Risk factors for methicillin-resistant Staphylococcus aureus skin and soft tissue infection in MRSA-colonized patients discharged from a Veterans Affairs hospital.

Currently, limited studies have quantified the risk of methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTIs) for MRSA-colonized patients on discharge from hospital. Our retrospective, case-control study identified independent risk factors for the development of MRSA SSTIs among such patients detected by active MRSA nasal screening in an acute care hospital by PCR on admission, and bacteriological cultures on discharge. Cases were MRSA-colonized patients aged ⩾18 years who developed a MRSA SSTI post-discharge and controls were those who did not develop a MRSA SSTI post-discharge. Controls were matched to cases by length of follow-up (±10 days) for up to 18 months. Potential demographic and clinical risk factors for MRSA infection were identified using electronic queries and manual chart abstraction; data were compared by standard statistical tests and variables with P values ⩽0·05 in bivariable analysis were entered into a logistic regression model. Multivariable analysis demonstrated prior hospital admission within 12 months (P = 0·02), prior MRSA infection (P = 0·05), and previous myocardial infarction (P = 0·01) were independently predictive of a MRSA SSTI post-discharge. Identification of MRSA colonization upon admission and recognition of risk factors could help identify a high-risk population that could benefit from MRSA SSTI prevention strategies.

The assessment of bone mineral content and density of the lumbar spine and proximal femur in US submariners.

UNLABELLED: The submarine environment is unique in that there is limited space and no sunlight, which may negatively affect skeletal health and lead to accelerated bone loss, osteoporosis, and fractures. INTRODUCTION: The primary purpose of this study was to determine whether there was an association with submarine service, specifically time spent at sea, and bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine and dual proximal femur (total hip and femoral neck) measured by DXA. METHODS: This is a cross-sectional study of 462 submariners 20-91 years old. Variables included in the analysis were age, height, race, alcohol intake, tobacco use, fracture history, conditions, and medications known to cause bone loss and osteoporosis and submarine service. RESULTS: Of the submarine service predictors, only serving onboard a diesel submarine was determined to be independently associated with a reduction in BMD of the total hip and femur neck, while no submarine service predictor increased the odds of having low BMD. In submariners 50+ years old, the age-adjusted prevalence of osteopenia was 15.7 % (lumbar spine) and 40.4 % (femur neck), while the prevalence of osteoporosis was 4.8 % (lumbar spine) and 4.2 % (femur neck), rates that did not differ from NHANES 2005-2008. In submariners <50 years old, 3.1 % was below the expected range for age. The proportion of submariners 50+ years old that met the FRAX criteria for pharmacological treatment was 12 %. CONCLUSIONS: Intermittent periods of submergence that can range from a few days to 3+ months do not appear to compromise skeletal health differently than the general population.

Comorbidity of postural orthostatic tachycardia syndrome and chronic fatigue syndrome in an Australian cohort.

