Cage subsidence after anterior cervical discectomy and fusion using a cage alone or combined with anterior plate fixation.

PURPOSE: To compare the extent of cage subsidence after anterior cervical discectomy and fusion (ACDF) using a cage alone or combined with anterior plate fixation, and to assess the effect of end plate removal on cage subsidence. METHODS: Records of 23 men and 13 women aged 32 to 82 (mean, 54) years who underwent ACDF for 61 levels using the Solis cage alone (n=46) or combined with anterior plate fixation (n=15) were reviewed. The extent of cage subsidence was determined by comparing immediately postoperative (within one week) with final follow-up radiographs. Cage subsidence was defined as the sum subsidence of the superior and inferior part of the cage into the vertebral body. Mild and major cage subsidence was defined as ≤2 mm and >2 mm, respectively. RESULTS: Patients who underwent ACDF using a cage alone or combined with anterior plate fixation were comparable in terms of age, gender, follow-up duration, and number of levels decompressed. Cage subsidence occurred in 33 (54%) of the 61 levels decompressed. In the cage alone group, the extent of cage subsidence was greater (1.68 vs. 0.57 mm, p=0.039) and the rate of major cage subsidence was higher (28% vs. 7%, p=0.08). The inferior part of the cage was more vulnerable to subsidence compared with the superior part (median subsidence: 3.0 vs. 1.4 mm, p<0.0001). Cage subsidence occurred more often when the end plate was removed rather than preserved (58% vs. 18%, p<0.002). CONCLUSION: The extent of cage subsidence was greater after ACDF with cage alone. Cage subsidence occurred more often when the end plate was removed. Additional anterior plate fixation is recommended when the end plate is removed.

Sedentary time and markers of inflammation in people with newly diagnosed type 2 diabetes.

BACKGROUND AND AIMS: We investigated whether objectively measured sedentary time was associated with markers of inflammation in adults with newly diagnosed type 2 diabetes. METHODS AND RESULTS: We studied 285 adults (184 men, 101 women, mean age 59.0 ± 9.7) who had been recruited to the Early ACTivity in Diabetes (Early ACTID) randomised controlled trial. C-reactive protein (CRP), adiponectin, soluble intracellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), and accelerometer-determined sedentary time and moderate-vigorous physical activity (MVPA) were measured at baseline and after six-months. Linear regression analysis was used to investigate the independent cross-sectional and longitudinal associations of sedentary time with markers of inflammation. At baseline, associations between sedentary time and IL-6 were observed in men and women, an association that was attenuated following adjustment for waist circumference. After 6 months of follow-up, sedentary time was reduced by 0.4 ± 1.2 h per day in women, with the change in sedentary time predicting CRP at follow-up. Every hour decrease in sedentary time between baseline and six-months was associated with 24% (1, 48) lower CRP. No changes in sedentary time between baseline and 6 months were seen in men. CONCLUSIONS: Higher sedentary time is associated with IL-6 in men and women with type 2 diabetes, and reducing sedentary time is associated with improved levels of CRP in women. Interventions to reduce sedentary time may help to reduce inflammation in women with type 2 diabetes.

Diet or diet plus physical activity versus usual care in patients with newly diagnosed type 2 diabetes: the Early ACTID randomised controlled trial.

BACKGROUND: Lifestyle changes soon after diagnosis might improve outcomes in patients with type 2 diabetes mellitus, but no large trials have compared interventions. We investigated the effects of diet and physical activity on blood pressure and glucose concentrations. METHODS: We did a randomised, controlled trial in southwest England in adults aged 30-80 years in whom type 2 diabetes had been diagnosed 5-8 months previously. Participants were assigned usual care (initial dietary consultation and follow-up every 6 months; control group), an intensive diet intervention (dietary consultation every 3 months with monthly nurse support), or the latter plus a pedometer-based activity programme, in a 2:5:5 ratio. The primary endpoint was improvement in glycated haemoglobin A(1c)(HbA(1c)) concentration and blood pressure at 6 months. Analysis was done by intention to treat. This study is registered, number ISRCTN92162869. FINDINGS: Of 593 eligible individuals, 99 were assigned usual care, 248 the diet regimen, and 246 diet plus activity. Outcome data were available for 587 (99%) and 579 (98%) participants at 6 and 12 months, respectively. At 6 months, glycaemic control had worsened in the control group (mean baseline HbA(1c) percentage 6·72, SD 1·02, and at 6 months 6·86, 1·02) but improved in the diet group (baseline-adjusted difference in percentage of HbA(1c) -0·28%, 95% CI -0·46 to -0·10; p=0·005) and diet plus activity group (-0·33%, -0·51 to -0·14; p<0·001). These differences persisted to 12 months, despite less use of diabetes drugs. Improvements were also seen in bodyweight and insulin resistance between the intervention and control groups. Blood pressure was similar in all groups. INTERPRETATION: An intensive diet intervention soon after diagnosis can improve glycaemic control. The addition of an activity intervention conferred no additional benefit. FUNDING: Diabetes UK and the UK Department of Health.

