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BACKGROUND: Controversy exists as to which surgical approach is best for total hip arthroplasty (THA). Previous studies suggested that the tissue-sparing anterior approach should result in a more rapid recovery requiring fewer postacute services, ultimately decreasing overall episodic cost. The purpose of this cross-sectional study was to determine if any significant differences exist between the anterior vs posterior approaches on postacute care service utilization, readmissions, or episodic cost. METHODS: Claims data from 26,773 Medicare fee-for-service beneficiaries receiving elective THAs (Medical Severity-Diagnosis Related Groups (MS-DRGs) 469/470) were analyzed. Claims data were collected from the 2-year period, January 2013 through December 2014. The posterior surgical approach was performed on 23,653 patients while 3120 patients received the anterior approach. RESULTS: Data analysis showed negligible effect sizes in postacute care service utilization, readmission rate, and cost between the surgical approaches for elective THA (MS-DRG 469 and 470). Average THA total episode cost was negligibly higher for procedures using the anterior approach compared to the posterior approach ($22,517 and $22,068, respectively). Statistically significant differences were observed in inpatient rehab and home health cost and service utilization. However, the effect sizes of these comparisons are negligible when accounting for the large sample size. All other comparisons showed minimal and statistically insignificant variation. CONCLUSION: The results indicate that surgical approach alone is not the primary driver of postacute care service utilization, quality outcomes, or cost. Other factors such as physician-led patient-focused care pathways, care coordination, rapid rehabilitation protocols, perioperative pain management protocols, and patient education are integral for effective patient care.

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Homeless people are susceptible to a range of health problems, yet in terms of health promotion, tend to be a hard-to-reach, marginalized group. Robust evidence regarding the ability to engage with this population via effective health promotion programmes is essential if policy and practice are to be informed to improve the health of homeless people. A structured review was conducted with the aim of examining what is known about community-based health promotion for homeless people. Six databases were searched and 8435 records screened. Thirteen studies met the inclusion criteria. A mixed-methods 'combined separate synthesis' approach was used to accommodate both quantitative and qualitative evidence within one review. Three themes emerged: (i) incorporating homelessness, (ii) health improving and (iii) health engaging. The review has implications for health promotion design, with evidence suggesting that as part of a tailored approach, homeless people must be actively involved in intervention development, ensuring that appropriate, acceptable and potentially effective individual elements are incorporated into community-based interventions.

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Biological complexity of mechanisms of autoimmune hemolytic anemia (AHAI) in chronic lymphocytic leukemia B (CLL) and the relation cause / effect between these two diseases has been extensively researched, but currently is still far from being completely understood. It is known that the immune system has an important role in the pathogenesis of autoimmune diseases but also in the chronic lymphoproliferative malignancies. In this process of autoimmunity associated with immunodeficiency, the CLL neoplastic cells, the non-malignant B cells, T cells, and the cellular microenvironment cells are also involved. CLL pathological lymphocytes change peripheral immune tolerance acting as an antigen presenting cells and / or cells expressing inhibitory cytokines. The two subpopulations of T cells also have an important place: self-reactive T helper cells (TH) and regulatory T cells (Treg). The Fas / Fas ligand - cell death mechanism has a significant role both in maintaining cellular homeostasis, malignant hematopoietic cell expansion and the development of autoimmune disorders, including AIHA. The article reviews the etiopathogenesis of the autoimmune mechanism of AIHA in CLL, and its impact on the prognosis and long - term survival of patients with chronic lymphocytic leukemia B.

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Chronic lymphocytic leukemia is still one of the most common hematologic malignancies. Finding a curative solution is the objective of numerous followed cases and clinical trials. Diagnosis is based on the interlocking of classic elements and newly identified prognostic factors but time to first treatment is still an open issue. CD38, ZAP 70, IgHV gene mutational status and cytogenetic changes are proven negatively influence the evolution of chronic lymphocytic leukemia. Whether through aggressive rapid evolution or by the difficulty of obtaining a complete remission or risk of early relapse, CLL is still important. Adapted to these prognostic factors, combined therapeutic regimens have proved to be effective in achieving a durable complete remission, new agents, with encouraging partial results, being studied. Requiring initial screening, for comparative purposes, a current and growing importance has minimal residual disease; its absence at the end of treatment represents a strong positive prognostic factor.

