Quality Improvement Within a Mental Health Setting: Alcohol Detoxification.

Aims We describe a clinical audit on alcohol detoxification, using NICE guidelines as a comparable standard. NICE guidelines recommend completing a thorough alcohol history, documentation of a physical examination including screening for Wernicke's encephalopathy, monitoring of vital signs and liver investigations. Breath alcohol level and standardised assessment of withdrawal should be completed in addition to documentation of chlordiazepoxide and thiamine prescriptions. The reported mental health service completed the first cycle of the audit as part of a large-scale, international audit on alcohol detoxification by the Prescribing Observatory for Mental Health, UK (POMH-UK). Two additional audit cycles were completed within the service to ensure continuous quality improvement and clinical effectiveness. Methods Retrospective chart reviews were performed for admissions within pre-defined 6-month periods. Inclusion criteria: ICD-10 F10 diagnosis; prescription of alcohol detoxification schedule. Results This mental health service demonstrated greater compliance with the NICE standards in comparison to other services in the POMH-UK audit. The second-cycle audit showed increased compliance in most areas compared to the initial results. The third-cycle audit focused on two specific areas that required improvement to optimise quality improvement - Breath Alcohol Level and Clinical Institute of Withdrawal Assessment, documentation of which improved from 79% to 85% and 39% to 91% respectively in the final audit cycle. Conclusion The results of this audit indicate that adherence to defined clinical standards within this mental health service exceeds that of the benchmark POMH-UK data. The effectiveness of electronic patient records in improving adherence to set clinical standards, specifically in relation to documentation of clinical parameters is evident. The report also confirms continued improved results with each audit cycle within the service.

Increased symptoms of stiffness 1 year after total knee arthroplasty are associated with a worse functional outcome and lower rate of patient satisfaction.

PURPOSE: Symptoms of stiffness after total knee arthroplasty (TKA) cause significant morbidity, but there is limited data to facilitate identification of those most at risk after surgery. Stratifying risk can aid earlier directed treatment options. METHODS: A retrospective cohort consisting of 2589 patients undergoing a primary TKA was identified from an established arthroplasty database. Patient demographics, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and short form (SF) 12 scores were collected pre-operatively and 1 year post-operatively. In addition, patient satisfaction was assessed for 1 year. Patients with a worse WOMAC stiffness score in 1 year were defined as the "increased" stiffness group and the other cohort as the non-stiffness group. RESULTS: At 1 year after surgery 129 (5%) patients had a significant increase in their stiffness symptoms (20%, 95% confidence interval (CI) 17.9-22.0, p < 0.001), and had significantly (all p < 0.001) less of an improvement in their pain, function and total WOMAC scores, and SF-12 scores compared to the non-stiffness group (n = 2460). Patient satisfaction was significantly lower (odds ratio (OR) 0.178, CI 0.121 to 0.262, p < 0.001) for the increased stiffness group. Logistic regression analysis identified male gender (OR 1.66, p = 0.02), lung disease (OR 2.06, p = 0.002), diabetes (OR 1.82, p = 0.02), back pain (OR 1.81, p = 0.005), and a pre-operative stiffness score of 44 or more (OR 5.79, p < 0.001) were significantly predictive of increased stiffness. CONCLUSION: Patients with increased symptoms of stiffness after TKA have a worse functional outcome and a lower rate of patient satisfaction, and patients at risk of being in this group should be informed pre-operatively. LEVEL OF EVIDENCE: Retrospective prognostic study, Level III.

Patient age of less than 55 years is not an independent predictor of functional improvement or satisfaction after total knee arthroplasty.

