Timing of procedural stroke and death in asymptomatic patients undergoing carotid endarterectomy: individual patient analysis from four RCTs.

BACKGROUND: The effectiveness of carotid endarterectomy (CEA) for stroke prevention depends on low procedural risks. The aim of this study was to assess the frequency and timing of procedural complications after CEA, which may clarify underlying mechanisms and help inform safe discharge policies. METHODS: Individual-patient data were obtained from four large carotid intervention trials (VACS, ACAS, ACST-1 and GALA; 1983-2007). Patients undergoing CEA for asymptomatic carotid artery stenosis directly after randomization were used for the present analysis. Timing of procedural death and stroke was divided into intraoperative day 0, postoperative day 0, days 1-3 and days 4-30. RESULTS: Some 3694 patients were included in the analysis. A total of 103 patients (2·8 per cent) had serious procedural complications (18 fatal strokes, 68 non-fatal strokes, 11 fatal myocardial infarctions and 6 deaths from other causes) [Correction added on 20 April, after first online publication: the percentage value has been corrected to 2·8]. Of the 86 strokes, 67 (78 per cent) were ipsilateral, 17 (20 per cent) were contralateral and two (2 per cent) were vertebrobasilar. Forty-five strokes (52 per cent) were ischaemic, nine (10 per cent) haemorrhagic, and stroke subtype was not determined in 32 patients (37 per cent). Half of the strokes happened on the day of CEA. Of all serious complications recorded, 44 (42·7 per cent) occurred on day 0 (20 intraoperative, 17 postoperative, 7 with unclear timing), 23 (22·3 per cent) on days 1-3 and 36 (35·0 per cent) on days 4-30. CONCLUSION: At least half of the procedural strokes in this study were ischaemic and ipsilateral to the treated artery. Half of all procedural complications occurred on the day of surgery, but one-third after day 3 when many patients had been discharged.

ANTECEDENTES: La efectividad de la endarterectomía carotídea (carotid endarterectomy, CEA) en la prevención de un accidente cerebrovascular depende de que este procedimiento tenga pocos riesgos. El objetivo de este estudio fue evaluar la frecuencia y el momento de aparición de las complicaciones tras una CEA, lo que podría clarificar los mecanismos subyacentes y ayudar a establecer una política de altas hospitalarias segura. MÉTODOS: Se utilizaron los datos de los pacientes incluidos en cuatro grandes ensayos de intervención carotídea (VACS, ACAS, ACST-1 y GALA; 1983-2007). Para el presente análisis se utilizaron los datos de pacientes sometidos a CEA por estenosis de la arteria carótida asintomática recogidos inmediatamente tras la aleatorización. Se consideraron diferentes intervalos entre el procedimiento, la muerte o el accidente cerebrovascular: intraoperatorio día 0, postoperatorio día 0, postoperatorio días 1-3 y postoperatorio días 4-30. RESULTADOS: En el análisis se incluyeron 3.694 pacientes. Se detectaron complicaciones graves relacionadas con el procedimiento en 103 (2,8%) pacientes (18 accidentes cerebrovasculares fatales, 68 accidentes cerebrovasculares no fatales, 11 infartos de miocardio fatales y 6 muertes por otras causas). De los 86 accidentes cerebrovasculares, 67 (78%) fueron ipsilaterales, 17 (20%) contralaterales y dos (2%) vertebrobasilares. Los accidentes cerebrovasculares fueron isquémicos en 45 (52%) casos, hemorrágicos en 9 (10%) y no se pudo determinar el subtipo de ictus en 32 (37%). La mitad de los accidentes cerebrovasculares ocurrieron el día de la CEA. De todas las complicaciones graves registradas, 44 (43%) ocurrieron en el día 0 (20 intraoperatorias, 17 postoperatorias y 7 en períodos poco definidos), 23 (22%) entre los días 1-3 y 36 (35%) entre los días 4-30. CONCLUSIÓN: En este estudio, al menos la mitad de los accidentes cerebrovasculares relacionados con la CEA fueron isquémicos e ipsilaterales respecto a la arteria tratada. La mitad de todas las complicaciones de la CEA ocurrieron el día de la cirugía, pero un tercio de los casos se presentaron después del día 3, cuando muchos pacientes ya habían sido dados de alta.

Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I.

BACKGROUND: M184V/I cause high-level lamivudine (3TC) and emtricitabine (FTC) resistance and increased tenofovir disoproxil fumarate (TDF) susceptibility. Nonetheless, 3TC and FTC (collectively referred to as XTC) appear to retain modest activity against human immunodeficiency virus-1 with these mutations possibly as a result of reduced replication capacity. In this study, we determined how M184V/I impacts virus load (VL) in patients failing therapy on a TDF/XTC plus nonnucleoside reverse-transcriptase inhibitor (NNRTI)-containing regimen. METHODS: We compared VL in the absence and presence of M184V/I across studies using random effects meta-analysis. The effect of mutations on virus reverse-transcriptase activity and infectiousness was analyzed in vitro. RESULTS: M184I/V was present in 817 (56.5%) of 1445 individuals with virologic failure (VF). Virus load was similar in individuals with or without M184I/V (difference in log10 VL, 0.18; 95% confidence interval, .05-.31). CD4 count was lower both at initiation of antiretroviral therapy and at VF in participants who went on to develop M184V/I. L74I was present in 10.2% of persons with M184V/I but absent in persons without M184V/I (P < .0001). In vitro, L74I compensated for defective replication of M184V-mutated virus. CONCLUSIONS: Virus loads were similar in persons with and without M184V/I during VF on a TDF/XTC/NNRTI-containing regimen. Therefore, we did not find evidence for a benefit of XTC in the context of first-line failure on this combination.

Blood pressure and risk of dementia and its subtypes: a historical cohort study with long-term follow-up in 2.6 million people.

BACKGROUND AND PURPOSE: Elevated blood pressure (BP) is prevalent and modifiable and has been hypothesized to lead to increased risk of dementia. DATA: Data on 2 593 629 people from the UK Clinical Practice Research Database aged ≥40 years with a BP measurement between 1992 and 2011 and no prior record of dementia were collected. METHODS: Poisson regression models were used to study the association between BP and physician-diagnosed dementia. BP is believed to fall during the prodromal phase of dementia development, so associations were investigated by categories of time since BP measurement (<5, 5-10, >10 years) and by subtypes of dementia. RESULTS: During a median follow-up of 8.2 years, 65 618 cases of dementia were observed: 49 161 Alzheimer's, 13 816 vascular dementia and 2541 other subtypes. For each 10 mmHg higher systolic BP, the future dementia risk was 9.2% (95% confidence interval 8.4%-10.0%) lower, but this association varied markedly by time since BP measurement. Short-term associations with dementia were inverse with a 15.8% (15.5%-17.0%) lower risk 0-5 years after BP measurement and a 5.8% (7.7%-4.4%) lower risk 5-10 years after BP measurement. During the period >10 years after BP measurement, dementia risk was only 1.6% (0.1%-3.0%) lower, with a 4.3% (2.5%-6.0%) lower risk of Alzheimer's disease and a 7.0% (3.8%-10.2%) higher risk of vascular dementia. CONCLUSIONS: Elevated BP is associated with decreased risk of dementia in the short term, possibly due to reverse causation. Long-term associations of BP with dementia are less marked and differ by dementia subtype.

HIV-1 subtype influences susceptibility and response to monotherapy with the protease inhibitor lopinavir/ritonavir.