OBJECTIVE: Patients with chronic fatigue syndrome (CFS) are frequently diagnosed with comorbid postural orthostatic tachycardia syndrome (POTS), suggesting a shared pathogenesis. The aim of this study was to examine the relationship between demographic characteristics, autonomic functioning and fatigue levels amongst CFS patients with and without comorbid POTS. DESIGN AND SETTING: All patients presenting to the CFS Discovery Clinic between 2009 and 2012 completed a 20-min standing task as part of their initial assessment. Heart rate and pulse pressure were recorded at baseline, at 2-min intervals poststanding, at the end of the task and following a recovery period. Average heart rate and pulse pressure variability were calculated from this data. Age, gender, length of illness and self-reported fatigue scores were also recorded. POTS patients were diagnosed by an orthostatic increase in heart rate >30 beats per min, concomitant symptoms of orthostatic intolerance and no orthostatic hypotension. Differences in autonomic functioning between POTS and CFS patients were compared using independent samples t-tests, whilst logistic and linear regressions were performed to examine the contribution of autonomic functioning to task completion and perceived fatigue, respectively. RESULTS: Comorbidity of CFS and POTS (CFS-POTS) was observed in 11% (33/306) of patients. CFS-POTS patients were significantly younger (P < 0.001), had a shorter length of illness (P = 0.034), experienced greater task difficulty (P = 0.002) and were able to stand for significantly shorter periods compared to the CFS-only patients (P < 0.001). CFS-POTS patients experienced significantly lower baseline diastolic blood pressure (P = 0.002), significantly higher heart rate and lower pulse pressures at each standing measurement. Early heart rate changes (P = 0.002) and overall heart rate change (P < 0.001) were significant predictors of completion status, whereas heart rate variability (P < 0.001) and female gender (P < 0.001) were significant predictors of increased perceived task difficulty. CONCLUSIONS: Haemodynamic and demographic differences between CFS-POTS and CFS-only patients suggest that the former group reflects a distinct subgroup of the CFS population. The findings highlight the utility of screening younger patients with fatigue for POTS, and identified heart rate variability as an important marker of fatigue for CFS patients in general.

Reliability and validity of the Visual Gait Assessment Scale for children with hemiplegic cerebral palsy when used by experienced and inexperienced observers.

This study investigated the reliability and validity of the Visual Gait Assessment Scale when used by experienced and inexperienced observers. Four experienced and six inexperienced observers viewed videotaped footage of four children with hemiplegic cerebral palsy on two separate occasions. Validity of the Scale was obtained by comparison with three-dimensional gait analysis (3DGA). The experienced observers generally had higher inter-observer and intra-observer reliability than the inexperienced observers. Both groups showed higher agreement for assessments made at the ankle and foot than at the knee and hip. The experienced observers had slightly higher agreement with 3DGA than the inexperienced observers. The inexperienced observers showed a learning effect and had higher inter-observer agreement and higher agreement with 3DGA in the second assessment of the videotapes. This scale can be used by inexperienced observers but is limited to observations in the sagittal plane and by poor reliability at the knee and hip for experienced and inexperienced observers.

Identification of a unique epigenetic sub-microenvironment in prostate cancer.

The glutathione S-transferase P1 (GSTP1) gene promoter is methylated in tumour cells in more than 90% of prostate carcinomas. Recently, GSTP1 promoter methylation was identified in tumour-associated stromal cells in addition to the tumour epithelium. To define the extent and location of stromal methylation, epigenetic mapping using pyrosequencing quantification of GSTP1 promoter methylation and an anatomical three-dimensional reconstruction of an entire human prostate specimen with cancer were performed. Normal epithelium and stroma, tumour epithelium, and tumour-associated stromal cells were laser capture-microdissected from multiple locations throughout the gland. As expected, the GSTP1 promoter in both normal epithelium and normal stromal cells distant from the tumour was not methylated and the tumour epithelium showed consistently high levels of promoter methylation throughout. However, tumour-associated stromal cells were found to be methylated only in a localized and distinct anatomical sub-field of the tumour, revealing the presence of an epigenetically unique microenvironment within the cancer. Morphologically, the sub-field consisted of typical, non-reactive stroma, representing a genomic alteration in cells that appeared otherwise histologically normal. Similar epigenetic anatomical mapping of a control prostate gland without cancer showed low background methylation levels in all cell types throughout the specimen. These data suggest that stromal cell methylation can occur in a distinct sub-region of prostate cancer and may have implications for understanding tumour biology and clinical intervention.

The Footprint method to assess transmalleolar axis.