INTRODUCTION: Management of the young patient with end-stage osteoarthritis of the knee is difficult, with surgical options of osteotomy, partial or total knee arthroplasty (TKA). The primary aim of this study was to assess whether age of less than 55 years was an independent predictor of functional outcome and satisfaction after total knee arthroplasty (TKA). The secondary aims were to identify pre-operative differences in patient demographics, comorbidity and function between patients less than 55 years old compared to those 55 years old and over. MATERIALS AND METHODS: A retrospective cohort consisting of 2589 patients undergoing a primary TKA was identified from an established arthroplasty database. Patient demographics, comorbidity, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Short Form (SF) 12 scores were collected pre-operatively and 1 year post-operatively. In addition, patient satisfaction was assessed at 1 year. Regression analysis was used to identify independent pre-operative predictors of change in the WOMAC and SF-12 scores, and patient satisfaction. RESULTS: Patients less than 55 years old were significantly less likely to be satisfied with the overall outcome of their TKA (OR 0.4, p = 0.001). After adjusting for confounding variables age group was not an independent predictor of overall satisfaction with overall outcome (OR 0.71, p = 0.16). Independent predictors of an increased risk of dissatisfaction with the overall outcome at 1 year were depression (OR 0.58, p = 0.008) and worse pre-operative SF-12 MCS (p = 0.04). CONCLUSION: Age of less than 55 years is not an independent predictor of functional outcome or rate of patient satisfaction after TKA. However, depression and poor mental health are significantly more prevalent in patients less than 55 years old and were independently associated with a lower satisfaction rate.

Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies.

BACKGROUND: Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. METHOD: We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). RESULTS: One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity. CONCLUSIONS: Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

Risk of new-onset heart failure in patients using sitagliptin: a population-based cohort study.

AIMS: To examine whether patients using sitagliptin at the time of an acute coronary syndrome event are at increased risk of incident heart failure compared with those not exposed. METHODS: Using US claims data, people with diabetes without a history of heart failure in the 3 years before hospitalization for acute coronary syndrome were identified for the period 2004 to 2010. We used a nested case-control design, whereby cases were patients who developed incident heart failure <30 days after admission to hospital for acute coronary syndrome and were matched by age and sex with up to 10 controls with no heart failure. Subjects exposed or not exposed to sitagliptin in the 90 days before acute coronary syndrome admission were compared using conditional logistic regression after adjustment for clinical and laboratory data, healthcare utilization and propensity scores. RESULTS: In total, 457 cases of heart failure developing de novo after diagnosis of acute coronary syndrome were matched to 4570 controls. The average age of the subjects was 55 years and 65% were male. Overall, 11 of 147 (7%) people exposed to sitagliptin developed heart failure compared with 446 of the 4880 people not exposed (9%, adjusted odds ratio 0.75, 95% CI 0.38-1.46; P=0.40). Sitagliptin exposure before acute coronary syndrome was not associated with an increased risk of death or heart failure combined (7% vs 9%, adjusted odds ratio 0.66, 95% CI 0.34-1.28). CONCLUSIONS: In our sample of patients who are at high risk of heart failure after acute coronary syndrome, sitagliptin exposure was not associated with an increased risk of de novo heart failure.

Rates and risk factors for recurrent pneumonia in patients hospitalized with community-acquired pneumonia: population-based prospective cohort study with 5 years of follow-up.

BACKGROUND: The rates and risk factors for developing recurrent pneumonia following hospitalization with community-acquired pneumonia (CAP) are poorly understood. METHODS: We examined a population-based cohort of patients with CAP who survived hospital admission and who were free of pneumonia for at least 3 months. We collected clinical, functional, and medication-related information and pneumonia severity index (PSI). Using linked databases we followed patients for 5 years and captured any clinical episode of pneumonia 90 days or more post-discharge. We used Cox proportional hazards models (adjusted for age, sex, PSI, functional status, medications) to determine rates and independent correlates of recurrent pneumonia. RESULTS: The final cohort included 2709 inpatients; 43% were 75 years or older, 34% were not fully independent, and 56% had severe pneumonia. Over 5 years of follow-up, 245 (9%; 95% confidence interval [CI], 8%-10%) patients developed recurrent pneumonia, and 156 (64%) of these episodes required hospitalization. Rate of recurrence was 3.0/100 person-years and median time to recurrence was 317 days (interquartile range, 177-569); 32 (13%) patients had 2 or more recurrences. In multivariable analyses only age >75 years (adjusted P = .047) and less than fully independent functional status (12% recurrence rate with impaired functional status vs 7% for fully independent; adjusted hazard ratio, 1.7; 95% CI, 1.3-2.2; P < .001) were significantly associated with recurrent pneumonia. CONCLUSIONS: One of 11 patients who survived CAP hospitalization had recurrent pneumonia over 5 years and those with impaired functional status were at particularly high risk. Recurrent pneumonia is common and more attention to preventive strategies at discharge and closer follow-up over the long-term seem warranted.