OBJECTIVE: PI susceptibility results from a complex interplay between protease and Gag proteins, with Gag showing wide variation across HIV-1 subtypes. We explored the impact of pre-treatment susceptibility on the outcome of lopinavir/ritonavir monotherapy. METHODS: Treatment-naive individuals who experienced lopinavir/ritonavir monotherapy failure from the MONARK study were matched (by subtype, viral load and baseline CD4 count) with those who achieved virological response ('successes'). Successes were defined by viral load <400 copies/mL after week 24 and <50 copies/mL from week 48 to week 96. Full-length Gag-protease was amplified from patient samples for in vitro phenotypic susceptibility testing, with susceptibility expressed as fold change (FC) relative to a subtype B reference strain. RESULTS: Baseline lopinavir susceptibility was lower in viral failures compared with viral successes, but the differences were not statistically significant (median lopinavir susceptibility: 4.4 versus 8.5, respectively, P = 0.17). Among CRF02_AG/G patients, there was a significant difference in lopinavir susceptibility between the two groups (7.1 versus 10.4, P = 0.047), while in subtype B the difference was not significant (2.7 versus 3.4, P = 0.13). Subtype CRF02_AG/G viruses had a median lopinavir FC of 8.7 compared with 3.1 for subtype B (P = 0.001). CONCLUSIONS: We report an association between reduced PI susceptibility (using full-length Gag-protease sequences) at baseline and subsequent virological failure on lopinavir/ritonavir monotherapy in antiretroviral-naive patients harbouring subtype CRF02_AG/G viruses. We speculate that this may be important in the context of suboptimal adherence in determining viral failure.

Predicting spasticity after stroke in those surviving to 12 months.

OBJECTIVE: To measure muscle tone in a cohort of patients 12 months after stroke and develop a preliminary model, using data recorded routinely after stroke, to predict who will develop spasticity. DESIGN: A cohort study. SETTING: Initially hospitalized but subsequently community-dwelling stroke survivors in Liverpool, United Kingdom. SUBJECTS: One hundred and six consecutively presenting stroke patients surviving to 12 months. MAIN OUTCOME MEASURES: Spasticity measured at a range of joints using the Tone Assessment Scale. RESULTS: The Tone Assessment Scale revealed spasticity in 38 (36%) patients and more severe spasticity in 21 (20%) of the 106 patients. Logistic regression analysis revealed that lower day 7 Barthel Index score and early arm or leg weakness were significant predictors of abnormal muscle tone; and lower day 7 Barthel Index score, left-sided weakness and ever smoked to be significant predictors of more severe muscle tone. CONCLUSIONS: Using the models, it may be possible to predict whether or not spasticity will develop in patients 12 months after stroke. The utility of the models is aided by their use of predictor variables that are routinely collected as part of stroke care in hospital and which are easy to measure. The models need testing prospectively in a new cohort of patients in order to test their validity, reliability and utility and to determine if other data could improve their efficiency.

Prevalence of spasticity post stroke.

OBJECTIVES: To establish the prevalence of spasticity 12 months after stroke and examine its relationship with functional ability. DESIGN: A cohort study of prevalence of spasticity at 12 months post stroke. SETTING: Initially hospitalized but subsequently community-dwelling stroke survivors in Liverpool, UK. SUBJECTS: One hundred and six consecutively presenting stroke patients surviving to 12 months. MAIN OUTCOME MEASURES: Muscle tone measured at the elbow using the Modified Ashworth Scale and at several joints, in the arms and legs, using the Tone Assessment Scale; functional ability using the modified Barthel Index. RESULTS: Increased muscle tone (spasticity) was present in 29 (27%) and 38 (36%) of the 106 patients when measured using the Modified Ashworth Scale and Tone Assessment Scale respectively. Combining the results from both scales produced a prevalence of 40 (38%). Those with spasticity had significantly lower Barthel scores at 12 months (p < 0.0001). CONCLUSION: When estimating the prevalence of spasticity it is essential to assess both arms and legs, using both scales. Despite measuring tone at several joints, spasticity was demonstrated in only 40 (38%) patients, lower than previous estimates.

