MORTALITY OF JAMAICAN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

A retrospective study of all patients with systemic lupus erythematosus(SLE) who died at the University Hospital of the West Indiesover a 14-year period is presented. The major cause of deathwas infection followed by renal failure. Gram-negative organismswere the major microbiological agents causing infections. Side-effectsof therapy were common, in particular bone marrow depressionand haemorrhage related to anticoagulants. It appears that controllingsevere lupus activity without increasing the risk of life-threateningcomplications remains an important goal in the treatment ofSLE. KEY WORDS: Systemic lupus erythematosus, Mortality, Infection, Anticoagulants, Jamaica     

A comparison of non-invasive continuous finger blood pressure measurement (Finapres) with intra-arterial pressure during prolonged head-up tilt

Simultaneous intra-radial and non-invasive (Finapres, Ohmeda)blood pressures were compared during prolonged head-up tilt,in eight patients (mean age 49 years) with malignant vasovagalsyncope. Twelve tilts were performed, of which eight resultedin vasovagal syncope. The mean bias (difference between Finapresand intra-arterial pressures) for systolic pressure was +0.7mmHg (standard deviation 11.3 mmHg) and for diastolic pressurewas +5.4 mmHg (standard deviation 7 mmHg). The within-tilt precision(standard deviation of the bias) of the non-invasive measurementsvaried between 2.9–12.4 mmHg (median 4.5 mmHg) for systoliccomparisons, and 1.6–8.4 mmHg (median 4.4 mmHg) for diastoliccomparisons. In all but one tilt highly significant positiveincreases in both systolic (median 7.1 mmHg) and diastolic bias(median 81 mmHg) occurred on tilt with respect to resting pre-tiltlevels. Independent of the absolute level of agreement, thenon-invasive measurements followed changes in intra-arterialpressure closely, with 89% of beat-to-beat changes in systolicpressure, and 95% of beat-to-beat changes in diastolic pressurefollowed to within ±2 mmHg. This study suggests thatthe Finapres is well suited for use during diagnostic tilt testing,demonstrating an acceptable within-tilt precision and closelyfollowing pressure changes during vasovagal syncope.     

ANALYSIS OF THE RET PROTO-ONCOGENE IN SPORADIC PARATHYROID ADENOMAS

Missense germline mutations of the RET proto-oncogene have recently been identified in the hereditary cancer syndromes MEN2A, MEN2B, and FMTC, all characterized by medullary carcinoma, but also including phaeochromocytoma in MEN2A and MEN2B and parathyroid disease in MEN2A. In addition, somatic RET proto-oncogene mutations have been identified in a subset of sporadic medullary carcinomas and phaeochromocytomas. This study investigated the possibility that RET plays a role in sporadic parathyroid neoplasia. Firstly, normal and neoplastic parathyroid tissues were screened for expression of the RET proto-oncogene, using an RT-PCR approach on autopsy material. Secondly, 20 archival parathyroid adenomas were screened for somatic mutations in the transmembrane region of RET, the region associated with germline mutations in MEN2A and hence parathyroid disease, using a PCR–solid phase direct sequencing approach. RET expression was identified in all the parathyroid tissues analysed. However, no mutations were identified in any of the 20 adenomas, suggesting either that other mechanisms of RET activation occur, such as translocation, or that RET plays a more minor role in the growth control of the parathyroid cells than in C cells or phaeochromocytes.     

CLINICAL SPASTICITY ASSESSMENT USING THE MODIFIED TARDIEU SCALE DOES NOT REFLECT JOINT ANGULAR VELOCITY OR RANGE OF MOTION DURING WALKING: ASSESSMENT TOOL IMPLICATIONS