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Acute myeloid leukemia (AML) is a heterogeneous disease in clinical presentation, outcome and therapeutic response. Cytogenetic and molecular characteristics are important prognostic indicators allowing the identification of distinct subtypes of AML, prognostic stratification and risk-adapted treatment. We present our experience during 5 years, in which we treated 245 patients with AML, of which we could genetically characterize 48 cases (26 females, 22 males) with a median age of 52 years. Cytogenetic analysis was performed by GTG banding on cultures of marrow cells treated with colcemid. Molecular analysis used RT-PCR performed on ABI 9700 platform in order to identify the following fusion genes: E2A-PBX1, TEL-AML1, AML1-ETO, PML-RARα, MLL-AF4, CBFC-MYH11, BCR-ABL, SIL-TAL, and MLL-AF9as well as mutations in Flt3, NPM1, WT1 genes. Fourteen patients were older than 60 years. In 12 we performed cytogenetic analysis showing 5 cases with complex karyotype, 2 normal karyotypes, 1 case of del(21), del (9), 11q- and t(3;15) respectively as well as 2 unevaluable karyotypes. These anomalies were associated with a high incidence of secondary AMLs (10/14) and with a low remission (CR) rate (5/14). Out of the 35 patients younger than 60 years, 25 were evaluated by cytogenetics showing a high incidence of favorable cytogenetic changes: 6 anomalies of chromosome 16 (5 inv (16) and 1 t (16; 16)), 3 t (15; 17), 3 cases of t (8; 21) of which 2 with additional abnormalities, 7 normal karyotypes and 1 case of 7q-, -y,-3 and respectively -8 associated with +18. In 25 cases molecular analysis was performed showing alterations in 21 patients: 6 cases with AML/ETO, 3 PML/RAR, 7 Flt3 mutations (2 associated with NPM1 mutation) as well as 1 case of isolated mutation of NPM1 and respectively WT1. CR rate was of 28/35. All cases with t (15; 17) and PML/RAR as well all cases with t (8; 21) and/or AML/ETO achieved CR. Out of the 7 cases with Flt3 mutations only 4 achieved CR including the 2 cases with associated NPM1 mutations. In our experience, genetic characteristics correlate with other prognostic markers such as age and secondary leukemia; "favorable" genetic anomalies were associated with a high CR rate; association of t (8; 21) with additional abnormalities did not influence CR rate.

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Neural crest cells originate in the dorsal neural tube but subsequently undergo an epithelial-to-mesenchymal transition (EMT), delaminate, and migrate to diverse locations in the embryo where they contribute to a variety of derivatives. Cadherins are a family of cell-cell adhesion molecules expressed in a broad range of embryonic tissues, including the neural tube. In particular, cadherin6B (Cad6B) is expressed in the dorsal neural tube prior to neural crest emigration but is then repressed by the transcription factor Snail2, expressed by premigratory and early migrating cranial neural crest cells. To examine the role of Cad6B during neural crest EMT, we have perturbed Cad6B protein levels in the cranial neural crest-forming region and have examined subsequent effects on emigration and migration. The results show that knock-down of Cad6B leads to premature neural crest cell emigration, whereas Cad6B overexpression disrupts migration. Our data reveal a novel role for Cad6B in controlling the proper timing of neural crest emigration and delamination from the neural tube of the avian embryo.