Critical impact of patient knowledge and bone density testing on starting osteoporosis treatment after fragility fracture: secondary analyses from two controlled trials.

UNLABELLED: Most patients are not treated for osteoporosis after their fragility fracture "teachable moment." Among almost 400 consecutive wrist fracture patients, we determined that better-than-average osteoporosis knowledge (adjusted odds = 2.6) and BMD testing (adjusted odds = 6.5) were significant modifiable facilitators of bisphosphonate treatment while male sex, working outside the home, and depression were major barriers. INTRODUCTION: In the year following fragility fracture, fewer than one quarter of patients are treated for osteoporosis. Although much is known regarding health system and provider barriers and facilitators to osteoporosis treatment, much less is understood about modifiable patient-related factors. METHODS: Older patients with wrist fracture not treated for osteoporosis were enrolled in trials that compared a multifaceted intervention with usual care controls. Baseline data included a test of patient osteoporosis knowledge. We then determined baseline factors that independently predicted starting bisphosphonate treatment within 1 year. RESULTS: Three hundred seventy-four patients were enrolled; mean age 64 years, 78 % women, 90 % white, and 54 % with prior fracture. Within 1 year, 86 of 374 (23 %) patients were treated with bisphosphonates. Patients who were treated had better osteoporosis knowledge at baseline (70 % correct vs 57 % for untreated, p < 0.001) than patients who remained untreated; conversely, untreated patients were more likely to be male, still working, and report depression. In fully adjusted models, osteoporosis knowledge was independently associated with starting bisphosphonates (adjusted OR 2.6, 95 %CI 1.3-5.3). Obtaining a BMD test (aOR 6.5, 95 %CI 3.4-12.2) and abnormal BMD results (aOR 34.5, 95 %CI 16.8-70.9) were strongly associated with starting treatment. CONCLUSIONS: The most important modifiable facilitators of osteoporosis treatment in patients with fracture were knowledge and BMD testing. Specifically targeting these two patient-level factors should improve post-fracture treatment rates.

Sex does not clinically influence the functional outcome of total knee arthroplasty but females have a lower rate of satisfaction with pain relief.

BACKGROUND: The aims were to assess whether sex had a clinically significant independent influence on the outcome of total knee arthroplasty (TKA) according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Short Form (SF-) 12 scores and patient satisfaction at 1 year. METHODS: A retrospective cohort of 3510 primary TKA were identified. Patient demographics, comorbidities, WOMAC and SF-12 scores were collected preoperatively and 1 year postoperatively. Patient satisfaction were assessed at 1 year. RESULTS: There were 1584 males and 1926 females. The preoperative WOMAC and SF-12 scores were significantly (p < 0.001) worse in females but were not greater than the minimal clinically important difference (MCID). When adjustments had been made for confounding differences, females showed a significantly greater improvement in their function (1.5 points, p = 0.03) and total (1.5 points, p = 0.03) WOMAC scores compared to males, but these were not greater than the MCID. When adjustments had been made for confounding differences, females were less likely to be satisfied with their pain relief (p = 0.03) relative to males. CONCLUSION: Sex does not clinically influence the knee specific outcome (WOMAC) or overall generic (SF-12) health 1 year after TKA. However, satisfaction with pain relief after TKA was significantly less likely in female patients. LEVEL OF EVIDENCE II: Prognostic retrospective cohort study.

