Survival rates in NYC in the era of combination ART

BACKGROUND: Since the advent of combined antiretroviral therapy in 1996, substantial decreases in HIV-related morbidity and mortality have been observed in the United States and other developed countries. To assess the effects on overall survival and for specific AIDS-defining illnesses (ADIs), survival among persons with AIDS (PWAs) in New York City (NYC) before and after the introduction of combination therapy was investigated. METHODS: Survival among 79,878 PWAs diagnosed between 1990 and 1998 and reported through March 2001 was estimated. Cumulative survival at 24 months among PWAs was estimated by actuarial methods, and Cox proportional hazards model adjusted for covariates was used to estimate the relative hazard (RH) of death for specific ADIs over time. RESULTS: Overall cumulative survival at 24 months increased from 43% among PWAs diagnosed during 1990-1995 to 76% for those diagnosed 1996-1998. Improving survival for all ADIs was found among PWAs diagnosed after 1995, but changes for immunoblastic lymphoma, primary lymphoma of the brain, and invasive cervical cancer were only moderate and were statistically (p >.05) insignificant. Burkitt lymphoma, immunoblastic lymphoma, invasive cervical cancer, and primary lymphoma of the brain had the highest RH of death among PWAs diagnosed after 1995. CONCLUSIONS: Substantial improvements in survival after 1995 were found for all PWAs but varied by gender, race, risk, socioeconomic status, and specific ADIs. Consistent with other studies, neoplastic ADIs have shown less improvement than other diseases after 1995. The relatively poor outcome of PWAs with neoplastic diseases requires further investigation.     

Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon

We have examined whether dietary polyamines influence the formation and initial growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rat colon. Effects of a combination of dietary polyamines at three dose levels (putrescine: 50, 280, 740 nmol/g; spermidine: 10, 261, 763 nmol/g; spermine: 1, 31, 91 nmol/g) in the polyamine-poor AIN-76A diet were studied in animals in two different experimental situations: animals treated with AOM alone and animals treated with AOM + difluoromethylornithine (DFMO), a specific inhibitor of endogenous polyamine synthesis. In both experimental situations, dietary polyamines enhanced the growth of ACF, expressed as the number of large ACF (foci with three or more aberrant crypts, ACF > or = 3), whereas the formation of ACF, expressed as the number of ACF, was apparently not altered. In animals treated with AOM alone, maximal growth enhancing effect on ACF was nearly obtained with the median level of dietary polyamine. In rats fed a low polyamine diet, basic AIN-76A, DFMO reduced the growth of AOM-induced ACF by 83%. This inhibitory effect of DFMO was counteracted by dietary polyamines in a dose- dependent manner, and it was abolished at the highest level of polyamines. In conclusion, it was demonstrated that dietary polyamines are able to enhance the growth of AOM-induced ACF. Further, dietary polyamines reversed the DFMO-caused inhibition of ACF growth, probably by compensating for the DFMO-reduced endogenous polyamine synthesis.      

Extended Use of the Control-IQ Closed-Loop Control System in Children With Type 1 Diabetes

OBJECTIVETo further evaluate the safety and efficacy of the Control-IQ closed-loop control (CLC) system in children with type 1 diabetes.RESEARCH DESIGN AND METHODSAfter a 16-week randomized clinical trial (RCT) comparing CLC with sensor-augmented pump (SAP) therapy in 101 children 6–13 years old with type 1 diabetes, 22 participants in the SAP group initiated use of the CLC system (referred to as SAP-CLC cohort), and 78 participants in the CLC group continued use of CLC (CLC-CLC cohort) for 12 weeks.RESULTSIn the SAP-CLC cohort, mean percentage of time in range 70–180 mg/dL (TIR) increased from 55 ± 13% using SAP during the RCT to 65 ± 10% using CLC (P < 0.001), with 36% of the cohort achieving TIR >70% plus time <54 mg/dL <1% compared with 14% when using SAP (P = 0.03). Substantial improvement in TIR was seen after the 1st day of CLC. Time <70 mg/dL decreased from 1.80% to 1.34% (P < 0.001). In the CLC-CLC cohort, mean TIR increased from 53 ± 17% prerandomization to 67 ± 10% during the RCT and remained reasonably stable at 66 ± 10% through the 12 weeks post-RCT. No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either cohort.CONCLUSIONSThis further evaluation of the Control-IQ CLC system supports the findings of the preceding RCT that use of a closed-loop system can safely improve glycemic control in children 6–13 years old with type 1 diabetes from the 1st day of use and demonstrates that these improvements can be sustained through 28 weeks of use.     