System, environmental, and policy changes: using the social-ecological model as a framework for evaluating nutrition education and social marketing programs with low-income audiences.

A variety of nutrition education interventions and social marketing initiatives are being used by the Food Stamp Program to improve food resource management, food safety, dietary quality, and food security for low-income households. The Social-Ecological Model is proposed as a theory-based framework to characterize the nature and results of interventions conducted through large public/private partnerships with the Food Stamp Program. In particular, this article suggests indicators and measures that lend themselves to the pooling of data across counties and states, with special emphasis on systems, environment, and public policy change within organizations at the community and state levels.

Reliability of measurements of muscle tone and muscle power in stroke patients.

OBJECTIVES: to establish the reliability of the modified Ashworth scale for measuring muscle tone in a range of muscle groups (elbow, wrist, knee and ankle; flexors and extensors) and of the Medical Research Council scale for measuring muscle power in the same muscle groups and their direct antagonists. DESIGN: a cross-sectional study involving repeated measures by two raters. We estimated reliability using the kappa statistic with quadratic weights (Kw). SETTING: an acute stroke ward, a stroke rehabilitation unit and a continuing care facility. SUBJECTS: people admitted to hospital with an acute stroke-35 patients, median age 73 (interquartile range 65-80), 20 men and 15 women. RESULTS: inter- and intra-rater agreement for the measurement of power was good to very good for all tested muscle groups (Kw = 0.84-0.96, Kw = 0.70-0.96). Inter- and intra-rater agreement for the measurement of tone in the elbow, wrist and knee flexors was good to very good (Kw = 0.73-0.96, Kw = 0.77-0.94). Inter- and intra-rater agreement for the measurement of tone in the ankle plantarflexors was moderate to good (Kw = 0.45-0.51, Kw = 0.59-0.64). CONCLUSIONS: the Medical Research Council scale was reliable in the tested muscle groups. The modified Ashworth scale demonstrated reliability in all tested muscle groups except the ankle plantarflexors. If reliable measurement of tone at the ankle is required for a specific purpose (e.g. to measure the effect of therapeutic intervention), further work will be necessary.

Reliability of the Tone Assessment Scale and the modified Ashworth scale as clinical tools for assessing poststroke spasticity.

OBJECTIVES: To establish reliability of the Tone Assessment Scale and modified Ashworth scale in acute stroke patients. SETTING: A North Liverpool university hospital. PATIENTS: Eighteen men and 14 women admitted with acute stroke and still in hospital at the study start date (median age, 74 yrs; median Barthel score, 8). MAIN OUTCOME MEASURES: The modified Ashworth scale and the Tone Assessment Scale. STUDY DESIGN: The 32 patients were examined with both scales on the same occasion by two raters (interrater comparison) and on two occasions by one rater (intrarater comparison). RESULTS: The reliability of the modified Ashworth scale was very good (kappa = .84 for interrater and .83 for intrarater comparisons). The reliability of the Tone Assessment Scale was not as strong as the modified Ashworth scale, with marked variability in the assessment of posture (kappa = .22 to .50 for interrater and .29 to .55 for intrarater comparisons) and associated reaction (kappa/kappaW = -.05 to .79 for interrater and .19 to .83 for intrarater comparisons). However, those aspects of the Tone Assessment Scale that addressed response to passive movement and that are scored similarly to the modified Ashworth scale showed good to very good interrater reliability (kappaW = .79 to .92) and good to very good intrarater reliability (kappaW = .72 to .86), except for the question related to movement at the ankle where agreement was only moderate (kappaW = .59). CONCLUSIONS: The modified Ashworth scale is reliable. The section of the Tone Assessment Scale relating to response to passive movement is reliable at various joints, except the ankle. It may assist in studies on the prevalence of spasticity after stroke and the relationship between tone and function. Further development of a measure of spasticity at the ankle is required. The Tone Assessment Scale is not reliable for measuring posture and associated reactions.