ObjectiveSpasticity assessment is often used to guide treatment decision-making. Assessment tool limitations may influence the conflicting evidence surrounding the relationship between spasticity and walking. This study investigated whether testing speeds and joint angles during a Modified Tardieu assessment matched lower-limb angular velocity and range of motion during walking.DesignObservational study.SubjectsThirty-five adults with a neurological condition and 34 assessors.MethodsThe Modified Tardieu Scale was completed. Joint angles and peak testing speed during V3 (fast) trials were compared with the same variables during walking in healthy people, at 0.40–0.59, 0.60–0.79 and 1.40–1.60 m/s. The proportion of trials in which the testing speed, start angle, and angle of muscle reaction matched the relevant joint angles and angular velocity during walking were analysed.ResultsThe Modified Tardieu Scale was completed faster than the angular velocities seen during walking in 88.7% (0.40–0.59 m/s), 78.9% (0.60– 0.79 m/s) and 56.2% (1.40–1.60 m/s) of trials. When compared with the normative dataset, 4.2%, 9.5% and 13.7% of the trials met all criteria for each respective walking speed.ConclusionWhen applied according to the standardized procedure and compared with joint angular velocity during walking, clinicians performed the Modified Tardieu Scale too quickly.LAY ABSTRACTSpasticity is an abnormal increase in muscle tightness, which is common following neurological injury. Spasticity has been shown to have a profound impact on an individual’s independence and quality of life. The main goal reported by patients in this population is to return to independent, normal walking. Yet, despite this there is a lack of consensus regarding the relationship between spasticity and walking outcomes. This may be due to a disconnect between clinical, bed-based assessment methods and how spasticity manifests during walking. This study aimed to establish how well a routine clinical assessment (the Modified Tardieu Scale) matched the speed and range of joint movement during walking. The findings suggest that, currently, clinicians performed the assessment too fast, which may lead to “false-positive” assessment findings. This may result in the identification and treatment of spasticity that is not impacting walking, leading to sub-optimal patient outcomes and significant healthcare wastage.Key words: muscle spasticity, patient outcome assessment, rehabilitation, brain injuries, gait, walking

Spasticity is a common impairment following neurological injury (1–5). The effective assessment and management of spasticity receives significant attention due to the detrimental effects it has on patient outcomes, carer burden, and quality of life (6, 7). Current spasticity guidelines recommend that only spasticity impacting function should receive intervention (8). As such, the role of a clinical assessment is to identify the presence of spasticity and decipher whether the spasticity warrants intervention, such as botulinum toxin-A (BoNT-A).Walking limitations are the most significant selfperceived, functional problem reported by individuals following neurological injury (9). A primary rehabilitation goal is often to improve walking independence, quality, speed, and endurance (10–12). In relation to spasticity, the clinician’s role is to identify whether spasticity is present, and subsequently determine if a patient’s walking may benefit from spasticity-related interventions.A definition of spasticity published by Pandyan et al. (13); “disordered sensori-motor control, resulting from an upper motor neurone lesion, presenting as intermittent or sustained involuntary activation of muscles’’, encompasses all the positive features of upper motor neurone syndrome (UMNS) under an umbrella term of spasticity. This terminology defines spasticity as a broader sensori-motor phenomenon (13), when compared with the more constrained, velocity-dependent definition published by Lance (14);”a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyper-excitability of the stretch reflexes, as one component of the UMNS” (14). For the purpose of this study, Lance’s definition has been used to define spasticity, since, with this definition, spasticity can be assessed as an individual construct. The Modified Tardieu Scale (MTS) is an often-recommended spasticity assessment, aligning with Lance’s (14) definition of spasticity (15–17). The MTS classifies the response of a relaxed muscle to a fast, passive stretch (V3). The assessment protocol involves a clinician moving the joint “as fast as possible” through its full range of motion (ROM) without specifying or measuring the speed of completion. The MTS is applied according to this standardized protocol regardless of the functional status or goals of the patient. For example, a household ambulator walking at ≤ 0.30 m/s is assessed at the same speed as a community ambulator walking at ≥ 0.80 m/s, whose muscles and joints are moving much faster when walking (18). This “one-size-fits” all approach does not take into account the variability in joint ROM and angular velocity (or speed of lowerlimb movement) with changes in walking speed (19). As such, the MTS may not sensitively discriminate individuals who have spasticity impacting their walking.While it is well established that interventions, such as BoNT-A, reduce spasticity at an impairment-based level, current treatment modalities for spasticity do not necessarily lead to improved walking outcomes (20–22). This may be because standardized protocols for scales such as the MTS do not reflect joint movement during walking (23–25). For example, if clinicians test at a speed that is slower than the joint angular velocity seen during walking, they may fail to identify spasticity that is affecting walking (i.e. false-negative). Conversely, if clinicians test at a speed that exceeds the joint angular velocity seen during walking, they may identify spasticity that is not impacting walking (i.e. false-positive).Matching the joint angles and testing speed of the MTS to the ROM and angular velocity seen during walking may assist in identifying patients who have spasticity impacting functional performance, leading to treatment decisions that optimize patient outcomes and healthcare resources. This study aimed to compare the joint start angle, angle of muscle reaction, and testing speed during a standardized MTS assessment of 4 major muscle groups of the lower-limb, collected in people with neurological conditions, with joint ROM and angular velocity in a healthy population walking at a range of speeds.     

