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Objectives Multimorbidity is the coexistence of two or more health conditions in an individual. Multimorbidity in younger adults is increasingly recognised as an important challenge. We assessed the prevalence of secondary care multimorbidity in mid-life and its association with premature mortality over 15 years of follow-up, in the Aberdeen Children of the 1950s (ACONF) cohort. Method A prospective cohort study using linked electronic health and mortality records. Scottish ACONF participants were linked to their Scottish Morbidity Record hospital episode data and mortality records. Multimorbidity was defined as two or more conditions and was assessed using healthcare records in 2001 when the participants were aged between 45 and 51 years. The association between multimorbidity and mortality over 15 years of follow-up (to ages 60–66 years) was assessed using Cox proportional hazards regression. There was also adjustment for key covariates: age, gender, social class at birth, intelligence at age 7, secondary school type, educational attainment, alcohol, smoking, body mass index and adult social class. Results Of 9625 participants (51% males), 3% had multimorbidity. The death rate per 1000 person-years was 28.4 (95% CI 23.2 to 34.8) in those with multimorbidity and 5.7 (95% CI 5.3 to 6.1) in those without. In relation to the reference group of those with no multimorbidity, those with multimorbidity had a mortality HR of 4.5 (95% CI 3.4 to 6.0) over 15 years and this association remained when fully adjusted for the covariates (HR 2.5 (95% CI 1.5 to 4.0)). Conclusion Multimorbidity prevalence was 3% in mid-life when measured using secondary care administrative data. Multimorbidity in mid-life was associated with premature mortality. [ABSTRACT FROM AUTHOR]

Purpose This is an ongoing prospective cohort aiming to examine the biopsychosocial health profiles and predictors of health outcomes of older patients with multimorbidity in primary care in Hong Kong. Participants From April 2016 to October 2017, 1077 patients aged 60+ years with at least two chronic diseases were recruited in four public primary care clinics in the New Territories East Region of Hong Kong. Findings to date After weighting, the patients had 4.1 (1.8) chronic conditions and 2.5 (1.9) medications on average; 37% forgot taking medication sometimes; 71% rated their health as fair or poor; 17% were frail; 73% reported one (21%) or two or more (52%) body pain areas; 62% were overweight/obese; 23% reported chewing difficulty, 18% reported incontinence; 36% had current stage 1/2 hypertension; 38% had handgrip strength below the cut-off; 10% screened positive in sarcopenia; 17% had mild or severer cognitive impairment; 17% had mild to severe depression; 16% had mild to severe anxiety; 50% had subthreshold to severe insomnia; 28% indicated being lonely; 12% needed help in at least one out of the five daily functions and the EuroQoL-5-Dimensions-5-Level index score was 0.81 (0.20) and its Visual Analogue Scale (VAS) score was 67.6 (14.6). In the past 12 months, 17% were hospitalised, 92% attended general outpatient clinics, 70% attended specialist outpatient clinics and 10% used elderly daycare centre services, the median out-of-pocket health cost was HK$1000 (US$150). Female and male patients showed significant differences in many biopsychosocial health aspects. Future plans With assessments and clinical data, the cohort can be used for understanding longitudinal trajectories of biopsychosocial health profiles of Chinese older patients with multimorbidity in primary care. We are also initially planning cohort studies on factors associated with various health outcomes, as well as quality of life and healthcare use. [ABSTRACT FROM AUTHOR]

Objective: Patients with multiple chronic health conditions are often managed in a disjointed fashion in primary care, with annual review clinic appointments offered separately for each condition. This study aimed to determine the cost-effectiveness of the 3D intervention, which was developed to improve the system of care. Design: Economic evaluation conducted alongside a pragmatic cluster-randomised trial. Setting; General practices in three centres in England and Scotland. Participants: 797 adults with three or more chronic conditions were randomised to the 3D intervention, while 749 participants were randomised to receive usual care. Intervention: The 3D approach: comprehensive 6-monthly general practitioner consultations, supported by medication reviews and nurse appointments. Primary and secondary outcome measures: The primary economic evaluation assessed the cost per quality-adjusted life year (QALY) gained from the perspective of the National Health Service (NHS) and personal social services (PSS). Costs were related to changes in a range of secondary outcomes (QALYs accrued by both participants and carers, and deaths) in a cost–consequences analysis from the perspectives of the NHS/PSS, patients/carers and productivity losses. Results: Very small increases were found in both QALYs (adjusted mean difference 0.007 (−0.009 to 0.023)) and costs (adjusted mean difference £126 (£−739 to £991)) in the intervention arm compared with usual care after 15 months. The incremental cost-effectiveness ratio was £18 499, with a 50.8% chance of being cost-effective at a willingness-to- pay threshold of £20 000 per QALY (55.8% at £30 000 per QALY). Conclusions: The small differences in costs and outcomes were consistent with chance, and the uncertainty was substantial; therefore, the evidence for the cost-effectiveness of the 3D approach from the NHS/PSS perspective should be considered equivocal. [ABSTRACT FROM AUTHOR]