Torsional deformities of the lower extremities are a common reason for an orthopaedic consultation and are also part of the evaluation of a patient in gait analysis. This study assessed the level of agreement between, and the repeatability of, the Footprint method and two other methods (Prone and Jig) of measuring the transmalleolar axis (TMA) clinically. The Footprint method measures the TMA as the patient sits by projecting the position of the malleoli downwards onto lined paper while the lines of the paper are aligned with the knee axis. The Prone method projects the position of the malleoli upwards onto the sole of the foot and this is related to the visually estimated knee axis. The Jig method uses a tropometer to relate the angle between the tibial tubercle and the two malleoli. Two assessors measured twelve subjects using the three methods and six subjects were re-measured approximately 1 week later for repeatability. There was poor agreement between the three methods but the Footprint method was the most repeatable (coefficient of repeatability: 5.4). One observer then assessed the repeatability of the effect of simulated equinus on the Footprint method in 10 normal subjects on 2 separate occasions 1 week apart. Equinus was obtained by having the subjects sit and firstly extend their knee and place the foot on the floor and secondly by placing the foot under consideration on a wedge. Both conditions introduced an offset into the measurement of the TMA when compared to the measurements with the ankle at neutral in the same subjects. The reliability of the Footprint method was then assessed using 10 inexperienced observers who measured nine normal subjects each on 2 separate occasions and their results compared with those from an experienced observer. The inexperienced observers were less repeatable than an experienced observer (coefficients of repeatability 9.2 and 6.9, respectively). We recommend that different methods of measuring TMA should not be used interchangeably in clinical practice. The Footprint method was the most repeatable of the three methods tested and can be used for patients who have fixed equinus but the measurement was less repeatable when used by inexperienced observers.

The effect of simulated hamstring shortening on gait in normal subjects.

The purpose of this study was to determine the effect of simulated hamstring shortening on gait in normal subjects. Six normal subjects wore an adjustable brace to simulate three different hamstring lengths. Evaluation of the physiological cost index (PCI) and gait analysis revealed that simulated hamstring shortening produced adverse affects in the gait of normal subjects. Significant effects were only observed when the popliteal angle exceeded 85 degrees (p<0.001) and included increased effort of walking (PCI), decreased speed, stride and step length; decreased hip flexion and increased knee flexion in stance, increased posterior pelvic tilt, decreased pelvic obliquity and rotation and premature ankle dorsi- and plantar-flexion in stance. These results emphasise the need to consider the effects of changing the length of the hamstrings on joints other than the hip and knee when assessing patients for hamstring lengthening.

Progranulin gene mutations associated with frontotemporal dementia and progressive non-fluent aphasia.

Frontotemporal lobar degeneration (FTLD) refers to a focal, non-Alzheimer form of cerebral degeneration that encompasses the distinct clinical syndromes of frontotemporal dementia (FTD), progressive non-fluent aphasia (PNFA) and semantic dementia. Some patients show tau-based pathological changes and in familial cases mutations have been identified in the microtubule-associated protein tau gene (MAPT) on chromosome 17q21. However, many cases are tau-negative, showing instead ubiquitin-immunoreactive (UBQ-ir) neuronal cytoplasmic inclusions and neurites, and in some familial cases UBQ-ir neuronal intranuclear inclusions of a lentiform appearance. Very recently, mutations have been identified in familial cases in the progranulin (PGRN) gene, also on chromosome 17q21. Clinical, pathological and molecular diversity within FTLD highlights the importance of careful examination of clinical-pathological-genetic relationships. This paper reports, for the first time, a clinico-pathological investigation of two FTLD families with PGRN mutations, and compares the clinical characteristics with those of patients studied in the department with MAPT mutations. The clinical profile associated with PGRN mutations constituted, in some patients, a prototypical picture of FTD and in others one of PNFA, both profiles occurring within the same family. Patients with PGRN mutations exhibited phonological deficits, whereas in patients with MAPT mutations language abnormalities, when present in addition to the prominent behavioural disorder, take the form of semantic disturbance. The findings provide compelling evidence for the link between FTD and PNFA, while raising the possibility of identifiable clinical differences between FTLD patients with MAPT and PGRN mutations.

The apolipoprotein E epsilon4 allele selectively increases the risk of frontotemporal lobar degeneration in males.