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OBJECTIVES: To describe the changes in functional ability (FA) taking place over 5 yr in patients with rheumatoid arthritis (RA) starting disease-modifying anti-rheumatic drug (DMARD) therapy, to investigate the factors having most influence upon FA and to compare these factors at baseline and after 5 yr of treatment. METHODS: Three hundred and sixty-six patients with active RA were studied as part of a 5-yr randomized controlled study of DMARD therapy. FA was assessed by Health Assessment Questionnaire (HAQ) score every 6 months. Multiple linear regression was used to identify factors affecting FA at baseline and at 5 yr. The independent variables used were age, sex, visual analogue scale (VAS) pain, Ritchie articular index, C-reactive protein (CRP), Larsen score and log-transformed morning stiffness (EMS). RESULTS: Mean HAQ score was 1.64 at baseline, improved by 21% at 1 yr and gradually returned towards baseline levels by 5 yr. At baseline only 34% of variance in HAQ score could be explained; the most significant explanatory variables were the Ritchie articular index and CRP. At 5 yr the variance explained was 60%. The Ritchie articular index remained the strongest factor followed by VAS pain, log(10) EMS and Larsen score. CONCLUSIONS: Improvement in function did occur after commencement of the first DMARD therapy but was not maintained to 5 yr. The most consistent factor affecting function was joint tenderness. Global pain and duration of EMS were of lesser importance. Disease activity measures such as the CRP exerted an influence in the earlier, more active stages of disease: radiographic damage assumed greater importance as the arthritis progressed.

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The objective of this study was to quantify the incidence of underlying cervical intraepithelial neoplasia (CIN) among women referred for colposcopy with three consecutive inadequate smears. The design was a retrospective cohort study analysing data from a regional colposcopy database at Cervical Screening Wales. Women who were referred to all the colposcopy clinics in Wales with three consecutive inadequate smears, the third inadequate smear being taken between 1 April 2001 and 31 March 2002 constituted the study population. The results of the fourth smear taken at the colposcopy clinic after three consecutive inadequate smears, the worst biopsy results from any of the subsequent colposcopies and the relationship between the result of the fourth smear taken at colposcopy clinic and any histology result were the main outcome measures. The accuracy of the colposcopic opinion was also examined. Of the 433 women identified as having been referred because of three consecutive inadequate smears, 302 were linked to either a subsequent smear and/or a biopsy result. An adequate smear result was available for 85% of these women when the smear was taken in the colposcopy clinic; 77% were reported as negative and 8% were abnormal. Of the 347 women seen in the colposcopy clinic, high-grade CIN was seen in 3% and low-grade lesion in 8%. The sensitivity and specificity of the fourth inadequate smear test in predicting underlying CIN were 15% and 84% respectively, with a positive predictive value of 8%. The sensitivity and specificity of colposcopy in predicting histological CIN among patients with three inadequate smears was 70% and 49%, respectively, and the positive predictive value was 44%. This study raises the question as to whether three consecutive inadequate smears should be considered as an indication for colposcopy, or merely for a further smear to be taken in circumstances where there is a greater likelihood getting an adequate result.

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Left ventricular hypertrophy (LVH) measured by electrocardiography (ECG LVH) in hypertensive patients has been shown to be associated with an increased risk of cardiovascular sequelae. Analysis of the determinants predisposing to ECG LVH may be helpful in the prevention of LVH. The Department of Health and Social Security Hypertension Care Computer Project studied 2994 hypertensive patients in whom an electrocardiogram was recorded while not on treatment. LVH was determined as the voltage sum SV1+RV5 or RV6>or=35 mm using Sokolow-Lyon voltage criteria. The relations were determined between the presence of LVH or voltage sum and different variables. Untreated systolic (SBP) and diastolic (DBP) blood pressure and pulse pressure were positively related to the increasing ECG voltage, while body mass index (BMI) and serum cholesterol were inversely related. Blood glucose and age did not correlate significantly. Patients with the presence of ECG LVH were more often men, black people, smokers and users of alcohol. In multiple logistic regression analyses, SBP, DBP, male gender and black race were positively, whereas BMI was negatively related to the presence of LVH. The positive relation of smoking and negative relation of serum cholesterol concentration to the presence of ECG LVH were apparent in men but not in women. This study confirms the adverse association between ECG LVH and SBP and DBP, male gender, black race and decreased BMI. It also addresses the less well-known associations of blood glucose, cholesterol, smoking and alcohol consumption.

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Two different objectives of psychological assessment procedures are identified. It is suggested that excessive caution in interpreting and reporting the results of such procedures can limit their value.