Objective: Impairment of mental well-being (anxiety, depression, stress) is common among people with multiple sclerosis (PwMS). Treatment options are limited, particularly for anxiety. The aim of this study was to update our previous systematic review (2014) and evaluate via meta-analysis the efficacy of mindfulness-based interventions (MBIs) for improving mental well-being in PwMS.Methods: Systematic searches for eligible randomised controlled trials (RCTs) were carried out in seven major databases (November 2017, July 2018), using medical subject headings and key words. Studies were screened, data extracted, quality appraised and analysed by two independent reviewers, using predefined criteria. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Mental well-being was the primary outcome. Random effects model meta-analysis was performed, with effect size reported as standardised mean difference (SMD).Results: Twelve RCTs including 744 PwMS were eligible for inclusion in the systematic review, eight had data extractable for meta-analysis; n=635. Ethnicity, socioeconomic status, comorbidity and disability were inconsistently reported. MBIs varied from manualised to tailored versions, lasting 6-9 weeks, delivered individually and via groups, both in person and online. Overall SMD for mental well-being (eight studies) was 0.40 (0.28-0.53), p<0.01, I2=28%; against active comparators only (three studies) SMD was 0.17 (0.01-0.32), p<0.05, I2 =0%. Only three adverse events were reported.Conclusions: MBIs are effective at improving mental well-being in PwMS. More research is needed regarding optimal delivery method, cost-effectiveness and comparative-effectiveness.Prospero Registration Number: CRD42018093171. [ABSTRACT FROM AUTHOR]

Objective Multimorbidity (the coexistence of two or more health conditions) is increasingly prevalent. No long-term cohort study has examined the impact of contemporaneously measured birth social class along with educational attainment on adult self-reported multimorbidity. We investigated the impact of educational attainment on the relationship between social class at birth and adult self-reported multimorbidity in the Aberdeen Children of the 1950s (ACONF) cohort. Methods A prospective cohort study using the ACONF cohort. ACONF included 12 150 individuals born in Aberdeen, Scotland 1950-1956. In 2001, 7184 (64%) responded to a questionnaire providing information including self-reported morbidity and educational attainment. The exposure was father's social class at birth from birth records and the outcome was selfreported multimorbidity. Logistic regression assessed the association between social class and multimorbidity with adjustment for gender, then by educational attainment and finally by childhood cognition and secondary school type. ORs and 95% CIs were presented. Results Of 7184 individuals (mean age 48, 52% female), 5.4% reported multimorbidity. Birth social class was associated with adult multimorbidity. For example, the OR of multimorbidity adjusted by gender was 0.62 (95% CI 0.39 to 1.00) in the highest social class group (I/II) in relation to the reference group (III (manual)) and was 1.85 (95% CI 1.19 to 2.88) in the lowest social class group. This was partially attenuated in all social class categories by educational attainment, for example, the OR was 0.74 (95% CI 0.45 to 1.21) in group I/II following adjustment. Conclusion Lower social class at birth was associated with developing multimorbidity in middle age. This was partially mediated by educational attainment and future research should consider identifying the other explanatory variables. The results are relevant to researchers and to those aiming to reduce the impact of multimorbidity. [ABSTRACT FROM AUTHOR]

Objective To identify potentially effective complementary approaches for musculoskeletal (MSK)-mental health (MH) comorbidity, by synthesising evidence on effectiveness, cost-effectiveness and safety from systematic reviews (SRs). Design Scoping review of SRs. Methods We searched literature databases, registries and reference lists, and contacted key authors and professional organisations to identify SRs of randomised controlled trials for complementary medicine for MSK or MH. Inclusion criteria were: published after 2004, studying adults, in English and scoring >50% on Assessing the Methodological Quality of Systematic Reviews (AMSTAR); quality appraisal checklist). SRs were synthesised to identify research priorities, based on moderate/good quality evidence, sample size and indication of costeffectiveness and safety. Results We included 84 MSK SRs and 27 MH SRs. Only one focused on MSK-MH comorbidity. Meditative approaches and yoga may improve MH outcomes in MSK populations. Yoga and tai chi had moderate/good evidence for MSK and MH conditions. SRs reported moderate/good quality evidence (any comparator) in a moderate/large population for: low back pain (LBP) (yoga, acupuncture, spinal manipulation/mobilisation, osteopathy), osteoarthritis (OA) (acupuncture, tai chi), neck pain (acupuncture, manipulation/manual therapy), myofascial trigger point pain (acupuncture), depression (mindfulness-based stress reduction (MBSR), meditation, tai chi, relaxation), anxiety (meditation/MBSR, moving meditation, yoga), sleep disorders (meditative/mind-body movement) and stress/distress (mindfulness). The majority of these complementary approaches had some evidence of safety--only three had evidence of harm. There was some evidence of cost-effectiveness for spinal manipulation/mobilisation and acupuncture for LBP, and manual therapy/manipulation for neck pain, but few SRs reviewed costeffectiveness and many found no data. Conclusions Only one SR studied MSK-MH comorbidity. Research priorities for complementary medicine for both MSK and MH (LBP, OA, depression, anxiety and sleep problems) are yoga, mindfulness and tai chi. Despite the large number of SRs and the prevalence of comorbidity, more high-quality, large randomised controlled trials in comorbid populations are needed. [ABSTRACT FROM AUTHOR]

