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This review aims to update the reader on advances in the understanding of haematological conditions that may arise in neurological practice. Thrombophilia, antiphospholipid antibody syndrome, thrombotic thrombocytopenic purpura, sickle cell and clonal disorders associated with neuropathy are discussed. [ABSTRACT FROM AUTHOR]

Aims: To investigate whether infants who died of SIDS were more likely to have higher acute and lifetime average exposures to outdoor carbon monoxide (CO) and nitrogen dioxide (NO2) than comparison healthy infants. Methods: A total of 169 case and 169 matched control infants born between 1988 and 1992, were studied. CO and NO2 concentrations, averaged for all days within the infant's lifespan, and the last 30 days, 7 days 3 days and 1 day of life were obtained from air pollutant data provided by the California Air Resources Board. Results: Based on monthly aggregated data, average CO and particularly NO2 were associated with SIDS count, even after adjustment for seasonal trends. SIDS outcome was not significantly associated with high average outdoor CO levels for any time period. However, high average outdoor NO2 levels on the last day of the infant's exposure period were significantly associated with SIDS; the adjusted odds ratio was 2.34 (95% CI 1.13 to 4.87). Conclusions: SIDS may be related to high levels of acute outdoor NO2 exposure during the last day of life. Further studies ore needed to replicate this finding. [ABSTRACT FROM AUTHOR]

Background: Amyloidosis refers to a heterogeneous group of disorders associated with the deposition of chemically distinct amyloid fibril proteins. Precise determination of chemical amyloid type has diagnostic, therapeutic, and prognostic relevance. Although immunohistochemical techniques are used routinely to determine the amyloid type, the results can be negative or inconclusive, so that biochemical characterisation is often required. The development and application of new biochemical microtechniques suitable for examination of extremely small tissue samples is essential for precise identification of the deposited amyloid proteins. Aims: To investigate biochemically the amyloid proteins present in a formalin fixed paraffin wax embedded orbital tissue from a patient with localised orbital amyloidosis in whom immunohistochemistry was not helpful in the determination of amyloid type. Methods: Extraction of amyloid proteins from fixed tissue and their identification was carried out by a recently developed microtechnique. An extremely small tissue sample was dewaxed and extracted with formic acid. The extracted material was analysed using electrophoresis, western blotting, and amino acid sequencing. Results: Biochemical examination of the extracted proteins showed the presence of immunoglobulin (Ig) derived amyloid proteins, which were composed of the N-terminal fragments of the Ig light chain κIII subtype (AL-κIll) (16, 8, and 3 kDa). Conclusions: This is the first chemically proved AL case reported in association with primary localised orbital amyloidosis. The biochemical microtechnique used was useful in achieving a precise diagnosis of amyloid disease, in a case where the results of routine immunohistochemical examination of amyloid were inconclusive. [ABSTRACT FROM AUTHOR]

Conclusions: The heterogeneity between the trials and the limited data result in considerable uncertainty about the value of long term anticoagulation compared with antiplatelet treatment. The risks of bleeding and the higher cost of anticoagulation make it an even less convincing treatment option. [ABSTRACT FROM AUTHOR]

Determines whether treatment with low dose of aspirin and heparin leads to a higher rate of live births than that achieved with low dose of aspirin alone in women with history of recurrent miscarriage associated with phospholipid antibodies. Intervention; Main outcome measures; Results.