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OBJECTIVE: Methylphenidate (MPH), the most commonly prescribed drug for attention-deficit/hyperactivity disorder (ADHD), has a short half-life, which necessitates multiple daily doses. The need for multiple doses produces problems with medication administration during school and after-school hours, and therefore with compliance. Previous long-acting stimulants and preparations have shown effects equivalent to twice-daily dosing of MPH. This study tests the efficacy and duration of action, in natural and laboratory settings, of an extended-release MPH preparation designed to last 12 hours and therefore be equivalent to 3-times-daily dosing. METHODS: Sixty-eight children with ADHD, 6 to 12 years old, participated in a within-subject, double-blind comparison of placebo, immediate-release (IR) MPH 3 times a day (tid), and Concerta, a once-daily MPH formulation. Three dosing levels of medication were used: 5 mg IR MPH tid/18 mg Concerta once a day (qd); 10 mg IR MPH tid/36 mg Concerta qd; and 15 mg IR MPH tid/54 mg Concerta qd. All children were currently medicated with MPH at enrollment, and each child's dose level was based on that child's MPH dosing before the study. The doses of Concerta were selected to be comparable to the daily doses of MPH that each child received. To achieve the ascending rate of MPH delivery determined by initial investigations to provide the necessary continuous coverage, Concerta doses were 20% higher on a daily basis than a comparable tid regimen of IR MPH. Children received each medication condition for 7 days. The investigation was conducted in the context of a background clinical behavioral intervention in both the natural environment and the laboratory setting. Parents received behavioral parent training and teachers were taught to establish a school-home daily report card (DRC). A DRC is a list of individual target behaviors that represent a child's most salient areas of impairment. Teachers set daily goals for each child's impairment targets, and parents provided rewards at home for goal attainment. Each weekday, teachers completed the DRC, and it was used as a dependent measure of individualized medication response. Teachers and parents also completed weekly standardized ratings of behavior and treatment effectiveness. To evaluate the time course of medication effects, children spent 12 hours in a laboratory setting on Saturdays and medication effects were measured using procedures and methods adapted from our summer treatment program. Measures of classroom behavior and academic productivity/accuracy were taken in a laboratory classroom setting during which children completed independent math and reading worksheets. Measures of social behavior were taken in structured, small-group board game settings and unstructured recess settings. Measures included behavior frequency counts, academic problems completed and accuracy, independent observations, teacher and counselor ratings, and individualized behavioral target goals. Reports of adverse events, sleep quality, and appetite were collected. RESULTS: On virtually all measures in all settings, both drug conditions were significantly different from placebo, and the 2 drugs were not different from each other. In children's regular school settings, both medications improved behavior as measured by teacher ratings and individualized target behaviors (the DRC); these effects were seen into the evening as measured by parent ratings. In the laboratory setting, effects of Concerta were equivalent to tid MPH and lasted at least through 12 hours after dosing. Concerta was significantly superior to tid MPH on 2 parent rating scores, and when asked, more parents preferred Concerta than preferred tid IR MPH or placebo. Side effects on children's sleep and appetite were similar for the 2 preparations. In the lab setting, both medications improved productivity and accuracy on arithmetic seatwork assignments, disruptive and on-task behavior, and classroom rule following. Both medications improved children's rule following and negative behavior in small group board games, as well as in unstructured recess settings. Individual target behaviors also showed significant improvement with medication across domains in the laboratory setting. Children's behavior across settings deteriorated across the laboratory day, and the primary effect of medication was to prevent this deterioration as the day wore on. Results support the use of background behavioral treatment in clinical trials of stimulant medication, and illustrate the utility of a measure of individualized daily target goals (ie, the DRC) as an objective measure of medication response in both the laboratory and natural school settings. CONCLUSION: This investigation clearly supports the efficacy of the Concerta long-acting formulation of MPH for parents who desire to have medication benefits for their child throughout the day and early evening. (ABSTRACT TRUNCATED)

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The vertebrate hindbrain is segmented into a series of transient structures called rhombomeres. Despite knowing several factors that are responsible for the segmentation and maintenance of the rhombomeres, there are still large gaps in understanding the genetic pathways that govern their development. To find previously unknown genes that are expressed within the embryonic hindbrain, a subtracted chick hindbrain cDNA library has been made and 445 randomly picked clones from this library have been analysed using whole mount in situ hybridisation. Thirty-six of these clones (8%) display restricted expression patterns within the hindbrain, midbrain or cranial neural crest and of these, twenty-two are novel and eleven encode peptides that correspond to or are highly related to proteins with previously uncharacterised roles during early neural development. The large proportion of genes with restricted expression patterns and previously unknown functions in the embryonic brain identified during this screen provides insights into the different types of molecules that have spatially regulated expression patterns in cranial neural tissue.