Double Dutch: looking at the usage of combined pill plus condom in girls under 25.

OBJECTIVE: To establish what proportion of young girls who were prescribed the contraceptive pill at Manchester family planning clinics have first remembered, and second followed, advice also to use the condom for protection from sexually transmitted infection. METHOD: An anonymous self-administered questionnaire was issued to all females up to the age of 25 years, who were already using the pill and who attended one of 20 different clinic locations. Questions included duration of present relationship, frequency of condom use and reasons for use or non-use. RESULTS: The age of respondents ranged from 13 to 25 years, with one-third in the group of 17-19-year-olds. Out of 104 responses, condoms were used most of the time by 29 girls, occasionally by 42 and never by 33. Only 15 of the 104 knew the phrase 'double Dutch'. Dual use most of the time primarily for sexually transmitted disease protection was reported by 23 girls. Previous treatment for sexually transmitted disease was reported by 14 girls, of whom half never used condoms and only three now used condoms most of the time. In the group of girls using condoms occasionally, 70% were using condoms primarily to cover missed pills, antibiotics, etc. Extrapolating from the number of condoms used in the past month and the fact that 80% of girls obtained their condoms from the clinic, the extra cost to the family planning budget is over 14,000 Pounds (over 22,500 Ecu) per year. CONCLUSION: Our result that 22% of young pill users regularly used condoms to protect from sexually transmitted diseases indicates that the message is understood, but the term 'double Dutch' is not.

Mortality following cotton defoliation: San Joaquin Valley, California, 1970-1990.

A proportional mortality study comparing the cotton-growing areas of the San Joaquin Valley with the rest of the State of California was performed by the Office of Environmental Health Hazard Assessment as a continuation of earlier studies related to mercaptan-releasing pesticides. This mortality study found a pattern of increased proportion of "respiratory causes" mortality (ICD codes 460-519), statistically significant at less than the .05 probability level, for 15 of 21 years between 1970 and 1990, for the time period during and immediately following cotton defoliation. Defoliants which have the potential to produce acute symptoms include DEF and Folex, both of which release odorous butyl mercaptan gas as a degradation product. This paper tests the hypothesis that exposure to cotton defoliant breakdown products may be associated with a disproportionate increase in mortality. Prediction of the mortality proportions by pounds of DEF and Folex used was not statistically significant in the unadjusted models or in models adjusted for air pollution variables. One air pollution adjustment factor, total suspended particulates, was a statistically significant independent mortality proportion predictor. This finding suggests that total suspended particulates, not defoliants, may be related to mortality differentials during defoliation season. Possible confounding by demographic variation of the counties was not controlled in the analysis.

Chemoenzymic synthesis of sialylated and fucosylated oligosaccharides having an N-acetyllactosaminyl core.

Several sialylated and fucosylated oligosaccharides, based upon the N-acetyllactosaminyl core structure, have been synthesized from a single trisaccharide glycoside, beta-D-GlcNAc-(1-->3)-beta-D-Gal-(1-->4)-beta-D-GlcNAc-OCH2(CH2)++ +7CO2CH3, by the sequential use of several glycosyltransferases and one sialidase. In these chemoenzymic syntheses, selective internal monofucosylation of a dimeric N-acetyl-lactosaminyl tetrasaccharide is achieved via two routes. It is demonstrated that the pentasaccharide beta-D-Gal-(1-->4)-beta-D-GlcNAc-(1-->3)-beta-D-Gal-(1-->4)-[alpha- L-Fuc-(1-->3)]-beta-D-GlcNAc-OCH2(CH2)7-CO2CH3 is an acceptor for the rat liver beta-D-Gal-(1-->3/4)-D-Glc-NAc alpha 2,3- and beta-D-Gal-(1-->4)-D-GlcNAc alpha 2,6-sialyltransferases. Among the structures obtained is the terminal hexasaccharide of the CD-65/VIM-2 epitope.

