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Biomedical subjects

Ajit Shah

Publications and source records attributed to Ajit Shah.

At least 19 recordsLinked to original sources

Severe domestic squalor: a review.

BACKGROUND: Referrals to clinical services of people living in severe domestic squalor are not uncommon. It is timely to review literature concerning and discussing such cases. METHOD: Using Medline, Psychinfo, Embase, CINAHL and reference lists from relevant publications, literature referring to over 1100 cases was identified and then reviewed. RESULTS: Half of those described as living in severe squalor are elderly. Outcomes of intervention are often poor. People living in severe squalor are most commonly diagnosed as having dementia, alcoholism or schizophrenia, though personality problems are evident in a high proportion. There is evidence to suggest that neglect of hygiene and of attention to cleanliness of accommodation may be largely attributable to frontal lobe changes. The review also revealed a second body of literature, not often cited in papers focussed on unclean living conditions and published in psychiatric or medical journals, that concludes that hoarding is most commonly due to obsessive-compulsive disorder (OCD). Accumulation of rubbish is described in over half of the case reports on severe domestic squalor, but it is suggested that this should only be called hoarding if it results from purposeful collection of items. Lack of impulse control may contribute to collecting behavior, resulting in reduction in living space if there is also a failure to discard. CONCLUSIONS: There is a need for further studies, using standardized ratings of living conditions, investigating and trying to understand the complex interplay of triggers and vulnerabilities, exploring how best to intervene and examining outcomes of interventions.

Aged↗

Pharmacokinetics, metabolism, and routes of excretion of intravenous irofulven in patients with advanced solid tumors.

Irofulven is currently in Phase 2 clinical trials against a wide variety of solid tumors and has demonstrated activity in ovarian, prostate, gastrointestinal, and non-small cell lung cancer. The objectives of this study were to determine its pharmacokinetics and route of excretion and to characterize its metabolites in human plasma and urine samples after a 30-min i.v. infusion at a dose of 0.55 mg/kg in patients with advanced solid tumors. Three patients were administered i.v. 100 microCi of [14C]irofulven over a 30-min infusion on day 1 of cycle 1. Serial blood and plasma samples were drawn at 0 (before irofulven infusion) and up to 144 h after the start of infusion. Urine and fecal samples were collected for up to 144 h after the start of infusion. The mean urinary and fecal excretion of radioactivity up to 144 h were 71.2 and 2.9%, respectively, indicating renal excretion was the major route of elimination of [14C]irofulven. The C(max), AUC(0-infinity), and terminal half-life values for total radioactivity were 1130 ng-Eq/ml, 24,400 ng-Eq . h/ml, and 116.5 h, respectively, and the corresponding values for irofulven were 82.7 ng/ml, 65.5 ng . h/ml, and 0.3 h, respectively, suggesting that the total radioactivity in human plasma was a result of the metabolites. Twelve metabolites of irofulven were detected in human urine and plasma by electrospray ionization/tandem mass spectrometry. Among these metabolites, the cyclopropane ring-opened metabolite (M2) of irofulven was found, and seven others were proposed as glucuronide and glutathione conjugates.

Antineoplastic Agents, Alkylating↗

Can risperidone and olanzapine in elderly patients with dementia and other mental disorders be discontinued?

BACKGROUND: In March 2004, the UK Committee of Safety of Medicines (CSM) informed clinicians that risperidone and olanzapine should not be used to treat behavioural and psychological symptoms of dementia (BPSD) because of increased risk of strokes with both drugs and increased risk of mortality with olanzapine. An audit to examine the implications of the implementation of the CSM guidance was undertaken. METHODS: All patients receiving these two drugs, in one psychogeriatric service, at the time of CSM guidance were identified and reviewed. Data on clinical and demographic features, patient and carer involvement in the review and clinical outcome of the efficacy of the overall treatment package at 6 month follow-up was ascertained from the case-notes. RESULTS: The main findings were: (i) all patients receiving risperidone or olanzapine were identified and reviewed at a median interval of 8 days after the CSM guidance; (ii) most patients and carers were involved in the initial review; (iii) risperidone and olanzapine were discontinued in 22 and 12 of the patients respectively, and in 19 of these patients another neuroleptic was substituted; (iv) there was no relationship between discontinuation of these two drugs and presence of cerebrovascular and cardiovascular risk factors; and, (v) there was no relationship between the clinical outcome of efficacy at six months and discontinuation of these two drugs. CONCLUSIONS: This study illustrates that it is possible to identify, review and follow-up patients on these two drugs and involve the patient and carer in the review, and clinical outcome of efficacy of the overall treatment package is not adversely affected by continuation or discontinuation of these two drugs.