OBJECTIVE: To determine whether polymorphic variations in the apolipoprotein E gene (APOE) are associated with increased risk of frontotemporal lobar degeneration (FTLD) when mutation in tau gene is absent. METHODS: The APOE gene was genotyped by polymerase chain reaction from DNA routinely extracted from blood or brain tissues. The APOE epsilon4 allele frequency in 198 patients with FTLD not associated with mutations in tau gene was compared with that of a control group of 756 normal individuals drawn from the same geographical region. Analyses were done according to clinical subtype or sex. RESULTS: The APOE epsilon4 allele frequency (19.4%) was increased (p = 0.01) in FTLD v the whole control group (14.1%), while the APOE epsilon2 allele frequency in FTLD (6.5%) was slightly lower than in controls (8.0%) (NS). The APOE epsilon4 allele frequency in men with FTLD (22.3%) was greater (p = 0.002) than in male controls (12.3%); the frequency in women (16.3%) was similar to that in female controls (14.8%) (NS). The APOE epsilon2 allele frequency in men with FTLD was 4.9% while in male controls it was 9.5% (p = 0.06), but there was no difference in women (7.5% v 7.9%, NS). Neither the APOE epsilon2 nor APOE epsilon4 allele frequency varied significantly between any of the clinical subtypes. CONCLUSIONS: In FTLD not associated with mutations in tau gene, possession of APOE epsilon4 allele in men roughly doubles the chances of developing disease, whereas this has no impact upon disease risk in women.

Characteristics of estrus before and after first insemination and fertility of heifers after synchronized estrus using GnRH, PGF2alpha, and progesterone.

Our objectives were to determine fertility of heifers after synchronization of estrus using PGF2alpha, preceded by progesterone (P4), GnRH, or both, and to examine the variability of estrual characteristics in heifers before first and second AI. Dairy (n = 247) and beef (n = 193) heifers were assigned randomly to each of three treatments: 1) 50 microg of GnRH (injected i.m.) administered on d -7 followed by 25 mg of PGF2alpha (i.m.) on d -1 (GnRH + PGF; modified Select Synch protocol); 2) placement of an intravaginal progesterone (P4)-releasing insert on d -7, PGF2alpha on d -1, and insert removal on d 0 (P4+PGF); and 3) 50 microg of GnRH plus a P4 insert on d -7, followed by 25 mg of PGF2alpha on d -1, and insert removal on d 0 (P4+GnRH+PGF). Characteristics of estrus were examined before first AI and before the next eligible AI (18 to 26 d later), including duration of estrus, number of standing events, and total and individual duration of standing events. In addition, all heifers were checked visually at least twice daily for estrus. Blood samples were collected on d -7, -1, and 0 for determination of P4, and pregnancy status was diagnosed by ultrasonography 27 to 34 d after AI. Rates of detected estrus were less (P < 0.05) in dairy than in beef heifers, and greater (P < 0.05) in heifers treated with P4. Pattern of conception and pregnancy rates among treatments differed between beef and dairy heifers (treatment x group interaction; P < 0.05). In dairy heifers, conception and pregnancy rates were greatest with P4+PGF, followed by P4+GnRH+PGF and GnRH+PGF, respectively. The opposite was observed among treatments in beef heifers. Administration of P4 without the preceding injection of GnRH produced the lowest pregnancy rates in beefheifers. Ofthe quantified sexual behavioral characteristics during the synchronized estrus, the number of standing events and total duration of standing events were greater (P < 0.01) than those observed during the next eligible estrus before second AI, whereas duration of estrus was unaffected.

Inherited frontotemporal dementia in nine British families associated with intronic mutations in the tau gene.