Objective: This study was designed to establish whether a ratio of three units of Dysport is equivalent to one unit of Botox for the treatment of cervical dystonia.Methods: Patients with predominantly rotational cervical dystonia, and a minimum of four previous Botox treatments, were randomised to receive either the clinically indicated dose of Botox or three times that dose in Dysport units. Study botulinum toxin was administered in a double blind fashion, to one or more clinically indicated muscles, at one or more sites per muscle. Patients returned for assessment two, four, eight, and 12 weeks after treatment.Results: A total of 73 patients (Dysport, 38; Botox, 35) were entered. The Dysport group received a mean (SD) dose of 477 (131) (range 240-720) Dysport units, and the Botox group received a mean (SD) dose of 152 (45) (range 70-240) Botox units. The mean (SEM) post-treatment Tsui scores for the Dysport group (4.8 (0.3)) and the Botox group (5.0 (0.3)) were not statistically different (p=0.66). The study had 91% power to detect a clinically significant difference of two points. Both groups showed substantial improvement in Tsui score by week 2 (mean (SD); Dysport, 46 (28)%; Botox, 37 (28)%), with a peak effect at week 4 (mean (SD); Dysport, 49 (29)%; Botox, 44 (28)%). A similar response profile was seen for other assessments of efficacy. The duration of effect, assessed by time to retreatment, was also similar (mean (SD); Dysport, 83.9 (13.6) days; Botox, 80.7 (14.4) days; p=0.85). During the study 22 of 38 (58%) Dysport patients reported 39 adverse events, and 24 of 35 (69%) Botox patients reported 56 adverse events (p=0.35). A global assessment of efficacy and safety considered that 29 of 38 (76%) Dysport patients and 23 of 35 (66%) Botox patients were treatment successes (p=0.32).Conclusion: Patients with predominantly rotational cervical dystonia treated with the clinically indicated dose of Botox or three times that dose in Dysport units show similar improvements and do not have significantly different safety profiles. [ABSTRACT FROM AUTHOR]

A case control study was conducted to test the hypothesis that socioeconomic status is positively associated with multiple myeloma incidence. One hundred and fifty-three myeloma cases and 459 controls were identified at the Duke University Medical Center at Durham, North Carolina. Study members were interviewed regarding indicators of socioeconomic status. The association of myeloma with family income (current and highest), education, occupation, home ownership, dwelling size, and an index of crowding in the home was examined by estimating relative risks. Among these indicators, only home ownership showed any association with multiple myeloma incidence (RR = 1.6, 95% CI: 1.0-2.6). The association of multiple myeloma with socioeconomic status that has been seen in earlier studies may have been due to underascertainment of disease in less advantaged groups. This association is disappearing as access to health care becomes more uniform across socioeconomic groups. [ABSTRACT FROM AUTHOR]

AIMS: To determine the costs and effectiveness of an anticoagulant nurse specialist service compared with a conventional consultant service based on two hospital sites in northwest Hertfordshire. METHODS: Sequential design comparing retrospectively the conduct and outcomes of a consultant service with a nurse specialist service over two six month periods. In each of the six month study periods, all new patients consecutively referred for anticoagulation over a three month period (group A) at the start of each study period and a random selection of patients who had already been attending the anticoagulant service for one year or more (group B) were included in the study. Group A patients wre followed for up to three months and group B patients for six months. The main outcome measures were costs of service provision and effectiveness. Costs included those for the use of the anticoagulant service, those related to general practitioner (GP) visits and hospitalisations, and running costs (staff time, laboratory tests, patient transport). Measures of effectiveness were the mean proportion of time patients spend in the therapeutic range, the number of drugs being taken that could interact adversely and/or inhibit haemostatic function, and patient and GP satisfaction with service provision. RESULTS: In the consultant service, for group A there were more patients aged 66-75 years (p = 0.004) and fewer patients aged more than 76 years (p = 0.001); and for group B, there were fewer patients on anticoagulation for cardiac conditions (p = 0.001), but more on anticoagulation for thromboembolic conditions (p = 0.02) than in the nurse specialist service. The clinic running costs of the nurse specialist service were 4.99 Pounds per attendance, compared with 4.75 Pounds in the consultant service. Including all other costs related to treatment, there was no statistically significant difference in cost per patient. There was no significant difference in the proportion of time patients spent in the therapeutic range between the consultant service and the nurse specialist service. In the nurse specialist service, fewer patients in group A were taking drugs that could interact adversely and/or inhibit haemostatic function (p = 0.01) and more patients were satisfied with service provision (p = 0.04) compared with the consultant service. There was no significant variation in GP satisfaction between the two services. CONCLUSION: In the provision of outpatient anticoagulation, the nurse specialist service was no more expensive than the consultant service and, using our primary outcome, at least as effective. The nurse specialist service has some clear advantages compared to the consultant service: provision of domicilliary care for housebound patients, fewer new patients taking drugs that could interact adversely and/or inhibit haemostatic function patients, it is preferred by newly referred patients to the consultant service, and it is as acceptable to their GPs. [ABSTRACT FROM PUBLISHER]