Pathways to the diagnosis of ovarian cancer in the UK: a cohort study in primary care.

OBJECTIVE: To identify the routes patients with ovarian cancer take between first symptom presentation and diagnosis. DESIGN: Cohort study. SETTING: The study took place in 39 general practices in Devon, UK. POPULATION: All ovarian cancer patients identified in the practices, with a diagnosis between 2000 and 2007 inclusive. METHODS: All patients had their cancer symptoms, referrals, and diagnoses identified and dated using their doctors' records. MAIN OUTCOME MEASURES: Numbers of patients taking specific routes to diagnosis, together with the time taken to diagnosis. RESULTS: Three main routes to diagnosis emerged. The first was the expected route of outpatient referral: 195 (92% of the total) had at least one of the seven ovarian cancer symptoms or an abdominal mass. A total of 123 (58%) were referred to a specialist, although only 65 (31%) were referred to a gynaecologist. Thirty-five (17%) were initially investigated within primary care by ultrasound scanning, and a further 35 (17%) were admitted as emergencies. The interval from first symptom to referral was similar across the different pathways, with a median (interquartile range) time between the first symptom presenting to primary care and first investigation or referral being 2.5 (0, 27.5) days. The median interval from first symptom reported in primary care to diagnosis was 74.5 (32, 159) days. CONCLUSIONS: Only a minority of ovarian cancer patients follow the expected route to diagnosis, of urgent referral to a gynaecologist. In most women, GPs rapidly identified the need to investigate. Avoidable delays generally occurred after the decision to investigate was made.

Men with cancer: is their use of complementary and alternative medicine a response to needs unmet by conventional care?

This qualitative study aims to investigate why men with cancer choose to use complementary and alternative medicine (CAM), and whether CAM is used to fill 'gaps' in conventional cancer care or as an 'alternative' to conventional treatment. Interviews were carried out with 34 CAM users recruited from a National Health Service (NHS) oncology department, an NHS homeopathic hospital and a private cancer charity offering CAM. Participants used therapies to improve quality of life, to actively 'fight' the disease and possibly prolong life, but rarely as an alternative to conventional treatment. Many were initially sceptical about CAM, but took a 'pragmatic' and 'consumerist' approach to getting their needs met. Gaps in conventional care included: lack of empathy and support during and after treatment, poor continuity of care, and lack of advice on self-help, diet and lifestyle. The skills of CAM therapists may enable them to tap into the underlying needs of men in a way that health professionals do not always have the time or the skills to achieve.

Model of chromosome motility in Drosophila embryos: adaptation of a general mechanism for rapid mitosis.

During mitosis, ensembles of dynamic MTs and motors exert forces that coordinate chromosome segregation. Typically, chromosomes align at the metaphase spindle equator where they oscillate along the pole-pole axis before disjoining and moving poleward during anaphase A, but spindles in different cell types display differences in MT dynamicity, in the amplitude of chromosome oscillations and in rates of chromatid-to-pole motion. Drosophila embryonic mitotic spindles, for example, display remarkably dynamic MTs, barely detectable metaphase chromosome oscillations, and a rapid rate of "flux-pacman-dependent" anaphase chromatid-to-pole motility. Here we develop a force-balance model that describes Drosophila embryo chromosome motility in terms of a balance of forces acting on kinetochores and kMTs that is generated by multiple polymer ratchets and mitotic motors coupled to tension-dependent kMT dynamics. The model shows that i), multiple MTs displaying high dynamic instability can drive steady and rapid chromosome motion; ii), chromosome motility during metaphase and anaphase A can be described by a single mechanism; iii), high kinetochore dynein activity is deployed to dampen metaphase oscillations, to augment the basic flux-pacman mechanism, and to drive rapid anaphase A; iv), modulation of the MT rescue frequency by the kinetochore-associated kinesin-13 depolymerase promotes metaphase chromosome oscillations; and v), this basic mechanism can be adapted to a broad range of spindles.

