoscopy and collected histological, clinical, and endoscopic data. RESULTS: Of the 301 included patients, 14 (4.7%) patients met the clinicopathological diagnostic definition of eosinophilic esophagitis. Presence of dysphagia, food bolus impaction, atopic background, and typical endoscopic features were the factors with the strongest association and diagnostic accuracy for eosinophilic esophagitis. The diagnostic yield in patients lacking symptoms of dysphagia or endoscopic features was negligible (0% and 1.9%, respectively). DISCUSSION: Routine esophageal biopsy sampling in patients with refractory reflux symptoms has a low diagnostic yield. Esophageal biopsies should only be obtained in patients with refractory reflux symptoms who also present with dysphagia (see Visual abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B792)