Predicting range of movement after knee replacement: the importance of posterior condylar offset and tibial slope.

We have attempted to quantify the influence of clinical, radiological and prosthetic design factors upon flexion following knee replacement. Our study examined the outcome following 101 knee replacements performed in two prospective randomized trials using similar cruciate retaining implants. Multivariate analyses, after adjusting for age, sex, diagnosis and the type of prosthesis revealed that the only significant correlates for range of movement at 12 months were the difference in posterior condylar offset ratio (p < 0.001), tibial slope (p < 0.001) and preoperative range of movement (p = 0.025). We found a moderate correlation between 12-month range of movement and posterior tibial slope (R = 0.58) and the difference of post femoral condylar offset (i.e, post-operative minus preoperative posterior condylar offset, R = 0.65). Posterior condylar offset had the greatest impact upon final range of movement highlighting this as an important consideration for the operating surgeon at pre-operative templating when choosing both the design and size of the femoral component.

Meaningful changes in the Short Form 12 physical and mental summary scores after total knee arthroplasty.

BACKGROUND: The aim of this study was to identify minimal clinically important difference (MCID), minimal important change (MIC) and minimal detectable change (MDC) for the Short Form (SF-) 12 physical and mental component summary (PCS, MCS) scores after total knee arthroplasty (TKA) using an anchor based methodology. METHODS: During a 10-year period, 2589 TKA were performed. SF-12 PCS and MCS scores were recorded preoperatively and at one year postoperatively. At one year, patients were asked "How much did the knee replacement surgery improve the quality of your life?" Their response was recorded as: a great improvement, moderate improvement, little improvement, no improvement at all, or the quality of my life is worse. Patients recording a little (n = 211) and no (n = 115) were used to calculate the MCID and the MIC. The MDC90 was calculated using distribution based methods for the whole cohort. RESULTS: The MCID was 1.8 (p = 0.04) for the PCS and 1.5 (p = 0.33) for the MCS score. The MIC was 2.7 (p = 0.04) for the PCS and -1.4 (p = 0.17) for the MCS score. The MDC90 was 8.9 for the PCS and 13.8 for the MCS score. CONCLUSION: The MCID for the PCS can be used to compare the outcomes between groups, and the MIC can be used to ensure that a clinical difference has been observed for a cohort of patients. The values for the MDC90 can be used to assess whether or not an individual patient has experienced a change.

Which patients are satisfied with their overall outcome but dissatisfied with their return to recreational activities after total knee arthroplasty?

BACKGROUND: The primary aim of this study was to assess whether patients dissatisfied with both recreational activities and overall outcome were different to those dissatisfied with recreational activities but satisfied with their overall outcome one year after total knee arthroplasty (TKA). METHODS: A retrospective cohort consisting of 3324 primary TKA were identified from an established arthroplasty database. Patient demographics, comorbidities, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Short Form (SF) 12 scores were collected pre-operatively and one year post-operatively. Overall patient satisfaction and satisfaction with recreational activities were assessed at one year. RESULTS: The rate of patient satisfaction with recreational activities (n = 2672, 80.4%) was significantly (odds ratio (OR) 0.47, 95% confidence intervals (CI) 0.41 to 0.54, p < 0.001) lower than satisfaction with the overall outcome (n = 2982, 89.7%). When adjusting for confounding variables older age (OR 1.03, p = 0.008), increasing BMI (OR 1.05, p = 0.01) and absence of hypertension (OR 0.66, p = 0.02) were independent predictors of being dissatisfied with recreational activities in isolation. The one-year components and total WOMAC scores were significant (p < 0.001) predictors of satisfaction with recreational activities and were reliable with an area under the curve of ≥0.82 CONCLUSION: Patients of older age, higher BMI and without hypertension are more likely to be dissatisfied with recreational activities despite being satisfied with their overall outcome.

Three groups of dissatisfied patients exist after total knee arthroplasty: early, persistent, and late.