Cigarette acquisition and proof of age among US high school students who smoke.

OBJECTIVE: To determine how US high school students who are under 18 years of age and who smoke obtain their cigarettes and whether they are asked for proof of age. DESIGN AND SETTING: Data from the Centers for Disease Control and Prevention's 1995, 1997, and 1999 national Youth Risk Behavior Surveys which employed national probability samples of students in grades 9-12 (ages 14-18 years). MAIN OUTCOME MEASURES: Associations of usual source of cigarettes and request for proof of age with variables such as sex, race/ethnicity, grade, and frequency of smoking. RESULTS: In 1999, among current smokers under age 18 years, 23.5% (95% confidence interval (CI), -4.5% to +4.5%) usually purchased their cigarettes in a store; among these students, 69.6% (95% CI -5.7% to +5.7%) were not asked to show proof of age. As days of past month smoking increased, reliance on buying cigarettes in a store (p < 0.001) and giving someone else money to buy cigarettes (p < 0.001) increased, and usually borrowing cigarettes decreased (p < 0.001). From 1995 to 1999, relying on store purchases significantly decreased (from 38.7% (95% CI -4.6% to + 4.6%) to 23.5% (95% CI -4.5% to +4.5%)); usually giving someone else money to buy cigarettes significantly increased (from 15.8% (95% CI -3.6% to +3.6%) to 29.9% (95% CI -4.5% to + 4.5%)). CONCLUSIONS: Stricter enforcement of tobacco access laws is needed to support other community and school efforts to reduce tobacco use among youth. Furthermore, effective interventions to reduce non-commercial sources of tobacco, including social, need to be developed and implemented.

Cluster randomised controlled trial comparing the effectiveness and cost-effectiveness of two primary care interventions aimed at improving attendance for breast screening.

OBJECTIVES: To examine the effectiveness and cost-effectiveness of two interventions based in primary care aimed at increasing uptake of breast screening. SETTING: 24 General practices with low uptake in the second round of screening (below 60%) in north west London and the West Midlands, UK. Participants were all women registered with these practices and eligible for screening in the third round. METHODS: Pragmatic factorial cluster randomised controlled trial, with practices randomised to a systematic intervention (general practitioner letter), an opportunistic intervention (flag in women's notes prompting discussion by health professionals), neither intervention, or both. Outcome measures were attendance for screening 6 months after the practices had been screened and cost-effectiveness of the interventions. RESULTS: 6,133 Women were included: 1,721 control; 1,818 letter; 1,232 flag; 1,362 both interventions. Attendance data were obtained for 5,732 (93%) women. The two interventions independently increased breast screening uptake in a logistic regression model adjusted for clustering, with the flag (odds ratio (OR) 1.43, 95% confidence interval (95% CI) 1.14 to 1.79; p=0.0019) marginally more effective than the letter (OR 1.31, 95% CI 1.05 to 1.64; p=0.015). Health service costs per additional attendance were 26 pounds (letter) and 41 pounds (flag). CONCLUSIONS: Although both interventions increased attendance for breast screening, the letter was the more cost-effective. Any decision to implement both interventions rather than just the letter will depend on whether the additional (41 pounds) costs are judged worthwhile in terms of the gains in breast screening uptake.

Improving attendance for breast screening among recent non-attenders: a randomised controlled trial of two interventions in primary care.

