Ammar Natalwala

Reasons for Hospital Admissions in Dementia Patients in Birmingham, UK, during 2002–2007

Background: There is a lack of evidence to explain why patients with dementia are admitted to a general hospital. Methods: Main reasons for hospitalisation were investigated in all patients admitted to a multi-ethnic general hospital during 2002–2007, by analysis of type of admission and primary diagnosis on admission. Anonymised data from the Hospital Activity Analysis Register was used to trace these patients; 505 were diagnosed with Alzheimer’s disease (AD), 283 with vascular dementia (VD) and 1,773 patients were classified as unspecified dementia (UnD). Logistic regression analysis was used to compare these groups to 53,123 age-matched controls. Statistical significance of p < 0.001 was accepted. Results: More dementia patients were admitted as emergency cases compared to controls (AD = 95.8%, VD = 95.4%, UnD = 96.7%, controls = 54.4%; p < 0.001 for all comparisons). The proportion of patients admitted for dementia as their primary diagnosis was small (AD = 5.9%, VD = 10.6%, UnD = 6.0%). Primary diagnoses such as syncope and collapse, bronchopneumonia, urinary tract infection and dehydration were more frequent in all dementia patients than controls. Conclusion: Dementia patients are frequently admitted as emergency cases, but dementia itself is often not the primary diagnosis. Earlier detection of the specific conditions mentioned above may reduce emergency hospital admissions amongst dementia patients.

Type-2 diabetes mellitus in schizophrenia: Increased prevalence and major risk factor of excess mortality in a naturalistic 7-year follow-up

OBJECTIVE Physical co-morbidity including type 2 diabetes mellitus is more prevalent in patients with schizophrenia compared to the general population. However, there is little consistent evidence that co-morbidity with diabetes mellitus and/or other diseases leads to excess mortality in schizophrenia. Thus, we investigated whether co-morbidity with diabetes and other somatic diseases is increased in schizophrenics, and if these are equally or more relevant predictors of mortality in schizophrenia than in age- and gender-matched hospitalised controls. METHODS During 2000-2007, 679 patients with schizophrenia were admitted to University Hospital Birmingham NHS Trust. Co-morbidities were compared with 88,778 age- and gender group-matched hospital controls. Predictors of mortality were identified using forward Cox regression models. RESULTS The prevalence of type 2 diabetes mellitus was increased in schizophrenia compared to hospitalised controls (11.3% versus 6.3%). The initial prevalence of type 2 diabetes mellitus was significantly higher in the 100 later deceased schizophrenic patients (24.0%) than in those 579 surviving over 7 years (9.2%). Predictors of mortality in schizophrenia were found to be age (relative risk [RR] = 1.1/year), type 2 diabetes mellitus (RR = 2.2), pneumonia (RR = 2.7), heart failure (RR = 2.9) and chronic renal failure (RR = 3.2). The impact of diabetes mellitus on mortality was significantly higher in schizophrenia than in hospital controls (RR = 2.2 versus RR = 1.1). In agreement, deceased schizophrenics had significantly suffered more diabetes mellitus than deceased controls (24.0 versus 10.5%). The relative risks of mortality for other disorders and their prevalence in later deceased subjects did not significantly differ between schizophrenia and controls. CONCLUSION Schizophrenics have more and additionally suffer more from diabetes: co-morbidity with diabetes mellitus is increased in schizophrenia in comparison with hospital controls; type 2 diabetes mellitus causes significant excess mortality in schizophrenia. Thus, monitoring for and prevention of type 2 diabetes mellitus is of utmost relevance in hospitalised patients with schizophrenia.