Genetic screening of 171 patients with frontotemporal lobar degeneration disclosed 14 patients, across nine pedigrees, with mutations in the intron to exon 10 in the tau gene, a region regulating the splicing of exon 10 via a stem loop mechanism. Thirteen of these patients had the +16 splice site mutation and one had the +13 splice site mutation. Affected members of all nine families presented with changes in behaviour and social conduct that were prototypical of frontotemporal dementia (FTD). In all patients with the +16 splice site mutation, the behavioural profile was characterized by disinhibition, restless overactivity, a fatuous affect, puerile behaviour and verbal and motor stereotypies. The single patient with the +13 mutation presented a contrasting picture of apathy and inertia. In addition, all patients had evidence of semantic loss. Pathologically, five of the six patients so far autopsied shared frontotemporal atrophy with involvement of the substantia nigra. The underlying histology was that of microvacuolar-type cortical degeneration with a few swollen cells. Tau pathology was widespread throughout the brain and present in neurones and glial cells, mostly in the frontal and temporal cortical regions. This was in the form of neurofibrillary tangles and amorphous tau deposits (pre-tangles); Pick bodies were not observed. Ultrastructurally, the tau filaments had a twisted, ribbon-like morphology distinct from the paired helical filaments of Alzheimer's disease. One patient died from an unrelated illness whilst in the early clinical stages of FTD. In this patient, cortical microvacuolar and astrocytic changes were absent, though there were scattered neurones and glial cells, immunoreactive to tau, throughout the cortical and subcortical regions. The disease process underlying the neurodegeneration within these inherited forms of FTD may therefore stem directly from early, primary alterations in the function of tau. All eight families with the +16 mutation seem to be part of a common extended pedigree, possibly originating from a founder member residing within the North Wales region of Great Britain.

Estimation of injecting drug users in the City of Edinburgh, Scotland, and number infected with human immunodeficiency virus.

OBJECTIVES: To estimate (1) the number of current and former injecting drug users (IDU) infected with human immunodeficiency virus (HIV) alive in Edinburgh, and (2) the total number of current injectors in the city. METHODS: The number of infected IDU was estimated using a local register of HIV infections with correction for incompleteness of the register. The number of injectors was estimated by two independent methods, one based on the HIV register, the other by log-linear modelling of four lists of IDU interviewed in a city-wide survey, and/or attending drug treatment agencies and family doctors because of drug use. MAIN OUTCOME MEASURES: Estimates for the period 1992-1994 of number of IDU infected with HIV, total number of IDU, and prevalence of injecting. RESULTS: The HIV register indicated that 371 infected drug users who had ever injected were alive and resident in Edinburgh. In all, 95% of infected survey respondents appeared in the register, leading to a corrected estimate of 472 infected ever injectors. From this the number of IDU currently injecting (i.e. in the previous 6 months) was estimated to be 1770 (95% CI: 1340-2240), and the prevalence of injecting as 8.0 (95% CI: 4.8-10.8) per 1000 Edinburgh residents aged 15-59 years. Log-linear modelling gave an estimate of 2070 (95% CI: 1360-2800) current injectors. CONCLUSIONS: The number of HIV-infected IDU in Edinburgh was estimated to be twice that in the larger nearby city of Glasgow, where a higher proportion of young adults currently injected drugs. Knowledge of the high prevalence of HIV in Edinburgh IDU (19.3%), the prescribing of oral substitutes, and counselling by doctors and drug workers are perceived reasons for the reduction in the prevalence of injecting which has occurred in Edinburgh in recent years. Such measures need to be continued to encourage further reduction of injecting.

Gender differences in HIV risk behaviour of injecting drug users in Edinburgh.

A multi-site sample of currently-injecting drug users (IDUs) comprising 344 men and 136 women was recruited in Edinburgh. Sixty-seven per cent of the sample said they had at some time used injecting equipment already used by another person and 25% admitted doing so in the 6 months before interview. Whereas women who injected with used equipment obtained it predominantly from a sexual partner, for men the source was more often a close friend or someone whose HIV status they were unlikely to know. In the 6 months before interview, 40% of men, compared with 20% of women, had more than one heterosexual partner. This difference was associated with a higher proportion of men with steady partners also having casual partners. Women IDUs were more likely to have regular partners who injected (57% vs 26%). Though sharing of injecting equipment has already diminished in Edinburgh, further measures are needed to eliminate it. For injectors here, the risk of infection from unprotected heterosexual intercourse may now be greater than that from sharing injecting equipment, particularly for women. Other methods of encouraging changes in sexual behaviour need to be investigated and successful ones promoted.