Distribution of HLA alleles in Portugal and Cabo Verde. Relationships with the slave trade route

HLA-A, -B , and -DR frequencies were analysed in populations from Portugal and the Madeira and Cabo Verde Archipelagos, aiming to characterize their genetic composition. Portuguese settlers colonized both Archipelagos in the 15th and 16th centuries. Madeira received many sub-Saharan slaves to work in the sugar plantations, and Cabo Verde served as a pivotal market in the Atlantic slave trade and was populated by individuals coming from the Senegambia region of the West African coast. The population of Madeira shows the highest genetic diversity and the presence of alleles and haplotypes usually linked to sub-Saharan populations, the haplotypes accounting for 3.5% of the total. Cabo Verde presents typical markers acknowledged to be of European or Ibero-Mediterranean origin, thus revealing the admixture of European settlers with Sub-Saharan slaves. Altogether the number of European haplotypes reaches 15% of the total. The Portuguese population shows a perceivable and significant heterogeneity both in allele and haplotype frequencies, unveiling a differential input of peoples from different origins. A PCA of the populations studied, plus other relevant ones, clearly shows gene heterogeneity in mainland Portugal as well as the differences and relationships between these populations and Madeira and Cabo Verde.     

Cytometric analysis and maturation characteristics of reticulocytes from myelodysplastic patients

Myelodysplasia is characterized by a hypoproliferative anaemia with ineffective intramedullary erythropoiesis. We have used the novel technology of the Bayer H3 analyser to characterize reticulocytes (RNA containing red cells) from 32 MDS patients and 10 elderly normal subjects. In comparison with reticulocytes from normal subjects, those from MDS patients were larger with a lower haemoglobin concentration. Reticulocytes from sidero blastic patients had a lower haemoglobin content and concentration than for refractory anaemia patients but no other differences between FAB subtypes were found. H3 reticulocyte RNA content parameters correlated poorly with those derived by the Sysmex R-1000, particularly in the MDS group. On reticulocyte maturation to red cells MDS patients concentrated haemoglobin more than normal subjects and this was most evident in the sidero blastic group. Platelet depletion of whole blood suggested that large platelets in the sidero blastic group may have partly contributed to this observation. Prospective evaluation of changes towards normal reticulocyte cytometric parameters may assist in assessment of early erythroid response to therapy in MDS patients.     

Nurse-led case management for community dwelling older people: an explorative study of models and costs

Aim To compare community matrons with other nurses carrying out case management for impact on service use and costs. Background In England, nurses working in general practice, as district nurses and disease-specific nurses, undertake use case management. Community matrons were introduced to case management to reduce unplanned hospitalizations of people with complex conditions. Methods Managers in three Primary Care Trusts (PCTs) identified four nurses/matrons engaged in case management. Nurses/matrons recruited five community-dwelling patients referred to them for case management. Patients reported use of health/social services for 9 months, 2008 to 2009. Nurses/matrons completed activity diaries. Results Service use data were available for 33 patients. Compared with other nurse case managers, community matrons had: smaller caseloads; more patient contact time (mean 364 vs. 80 minutes per patient per month); and older patients (mean age 81 vs. 75 years, P = 0.03) taking more medications (mean 8.9 vs. 5.6, P = 0.014). Monthly costs were significantly higher for patients managed by community matrons (add £861), and who lived alone (add £696). Hospitalizations were not associated with patient or service delivery factors. Conclusion Further research on cost-effectiveness of case management models is required. Implications for Nursing Management The case for continued investment in community matrons remains to be proven.     

Power of variance component linkage analysis to detect quantitative trait loci

Expressions are derived for the sample size required to achieve a given power in variance component linkage analysis of a quantitative trait in unascertained samples. For simplicity an additive model, comprising effects due to a single QTL, residual additive genetic factors, and individual-specific random environmental variation, is considered. Equations are given relating sample size to trait heritability for sibpairs, sib trios, nuclear families having two and three sibs, and arbitrary relative pairs. The effects of nonzero residual additive genetic variance and parental information are discussed, and a scale relationship for sample sizes with sibships and nuclear families is derived. For larger sampling structures such as extended pedigrees the inheritance space is randomly sampled and the relevant equations are solved numerically. Comparative power curves are presented for sibships of size 2–4 and for an extended pedigree of 48 individuals. Simulation results for sibpairs confirm the validity of the theoretical results.