Administration, Oral↗

Phase II trial of DNA methyltransferase 1 inhibition with the antisense oligonucleotide MG98 in patients with metastatic renal carcinoma: a National Cancer Institute of Canada Clinical Trials Group investigational new drug study.

DNA methyltransferases (DNMTs) methylate DNA, promoting local chromatin condensation and consequent repression of gene expression. The purpose of this two-stage phase II trial was to assess the antitumor activity of MG98, a second generation antisense oligodeoxynucleotide inhibitor of human DNMT 1, in patients with metastatic renal carcinoma (MRC). Untreated adult patients with measurable MRC were treated with MG98 at a dose of 360 mg/m2 via 2-h iv infusion twice weekly for three consecutive weeks out of four. The primary endpoint was objective response or absence of progression for at least eight weeks. Pharmacokinetics and DNMT1 mRNA levels in peripheral blood mononuclear cells (PBMCs) were also analyzed at pre-specified intervals. Seventeen eligible patients received a median of two cycles of treatment (range, 1-7), and no objective responses were seen. Nine patients had progressive disease, six had stable disease, and the study was stopped after the first stage. The most common symptomatic toxicities were rigors, fatigue, fever, and nausea. Hematological toxicity was mild. Seven patients treated with prior nephrectomy had grade 3 or 4 elevations in hepatic transaminases. Significantly higher Cmax and AUC(0-->inf) values were observed in these patients. No conclusive pattern of decreased DNMT1 activity in PBMCs was detected post MG98 treatment. The lack of objective responses observed may be explained by a lack of target effect or the choice of tumor type. Transaminitis was observed in patients with prior nephrectomy and appeared to be associated with altered drug exposure in these patients.

Adult↗

Pharmacokinetic evaluation and safety profile of a 15-minute versus 30-second infusion of palonosetron in healthy subjects.

Palonosetron is a potent, selective 5-HT(3) receptor antagonist effective in the prevention of acute and delayed chemotherapy-induced nausea and vomiting. In practice, 5-HT(3) receptor antagonists, including palonosetron, are often coadministered with dexamethasone over approximately 15 minutes, although the approval of palonosetron was based on administration as a 30-second infusion. This open-label, randomized, 2-way crossover trial compared the pharmacokinetics and safety of palonosetron 0.25 mg administered as a 15-minute 50-mL intravenous infusion with a 30-second 5-mL infusion. Aside from an anticipated 40% decrease in maximum plasma concentration after a 15-minute infusion, the pharmacokinetics of palonosetron (including area under the plasma concentration-time curve [AUC], plasma elimination half-life, total body clearance, and apparent volume of distribution at steady state) were similar for both treatments. Both treatments were well tolerated, with no significant changes in vital signs or electrocardiograms. Palonosetron infused over 15 minutes is well tolerated, with an AUC(0-infinity) equivalent to a 30-second infusion.

Adolescent↗

An audit of a specialist old age psychiatry liaison service to a medium and a high secure forensic psychiatry unit.

The elderly prison population is increasing and there is a significant amount of unidentified psychiatric morbidity among elderly prisoners. A sizeable number of elderly subjects are referred to regional forensic units. These units are able to provide advice but are reluctant to admit frail, physically ill and vulnerable elderly into their unit because the ward environment is considered inappropriate for them. A sizeable number of inpatients in medium and high secure units are elderly. This paper is an exploratory audit of referrals from a medium and high secure forensic psychiatry unit to a specialist consultation-only liaison old age psychiatry service, which was specifically developed to service the forensic unit. The demographic and clinical characteristics of the patients seen by this specialist service were similar to elderly inpatients in medium and high secure units. All referrals were judged to be appropriate and new management advice was provided in all cases. Main reasons for referral included diagnostic advice, placement advice and treatment advice. Establishing a diagnosis of dementia was considered important because Alzheimer's disease and Lewy body dementia can be treated with cholinesterase inhibitors. Placement advice was the most difficult to provide because of paucity of residential and nursing homes able and willing to accept patients with a forensic history. There is a need for a comprehensive model of specialist forensic old age psychiatry service at a regional or supraregional level. A consensus needs to be reached on the exact configuration of such a service.