Objectives Recent evidence has highlighted the high prevalence and impact of multimorbidity, but the evidence base for improving management is limited. We have tested a new complex intervention for multimorbidity (the 3D model). The paper describes the baseline characteristics of practices and patients in order to establish the external validity of trial participants. It also explores current 'usual primary care' for multimorbidity, against which the 3D intervention was tested. Design Analysis of baseline data from patients in a cluster-randomised controlled trial and additional data from practice staff. Setting Primary care in the UK. Participants Patients with multimorbidity (n=5253) and 154 practice staff. Primary and secondary outcome measures Using surveys and routinely available data, we compared the characteristics of participating and non-participating practices and participating and non-participating eligible patients. Baseline questionnaire data from patient participants was used to examine participant illness burden, treatment burden and perceptions of receiving patient-centred care. We obtained data about usual care preintervention from practice staff using questionnaires and a structured pro forma. Results Participating practices were slightly larger, in less deprived areas, and with slightly higher scores for patient satisfaction compared with non-participating practices. Patients with dementia or learning difficulties were likely to be excluded by their general practitioners, but comparison of participants with non-participants identified only minor differences in characteristics, suggesting that the sample was otherwise representative. Patients reported substantial illness burden, and an important minority reported high treatment burden. Although patients reported relatively high levels of satisfaction with care, many reported not having received potentially important components of care. Conclusion This trial achieved good levels of external validity. Although patients were generally satisfied with primary care services, there was significant room for improvement in important aspects of care for multimorbidity that are targeted by the 3D intervention. [ABSTRACT FROM AUTHOR]

Background: There is continuing concern about effects of concussion in athletes, including risk of the neurodegenerative disease chronic traumatic encephalopathy. However, information on long-term health and wellbeing in former athletes is limited.Method: Outcome after exposure to repeated brain injury was investigated in 52 retired male Scottish international rugby players (RIRP) and 29 male controls who were similar in age and social deprivation. Assessment included history of playing rugby and traumatic brain injury, general and mental health, life stress, concussion symptoms, cognitive function, disability and markers of chronic stress (allostatic load).Results: The estimated number of concussions in RIRP averaged 14 (median=7; IQR 5-40). Performance was poorer in RIRP than controls on a test of verbal learning (p=0.022) and of fine co-ordination of the dominant hand (p=0.038) and not significantly different on other cognitive tests (p>0.05). There were no significant associations between number of concussions and performance on cognitive tests. Other than a higher incidence of cardiovascular disease in controls, no group differences were detected in general or mental health or estimates of allostatic load. In RIRP, persisting symptoms attributed to concussion were more common if reporting more than nine concussions (p=0.028), although these symptoms were not perceived to affect social or work functioning.Conclusions: Despite a high number of concussions in RIRP, differences in mental health, social or work functioning were not found late after injury. Subtle group differences were detected on two cognitive tests, the cause of which is uncertain. Prospective group comparison studies on representative cohorts are required. [ABSTRACT FROM AUTHOR]

Objectives: The aetiology of bone marrow lesions (BMLs) in knee osteoarthritis (OA) is poorly understood. We employed three-dimensional (3D) active appearance modelling (AAM) to study the spatial distribution of BMLs in an OA cohort and compare this with the distribution of denuded cartilage.Methods: Participants were selected from the Osteoarthritis Initiative progressor cohort with Kellgren-Lawrence scores ≥2, medial joint space narrowing and osteophytes. OA and ligamentous BMLs and articular cartilage were manually segmented. Bone surfaces were automatically segmented by AAM. Cartilage thickness of <0.5 mm was defined as denuded and ≥0.5-1.5 mm as severely damaged. Non-quantitative assessment and 3D population maps were used for analysing the comparative position of BMLs and damaged cartilage.Results: 88 participants were included, 45 men, mean age (SD) was 61.3 (9.9) years and mean body mass index was 31.1 (4.6) kg/m(2). 227 OA and 107 ligamentous BMLs were identified in 86.4% and 73.8% of participants; OA BMLs were larger. Denuded cartilage was predominantly confined to a central region on the medial femur and tibia, and the lateral facet of the trochlear femur. 67% of BMLs were colocated with denuded cartilage and a further 21% with severe cartilage damage. In the remaining 12%, 25/28 were associated with cartilage defects. 74% of all BMLs were directly opposing (kissing) another BML across the joint.Conclusions: There was an almost exclusive relationship between the location of OA BML and cartilage denudation, which itself had a clear spatial pattern. We propose that OA, ligamentous and traumatic BMLs represent a bone response to abnormal loading. [ABSTRACT FROM AUTHOR]