AIMS: To develop a method for evaluating the start of anticoagulation treatment in inpatients. METHODS: One hundred case notes were audited using a proforma based on local guidelines in accordance with British Society for Haematology recommendations. RESULTS: Confirmatory investigations were done in 93% and 79% of patients with symptomatic deep venous thrombosis and pulmonary embolism, respectively. Identification of patients' risk factors for anticoagulation by history taking and laboratory tests was often inadequate: baseline coagulation screen, platelet count, liver function and renal function tests were done in 52%, 95%, 70% and 87% of cases, respectively. There was a tendency to undertreat patients: 33% of the activated partial thromboplastin times (APTT) and 58% of the International Normalised Ratios (INR) were subtherapeutic. The heparin-warfarin crossover period was particularly problematic: 37% stopped heparin without an INR that day, or had an INR of less than 2. Microscopic haematuria was monitored occasionally. Of the 62 patients continuing anticoagulation, 72% were discharged with the final INR in the therapeutic range. At discharge, only 74% of patients had documented appointments for the anticoagulant Clinic, the period between discharge and appointment ranging from 0 to 12 days. Of the 25 cases with an appointment exceeding four days after discharge, only six (24%) had arrangements for an interim INR check. CONCLUSIONS: The experience allowed the proforma to become streamlined to a more practical, reliable, and valid tool for use elsewhere. Findings will be fed back to the hospital staff to promote practice improvements before closing the audit loop by re-evaluating practice. Further studies are in progress to identify barriers experienced by doctors in implementing the guidelines and problems in the process of referral to the anticoagulant clinic. [ABSTRACT FROM PUBLISHER]

The prevalence of lupus anticoagulant, using the dilute Russell's viper venom time (DRVT), was determined in 22 patients with mild to severe haemophilia A to see if there was any association with the presence of viral disease. Twelve haemophiliacs (58%) were lupus anticoagulant positive, with a mean patient:control ratio of 1.24 (range 1.15-1.52, normal range 0.84-1.06 which partially corrected with lysed, washed platelets). Nine of these patients were IgG or IgM, or both, anticardiolipin antibody positive and nine were human immunodeficiency virus (HIV) antibody positive, but associations between lupus anticoagulant, anticardiolipin antibodies, and HIV antibody positivity were not significant. Mixing studies of normal plasma and immune depleted factor VIII deficient plasma showed that the DRVT ratio increased when the factor VIII concentration fell below 0.15 IU/ml. There was no significant association between plasma factor VIII concentration and positive DRVT results in haemophiliacs. The addition of porcine factor VIII concentrate produced no correction in eight of the 12 with DRVTs indicative of lupus anticoagulant, suggesting that these were prolonged by antiphospholipid activity. It is concluded that the presence of lupus anticoagulant and anticardiolipin antibodies in haemophiliacs may represent an antiphospholipid response to viraemic challenge, not only to HIV but also to other viral antigens, and that a very low factor VIII concentration may produce a false positive DRVT result. [ABSTRACT FROM PUBLISHER]

Two patients with low random serum vitamin K1 concentrations but with normal prothrombin times and normal biological assays of the vitamin K dependent coagulation proteins were treated with an N-methyl-thiotetrazole cephalosporin (cefotetan) postoperatively. Four to six days later both patients developed a prolonged prothrombin time and a noticeable and specific lowering of the clotting activities of factors II, VII, IX and X, though the serum vitamin K1 concentrations remained unchanged. Crossed immunoelectrophoresis of prothrombin showed the appearance of a second peak corresponding to descarboxyprothrombin (PIVKA II). These abnormalities corrected after vitamin K administration. These data are consistent with the hypothesis that cephalosporins with an N-methyl-thiotetrazole side chain inhibit the hepatic utilisation of vitamin K but that this only causes hypoprothrombinaemia when liver reserves of vitamin K are low. [ABSTRACT FROM PUBLISHER]