Alzheimer's disease and co-morbidity: Increased prevalence and possible risk factors of excess mortality in a naturalistic 7-year follow-up

BACKGROUND Subjects with late-onset Alzheimers disease (AD) have to be sufficiently healthy to live long enough to experience and to be diagnosed with dementia in later life. In contrast, neurodegeneration and cognitive deficits in AD may increase the frequency of co-morbid disorders and their possible influence on mortality. Consequently, we investigated whether the pattern of co-morbidity and its relevance for later death differed between hospitalized AD and age-matched controls subjects. METHODS Co-morbid diseases with a prevalence of more than 1% at hospital admission were compared between 634 hospitalized AD and 72,244 control subjects aged above 70 years admitted to the University of Birmingham NHS Trust between 1 January 2000 to 31 December 2007. Risk factors, i.e. co-morbid diseases that were predictors of mortality within the 7-year follow-up, were identified and compared. RESULTS Subjects with AD suffer more eating disorders, infections, brain diseases and neck of femur fractures than other hospitalized elderly patients. In contrast, some cardiovascular diseases and diabetes mellitus were less prevalent in AD subjects in comparison with hospitalized controls. Diseases that might have contributed to later mortality in AD were pneumonia, ischemic heart disease and gastroenteritis, but there were no significant differences in their impact on mortality compared to other hospitalized elderly subjects with the same co-morbidities in multivariate logistic regression analyses. CONCLUSION Patients with AD have a different pattern of co-morbidity, but die from the same diseases as other hospitalized patients. Infections including pneumonia and diseases that may occur secondary to neurodegeneration and cognitive decline may need special attention in patients with AD who may not be able to identify or report the early symptoms. Preventive measures may be helpful to reduce the high risk and fatal consequences of undetected disease in AD.

Apolipoprotein E allele 4 is not a sufficient or a necessary predictor of the development of Mild Cognitive Impairment.

The presence of Mild Cognitive Impairment (MCI) and of an apolipoprotein E (apoE) varepsilon4 allele both predict the development of Alzheimers disease. However, the extent to which this allele also predicts the development of MCI is unclear even though MCI is an early transitional stage in the development of Alzheimers disease. The present study investigates the prevalence of the apoE varepsilon4 allele in incipient MCI. Participants were recruited from the population-based Leipzig Longitudinal Study of the Aged (LEILA75+). All subjects who were initially cognitively healthy, i.e. did not meet MCI criteria described by Petersen [Petersen RC. Mild cognitive impairment. J Intern Med 2004; 256(3): 183-94], and whose apoE status could be determined were followed-up. After 4.5 years, 15.5% of the cognitively healthy target population had developed MCI. The frequencies of the apoE varepsilon4 genotype did not differ between individuals with incipient MCI (12.9%) and individuals who remained cognitively healthy during the study (18.4%, p>0.5). Consequently, the apoE varepsilon4 genotype is not a necessary or sufficient risk factor for MCI. Further studies need to investigate the influence of the whole range of genetic and environmental risk factors on the course of Alzheimers disease including the initial development of MCI and the later conversion to Alzheimers disease.

Length of hospital stay is shorter in black and ethnic minority patients with diabetes.

Diabet. Med. 29, 830–831 (2012)

Increasing prevalence of haemorrhagic stroke among South Asian patients in the United Kingdom from 1997 to 2005

We congratulate Low and Redfern for their sharply observed case on isolated and transient taste alteration after temporal bone fracture. Their report not only underlines the need for prospective studies concerning the incidence of taste disorders after temporal bone fractures but also brings up an old hypothesis concerning the variability of taste pathways. Indeed, there is almost no information on taste disorders after temporal bone fractures and even the textbooks in the field do not clear up this lack of knowledge. Besides an old and extensively cited report of Sumner, there are no good studies that have focused on post-traumatic taste disorder. The exact course of fibers carrying taste sensation was debatable up until the end of the 19th century. Since then it has been acknowledged that the anterior two-thirds of the tongue are supplied by the chorda tympani, which runs through the middle ear cavity. This was underlined and confirmed by multiple case reports and studies that focused on taste function after middle ear surgery. However, like most anatomical structures, there are claims of variations. Variants in the course of taste pathways was first proposed by Schwartz and Weddell in 1938. They proposed that in a few patients, taste fibers run from the intermediate nerve to the geniculate ganglion, and then instead of following the chorda tympani, join the major superior petrosal nerve, and use this nerve’s anastomosis to the otic ganglion which are called the sphenoidale nerves. From the otic ganglion they reach the chorda and the lingual nerve via an anastomosis between chorda tympani and otic ganglion. This pathway bypasses the middle ear and is thus not concerned by any middle ear disease or surgery that classically affects ipsilateral taste function. Although this alternative taste pathway has not attracted a lot of attention, several clinical studies suggest that rather than it accounting for all taste qualities, it was restricted to certain