Objective: To assess the nature and extent of physical health comorbidities in people with schizophrenia and related psychoses compared with controls. Design: Cross-sectional study. Setting: 314 primary care practices in Scotland. Participants: 9677 people with a primary care record of schizophrenia or a related psychosis and 1 414 701 controls. Main outcome measures Primary care records of 32 common chronic physical-health conditions and combinations of one, two and three or more physical health comorbidities adjusted for age, gender and deprivation status. Results: Compared with controls, people with schizophrenia were significantly more likely to have one physical-health comorbidity (OR 1.21, 95% CI 1.16 to 1.27), two physical-health comorbidities (OR 1.37, 95% CI 1.29 to 1.44) and three or more physical-health comorbidities (OR 1.19, 95% CI 1.12 to 1.27). Rates were highest for viral hepatitis (OR 3.98, 95% CI 2.81 to 5.64), constipation (OR 3.24, 95% CI 3.00 to 4.49) and Parkinson's disease (OR 3.07, 95% CI 2.42 to 3.88) but people with schizophrenia had lower recorded rates of cardiovascular disease, including atrial fibrillation (OR 0.62, 95% CI 0.51 to 0.73), hypertension (OR 0.71, 95% CI 0.67 to 0.76), coronary heart disease (OR 0.75, 95% CI 0.61 to 0.71) and peripheral vascular disease (OR 0.83, 95% CI 0.71 to 0.97). Conclusions: People with schizophrenia have a wide range of comorbid and multiple physical-health conditions but are less likely than people without schizophrenia to have a primary care record of cardiovascular disease. This suggests a systematic under-recognition and under treatment of cardiovascular disease in people with schizophrenia, which might contribute to substantial premature mortality observed within this patient group. [ABSTRACT FROM AUTHOR]

BACKGROUND: Medical revalidation decisions need to be reliable if they are to reassure on the quality and safety of professional practice. This study tested an innovative method in which general practitioners (GPs) were assessed on their reflection and response to a set of externally specified feedback. SETTING AND PARTICIPANTS: 60 GPs and 12 GP appraisers in the Tayside region of Scotland, UK. METHODS: A feedback dataset was specified as (1) GP-specific data collected by GPs themselves (patient and colleague opinion; open book self-evaluated knowledge test; complaints) and (2) Externally collected practice-level data provided to GPs (clinical quality and prescribing safety). GPs' perceptions of whether the feedback covered UK General Medical Council specified attributes of a 'good doctor' were examined using a mapping exercise. GPs' professionalism was examined in terms of appraiser assessment of GPs' level of insightful practice, defined as: engagement with, insight into and appropriate action on feedback data. The reliability of assessment of insightful practice and subsequent recommendations on GPs' revalidation by face-to-face and anonymous assessors were investigated using Generalisability G-theory. MAIN OUTCOME MEASURES: Coverage of General Medical Council attributes by specified feedback and reliability of assessor recommendations on doctors' suitability for revalidation. RESULTS: Face-to-face assessment proved unreliable. Anonymous global assessment by three appraisers of insightful practice was highly reliable (G=0.85), as were revalidation decisions using four anonymous assessors (G=0.83). CONCLUSIONS: Unlike face-to-face appraisal, anonymous assessment of insightful practice offers a valid and reliable method to decide GP revalidation. Further validity studies are needed. [ABSTRACT FROM AUTHOR]

The article discusses the medical examination of a 63-year-old man with a three-month history of non-specific generalized headache. He experienced episodes of odd behavior and forgetfulness. The patient was a non-smoker and had been in good health with no history of medical problems. He used to work as a secondary school teacher but had retired and opted to focus on horticulture.