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Induction, migration and differentiation of the neural crest are crucial for the development of the vertebrate embryo, and elucidation of the underlying mechanisms remains an important challenge. In the past year, a novel signal regulating the formation of neural crest cells has been identified, and advances have been made in uncovering roles for bone morphogenetic protein signals and for a transcription factor in the onset of neural crest migration. There have been new insights into the migration and plasticity of branchial neural crest cells. Important progress has been made in dissecting the roles of bone morphogenetic protein, Wnt and Notch signalling systems and their associated downstream transcription factors in the control of neural crest cell differentiation.

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OBJECTIVE: An elevated acute-phase response is associated with increased radiologic damage in rheumatoid arthritis (RA), but development of damage in previously normal joints ("new joint involvement") has not previously been investigated. This study was undertaken to investigate the hypothesis that when there is suppression of disease activity as judged by the C-reactive protein level, new joint involvement is reduced to a greater extent than is progression in already damaged joints ("damaged joint progression"). METHODS: Three hundred fifty-nine patients with active RA were studied as part of a 5-year randomized, prospective, open-label study of disease-modifying antirheumatic drug therapy. Time-averaged CRP was calculated from samples obtained every 6 months, and patients were divided into groups with CRP values of <6, 6-<12, 12-<25, and > or =25 mg/liter. Radiographs of the hands and feet were scored by the Larsen method; a damaged joint was defined as one with a score of > or =2. RESULTS: The rank correlation between time-integrated CRP and increase in Larsen score was 0.50; the correlation increased to 0.59 for patients entering the study with disease duration of < or =2 years. The percentage of new joint involvement over 5 years varied markedly with time-integrated CRP, from 7.3% in the CRP <6 mg/liter group to 39.1% in the CRP > or =25 mg/liter group (5.4-fold increase). The percentage of damaged joint progression increased from 26.1% in the CRP <6 mg/liter group to 41.6% in the CRP > or =25 mg/liter group (1.6-fold increase). CONCLUSION: The results of this study provide further confirmation that high CRP levels over time are associated with greater radiologic progression. Although radiologic progression still occurred in both previously normal and damaged joints despite the presence of normal CRP levels, this consisted of proportionately less new joint involvement compared with damaged joint progression. These findings support the idea that disease-suppressive therapy should be instituted at an early stage in patients with RA, before erosive damage has occurred.

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OBJECTIVE: Recent studies have shown inconsistent results on the risk of cancer in hypertensive patients using calcium channel blockers (CCBs) and angiotensin-converting enzyme (ACE) inhibitors. We investigated a large number of patients from the Department of Health Hypertension Care Computing Project (DHCCP) observational database treated with these drugs for hypertension to see whether the use of CCBs for hypertension is associated with an increased risk of cancer mortality and the use of ACE inhibitors with a reduction. DESIGN: Matched case-control study and a longitudinal study of survival from 1 year after presentation. PATIENTS: A total of 11663 patients treated for hypertension from 1971 through 1987. They were recruited on presentation to one of the hospital hypertension clinics or general practices involved. MAIN OUTCOME MEASURES: Death with any mention of cancer on the death certificate in patients treated with an Index drug group; CCBs, ACE inhibitors, beta adrenergic blocking drugs (BBs), or receiving a diuretic. The treatment groups were mutually exclusive. RESULTS: A total of 391 cases of cancer were matched with 1050 controls. In this case-control study the adjusted relative risk estimate in comparison to diuretic treatment for CCBs was 0.79 (95% CI 0.37 to 1.69), and for CCBs plus a diuretic, 1.05 (0.65 to 1.69). Non-significant results were also observed for ACE inhibitors (1.48 (0.43 to 5.1), and 1.40 (0.56 to 3.50) with a diuretic), and also for the BB and methyldopa groups. In the longitudinal survival study, the adjusted relative risk estimate for CCBs was 1.1 (0.60 to 1.94) and 1.0 (0.53 to 1.86) for CCBs plus a diuretic, and for ACE inhibitors 1.33 (0.37 to 4.76) and 1.47 (0.67 to 3.23), respectively. CONCLUSIONS: In this population there was no increased cancer mortality with the use of CCBs and a relative risk greater than 1.7 to 2.0 was excluded with 95% confidence. The suggestion that ACE inhibitors reduce cancer mortality was not supported with best estimates of relative risk of 1.3 to 1.5 and exclusion of values less than 0.4 to 0.7.