OBJECTIVES: To examine the effectiveness and cost-effectiveness of two primary care based interventions aimed at increasing breast screening uptake for women who had recently failed to attend. SETTING: 13 General practices with low uptake in the second round of breast screening (below 60%) in north west London and the West Midlands, United Kingdom. Participants were women in these practices who were recent non-attenders for breast screening in the third round. METHODS: Pragmatic factorial randomised controlled trial, with people randomised to a systematic intervention (general practitioner letter), an opportunistic intervention (flag in women's notes prompting discussion by health professionals), neither intervention, or both. Outcome measures were attendance for screening 6 months after randomisation and cost-effectiveness of the interventions. RESULTS: 1,158 Women were individually randomised as follows: 289 control; 291 letter; 290 flag; 288 both interventions. Attendance was ascertained for 1,148 (99%) of the 1,158 women. Logistic regression adjusting for the other intervention and practice produced an odds ratio (OR) for attendance of 1.51 (95% confidence interval (95% CI 1.02 to 2.26; p=0.04) for the letter, and 1.39 (95% CI 0.93 to 2.07; p=0.10) for the flag. Health service costs/ additional attendance were 35 pounds (letter) and 65 pounds (flag). CONCLUSIONS: Among recent non-attenders, the letter was effective in increasing breast screening attendance. The flag was of equivocal effectiveness and was considerably less cost-effective than the letter.

The distress and risk assessment method (DRAM).

Our aim was to judge the influence of preoperative psychological disturbance on the outcome of lumbar discectomy. We evaluated 66 patients, before and after operation, using a self-administered questionnaire. Disability was assessed using the Oswestry disability index and psychological disturbance the Distress and Risk Assessment Method (DRAM) score. Patients were classified as normal, at risk or distressed, and the outcome of surgery in the three groups was compared at a follow-up of six months. The mean self-reported preoperative disability was significantly higher in those with psychological disturbance. A total of 54 patients (82%) returned completed postoperative questionnaires. Postoperative disability scores at six months were not significantly different in the three risk groups. Psychological disturbance improved after surgery. Our study suggests that the early outcome of lumbar discectomy is not affected by preoperative psychological disturbance. We conclude that a patient with a symptomatic prolapsed intervertebral disc should not be denied surgery on the basis of preoperative psychological assessment.

Reviews of evidence regarding interventions to reduce tobacco use and exposure to environmental tobacco smoke.

This report presents the results of systematic reviews of effectiveness, applicability, other effects, economic evaluations, and barriers to use of selected population-based interventions intended to reduce tobacco use and exposure to environmental tobacco smoke. The related systematic reviews are linked by a common conceptual approach. These reviews form the basis of recommendations by the Task Force on Community Preventive Services (TFCPS) regarding the use of these selected interventions. The TFCPS recommendations are presented on page 67 of this supplement.

Relationship between cigarette, smokeless tobacco, and cigar use, and other health risk behaviors among U.S. high school students.

This study examined relationships between tobacco use and use of other substances, intentional injury risk behaviors, and sexual risk behaviors among US high school students. Data about tobacco use and other health risk behaviors were analyzed from the 1997 national Youth Risk Behavior Survey implemented by the Centers for Disease Control and Prevention. One-fourth of students (24%) reported current use of a single tobacco product (i.e., cigarettes, smokeless tobacco, or cigars during the 30 days preceding the survey), and 19.5% reported currently using more than one tobacco product. Generally, students who reported current tobacco use also reported engaging in other substance use, intentional injury risk behaviors, and sexual risk behaviors. For many risk behaviors, these results were especially pronounced among students who reported using two or all three tobacco products. Programs designed to prevent tobacco use should consider that such use often occurs concomitantly with other health risk behaviors.

Roles of motor proteins in building microtubule-based structures: a basic principle of cellular design.

Eukaryotic cells must build a complex infrastructure of microtubules (MTs) and associated proteins to carry out a variety of functions. A growing body of evidence indicates that a major function of MT-associated motor proteins is to assemble and maintain this infrastructure. In this context, we examine the mechanisms utilized by motors to construct the arrays of MTs and associated proteins contained within the mitotic spindle, neuronal processes, and ciliary axonemes. We focus on the capacity of motors to drive the 'sliding filament mechanism' that is involved in the construction and maintenance of spindles, axons and dendrites, and on a type of particle transport called 'intraflagellar transport' which contributes to the assembly and maintenance of axonemes.

Cytoplasmic dynein is required for poleward chromosome movement during mitosis in Drosophila embryos.