Objective: To evaluate open-angle glaucoma patients, who were insufficiently controlled on latanoprost mono- therapy, to determine the 24 h intraocular pressure (lOP) efficacy and safety when changing them to dorzolamide/timolol (DTFC) or latanoprost/timolol fixed combination (LTFC) or adding DTFC. Methods: A prospective, observer-masked, placebo-controlled, crossover, comparison. Consecutive adults with primary open-angle or exfoliative glaucoma who exhibit a mean baseline lOP >21 mm Hg on latanoprost monotherapy were randomised for 3 months to: OTFC, LTFC or DTFC and latanoprost. Patients were then crossed over to the next treatment for periods 2 and 3. At the end of the latanoprost run-in and after each 3-month treatment period, patients underwent 24 h lOP monitoring. Results: 31 patients completed this study. All three adjunctive therapies significantly reduced the lOP at each time point and for the mean 24 h curve, except at 18:00 and 02:00 with DTFC and 02:00 with LTFC. When the three treatments were compared directly, the DTFC and latanoprost therapy demonstrated lower lOPs versus the other treatment groups, including: the mean 24 h pressure, maximum as well as minimum levels and individual time points following a modified Bonferroni correction (p<0.0032). Conclusions: This study showed DTFC, LTFC and the addition of DTFC to latanoprost significantly decrease the lOP compared with latanoprost alone, but the latter therapy regime yields the greatest OP reduction. [ABSTRACT FROM AUTHOR]

Background: In the USA, the lack of processes standardisation in histopathology laboratories leads to less than optimal quality, errors, inefficiency and increased costs. The effectiveness of large-scale quality improvement initiatives has been evaluated rarely. Aim: To measure the effect of implementation of a Lean quality improvement process on the efficiency and quality of a histopathology laboratory section. Methods: A non-concurrent interventional cohort study from 1 January 2003 to 31 December 2006 was performed, and the Lean process was implemented on 1 January 2004. Also compared was the productivity of the Lean histopathology section to a sister histopathology section that did not implement Lean processes. Pre- and post-Lean specimen turnaround time and productivity ratios (work units/full time equivalents) were measured. For 200 Lean interventions, a 5-part Likert scale was used to assess the impact on error, success and complexity. Results: In the Lean laboratory, the mean monthly productivity ratio increased from 3439 to 4074 work units/ full time equivalents (p

Aim: To evaluate 24 h intraocular pressure (lOP) and blood pressure (BP) with bimatoprost or latanoprost in patients with normal-tension glaucoma. Design: Prospective, randomised, crossover, active-controlled, observer-masked study. Methods: After a 6-week medicine-free period, we randomised patients to either latanoprost or bimatoprost for 8 weeks and then to the opposite medicine for 8 weeks. At baseline, and at the end of each treatment period, we evaluated lOP and BP at 08:00 and then every 2 h over the 24 h day. Diastolic ocular perfusion pressure (DOPP) was calculated from the above parameters. Results: Forty completed patients had a 24 h untreated baseline lOP of 15.5 (2.3) mm Hg, and a DOPP of 59.2 (6.1) mm Hg. Both treatments lowered lOP at each time point (p<0.006), and over the 24 h curve (p<0.001, both medicines 13.1 mm Hg, 16% decrease). No difference existed between treatments in absolute lOP, at each time point, and over the 24 h curve (p⩾0.26). Additionally, no differences were found between treated 24 h systolic (p⩾0.29) and diastolic BP )p⩾0.12). The mean 24 h DOPP for latanoprost was increased from baseline (3%, p = 0.031) but not for bimatoprost (2%, p = 0.21). However, no difference in DOPP existed between treatments at any time point or over the 24 h curve (p⩾0.17). No difference was observed between treatments for any adverse event (p>0.05). Conclusions: In patients with normal-tension glaucoma, both bimatoprost and latanoprost reduce the 24 h intraocular pressure from untreated baseline to a similar extent. Latanoprost is associated with slightly improved ocular diastolic perfusion pressure over 24 h but similar absolute perfusion levels to that of bimatoprost. [ABSTRACT FROM AUTHOR]

Aims: To evaluate efficacy and safety in patients with ocular hypertension or open angle glaucoma changed to latanoprost/timolol fixed combination (LTFC). Methods: A prospective, multicentre, historical control in which qualified patients had their previous therapy substituted by LTFC and were followed for at least 2 months. Results: In 1676 patients LTFC was continued in 93% throughout the observation period. In all patients LTFC reduced the intraocular pressure (IOP) from 20.6 (SD 3.8) to 17.7 (3.0) mm Hg (p<0.001) compared to previous monotherapies including latanoprost, timolol, α agonists or carbonic anhydrase inhibitors (CAI). LTFC provided more efficacy after changing from adjunctive therapies including: a β blocker added to either CAI, α agonist, or pilocarpine, or CAI added to an α agonist, or latanoprost added to either CAI, α agonist, or β blocker (unfixed combination), and travoprost added to timolol (p<0.007). LTFC was as effective as latanoprost used with dorzolamide/timolol fixed combination (-0.9 mm Hg, p =0.1792). The most common reason to discontinue therapy was lack of efficacy (n = 70, 4%) and adverse event (n = 17, 1%). Conclusion: In a clinical selling, patients who have their monotherapy or adjunctive therapy substituted with LTFC may experience reduced IOP, good tolerability, and continuation of therapy for the first 2-3 months of treatment. [ABSTRACT FROM AUTHOR]