Aged↗

Mortality in Alzheimer's disease: a comparative prospective Korean study in the community and nursing homes.

OBJECTIVE: To test a hypothesis that Alzheimer's disease (AD) patients in nursing homes have higher mortality rate than do AD patients cared for at home and to investigate the predictors of mortality in AD. DESIGN: A one-year prospective follow-up in Korea. METHODS: A total of 252 subjects (107 in the community, 145 in a nursing home) were longitudinally assessed at baseline, 6 months and 12 months. Mortality rates between groups were compared using Kaplan-Meier curve and log-rank statistics. Relative risks (RRs) were examined by the Cox proportional hazards model. RESULTS: Overall one-year mortality rate in AD was 18.7%. There was no statistically significant difference in AD mortality rates between patients who continued to be cared for at home and AD patients in the nursing home. After controlling for age, group (nursing home or community), severity of dementia, Mini-Mental State Examination (MMSE) score and vascular risk factors, there remained advanced age [risk ratio (RR) 1.06; 95% confidence interval (CI) 1.04-1.09], advanced Global Deterioration Scale (GDS) stage (RR 1.98; 95% CI 1.41-2.77), longer duration of AD (RR 1.07; 95% CI 1.04-1.10), presence of tactile hallucination (RR 1.74; 95% CI 1.08-2.78), wandering (RR 1.89; 95% CI 1.18-3.02) and depression (RR 1.07; 95% CI 1.02-1.10) as independent predictors of mortality in AD. This may be the first study demonstrating presence of tactile hallucination as a strong predictor of mortality in AD. CONCLUSION: This study does not support the hypothesis of a higher AD mortality rate in nursing homes.

Activities of Daily Living↗

Behavioural and psychological signs and symptoms of dementia across cultures: current status and the future.

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) have been poorly studied in developing countries, in ethnic minority groups in a given country and in cross-national studies. METHODS: The literature on BPSD from developing countries, ethnic minority groups in a given country and cross-national studies was examined. RESULTS: There is emerging literature on BPSD from the settings was studied. These studies provide useful preliminary data on the prevalence and correlates of BPSD. Moreover, the data illustrate possible cross-cultural differences in BPSD and their correlates. A number of instruments measuring either individual BPSD within a BPSD domain, measuring features of a BPSD domain or features of a range of BPSD domains have been developed in languages other than English for use in developing countries and ethnic minority groups in a given country. CONCLUSIONS: There is a need for methodologically similar and uniform studies of BPSD across countries and ethnic groups in a given country using appropriately validated instruments. It is suggested that a consensus should be reached by researchers on the best instrument(s) to be developed in languages other than English for use in these settings and, in turn, these instruments should be developed using appropriate methodology. This could allow identification of the genetic and environmental aetiology of BPSD and the influence of gene-environment interaction.

Aged↗

A comparative study of behavioral and psychological symptoms of dementia in patients with Alzheimer's disease and vascular dementia referred to psychogeriatric services in Korea and the U.K.

BACKGROUND: There is a paucity of cross-cultural studies of behavioral and psychological symptoms of dementia (BPSD). METHOD: BPSD were examined in consecutive series of referrals to a psychogeriatric service in Korea and the U.K. using the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale and the Cornell Scale for Depression in Dementia (CSDD). Results were analyzed separately for Alzheimer's disease and vascular dementia. RESULTS: Koreans in both diagnostic groups had lower Mini-mental State Examination (MMSE) scores and higher BEHAVE-AD total and subscale scores for most subscales. In both countries, for both diagnostic groups, the total BEHAVE-AD score and several subscale scores were negatively correlated with the MMSE scores. Logistic regression analysis for Alzheimer's disease revealed that BEHAVE-AD total and most subscale scores independently predicted the country of origin in addition to the MMSE scores predicting the same. CONCLUSIONS: These differences in BPSD are most likely explained by the lower MMSE scores in the Korean sample. However, genuine differences in BPSD between the two countries can only be critically examined in a cross-cultural population-based epidemiological study for both diagnostic categories using validated instruments to measure BPSD and controlling for the influence of MMSE score.