In the echocardiographic assessment of patients with pericardial effusions, the apparent width of the echo-free space between the left ventricular posterior wall and the parietal pericardium is commonly used to estimate the amount of pericardial fluid present. In 4 patients with pericardial effusions, we showed a distinct disparity between the widths of the posterior pericardial space at different levels of the left ventricular posterior wall. In 2 of them, a 'swinging heart' appearance was recorded when the ultrasoound beam was directed caudally, but not when its direction was cephalad or less caudad. It is suggested that the left ventricle should be scanned at all possible sites to minimise potential errors in estimating the amount of a pericardial effusion. [ABSTRACT FROM PUBLISHER]

A new method for the measurement of capillary fragility based on the time of appearance of petechiae under standardized conditions has been used to study 88 non-diabetics and 211 patients attending a diabetic clinic. In the former the capillary fragility increased with age. In the diabetic group 78 out of 195 patients had complications, and in all age groups these latter patients had more fragile capillaries. In general the capillary fragility was greater in patients taking insulin than in those taking antidiabetic tablets or on diet alone, and in the first group capillary fragility was greatest in those receiving more than 50 units daily and least in those receiving less than 25 units daily. Capillary fragility measurement by this method may be of value in assessment, prognosis, and studying the response to treatment in diabetes. [ABSTRACT FROM PUBLISHER]

The effect of 50 mg. of sustained release phenformin capsules administered twice daily was compared with a placebo as an aid to weight reduction in obese non-diabetic patients. Phenformin and placebo were administered alternately in two three-month periods. Weight loss on a 1,200-calorie diet was greater in the first three months than in the second three months regardless of treatment. There was no difference in weight loss between the phenformin and placebo groups in either the first or second three-month period. Serum cholesterol levels tended to fall in association with weight loss, but not apparently in relation to the size of the weight loss or to the treatment. [ABSTRACT FROM PUBLISHER]

The article presents information about a survey of 100 patients suffering from coronary heart disease. Each set of medical and nursing records was assessed independently by two specialist registrars. Pro-formas were then compared, differences discussed and, with further reference to the case notes, resolved. Questionnaires were then sent to surviving patients requesting a current medication list, details of aspirin use, smoking status and involvement in coronary rehabilitation. Three hundred and fifty six patient records were examined.

Recurrent parotitis in children is a well described but rare condition of unknown cause. The clinical features of 11 children with recurrent parotitis are described. [ABSTRACT FROM AUTHOR]