Background/aims: To evaluate the efficacy of brimonidine purite versus dorzolamide given twice daily in primary open angle glaucoma or ocular hypertensive subjects. Methods: In this double masked, multicentre, prospective, crossover comparison 33 subjects were randomised to brimonidine purite or dorzolamide for the first 4 week treatment period alter a 4 week washout. Subjects began the opposite treatment for the second 4 week period after another 4 week washout. Intraocular pressure (lOP) was measured at 08:00 (trough) and 10:00, 18:00, and 20:00 hours after dosing at each baseline and at the end of each treatment period. Results: The baseline diurnal lop was 22.9 (SD 2.8) for brimonidine purite and 22.2 (SD 2.4) mm Hg for dorzolomide. The trough lOP following 4 weeks of therapy was 21.0 (SD 3.7) for brimonidine purite and 21.0 (SD 3.1) mm Hg for dorzolamide (p = 0.90). The mean diurnal lOP was 19.3 (SD 3.1) for brimonidine purite and 19.8 (SD 2.4) mm Hg for dorzolamide (p=0.46). Dorzolomide caused more ocular stinging upon instillation (n = 8) than brimonidine purite (n = 1) (p = 0.02). No statistical differences existed between groups for systemic adverse events. Conclusions: This study suggests that brimonidine purite and dorzolamide each given twice daily have similar efficacy in primary open angle glaucoma or ocular hypertensive subjects. However, a trend was observed at 10:00 of greater brimonidine purite efficacy compared with dorzolamide. [ABSTRACT FROM AUTHOR]

Provides information on a study that compared associations of lead biomarkers with renal function in current and former lead workers in South Korea. Methodology of the study; Results and discussion on the study; Conclusions.

Presents letters to the 'British Medical Journal' about a variety of topics. Length of patient consultations with doctors; Drawbacks of telephone consultations; Value of knee imaging by general practitioners; Hormone replacement therapy; Reducing unintended adolescent pregnancy; Others.

This paper presents the clinical and pathological findings in 40 consecutive patients seen with primary tumours arising from the lacrimal gland. Twenty patients had a benign mixed-cell tumour. They presented in a recognisable clinical manner with a painless mass in the region of the lacrimal gland which slowly enlarged over a period of at least 1 year before consultation. Twenty patients had a carcinoma of the lacrimal gland. They had a short history and experienced pain. On clinical grounds they could not be distinguished from inflammatory lesions in the region of the lacrimal gland. The method of treating these 2 groups of patients is described and methods of dealing logically with their problems are suggested. [ABSTRACT FROM PUBLISHER]

Objectives: Previous research suggests that binding of lead by delta-aminolevulinic acid dehydratase (ALAD) may vary by ALAD genotype. This hypothesis was tested by examining whether ALAD genotype modifies urinary lead excretion (DMSA chelatable lead) after oral administration of dimercaptosuccinic acid (DMSA).Methods: 57 South Korean lead battery manufacturing workers were given 5 mg/kg oral DMSA and urine was collected for four hours. Male workers were randomly selected from two ALAD genotype strata (ALAD1-1, ALAD1-2) from among all current workers in the two plants (n = 290). Subjects with ALAD1-1 (n = 38) were frequency matched with subjects with ALAD1-2 (n = 19) on duration of employment in the lead industry. Blood lead, zinc protoporphyrin, and plasma aminolevulinic acid concentrations, as well as ALAD genotype, duration of exposure, current tobacco use, and weight were examined as predictors or effect modifiers of levels of DMSA chelatable lead.Results: Blood lead concentrations ranged from 11 to 53 micrograms/dl, with a mean (SD) of 25.4 (10.2) micrograms/dl. After 5 mg/kg DMSA orally, the workers excreted a mean (SD) 85.4 (45.0) micrograms lead during a four hour urine collection (range 16.5-184.1 micrograms). After controlling for blood lead concentrations, duration of exposure, current tobacco use, and body weight, subjects with ALAD1-2 excreted, on average, 24 micrograms less lead during the four hour urine collection than did subjects with ALAD1-1 (P = 0.05). ALAD genotype seemed to modify the relation between plasma delta-aminolevulinic acid (ALA) and DMSA chelatable lead. Workers with ALAD1-2 excreted more lead, after being given DMSA, with increasing plasma ALA than did workers with ALAD1-1 (P value for interaction = 0.01).Conclusions: DMSA chelatable lead may partly reflect the stores of bioavailable lead, and the current data indicate that subjects with ALAD1-2 have lower stores than those with ALAD1-1. These data provide further evidence that the ALAD genotype modifies the toxicokinetics of lead-for example, by differential binding of current lead stores or by differences in long-term retention and deposition of lead. [ABSTRACT FROM AUTHOR]