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Maternal smoking rates in pregnancy have declined, particularly in the non-manual social classes, and perinatal mortality rates have fallen over the last 20 years. We have therefore re-evaluated the relationship between maternal cigarette smoking and pregnancy outcome against this background. A total of 608 stillbirths and 634 infant deaths were identified using the All Wales Perinatal Survey. The cause of death was classified using the clinicopathological system. Maternal smoking rates and social class groupings were compared with those in a cohort of 16047 survivors born to women resident in South Glamorgan. The smoking rate was 37.8% in mothers of babies who died compared with 27.2% in mothers of survivors, an odds ratio (OR) of 1.63 [95% CI 1.44, 1.84]. The OR for unexplained stillbirth was 1.72 [95% CI 1.38, 2.13], placental abruption 2.07 [95% CI 1.29, 3.31], infection 3.70 [95% CI 2.23, 6.13] and sudden infant death syndrome 4.84 [95% CI 3.05, 7.69]. Maternal smoking was not associated with death due to prematurity or a congenital anomaly. Despite changes in smoking habits and the causes of perinatal death, smoking during pregnancy continues to be strongly associated with fetal and infant mortality. It is important that health promotion activities are effective in reducing smoking during pregnancy.

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The structure of the legal concept of unfitness to stand trial and how it corresponds to psychometric concepts is examined. We conclude that psychometric attempts at quantification and measurement are logically flawed, because they inappropriately treat fitness/unfitness as an individual trait rather than as situation-specific conjunctive/disjunctive concepts. It is argued that, whereas psychometric approaches may be suitable for measuring single components of unfitness, an overall "fitness" score is meaningless and that the assessment should focus on elements of unfitness. The determination of unfitness requires the simultaneous consideration of several different individual capabilities in reference to the demands of a specific trial. The quantification of these specific capabilities by psychologists can assist psychiatrists and the court, but the evaluation of their influence on unfitness in the instant case must be left to the court.

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BACKGROUND: The UK has published observed cohort survival figures for subjects with cystic fibrosis born since 1968. Prior to 1968 cohorts cannot be established directly from routine data as cystic fibrosis was classified with a number of unrelated conditions in ICD7. Reported here are interrupted survival curves from 1978 for patients with cystic fibrosis born before 1968. METHODS: Life tables for the three year cohorts born between 1947 and 1967 were constructed by firstly estimating the numbers of patients with cystic fibrosis born in each cohort from live birth data and the disease incidence. The number of the estimated cohort that had survived to 1978 is known, which enables the proportion surviving to 1978 to be calculated. The survival of these cohorts after 1978 can be calculated in the usual way. RESULTS: The survival for each successive cohort was better than that of the previous one, but most of the improvements appear to have taken place up to the age of about 20 years. Only 3% of the 1947-49 cohort survived to 30 years of age compared with 21% for the 1965-67 cohort, and 3% of the 1953-55 cohort survived to 40 years of age. For the later cohorts the mortality rate for those aged between 26 and 30 years appears to be about 50 per 1000 per year. CONCLUSIONS: While the trend in the numbers surviving into later adulthood is upwards, the mortality rates for these ages does not appear to be improving. It is not possible to tell from these data whether the high mortality rates in adulthood will improve with better resourced adult clinics or with improved treatment during childhood.

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