Cardiovascular risk factors in vascular dementia and ischaemic stroke.

factors for the development of vascular dementia using a step-wise forward conditional model. Only variables that significantly improved the model fit (p ! 0.05) were included in the final model. Between 2000 and 2006 there were 440 patients diagnosed with vascular dementia and 2,575 diagnosed with ischaemic stroke. The mean age and gender distribution are described in table 1 . Mean age was not significantly different between vascular dementia and stroke patients. Surprisingly, the prevalence of common cardiovascular risk factors was significantly lower in vascular dementia patients compared to ischaemic stroke patients, and is shown in table 1 . Regression analysis revealed that only age (OR = 1.04; 95% CI = 1.03–1.05; p ! 0.001) and stroke (OR = 583.9; 95% CI = 360.2–946.2; p ! 0.001) were significant risk factors for the development of vascular dementia. However age (OR = 1.06; 95% CI = 1.05–1.07; p ! 0.001), male gender (OR = 1.15; 95% CI = 1.08–1.22; p ! 0.001), atrial fibrillation (OR = 1.43; 95% CI = 1.27–1.61; p ! 0.001), hypertension (OR = 1.47; 95% CI = 1.34–1.60; p ! 0.001) and diabetes mellitus (OR = 1.28; 95% CI = 1.16–1.41; p ! 0.001) were significant risk factors for the development of ischaemic stroke. The disparity in risk factors for the development of vascular dementia in comparison to ischaemic stroke is surprising given that ischaemic stroke is by far the biggest risk factor for the development of vascular dementia [5] . It seems the vascular dementia patients are healthier in terms of the number of cardiovascular risk factors. Could it be that patients with more cardiovascular risk factors die earlier because of cardiovascular diseases associated with a high rate of mortality, before the development of vascular dementia? Vascular or multi-infarct dementia is the second most common type of dementia, and ischaemic stroke is widely recognised as the most common aetiological factor [1] . The risk factors for ischaemic stroke are well documented and the most common include age, male gender, hypertension, diabetes mellitus, atrial fibrillation and hyperlipidaemia [2] . Given the aetiological link between ischaemic stroke and vascular dementia, we envisaged a similar risk factor profile amongst vascular dementia patients in a large multiethnic inner-city patient population admitted to a teaching hospital in Birmingham, UK, during the period 2000–2006. Vascular dementia, ischaemic stroke diagnoses and associated risk factors were anonymously traced using the International Classification of Diseases version 10 (ICD-10) criteria, which did not change during this study period. Similar methods have been previously used and are described by Gunarathne et al. [3, 4] . Care was taken to exclude patients with Alzheimer’s disease and mixed dementia. Binomial logistic regression was used to determine the risk Received: March 9, 2008 Accepted: March 10, 2008 Published online: June 18, 2008

Cardiovascular Risk Profiles amongst Women in a Multiethnic Population in Inner City Britain: A Potential Impact of Anaemia

