Impact of cholinesterase inhibitors or memantine on survival in adults with Down syndrome and dementia: clinical cohort study.

BACKGROUND: There is little evidence to guide pharmacological treatment in adults with Down syndrome and Alzheimer's disease. Aims To investigate the effect of cholinesterase inhibitors or memantine on survival and function in adults with Down syndrome and Alzheimer's disease. METHOD: This was a naturalistic longitudinal follow-up of a clinical cohort of 310 people with Down syndrome diagnosed with Alzheimer's disease collected from specialist community services in England. RESULTS: Median survival time (5.59 years, 95% CI 4.67-6.67) for those on medication (n = 145, mainly cholinesterase inhibitors) was significantly greater than for those not prescribed medication (n = 165) (3.45 years, 95% CI 2.91-4.13, log-rank test P<0.001). Sequential assessments demonstrated an early effect in maintaining cognitive function. CONCLUSIONS: Cholinesterase inhibitors appear to offer benefit for people with Down syndrome and Alzheimer's disease that is comparable with sporadic Alzheimer's disease; a trial to test the effect of earlier treatment (prodromal Alzheimer's disease) in Down syndrome may be indicated. Declaration of interest A.S. has undertaken consulting for Ono Pharmaceuticals, outside the submitted work. Z.W. has received a consultancy fee and grant from GE Healthcare, outside the submitted work.

Predictors of Age of Diagnosis and Survival of Alzheimer's Disease in Down Syndrome.

BACKGROUND: People with Down syndrome (DS) are an ultra-high risk population for Alzheimer's disease (AD). Understanding the factors associated with age of onset and survival in this population could highlight factors associated with modulation of the amyloid cascade. OBJECTIVE: This study aimed to establish the typical age at diagnosis and survival associated with AD in DS and the risk factors associated with these. METHODS: Data was obtained from the Aging with Down Syndrome and Intellectual Disabilities (ADSID) research database, consisting of data extracted from clinical records of patients seen by Community Intellectual Disability Services (CIDS) in England. Survival times when considering different risk factors were calculated. RESULTS: The mean age of diagnosis was 55.80 years, SD 6.29. Median survival time after diagnosis was 3.78 years, and median age at death was approximately 60 years. Survival time was associated with age of diagnosis, severity of intellectual disability, living status, anti-dementia medication status, and history of epilepsy. Age at diagnosis and treatment status remained predictive of survival time following adjustment. CONCLUSION: This study provides the best estimate of survival in dementia within the DS population to date, and is in keeping with previous estimates from smaller studies in the DS population. This study provides important estimates and insights into possible predictors of survival and age of diagnosis of AD in adults with DS, which will inform selection of participants for treatment trials in the future.

Dementia diagnostic criteria in Down syndrome.

OBJECTIVE: Dementia is a common clinical presentation among older adults with Down syndrome. The presentation of dementia in Down syndrome differs compared with typical Alzheimer's disease. The performance of manualised dementia criteria in the International Classification of Diseases (ICD)-10 and Diagnostic and Statistical Manual of Mental Disorders-IV-Text Revision (DSM-IV-TR) is uncertain in this population.We aimed to determine the concurrent validity and reliability of clinicians' diagnoses of dementia against ICD-10 and DSM-IV-TR diagnoses. Validity of clinical diagnoses were also explored by establishing the stability of diagnoses over time. METHODS: We used clinical data from memory assessments of 85 people with Down syndrome, of whom 64 (75.3%) had a diagnosis of dementia. The cases of dementia were presented to expert raters who rated the case as dementia or no dementia using ICD-10 and DSM-IV-TR criteria and their own clinical judgement. RESULTS: We found that clinician's judgement corresponded best with clinically diagnosed cases of dementia, identifying 84.4% cases of clinically diagnosed dementia at the time of diagnosis. ICD-10 criteria identified 70.3% cases, and DSM-IV-TR criteria identified 56.3% cases at the time of clinically diagnosed dementia. Over time, the proportion of cases meeting ICD-10 or DSM-IV-TR diagnoses increased, suggesting that experienced clinicians used their clinical knowledge of dementia presentation in Down syndrome to diagnose the disorder at an earlier stage than would have been possible had they relied on the classic description contained in the diagnostic systems. CONCLUSIONS: Clinical diagnosis of dementia in Down syndrome is valid and reliable and can be used as the standard against which new criteria such as the DSM-5 are measured.

When to seek health care: a duration analysis for malaria patients in Nepal.

We find that the log-normal distribution of care-seeking time - the number of days from the onset of symptoms of malaria to when a patient seeks treatment from a provider - best described the treatment-seeking behavior of malaria patients in rural areas of two districts of Nepal. The care-seeking rate, or the probability of seeking care, was low on the first day of the symptoms; it increased sharply over the first five days and then gradually declined. Since at the time of the research there was a system of malaria workers taking monthly surveillance rounds of each house to detect and treat malaria cases, patients, instead of traveling to a provider for care, generally waited for malaria workers to arrive at home when the wait for malaria workers was short. But, the probability of seeking care on any day rose if the wait was longer. Women generally tended to wait longer for the malaria workers in order to receive treatment at home. Patient's age, household size, education, and the type of malaria species infecting the patient had no significant effect on care-seeking rate. Given an assumption that a wait of 100 days for a malaria worker would effectively represent total absence of surveillance program, the estimated model predicted higher care-seeking rates under no surveillance program than under the monthly surveillance program.

Outcome of Lichtenstein operation: a prospective evaluation of sixty-four patients.

To assess the feasibility and safety of open tension-free mesh repair (Lichtenstein operation) of inguinal hernias on ambulatory surgery basis. A prospective study of the Lichtenstein operation on 64 patients of inguinal hernias who were operated the authors and surgical trainees at Unit III, Department of General Surgery at National Academy of Medical Sciences (NAMS), Nepal from April 13, 2004 to April 31, 2006. Data related to age, sex, characteristics of the hernia, feasibility of the Lichtenstein operation under unmonitored local anesthesia and its surgical outcomes were compiled prospectively. The inguinal hernia was virtually a disease of male patients. In this study, male: female ratio was 63:1. Majority (84.4 %) of the inguinal hernias were safely operated under local infiltration anesthesia on day surgery basis with minimal morbidity rate (14.0%). The inguinal hernia is one of the common surgical problems of the adult population. The Lichtenstein operation can be safely performed on ambulatory surgery under unmonitored local anesthesia with a low morbidity. Hence, local anesthesia technique for the hernia repair is a viable alternative to spinal or general anesthesia.

Willingness to pay and determinants of choice for improved malaria treatment in rural Nepal.

A logit model is used to estimate provider choice from six types by malaria patients in rural Nepal. Patient characteristics that influence choice include travel costs, income category, household size, gender, and severity of malaria. Income effects are introduced by assuming the marginal utility of money is a step function of expenditures on the numeraire. This method of incorporating income effects is ideally suited for situations when exact income data is not available. Significant provider characteristics include wait time for treatment and wait time for laboratory results. Household willingness to pay (wtp) is estimated for increasing the number of providers and for providing more sites with blood testing capabilities. Wtp estimates vary significantly across households and allow one to assess how much different households would benefit or lose under different government proposals.