The movement of chromosomes during mitosis occurs on a bipolar, microtubule-based protein machine, the mitotic spindle. It has long been proposed that poleward chromosome movements that occur during prometaphase and anaphase A are driven by the microtubule motor cytoplasmic dynein, which binds to kinetochores and transports them toward the minus ends of spindle microtubules. Here we evaluate this hypothesis using time-lapse confocal microscopy to visualize, in real time, kinetochore and chromatid movements in living Drosophila embryos in the presence and absence of specific inhibitors of cytoplasmic dynein. Our results show that dynein inhibitors disrupt the alignment of kinetochores on the metaphase spindle equator and also interfere with kinetochore- and chromatid-to-pole movements during anaphase A. Thus, dynein is essential for poleward chromosome motility throughout mitosis in Drosophila embryos.

Acute cauda equina syndrome caused by a gas-containing prolapsed intervertebral disk.

Gas production as a part of disk degeneration can occur, but it rarely causes clinical nerve compression syndromes. A rare case of gaseous degeneration in a prolapsed lumbar intervertebral disk causing acute cauda equina syndrome is described. Radiologic features and intraoperative findings are reported. A 78-year-old woman with severe lumbar canal stenosis had acute cauda equina syndrome. Magnetic resonance imaging revealed a large disk protrusion, and she underwent an urgent operation for this. Surgery confirmed the severe lumbar canal stenosis, but the disk prolapse contained gas that had caused the nerve compression.

Antagonistic microtubule-sliding motors position mitotic centrosomes in Drosophila early embryos.

The positioning of centrosomes, or microtubule-organizing centres, within cells plays a critical part in animal development. Here we show that, in Drosophila embryos undergoing mitosis, the positioning of centrosomes within bipolar spindles and between daughter nuclei is determined by a balance of opposing forces generated by a bipolar kinesin motor, KLP61F, that is directed to microtubule plus ends, and a carboxy-terminal kinesin motor, Ncd, that is directed towards microtubule minus ends. This activity maintains the spacing between separated centrosomes during prometaphase and metaphase, and repositions centrosomes and daughter nuclei during late anaphase and telophase. Surprisingly, we do not observe a function for KLP61F in the initial separation of centrosomes during prophase. Our data indicate that KLP61F and Ncd may function by crosslinking and sliding antiparallel spindle microtubules in relation to one another, allowing KLP61F to push centrosomes apart and Ncd to pull them together.

Racial and ethnic differences in serum cotinine levels of cigarette smokers: Third National Health and Nutrition Examination Survey, 1988-1991.

CONTEXT: Cotinine, a metabolite of nicotine, is a marker of exposure to tobacco smoke. Previous studies suggest that non-Hispanic blacks have higher levels of serum cotinine than non-Hispanic whites who report similar levels of cigarette smoking. OBJECTIVE: To investigate differences in levels of serum cotinine in black, white, and Mexican American cigarette smokers in the US adult population. DESIGN: Third National Health and Nutrition Examination Survey, 1988-1991. PARTICIPANTS: A nationally representative sample of persons aged 17 years or older who participated in the survey. OUTCOME MEASURES: Serum cotinine levels by reported number of cigarettes smoked per day and by race and ethnicity. RESULTS: A total of 7182 subjects were involved in the study; 2136 subjects reported smoking at least 1 cigarette in the last 5 days. Black smokers had cotinine concentrations substantially higher at all levels of cigarette smoking than did white or Mexican American smokers (P<.001). Serum cotinine levels for blacks were 125 nmol/L (22 ng/mL) (95% confidence interval [CI], 79-176 nmol/L [14-31 ng/mL]) to 539 nmol/L (95 ng/mL) (95% CI, 289-630 nmol/L [51-111 ng/mL]) higher than for whites and 136 nmol/L (24 ng/mL) (95% CI, 85-182 nmol/L [15-32 ng/mL]) to 641 nmol/L (113 ng/mL) (95% CI, 386-897 nmol/L [68-158 ng/mL]) higher than for Mexican Americans. These differences do not appear to be attributable to differences in environmental tobacco smoke exposure or in number of cigarettes smoked. CONCLUSIONS: To our knowledge, this study provides the first evidence from a national study that serum cotinine levels are higher among black smokers than among white or Mexican American smokers. If higher cotinine levels among blacks indicate higher nicotine intake or differential pharmacokinetics and possibly serve as a marker of higher exposure to cigarette carcinogenic components, they may help explain why blacks find it harder to quit and are more likely to experience higher rates of lung cancer than white smokers.