Structure of the archaeal transfer RNA nucleoside G*-15 (2-amino-4,7-dihydro- 4-oxo-7-beta-D-ribofuranosyl-1H-pyrrolo[2,3-d]pyrimidine-5-carboximi dam ide (archaeosine)).

A number of post-transcriptional modifications in tRNA are phylogenetically characteristic of the bacterial, eukaryal, or archaeal domains, both with respect to sequence location and molecular structure at the nucleoside level. One of the most distinct such modifications is nucleoside G*, located in archaeal tRNA at position 15, which in bacterial and eukaryal tRNAs is a conserved site involved in maintenance of the dihydrouridine loop-T-loop tertiary interactions. G* occurs widely in nearly every branch of the archaeal phylogenetic domain, in contrast to its absence in all reported bacterial and eukaryal tRNA sequences. The structure of G*-15 is 2-amino-4,7-dihydro-4-oxo-7-beta-D-ribofuranosyl-1H- pyrrolo[2,3-d]pyrimidine-5-carboximidamide (7-formamidino-7-deazaguanosine), which is a non-purine, non-pyrimidine ribonucleoside; its structure thus reflects extensive modification beyond the guanine-15 specified by corresponding gene sequences. The structure was established by mass spectrometry, and in particular from collision-induced dissociation mass spectra of derivatives formed by microscale permethylation, and is confirmed by chemical synthesis.

Development of a clinical measure of postural control for assessment of adaptive seating in children with neuromotor disabilities.

The primary purposes of this article are to review the literature on seating assessment and to describe the development of a clinical evaluation scale, the Seated Postural Control Measure (SPCM), for use with children requiring adaptive seating systems. The SPCM is an observational scale of 22 seated postural alignment items and 12 functional movement items, each scored on a four-point, criterion-referenced scale. A secondary purpose of this article is to report the reliability of the seven-point Level of Sitting Scale (LSS). Interrater and test-retest reliability of the SPCM items and the one-item LSS were evaluated on a sample of 40 children with developmental disabilities who sat with and without their seating systems. Kappa values of .75 or higher were considered excellent, .40 to .74 as fair to good, and less than .40 as poor. The interrater reliability tests for the two seated conditions and the two test sessions conducted 3 weeks apart yielded overall item Kappa coefficient means of .45 for the alignment section and .85 for the function section. Test-retest results for the SPCM items were less satisfactory, with item Kappa coefficient means for the two seating conditions and raters of .35 and .29 for alignment and function, respectively. Reliability results did not appear to be consistently better among seating conditions, raters, or test sessions. Kappa coefficients for the LSS were fair to good for both interrater and test-retest reliability. Plans for future development of the SPCM and LSS are discussed.

Altered sex differentiation of hepatic ethylmorphine N-demethylation in the male rat following neonatal methadone exposure.

Since acute methadone treatment reduces serum androgen levels in adult male rats, we have investigated the effect of exposure of neonatal rats to methadone (M) on the "neonatal imprinting" of hepatic monooxygenase by testosterone. The kinetic constants for ethylmorphine N-demethylation (ED) in hepatic microsomes of adult rats are sex-related (female Km greater than male Km and male Vmax greater than female Vmax). Treatment of male neonates with M (2.5 mg/kg, sc) during the first 5 postnatal days resulted in an elevation of the Km, but no significant changes in the Vmax for ED in adult life. The M-induced "feminization" of the Km for ED could be prevented by a single dose of testosterone propionate (TP) given to the neonates on day 2 following birth. M treatment also reduced in a reversible manner neonatal serum androgen levels: Decreased androgen levels were not observed beyond the fifth postnatal day. These data suggest that the feminizing effect of M may be related to a reversible chemical castration effect during a critical neonatal period. Our studies also show that the imprinting of the Km and Vmax for ED do not occur during the identical period.