The risk of diabetes is markedly reduced in men with iron deficiency anaemia (IDA). The nature of this relationship in women is not clear, nor is there information about the influence of ethnicity, given the increased susceptibility of diabetes amongst South Asians and Afro-Caribbeans. We reviewed 3563 patients with a diagnosis of anaemia from 2000 to 2007. The age-adjusted prevalence of vitamin B12 deficiency and IDA was calculated, together with cardiovascular comorbidities amongst Caucasians, South Asians, and Afro-Caribbeans. The prevalence of vitamin B12 deficiency (women only) or IDA was markedly higher in South Asians compared to Caucasians and Afro-Caribbeans. Among women with IDA, diabetes was more prevalent among South Asians (45%, 95% CI 39.0–51.0) compared to Caucasians (3.0%, 2.1–4.0); P < 0.001. Among South Asian women with vitamin B12 deficiency, the prevalence of diabetes was reduced 8.5% (5.2–12.0). South Asian women with vitamin B12 deficiency had a higher prevalence of myocardial infarction (MI) and ischemic heart disease (IHD), but this relationship was reversed in IDA. IDA is associated with a greater prevalence of diabetes in South Asian women, but it is not coordinated by a greater risk of macrovascular complications. Given the cardiovascular impact of diabetes in South Asians, this association merits further study in relation to its pathophysiological implication.

Preparation, characterization, and banking of clinical-grade cells for neural transplantation: Scale up, fingerprinting, and genomic stability of stem cell lines

Parkinsons disease is a complex and progressive neurodegenerative condition that is characterized by the severe loss of midbrain dopaminergic (mDA) neurons, which innervate the striatum. Cell transplantation therapies to rebuild this dopaminergic network have been attempted for over 30 years. The most promising outcomes were observed when human fetal mesencephalic tissue was used as the source of cells for transplantation. However, reliance on terminations for a Parkinsons therapy presents significant logistical and ethical hurdles. An alternative source of transplantable mDA neurons is urgently needed, and the solution may come from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). Protocols to differentiate hESCs/iPSCs toward mDA neurons are now robust and efficient, and upon grafting the cells rescue preclinical animal models of Parkinsons disease. The challenge now is to apply Good Manufacturing Practice (GMP) to the academic discoveries and protocols to produce clinical-grade transplantable mDA cells. Major technical and logistical considerations include (i) source of hESC or iPSC line, (ii) GMP compliance of the differentiation protocol and all reagents, (iii) characterization of the cell product in terms of identity, safety, and efficacy, (iv) characterization of genomic state and stability, and (v) banking of a transplantation-ready cell product. Approaches and solutions to these challenges are reviewed here.

Comparison of time taken from initial presentation to histological diagnosis of Glioblastoma Multiforme (GBM) in Birmingham, United Kingdom and Strasbourg, France

BACKGROUND The aim of this study was to investigate possible delays in referral time for Glioblastoma multiforme (GBM) patients diagnosed at two similar neurosurgical centres (in Birmingham, UK and Strasbourg, France) and their impact on survival. Differences in the referral patterns for GBM patients within these healthcare systems may affect subsequent management and are potential targets to optimise the care of patients with GBM. METHODS Medical case notes of 105 GBM patients in Birmingham and 81 in Strasbourg, admitted during October 2006 and April 2008, were reviewed. Data regarding demographic details, route of admission, presenting symptoms, date of initial presentation to a medical professional and dates of the first CT or MRI scan, first neurosurgical intervention, histological diagnosis and mortality was recorded. RESULTS The median time taken from initial presentation to first neurosurgical intervention was lower in Birmingham compared to Strasbourg (13 vs. 21 days, respectively; p=0.026). Similarly, the time taken from initial presentation to histological diagnosis was lower in Birmingham (15 vs. 24 days, respectively; p=0.011). However, survival was poorer in Birmingham than Strasbourg (p=0.001) and age (HR=1.029; 95%CI 1.010-1.048; p=0.003) and time from initial presentation to neurosurgical intervention (HR=0.993; 95%CI 0.988-0.998; p=0.011) were predictors of mortality in these groups. CONCLUSION Patients in Birmingham are diagnosed with GBM more rapidly than those in Strasbourg but they have poorer survival. Differences in disease severity may partially account for the observed results and further large scale work is required to support this study.