Objective: We investigated the contribution of small vessel disease (SVD) to anticoagulant-associated intracerebral haemorrhage (ICH)., Methods: Clinical Relevance of Microbleeds in Stroke-2 comprised two independent multicentre observation studies: first, a cross-sectional study of patients with ICH; and second, a prospective study of patients taking anticoagulants for atrial fibrillation (AF) after cerebral ischaemia. In patients with ICH, we compared SVD markers on CT and MRI according to prior anticoagulant therapy. In patients with AF and cerebral ischaemia treated with anticoagulants, we compared the rates of ICH and ischaemic stroke according to SVD burden score during 2 years follow-up., Results: We included 1030 patients with ICH (421 on anticoagulants), and 1447 patients with AF and cerebral ischaemia. Medium-to-high severity SVD was more prevalent in patients with anticoagulant-associated ICH (CT 56.1%, MRI 78.7%) than in those without prior anticoagulant therapy (CT 43.5%, p<0.001; MRI 64.5%, p=0.072). Leukoaraiosis and atrophy were more frequent and severe in ICH associated with prior anticoagulation. In the cerebral ischaemia cohort (779 with SVD), during 3366 patient-years of follow-up the rate of ICH was 0.56%/year (IQR 0.27-1.03) in patients with SVD, and 0.06%/year (IQR 0.00-0.35) in those without (p=0.001); ICH was independently associated with severity of SVD (HR 5.0, 95% CI 1.9 to 12.2,p=0.001), and was predicted by models including SVD (c-index 0.75, 95% CI 0.63 to 0.85)., Conclusions: Medium-to-high severity SVD is associated with ICH occurring on anticoagulants, and independently predicts ICH in patients with AF taking anticoagulants; its absence identifies patients at low risk of ICH. Findings from these two complementary studies suggest that SVD is a contributory factor in ICH in patients taking anticoagulants and suggest that anticoagulation alone should no longer be regarded as a sufficient 'cause' of ICH., Trial Registration: NCT02513316., Competing Interests: Competing interests: DJS: Scientific advisory boards: Bayer and Pfizer. Compensation for educational efforts: Stago. DJW: speaking honoraria: Bayer. DJW: personal fees from Bayer and Portola., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objective: To evaluate the influence of intracerebral haemorrhage (ICH) location on stroke outcomes., Methods: We included patients recruited to a UK hospital-based, multicentre observational study of adults with imaging confirmed spontaneous ICH. The outcomes of interest were occurrence of a cerebral ischaemic event (either stroke or transient ischaemic attack) or a further ICH following study entry. Haematoma location was classified as lobar or non-lobar., Results: All 1094 patients recruited to the CROMIS-2 (Clinical Relevance of Microbleeds in Stroke) ICH study were included (mean age 73.3 years; 57.4% male). There were 45 recurrent ICH events (absolute event rate (AER) 1.88 per 100 patient-years); 35 in patients presenting with lobar ICH (n=447, AER 3.77 per 100 patient-years); and 9 in patients presenting with non-lobar ICH (n=580, AER 0.69 per 100 patient-years). Multivariable Cox regression found that lobar ICH was associated with ICH recurrence (HR 8.96, 95% CI 3.36 to 23.87, p<0.0001); similar results were found in multivariable completing risk analyses. There were 70 cerebral ischaemic events (AER 2.93 per 100 patient-years); 29 in patients presenting with lobar ICH (AER 3.12 per 100 patient-years); and 39 in patients with non-lobar ICH (AER 2.97 per 100 patient-years). Multivariable Cox regression found no association with ICH location (HR 1.13, 95% CI 0.66 to 1.92, p = 0.659). Similar results were seen in completing risk analyses., Conclusions: In ICH survivors, lobar ICH location was associated with a higher risk of recurrent ICH events than non-lobar ICH; ICH location did not influence risk of subsequent ischaemic events., Trial Registration Number: NCT02513316., Competing Interests: Competing interests: HC has received institutional research support from Bayer; honoraria for lectures and an Advisory Board from Bayer, diverted to a local charity; and travel/accommodation expenses for participation in scientific meetings covered by Bayer. GL acts as a consultant for Bayer/Janssen, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon and Daiichi-Sankyo, and as a speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim and Daiichi-Sankyo; no fees are directly received personally. DJW has received honoraria for consultancy and lectures from Bayer, Portola and Alnylam. The remaining authors report no disclosures or conflicts of interest relevant to the manuscript., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Haptoglobin is a haemoglobin-scavenging protein that binds and neutralises free haemoglobin and modulates inflammation and endothelial progenitor cell function. A HP gene copy number variation (CNV) generates HP1 and HP2 alleles, while the single-nucleotide polymorphism rs2000999 influences their levels. The HP1 allele is hypothesised to improve outcome after spontaneous (non-traumatic) intracerebral haemorrhage (ICH). We investigated the associations of the HP CNV genotype and rs2000999 with haematoma volume, perihaematomal oedema (PHO) volume, functional outcome and mortality after ICH., Methods: We included patients with neuroimaging-proven ICH, available DNA and 6-month follow-up in an observational cohort study (CROMIS-2). We classified patients into three groups according to the HP CNV: 1-1, 2-1 or 2-2 and also dichotomised HP into HP1-containing genotypes (HP1-1 and HP2-1) and HP2-2 to evaluate the HP1 allele. We measured ICH and PHO volume on CT; PHO was measured by oedema extension distance. Functional outcome was assessed by modified Rankin score (unfavourable outcome defined as mRS 3-6)., Results: We included 731 patients (mean age 73.4, 43.5% female). Distribution of HP CNV genotype was: HP1-1 n=132 (18.1%); HP2-1 n=342 (46.8%); and HP2-2 n=257 (35.2%). In the multivariable model mortality comparisons between HP groups, HP2-2 as reference, were as follows: OR HP1-1 0.73, 95% CI 0.34 to 1.56 (p value=0.41) and OR HP2-1 0.5, 95% CI 0.28 to 0.89 (p value=0.02) (overall p value=0.06). We found no evidence of association of HP CNV or rs200999 with functional outcome, ICH volume or PHO volume., Conclusion: The HP2-1 genotype might be associated with lower 6-month mortality after ICH; this finding merits further study., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: The optimal time to start oral anticoagulant (OAC) in patients with ischaemic stroke due to non-valvular atrial fibrillation (AF) is unknown. We reviewed OAC timing in relation to 90-day clinical outcomes as a post hoc analysis from a prospective multicentre observational study., Methods: We included patients with data on time to initiation of OAC from CROMIS-2 (Clinical Relevence Of Microbleeds In Stroke-2), a prospective observational inception cohort study of 1490 patients with ischaemic stroke or transient ischaemic attack (TIA) and AF treated with OAC. The primary outcome was the composite outcome of TIA, stroke (ischaemic stroke or intracranial haemorrhage) or death within 90 days of the qualifying stroke or TIA. We performed adjusted logistic regression analyses to compare early (0-4 days) and later (≥5 days or never started) OAC initiation., Results: We included 1355 patients, mean age 76 (SD 10), 580 (43%) women. OAC was started early in 358 (26%) patients and later (or not at all) in 997 (74%) patients. The event rate within 90 days was 48/997 (5%) in the late-OAC group (2 intracranial haemorrhages, 18 ischaemic strokes or TIAs and 31 deaths (three deaths were as a result of new ischaemic strokes)) versus 7/358 (2%) in the early-OAC group (5 ischaemic strokes or TIAs and 2 deaths). In adjusted analyses, late OAC was not associated with the composite outcome (adjusted OR 1.17, 95% CI 0.48 to 2.84, p=0.736)., Conclusion: In adjusted analyses, early OAC after acute ischaemic stroke or TIA associated with AF was not associated with a difference in the rate of the composite outcome of stroke, TIA or death at 90 days, compared with late OAC. However, despite adjustment for important baseline factors, patients selected for early OAC and late OAC might still have differed in important respects; evaluation of OAC timing in adequately powered randomised trials is required., Clinical Trial Registration: NCT02513316., Competing Interests: Competing interests: HC has received institutional research support from Bayer; honoraria for lectures and an Advisory Board from Bayer, diverted to a local charity; and travel/accommodation expenses for participation in scientific meetings covered by Bayer and Boehringer Ingelheim. GYHL is consultant for Bayer/Janssen, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon and Daiichi-Sankyo; speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim and Daiichi-Sankyo. No fees are directly received personally. The remaining authors report no disclosures or conflicts of interest relevant to the manuscript., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

There is an extensive ethical debate regarding the justifiability of doctors nudging towards healthy behaviour and better health-related choices. One line of argument in favour of nudging is based on empirical findings, according to which a healthy majority among the public support nudges. In this paper, we show, based on an experiment we conducted, that, in health-related choices, people's ethical attitudes to nudging are strongly affected by the point of view from which the nudge is considered. Significant differences have been found between doctors' ethical attitude to clinical nudging and that of patients. We show how these differences weaken the argument for nudging from public support. Moreover, our findings raise concerns regarding doctors' ability to nudge ethically according to their own standards, as they may underestimate the degree of harm medical nudges can cause to informed consent, doctor-patient trust and other important ethically relevant features of health-related choices., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)