OBJECTIVES--To validate a provocative chelation test with 2,3-dimercaptosuccinic acid (DMSA) by direct comparison with the standard ethylene diamine tetraacetic acid (EDTA) test in the same subjects; and to compare and contrast the predictors of lead excretion after DMSA with those after EDTA. A metal chelating agent given orally, DMSA may mobilise and enhance the excretion of lead from the storage sites in the body that are most directly relevant to the health effects of lead. A provocative chelation test with DMSA could thus have wide potential application in clinical care and epidemiological studies. METHODS--34 male lead workers in the Republic of Korea were given a single oral dose of 10 mg/kg DMSA, urine was collected over the next eight to 24 hours, and urine volume and urinary lead concentration determined at 0, 2, 4, 6, 8, and 24 hours. Either two weeks before or two weeks after the dose of DMSA 17 of these workers also received 1 g intravenous EDTA followed by an eight hour urine collection with fractionation at 0, 2, 4, 6, and 8 hours. RESULTS--Urinary lead concentration peaked at two hours after DMSA and four hours after EDTA. Lead excretion after DMSA was less than after EDTA, and cumulative excretion after DMSA plateaued at six to eight hours. The two hour and four hour cumulative lead excretions after DMSA were highly correlated with the eight hour total (r = 0.76 and 0.95). In multiple linear regression analyses, blood lead was found to be an important predictor of EDTA-chelatable lead, whereas urinary aminolevulinic acid (ALAU) was associated with DMSA-chelatable lead. Notably, lead excretion after DMSA was greatly increased if EDTA was given first. An earlier dose of EDTA also modified the relation between ALAU and DMSA-chelatable lead in that workers who received EDTA before DMSA showed a much steeper dose-response relation between these two measures. CONCLUSIONS--The predictors of lead excretion after DMSA and EDTA are different and an earlier dose of EDTA may increase lead excretion after a subsequent dose of DMSA. The results suggest that two hour or four hour cumulative lead excretion after DMSA may provide an estimate of lead in storage sites that are most directly relevant to the health effects of lead. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the current evidence that cumulative exposure to inorganic lead is associated with decreased performance in neurobehavioural tests in adults.Methods: 21 unique studies were reviewed from 28 published manuscripts. An algorithm was developed to determine the usefulness of each study on the basis of exposure assessment, control of confounding variables, methods of subject selection, test conditions, and data analysis. Highest emphasis was placed on the use of cumulative measures of exposure or absorption.Results: Only three studies used a measure of cumulative exposure to or absorption of lead, and two others used duration of exposure as a surrogate for cumulative exposure. All other studies used a measure that did not adequately estimate cumulative exposure to lead, most often current blood lead concentration. 20 of the studies controlled for age as a confounding variable, although in several studies the possibility for residual confounding by age remained. 16 studies controlled for intellectual ability before exposure; all of them used educational level for this purpose. Of the five studies that used direct or surrogate measures of cumulative exposure to or absorption of lead, two were thought to be of low usefulness because of inadequate duration of exposure. The three remaining studies found stronger associations of neurobehavioural performance with recent exposure measures than with those of cumulative exposure.Conclusion: The current scientific literature provides inadequate evidence to conclude whether or not cumulative exposure to or absorption of lead adversely affects performance in neurobehavioural tests in adults. The current evidence is flawed because of inadequate estimation of cumulative exposure to or absorption of lead and inadequate control for age and intellectual ability before exposure. [ABSTRACT FROM AUTHOR]

Objectives: To describe 6 h urinary lead excretion (6 h PbU) after 1 g intravenous ethylene diamine tetraacetic acid (EDTA) in organolead manufacturing workers with mixed exposure to organic and inorganic lead; to determine the predictors of lead excretion (PbU); and to determine the extent to which internal lead stores and ongoing external exposure govern blood concentrations of lead (PbB).Methods: A case series of 21 active workers were studied. Personal industrial hygiene data, grouped by 29 exposure zones, in combination with personal interviews about work location and times were used to derive several measures of recent and cumulative exposure to organic and inorganic lead. The average exposure intensities assigned to the 29 zones ranged from 4 to 119 micrograms/m3 (0.02-0.57 mumol/m3 as lead) for organic lead and from 1 to 56 micrograms/m3 (0.004-0.27 mumol/m3) for inorganic lead.Results: After controlling for age, 6 h PbU was significantly and positively correlated with summary measures of PbB--for example, lifetime peak PbB, time weighted PbB--and zinc protoporphyrin concentrations--for example, lifetime peak zinc protoporphyrin, time weighted zinc protoporphyrin--but not with measures of estimated external exposure--for example, duration of exposure and cumulative exposure to inorganic or organic lead. Among workers with higher chelatable lead burdens (6 h PbU > or = 212.4 micrograms (1.03 mumol) divided at the median), there was no apparent relation between recent inorganic lead exposure and PbB at the time of chelation. Among workers with lower chelatable lead burdens (6 h PbU < 212.4 micrograms (1.03 mumol) however, there was a significant relation between exposure and effect between recent exposure to inorganic lead and PbBs.Conclusion: These findings are consistent with the concept of physiological dampening. The high chelatable lead burden, a source of internal exposure, dampens the effect of external exposure on PbBs. The data suggest that in organolead workers with high chelatable lead burdens, PbBs may be more influenced by internal lead stores than by variations in airborne exposure to organic and inorganic lead. [ABSTRACT FROM AUTHOR]