Inhibition of a mitotic motor compromises the formation of dendrite-like processes from neuroblastoma cells.

Microtubules in the axon are uniformly oriented, while microtubules in the dendrite are nonuniformly oriented. We have proposed that these distinct microtubule polarity patterns may arise from a redistribution of molecular motor proteins previously used for mitosis of the developing neuroblast. To address this issue, we performed studies on neuroblastoma cells that undergo mitosis but also generate short processes during interphase. Some of these processes are similar to axons with regard to their morphology and microtubule polarity pattern, while others are similar to dendrites. Treatment with cAMP or retinoic acid inhibits cell division, with the former promoting the development of the axon-like processes and the latter promoting the development of the dendrite-like processes. During mitosis, the kinesin-related motor termed CHO1/MKLP1 is localized within the spindle midzone where it is thought to transport microtubules of opposite orientation relative to one another. During process formation, CHO1/ MKLP1 becomes concentrated within the dendrite-like processes but is excluded from the axon-like processes. The levels of CHO1/MKLP1 increase in the presence of retinoic acid but decrease in the presence of cAMP, consistent with a role for the protein in dendritic differentiation. Moreover, treatment of the cultures with antisense oligonucleotides to CHO1/MKLP1 compromises the formation of the dendrite-like processes. We speculate that a redistribution of CHO1/MKLP1 is required for the formation of dendrite-like processes, presumably by establishing their characteristic nonuniform microtubule polarity pattern.

Breast screening: a randomised controlled trial in UK general practice of three interventions designed to increase uptake.

STUDY OBJECTIVES: To determine the relative effectiveness of three interventions designed to increase the uptake of breast screening. DESIGN: Randomised controlled trial of a nurse visit with health education (group A), nurse visit without health education (group B), and GP letter (group C). SETTING: The area of south east London served by the Butterfly Walk Breast Screening Unit in Camberwell. PARTICIPANTS: Women aged between 50 and 64 years who were registered with 27 GPs in the Lambeth, Southwark and Lewisham family health services authority and who had not attended for first round screening. MAIN RESULTS: Altogether 799 women were randomly allocated to the three groups. In general, delivering the nurse based interventions proved difficult. In group A, 11.4% (95% CI 7.9, 14.9%) of women subsequently attended for screening compared with 7.8% (95% CI 5.1, 11.4%) in group B and 13.1% (95% CI 7.9, 18.4%) in group C. The differences between the groups (95% CIs) were not statistically significant: A versus C, -1.7% (-8.0, +4.6%); B versus C, -5.3% (-11.3, +0.7%); A versus B, +3.6% (-1.0, +8.2%). CONCLUSIONS: A personal letter from the GP seems to be at least as effective at increasing the uptake of breast screening in non-attenders as a nurse making a home visit to discuss the issue of breast screening, and is not noticeably less effective than a visit at which a health education intervention is delivered. It is possible that the GP letter is considerably more effective than either of the two interview-based interventions. With regard to implementing strategies which will increase breast screening uptake and are cost effective, further trials of similar minimal interventions in primary care are required.

Lung cancer in nonsmoking women. Histology and survival patterns.

BACKGROUND: Despite the widespread view that important clinical and etiologic differences exist between histologic categories of lung cancer, few studies have examined the accuracy of hospital-reported pathologic diagnoses of lung cancer. METHODS: A review of pathologic material and an assessment of survival patterns were conducted in conjunction with a recently completed case-control study of lung cancer among nonsmoking women in Missouri. Using established protocols, tissue slides from tumors of 482 patients were reviewed by 3 pathologists. RESULTS: Adenocarcinoma was the most common histologic type among former smokers and lifetime nonsmokers. The overall agreement rate between the original and review diagnoses was 65.6%. The positive predictive value ranged from 0.33 for bronchioalveolar carcinomas to 0.84 for adenocarcinomas. Agreement rates for small, medium, and large hospitals were 63.1, 66.6, and 66.2%, respectively. Survival rates were highest for bronchioalveolar carcinoma and lowest for small cell carcinoma. CONCLUSION: Given the importance of lung cancer to public health and the need to examine risk by histologic type, these data indicate that pathologic review of registry-reported lung cancer cases may be an important component of large scale studies of etiology.