AIMS: The primary aim of this study was to assess whether patient satisfaction one year after total knee arthroplasty (TKA) changed with longer follow-up. The secondary aims were to identify predictors of satisfaction at one year, persistence of patient dissatisfaction, and late onset dissatisfaction in patients that were originally satisfied at one year. PATIENTS AND METHODS: A retrospective cohort consisting of 1369 patients undergoing a primary TKA for osteoarthritis that had not undergone revision were identified from an established arthroplasty database. Patient demographics, comorbidities, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, and Short Form 12 (SF-12) questionnaire scores were collected preoperatively, and one and five years postoperatively. In addition, patient satisfaction was assessed at one and five years postoperatively. Logistic regression analysis was used to identify independent predictors of satisfaction at one and five years. RESULTS: The overall rate of satisfaction did not change from one (91.7%, n = 1255) to five (90.1%, n = 1234) years (p = 0.16). Approximately half (n = 53/114) of the patients who were dissatisfied at one year became satisfied with their TKA at five years, whereas 6% (n = 74/1255) of those who were satisfied at one year became dissatisfied at five years. At one year, patients with lung disease (p = 0.04), with depression (p = 0.001), with back pain (p < 0.001), undergoing unilateral TKA (p = 0.001), or with a worse preoperative WOMAC pain score (p = 0.04) were more likely to be dissatisfied. Patients with gastric ulceration (p = 0.04) and a worse WOMAC stiffness score (p = 0.047) were at increased risk of persistent dissatisfaction at five years. In contrast, a worse WOMAC pain score (p = 0.01) at one year was a predictor of dissatisfaction in previously satisfied patients at five years. CONCLUSION: Three groups of dissatisfied patients exist after TKA: 'early' dissatisfaction at one year, 'persistent' dissatisfaction with longer follow-up, and 'late' dissatisfaction developing in previously satisfied patients at one year. All three groups have different independent predictors of satisfaction, and potentially addressing risk factors specific to these groups may improve patient outcome and their satisfaction. Cite this article: Bone Joint J 2018;100-B:161-9.

The rate and predictors of patient satisfaction after total knee arthroplasty are influenced by the focus of the question: a standard satisfaction question is required.

Aims: The primary aim of this study was to assess the rate of patient satisfaction one year after total knee arthroplasty (TKA) according to the focus of the question asked. The secondary aims were to identify independent predictors of patient satisfaction according to the focus of the question. Patients and Methods: A retrospective cohort of 2521 patients undergoing a primary unilateral TKA were identified from an established regional arthroplasty database. Patient demographics, comorbidities, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and 12-Item Short-Form Health Survey (SF-12) scores were collected preoperatively and one year postoperatively. Patient satisfaction was assessed using four questions, which focused on overall outcome, activity, work, and pain. Logistic regression analysis was used to identify independent preoperative predictors of increased stiffness when adjusting for confounding variables. Results: Using patient satisfaction with the overall outcome (n = 2265, 89.8%) as the standard, there was no difference in the rate of satisfaction for pain relief (n = 2277, odds ratio (OR) 0.95, 95% confident intervals (CI) 0.79 to 1.14, p = 0.60), but patients were more likely to be dissatisfied with activities (79.3%, n = 2000/2521, OR 2.22, 95% CI 1.96 to 2.70, p < 0.001) and work (85.8%, n = 2163/2521, OR 1.47, 95% CI 1.23 to 1.75, p < 0.001). Logistic regression analysis identified different predictors of satisfaction for each of the focused satisfaction questions. Overall satisfaction was influenced by diabetes (p = 0.03), depression (p = 0.004), back pain (p < 0.001), and SF-12 physical (p = 0.008) and mental (p = 0.01) components. Satisfaction with activities was influenced by depression (p = 0.001), back pain (p < 0.001), WOMAC stiffness score (p = 0.03), and SF-12 physical (p < 0.001) and mental (p < 0.001) components. Satisfaction with work was influenced by depression (p = 0.007), back pain (p < 0.001), WOMAC function (p = 0.04) and stiffness (p = 0.05) scores, and SF-12 physical (p < 0.001) and mental (p < 0.001) components. Satisfaction with pain relief was influenced by diabetes (p < 0.001), back pain (p < 0.001), and SF-12 mental component (p = 0.04). Conclusion: The focus of the satisfaction question significantly influences the rate and the predictors of patient satisfaction after TKA. Cite this article: Bone Joint J 2018;100-B:740-8.