Five percutaneous biopsy and 17 necropsy liver specimens were analysed histologically and chemically for iron content in 22 patients receiving dialysis for chronic renal failure, 13 of whom were given intravenous iron-dextran. Brissot scores for assessing histological hepatic iron deposition and chemically measured liver iron concentrations correlated closely. Both variables depended on total cumulative dose of iron, and to a lesser extent, on time since the last dose. Fibrosis (seen in five patients) was minimal and non-specific. Electron microscopic examination showed that there was no generalised damage and confirmed the presence of iron in the hepatocytes in the form of ferritin. High liver iron concentrations, in excess of 1000 micrograms/100 mg dry weight, were seen in two patients. Four others given comparable cumulated amounts (18-23 g iron) did not have such high concentrations. Plasma ferritin concentrations were high in eight patients, some with and some without fibrosis. The risk of temporarily high iron deposition in the liver causing damage seemed to be minimal when weighed against the benefit of increased haemoglobin in most of the patients. Intravenous iron treatment merits further evaluation, particularly with the advent of erythropoietin treatment, which requires continuously available iron. [ABSTRACT FROM PUBLISHER]

The article presents a case study of a 58-year-old man who is experiencing a difficulty of finishing a round of golf due to an abnormal sensation around his abdomen and weakness of his legs. It says that the patient has showed an evidence of cerebral lymphoma five months after presenting with acute confusion and drowsiness. It adds that five cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) chemotherapy was received by the patient.

The article discusses how the care of patients with multimorbidities can be improved by use of a new technology. The new technology involves bringing together guidelines on individual conditions and tailoring the advice to each individual's personal condition. Some guidelines to help clinicians in treatment of these patients include cross reference guidelines using electronic delivery, provide guidance about treatments most likely to benefit and least likely to harm, and make better use of existing evidence. However, all guidelines do have their limitations, which is where physician experience comes into play. Patient circumstances and preferences should be paid heed to.

Focuses on the organization of community mental health care. Improvement of medical education in psychiatry; Encouragement of team work with general practitioners; Discussion on the treatment of doctors with the patients.

Single eye visual fields and contrast sensitivity were assessed in 60 subjects, who were being followed up in a glaucoma clinic for manifest glaucoma or a suspicion of glaucoma because of raised intraocular pressure. The Fieldmaster 5000 (static/kinetic perimeter) was used for the visual fields, and a Vistech wall chart sine wave grating test was used for contrast sensitivity measurements. The subjects were divided into three groups--defect (D), suspect (S) and normal (N)--on the basis of their perimetric findings by subjective grading of 16 perimetric scoring categories for each visual field. The mean Vistech sensitivity levels were not found to be significantly different between the D, S, and N field subgroups at any of the five spatial frequencies provided on the test charts (1.5, 3, 6, 12, and 18 cycles per degree). Complex algorithms combining results from two or more spatial frequencies also failed to yield any significant differences between the groups. Diagnostic sensitivity and specificities relating Vistech contrast sensitivity findings to groups N and D never concomitantly exceeded 60%. [ABSTRACT FROM PUBLISHER]

We report a female case of orofaciodigital syndrome type I (OFD I) associated with polycystic kidneys and agenesis of the corpus callosum. She had chronic renal failure requiring maintenance dialysis and significant neurological deficits. Her mother had less severe OFD I associated with polycystic kidneys but her renal function was normal and there was no clinical or radiological evidence of a structural abnormality of the brain. [ABSTRACT FROM PUBLISHER]

A response by W. C. Stewart, R. Feldman and M. A. Mychaskiw to a letter to the editor about their article regarding the evidence of ocular blood flow in the pathogenesis and treatment of glaucoma..

An abstract of the article "A Diagnostic Dilemma: Rapid Cognitive Decline With White Matter Disease," by S. L. Miller, W. Stewart, C. Santosh, and colleagues is presented.

Evaluates neurobehavioral testing in workers exposed to lead in occupational conditions.