Neuroprotective Effects of Lithium: Implications for the Treatment of Alzheimer’s Disease and Related Neurodegenerative Disorders

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Long-Term Lithium Treatment Reduces Glucose Metabolism in the Cerebellum and Hippocampus of Nondemented Older Adults: An [18F]FDG-PET Study

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Low platelet iPLA2 activity predicts conversion from mild cognitive impairment to Alzheimer’s disease: a 4-year follow-up study

Reduced phospholipase A₂ (PLA₂) activity has been reported in the brain and in blood cells of patients with Alzheimer’s disease (AD). Individuals with mild cognitive impairment (MCI) are at increased risk of developing AD. In the present study, we determined the activity of distinct PLA₂ subgroups (iPLA₂, sPLA₂ and cPLA₂) in older adults with MCI as compared to patients with mild dementia due to AD and to cognitively healthy controls. We investigated whether decreased PLA₂ activity at baseline is associated with the progression of MCI to AD upon follow-up during a period of 4 years. The activity of PLA₂ subgroups was determined in platelets from 169 elderly adults. Progression of MCI to AD was ascertained by standard clinical criteria for AD upon follow-up. At baseline, iPLA₂ activity was significantly decreased (p = 0.001) in patients with AD and MCI as compared to controls. Patients with MCI who progressed to AD during follow-up showed significantly lower iPLA₂ activity at baseline as compared to patients with MCI who did not progress to AD (p = 0.009). Moreover, subjects from the control group at baseline who progressed to MCI during follow-up had lower sPLA₂ and cPLA₂ (p = 0.014 and p = 0.009, respectively). Our findings suggest that low platelet iPLA₂ activity may be a risk marker for AD in subjects with MCI. Moreover, low sPLA₂ and cPLA₂ were related to cognitive decline in healthy controls, suggesting a relationship with the very early stages of the disease.     

Reduced phospholipid breakdown in Alzheimer’s brains: a 31P spectroscopy study

Background Abnormalities of membrane phospholipid metabolism have been described in Alzheimers disease (AD). We investigated, with the aid of ³¹P magnetic resonance spectroscopy, the in vivo intracerebral availability of phosphomonoesters (PME) and phosphodiesters (PDE) in patients with AD.Methods Eighteen outpatients with mild or moderate probable AD and 16 nondemented elderly volunteers were assessed with the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) and its cognitive subscale of the CAMDEX schedule (CAMCOG). Scans were performed on a 1.5 T magnetic resonance imager addressing a 40-cm³ voxel in the left prefrontal cortex. Main outcome measures were mean relative peak areas of PME and PDE, which provide an estimate of membrane phospholipid metabolism.Results PME resonance and the PME/PDE ratio were increased in AD patients as compared to controls (p<0.05). PME was negatively correlated with global cognitive performance as shown by the Mini-Mental State Examination (r_s=–0.36, p=0.05) and CAMCOG scores (r_s=–0.49, p=0.007), as well as with discrete neuropsychological functions, namely, memory (r_s=–0.53, p=0.004), visual perception (r_s=–0.54, p=0.003), orientation (r_s=–0.36, p=0.05), and abstract thinking (r_s=–0.48, p=0.01).Conclusions We provide evidence of reduced membrane phospholipid breakdown in the prefrontal cortex of mild and moderately demented AD patients. These abnormalities correlate with neuropsychological deficits that are characteristic of AD.     

Epidemiological survey of epilepsy in the primary school population in Buenos Aires

BACKGROUND: Most studies carried out in Latin America have shown greater rates of epilepsy and generalized seizures than those observed in developed countries, in spite of lower numbers of patients receiving treatment. To date, studies in Argentina have been insufficient to establish true prevalence. OBJECTIVE: To determine the prevalence of epilepsy in primary school children in Buenos Aires, together with rates of different seizure types, treatments prescribed, diagnoses made and number of inadequate therapies administered, as well as the relationship between epilepsy and learning difficulties. DESIGN AND METHOD: A cross-sectional study was carried out on 10% of the entire primary school population of Buenos Aires through randomized, systematic, representative and conglomerate sampling of public and private school students. A total of 26,270 responses were received (83.1% of the population) to a specially designed questionnaire, with 96.4% sensitivity and 41.5% specificity, respectively. Interviews were conducted in all probable epilepsy cases as well as in a random sample of probable negative ones. RESULTS: Eighty-four children with epilepsy were detected (lifetime prevalence 3.2 per thousand; active prevalence 2.6 per thousand), in whom generalized seizures predominated (57.1%). Ninety-three percent of cases diagnosed were currently under, or had previously received antiepileptic drug (AED) therapy. Almost 1% of the primary school population studied had a prior diagnosis and/or received AED for dysrhythmia or epilepsy. The percentage of grade repeaters in the general population and in children with epilepsy was 8.4 and 26.2%, respectively. CONCLUSIONS: (1) The prevalence of epilepsy in primary school children in Buenos Aires is similar to that reported for developed countries; (2) a slight prevalence for generalized seizures was observed; (3) 93% of cases received AEDs; (4) misdiagnoses and unnecessary treatments exceeded correct diagnoses and adequate therapy, and (5) disease presence and/or treatment were associated with poorer school performance.