Aged↗

Effect of antipsychotics on mortality in elderly patients with dementia: a 1-year prospective study in a nursing home.

BACKGROUND AND OBJECTIVES: The use of risperidone or olanzapine to treat behavioral problems associated with dementia is no longer recommended in the U.K. because of the increased risk of cerebrovascular adverse effects (CVAEs) and/or mortality. To evaluate the risks and benefits of antipsychotics, we measured the rate of mortality in patients with dementia, Alzheimer's disease (AD) and vascular/mixed dementia and compared mortality rates between those who had received antipsychotics and those who had not received antipsychotics. METHODS: A total of 273 subjects were assessed at baseline, 6 months and 12 months using a 1-year prospective follow-up design. Mortality rates between groups were compared using a Kaplan-Meier curve and log-rank statistics. Relative risks (RRs) were examined by the Cox proportional-hazards model. RESULTS: The overall 1-year mortality rate in dementia was 23.8%. The mortality rate in those who had not received antipsychotics (26.8%) was higher than that in those who had received antipsychotics (20.6%). RR and 95% confidence interval (CI) of mortality, when we compared those who had not received antipsychotics with those who had received antipsychotics, was 1.277 (95% CI 1.134-1.437) after controlling for age, severity of dementia, medical comorbidities, cognitive impairment (measured by the Korean version of the Mini-mental State Examination (MMSE)) and behavioral and psychological symptoms of dementia (BPSD), measured by the Behavioral Pathology in Alzheimer's Disease Rating Scale, Korean version (BEHAVE-AD-K). When those who had not received antipsychotics were compared with those who had received both risperidone and haloperidol, RR (95% CI) was 1.225 (1.101-1.364). CONCLUSION: This study does not support reports that antipsychotics increase mortality in dementia.

Aged↗

Intraoperative monitoring of the recurrent laryngeal nerve using acoustic, free-run, and evoked electromyography.

The purpose of this study was to explore advantages and disadvantages of electrodes used for monitoring of the recurrent laryngeal nerve (RLN) and to determine the postoperative outcome in 135 patients. A pilot study examined 11 patients to compare the clinical performance of two commercially available recording electrodes and three stimulation electrodes for RLN neuromonitoring. After determining the most reliable and consistent stimulating/recording electrode combination, 124 patients were then monitored. In a total of 135 patients there was no permanent iatrogenic nerve damage to the RLN, although 2 patients developed transient vocal hoarseness that resolved shortly postoperatively. An initial "searching" current for evoked electromyography (EMG) was delivered at 0.7 mA and then decreased to a value of 0.35 mA, which reliably elicited RLN stimulation with a minimal incidence of false-positive results. The combination of auditory feedback from the mechanically elicited EMG and a control channel involving EMG monitoring of an additional peripheral muscle improved the detection of artifact and improved the clinical efficacy of intraoperative electromyography. A video camera showed the surgical manipulation on the EMG screen, allowing the neurophysiologist to correlate dissection with RLN status and location. Auditory responses from the nerve helped to determine the type of distress the RLN was encountering.

Acoustic Stimulation↗

Factors associated with the recent decline in suicide rates in the elderly in England and Wales, 1985-1998.