Effect of anticonvulsant drugs on the rate of folate catabolism in mice.

An increase in folate catabolism has been suggested as the cause of the folate deficiency observed in many clinical conditions, including chronic anticonvulsant therapy. Previous studies have shown that the radioactive catabolites, excreted after an equilibration period of 3 d, consisted exclusively of folates that had been cleaved to produce pteridines and p-aminobenzoylglutamate, most of which was excreted as acetamidobenzoylglutamate. We have developed an experimental animal model using mice to determine the rate of catabolism of [3H]pteroylglutamate (folic acid) by the quantitative estimation of [3H]p-aminobenzoylglutamate and [3H]acetamidobenzoylglutamate in urine. Administration of diphenylhydantoin at three different doses (0.5, 20, and 50 mg/kg) significantly increased the rate of catabolism as measured by an increase in both the mean daily excretion and the cumulative excretion of these catabolites. Administration of intramuscular phenobarbitone on the other hand, did not affect the rate of catabolism, when compared with controls.

Prevalence of dementia in the United States: the aging, demographics, and memory study.

AIM: To estimate the prevalence of Alzheimer's disease (AD) and other dementias in the USA using a nationally representative sample. METHODS: The Aging, Demographics, and Memory Study sample was composed of 856 individuals aged 71 years and older from the nationally representative Health and Retirement Study (HRS) who were evaluated for dementia using a comprehensive in-home assessment. An expert consensus panel used this information to assign a diagnosis of normal cognition, cognitive impairment but not demented, or dementia (and dementia subtype). Using sampling weights derived from the HRS, we estimated the national prevalence of dementia, AD and vascular dementia by age and gender. RESULTS: The prevalence of dementia among individuals aged 71 and older was 13.9%, comprising about 3.4 million individuals in the USA in 2002. The corresponding values for AD were 9.7% and 2.4 million individuals. Dementia prevalence increased with age, from 5.0% of those aged 71-79 years to 37.4% of those aged 90 and older. CONCLUSIONS: Dementia prevalence estimates from this first nationally representative population-based study of dementia in the USA to include subjects from all regions of the country can provide essential information for effective planning for the impending healthcare needs of the large and increasing number of individuals at risk for dementia as our population ages.

Reversible cytotoxic cerebral edema in cerebral fat embolism.

We present a case of cerebral fat embolism (CFE) that demonstrated evidence of diffuse white matter cytotoxic edema on diffusion-weighted magnetic resonance imaging, in addition to punctate hyperintensities on T2-weighted and diffusion-weighted imaging. The case suggests that CFE represents a combination of occlusive arteriolar disease and secondary neurotoxicity.

The metabolic consequences of vitamin B-12/methionine deficiency in rats.

The synthesis of liver pteroylglutamates (folates) from injected [3-H]-pteroylglutamic acid was investigated in vitamin B-12 methionine-deficient rats and pair-fed controls using improved extraction and chromatographic procedures to identify the monoglutamyl derivatives present. Livers from deficient animals had significantly increased levels of radioactive 5-methyltetrahydropteroylglutamate detected after conjugase treatment of extracts and significantly decreased levels of radioactive tetrahydropteroylglutamate and formylated derivatives. However, that this is only a temporary effect and the result of a decreased rate of equilibration of the exogenous radioactivity was shown by measuring the fully equilibrated endogenous pools. This was done by microbiological assay of the endogenous liver folates with Lactobacillus casei. No significant difference was found between deficient animals and controls in the proportion of the endogenous microbiologically active derivatives present. These results in the rat do not support the idea that in vitamin B-12 deficiency the cellular folates accumulate as the reduced 5-methyl derivative, resulting in inadequate amount of the other cofactors to partipicate in nucleic acid biosynthesis.