Progression of HIV: follow-up of Edinburgh injecting drug users with narrow seroconversion intervals in 1983-1985.

OBJECTIVE: To describe progression and survival of individuals infected with HIV by injecting drug use in Edinburgh. DESIGN AND METHODS: From 313 HIV-infected patients with retrospectively estimated narrow seroconversion intervals, 260 infected via injecting drug use in the years 1983-1985 were selected for the study group. MAIN OUTCOME MEASURES: The effects of gender, age, human leukocyte antigen (HLA) type and zidovudine (ZDV) treatment on progression and survival from seroconversion; Weibull estimates of the AIDS incubation distribution and the overall survival distribution; slopes of absolute CD4 lymphocyte loss (on the square root scale) and loss of CD4 percentage. RESULTS: The cumulative progression rates at 10 years were 68% to CDC stage IV and 31% to AIDS with a mortality rate of 25%. Three-year survival rates for AIDS and CDC stage IV cases were 25 and 72%, respectively. Gender and age effects on progression or overall survival were not found, although those aged over 30 years experienced poorer survival from AIDS. A strong HLA (A1, B8, DR3) association with faster progression and poorer survival was found. Median survival was estimated by Weibull distribution to be 12.6 years; median AIDS-free time was estimated to be 11.6 years. CD4 cell loss was approximately linear when transformed to the square root scale as was the decline in CD4 percentage. Only HLA effects on slopes were found: A1,B8, DR3 was significantly associated with faster loss of both absolute CD4 cells and CD4 percentage (P < 0.001) and B27 was significantly associated with slower loss of CD4 percentage (P = 0.01). CONCLUSIONS: Edinburgh IDU do not seem to progress more rapidly than other cohorts with predominantly different risk activities. Older age was associated with poorer survival from AIDS but no gender effect was found for progression or overall survival. The clearest significant association with AIDS progression, mortality and loss of CD4 cells was the phenotype HLA A1,B8,DR3. In contrast HLA B27 was associated with slower loss of CD4 cells.

Association of HLA types A1-B8-DR3 and B27 with rapid and slow progression of HIV disease.

We examined how HLA types A1-B8-DR3 and B27 were related to progression of clinical disease and rate of loss of CD4 lymphocytes in the Edinburgh City Hospital cohort of HIV-positive patients, mainly injection drug users. Patients (n = 692) were prospectively followed from 1985 through March 1994. Accurately estimated seroconversion times were determined retrospectively for a subgroup of 313 (45%). Of 262 patients (39%) who were fully or partially HLA typed, 155 (50%) had known seroconversions. Of 34 patients typed positive for A1-B8-DR3, 29 progressed to CDC stage IV, 22 to AIDS and 20 died. Twelve patients were typed positive for B27; six of these progressed to CDC stage IV, one to AIDS and none died. In a proportional hazards analysis of the 313 patients with known seroconversions, A1-B8-DR3 was significantly associated with covariate-adjusted relative risks of 3.7 (95% CI 1.9-7.2), 3.1 (1.6-6.0) and 1.9 (1.1-3.2) for progression from seroconversion to death, AIDS and CDC stage IV, respectively. Events for B27 were too rare to include B27 in analyses to death and AIDS, but B27 was significantly associated with slower progression to CDC stage IV (0.3, CI 0.1-0.9). Random effects growth curve models were used to estimate individual rates of loss of square root CD4 count and loss of CD4 percentage, for 603 and 617 patients, respectively. A1-B8-DR3 was associated with rapid loss of both markers (p = 0.02 and p = 0.01, respectively); B27 was associated with slow loss of both markers (p = 0.04 and p < 0.005).