Elderly suicide rates have declined in recent years in several countries including England and Wales. This study examined the association between a trend of decline in age-specific suicide rates in the elderly in England and Wales and changes in various health and social factors for the period 1985 to 1998. Data on age-specific suicide rates was ascertained from the annual mortality statistics for the years 1985 to 1998. Data on the various health and social variables was ascertained from both the Statistics Division at the Department of Health and the Health and Personal Social Services Statistics, the yearly publications of the Department of Health from 1985 to 1998. The main findings of this study were (i) a significant negative correlation between the number of general practitioners and all categories of whole-time-equivalent (WTE) hospital medical staff and suicide rates for each of the four five-year age bands for males and females after the age of 65; (ii) a significant negative correlation between the number of new outpatient appointments for mental illness and suicide rates in males and females for each of the four five-year age bands between the ages 65-85 years; (iii) a significant positive correlation between the average daily number of available beds for mental illness and elderly suicide rates, for all five-year age bands between the ages 65-85 years; (iv) a significant negative correlation between the number of field social work staff and day centre staff and elderly suicide rates for each of the four five-year age bands after the age of 65 for males and females; and, (v) a significant positive correlation between the total number of elderly in all residential homes and the number of elderly in local authority residential homes and elderly suicide rates for each of the four five-year age bands between the ages 65-85 years for males and females. A trend of decline in age-specific suicide rates in the elderly in England and Wales from 1985 to 1998 was significantly associated with changes in various health and social variables. These included the number of general practitioners and hospital medical staff, the hospital psychiatric services, the number of local authority staff and the number of elderly residents in accommodation supported by a local authority. The results of this study suggest that changes in these variables may be important factors contributing to the recent decline in suicide rates but this effect should be viewed in the context of other health and social factors.

Age Factors↗

The impact of trends in psychotropic prescribing on the method of suicide in the elderly.

Suicide rates in the elderly have declined in many countries in recent years. This decline has been reported to be associated with increased prescribing of antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), antipsychotics and antimanic drugs and reduced prescribing of barbiturates, hypnotics and sedatives. This study examined the relationship between prescribing patterns of individual psychotropic drugs and suicide rates by specific methods of elderly suicides. There was a negative correlation between the prescription of tricyclic antidepressants, selective serotonin reuptake inhibitors, antipsychotics, antimanic drugs and non-opiate analgesics and a decline in elderly suicide rates due to poisoning by solid and liquid substances, hanging, strangulation and suffocation, drowning, firearms and explosives, and jumping from high places. There was a positive correlation between the prescription of barbiturates, hypnotics and sedatives and elderly suicide rates due to poisoning by solid and liquid substances, hanging, strangulation and suffocation, drowning, firearms and explosives, and jumping from high places. This study demonstrated that changes in prescribing patterns of individual psychotropic drugs do influence elderly suicide rates of the commonly used methods of suicide and suggest that this may be due to more accurate diagnostic-specific prescribing of psychotropic drugs.

Aged↗

Bournewood--the future.

The recent ruling on the Bournewood Case by the European Court of Human Rights could have serious implications for Health and Social Services. We have summarised the pathway that has been followed in reaching this outcome and sought to examine the possible adverse consequences of this ruling, both for the Health Service and for the people whom we seek to treat. Finally, we have also examined ways in which the Mental Capacity Bill and draft Mental Health Bill could possibly provide solutions to this dilemma.

Hospitals, Public↗

Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers.

Palonosetron (Aloxi(R), Onicit(R)) is a potent, single stereoisomeric 5-HT(3) receptor antagonist developed to prevent chemotherapy-induced nausea and vomiting. The pharmacokinetics and metabolic disposition of a single intravenous [(14)C]-palonosetron (10 microg/kg, 0.8 microCi/kg) bolus dose were evaluated in six healthy volunteers (three males, three females) using serial blood, plasma, urine and fecal samples obtained over 10 days. The safety, tolerability and cardiac effects were assessed. Radiolabeled metabolic characterization revealed that unchanged palonosetron accounted for 71.9% of the total radioactivity in plasma over 96 h, with an extensive distribution volume (8.34 l/kg) and mean plasma elimination half-life of 37 h. Approximately 83% of the dose was recovered in urine ( approximately 40% as unchanged drug, with 50% metabolized; M9 and M4 were the major metabolites) and 3.4% in feces. Hydrolysis of urine samples suggests that the metabolites are not beta-glucuronide or sulfate conjugates of the parent drug or metabolites. The blood to plasma concentration ratio of the total radioactivity was 1.2, on average, indicating little selective partitioning in erythrocytes. Palonosetron was generally well tolerated; headache was the most frequently reported adverse event. Electrocardiograms and 72 h Holter monitoring revealed no clinically significant changes. Palonosetron circulates in plasma mainly as the parent drug. Renal elimination is the primary excretion route, with parent drug and metabolites M9 and M4 accounting for the majority of palonosetron disposition. These results indicate that both renal and hepatic routes are involved in the elimination of palonosetron from the body.

Adult↗