Folate/vitamin B12 inter-relationships.

Folate deficiency causes anaemia owing to impaired purine and pyrimidine biosynthesis. Vitamin B12 deficiency causes an identical anaemia owing to metabolic trapping of intracellular folate. Vitamin B12 also causes nerve damage. Unlike the anaemia, the nerve damage is probably owing to inhibition of methyltransferase involved in nerve cell biosynthesis. This decreased activity is owing to a reduction in the availability of SAM, the methyl donor, together with product inhibition by its demethylated form, SAH.

Cost-effectiveness of the lower treatment goal (of JNC VI) for diabetic hypertensive patients. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

BACKGROUND: The recommendation of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) to lower blood pressure (BP) in diabetic patients to less than 130/85 mm Hg may have negative economic consequences. A formal cost-effectiveness analysis was therefore performed, comparing the costs and potential benefits of a BP goal of less than 140/90 mm Hg (as recommended by JNC V) vs less than 130/85 mm Hg (as inJNC VI). METHODS: A 24-cell computer model was populated with costs (1996 dollars), relative risks, and age-specific base-line rates for death and 4 nonfatal adverse events (stroke, myocardial infarction, heart failure, and end-stage renal disease), derived from published data. Costs and benefits were discounted at 3%. RESULTS: For 60-year-old diabetic persons with hypertension, treating to the lower BP goal increases life expectancy by 0.48 (discounted) years and lowers (discounted) lifetime medical costs by $1450 compared with treating BP to less than 140/90 mm Hg. The lower treatment BP goal results in an overall cost savings over a wide range of initial conditions, and for nearly all analyses for patients older than 60 years. CONCLUSIONS: Any incremental treatment for 60-year-olds that costs less than $414 annually and successfully lowers BP from below 140/90 to below 130/85 mm Hg would be cost saving in the long term, due to the reduction in attendant costs of future morbidity. The lower treatment goal recommended for high-risk hypertensive patients compares favorably in cost-effectiveness with many other frequently recommended treatment strategies, and saves money overall for patients aged 60 years and older.

Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention.

BACKGROUND: Results from prospective studies of serum homocysteine levels and ischemic heart disease (IHD) are inconclusive. We carried out a further prospective study to help clarify the position. METHODS: In the British United Provident Association (BUPA) prospective study of 21,520 men aged 35 to 64 years, we measured homocysteine levels in stored serum samples and analyzed data from 229 men without a history of IHD at study entry who subsequently died of IHD and 1126 age-matched control subjects (nested case-control design). RESULTS: Serum homocysteine levels were significantly higher in men who died of IHD than in men who did not (mean, 13.1 vs 11.8 micromol/L; P<.001). The risk of IHD among men in the highest quartile of serum homocysteine levels was 3.7 times (or 2.9 times after adjusting for other risk factors) the risk among men in the lowest quartile (95% confidence interval [CI], 1.8-4.7). There was a continuous dose-response relationship, with risk increasing by 41% (95% CI, 20%-65%) for each 5-micromol/L increase in the serum homocysteine level. After adjustment for apolipoprotein B levels and blood pressure, this estimate was 33% (95% CI, 22%-59%). In a meta-analysis of the retrospective studies of homocysteine level and myocardial infarction, the age-adjusted association was stronger: an 84% (95% CI, 52%-123%) increase in risk for a 5-micromol/L increase in the homocysteine level, possibly because the participants were younger; the relationship between serum homocysteine level and IHD seems to be stronger in younger persons than in older persons. CONCLUSIONS: Our positive results help resolve the uncertainty that resulted from previous prospective studies. The epidemiological, genetic, and animal evidence together indicate that the association between serum homocysteine level and IHD is likely to be causal. A general increase in consumption of the vitamin folic acid (which reduces serum homocysteine levels) would, therefore, be expected to reduce mortality from IHD.