A preliminary cost effectiveness analysis of an intervention to reduce homelessness among the mentally ill

The Critical Time Intervention Project is a three-year clinical trial which tests a time-limited, supportive intervention to reduce recurrent homelessness among mentally ill men moving from a shelter to the community. Along with a comparison of nights spent homeless and other outcomes, the evaluation of the Critical Time Intervention includes a comparison of the relative costs of the intervention, compared to usual treatment. Such cost effectiveness analyses are difficult to perform and are rarely applied to mental health treatments. This paper presents the general scheme of this analysis and discusses critical issues in the construction and measurement of cost variables. Preliminary results which have implications for the cost analysis are presented.     

Polymorphism and drug-selected mutations in the protease gene of human immunodeficiency virus type 2 from patients living in Southern France

The susceptibility of human immunodeficiency virus type 2 (HIV-2) to protease inhibitors (PI) is largely unknown. We studied HIV-2 protease genes from 21 HIV-2-infected patients who were exposed or not exposed to PI. The aim of this study was (i). to characterize the polymorphism of HIV-2 protease in the absence of drug, (ii). to know whether the HIV-2 protease gene naturally harbors HIV-1 drug resistance codons, and (iii). to identify mutations emerging under PI-selective pressure. Sixty-five HIV-2 RNA or proviral DNA samples were directly sequenced from the plasma or peripheral blood mononuclear cells of 8 patients who had received PI and 13 patients who had never received any antiretroviral. In untreated patients, the highest amino acid variability in HIV-2 protease was observed at positions 14, 40, 43, 46, 65 and 70, and seven codons (10V, 32I, 36I, 46I, 47V, 71V, and 73A) associated with drug resistance in HIV-1 were highly prevalent. In addition, at six positions (positions 7, 46, 62, 71, 90, and 99), the amino acid variability or the amino acid frequencies or both differed significantly in PI-treated and untreated patients, suggesting that mutations 7K-->R, 46V-->I, 62V-->A/T, 71V-->I, 90L-->M and 99L-->F were occurring under PI-selective pressure. At these positions, at least one sample simultaneously harbored both wild-type and mutated codons, while substitutions at positions 62, 71, 90, and 99 were confirmed in a longitudinal analysis. Moreover, the presence of codons 46I and 99F in the absence of drug in HIV-2 subtype B proteases may reflect natural resistance to PI. In conclusion, the present study revealed that HIV-2 strains harbor specific patterns of natural polymorphism and resistance.     

Association analysis of chromosome 1 migraine candidate genes

Background  

Migraine with aura (MA) is a subtype of typical migraine. Migraine with aura (MA) also encompasses a rare severe subtype Familial Hemiplegic Migraine (FHM) with several known genetic loci. The type 2 FHM (FHM-2) susceptibility locus maps to chromosome 1q23 and mutations in the ATP1A2 gene at this site have recently been implicated. We have previously provided evidence of linkage of typical migraine (predominantly MA) to microsatellite markers on chromosome 1, in the 1q31 and 1q23 regions. In this study, we have undertaken a large genomic investigation involving candidate genes that lie within the chromosome 1q23 and 1q31 regions using an association analysis approach.     

Investigation of Gamma-aminobutyric acid (GABA) A receptors genes and migraine susceptibility

Background  

Migraine is a neurological disorder characterized by recurrent attacks of severe headache, affecting around 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the number and type of genes involved is still unclear. Prior linkage studies have reported mapping of a migraine gene to chromosome Xq 24–28, a region containing a cluster of genes for GABA A receptors (GABRE, GABRA3, GABRQ), which are potential candidate genes for migraine. The GABA neurotransmitter has been implicated in migraine pathophysiology previously; however its exact role has not yet been established, although GABA receptors agonists have been the target of therapeutic developments. The aim of the present research is to investigate the role of the potential candidate genes reported on chromosome Xq 24–28 region in migraine susceptibility. In this study, we have focused on the subunit GABA A receptors type ε (GABRE) and type θ (GABRQ) genes and their involvement in migraine.     

Reciprocal influence of HIV and HCV infections in co-infected patients and the involvement of HAART

The reciprocal influence of HIV-HCV co-infection was established prior to the era of highly active retroviral therapy (HAART) and continues to be a topic of debate, including the question of which infection to treat first.     

Nursing station order entry for hospital computers

Tired of illegible labels, unlabeled specimens, and frantic phone calls asking what happened to specimens? This lab was and devised a system to allow test ordering and label printing from nurse stations.     

Substitution at the F-ring N-imide of the indolocarbazole antitumor drug NB-506 increases the cytotoxicity, DNA binding, and topoisomerase I inhibition activities.

The antitumor drug NB-506, which is currently undergoing phase I/II clinical trials, contains a DNA-intercalating indolocarbazole chromophore substituted with a glucose residue. In addition to interacting with DNA, the drug stabilizes the topoisomerase I-DNA covalent complex. To reinforce the DNA binding and anti-topoisomerase I activities of NB-506, an analogue containing a new substituent on the naphthalimide ring F was synthesized. The N-formylamino group of NB-506 has been replaced with a more hydrophilic group, N-bis(hydroxymethyl)methylamino. In this study we show that the incorporation of a longer substituent on the N6 position effectively reinforces both the interaction with DNA and the capacity of the drug to maintain the integrity of the topoisomerase I-DNA covalent complexes. The strength and the mode of binding of the drugs to DNA were studied by complementary biophysical techniques including absorption, fluorescence, and circular and linear dichroism. Various biochemical procedures were applied to investigate the effects on human topoisomerase I using plasmid DNA as well as restriction fragments. The drug binding sites and the positions of the topoisomerase I-mediated cleavage sites were mapped with nucleotide resolution using footprinting and sequencing techniques. Cytotoxicity measurements performed with various human cancer cell lines (HCT-116, DLD-1, MKN-45) indicate that the newly designed drug is 3 to 4 times more toxic to colon and gastric cancer cells than NB-506. Therefore, the results suggest that the antitumor activity of indolocarbazole-based drugs can be enhanced by incorporating DNA and/or topoisomerase I reactive groups. They also support the hypothesis that the substituent on the imide nitrogen on the F ring of NB-506 has direct interaction with the molecular target. The study helps to define the structure-activity relationships in the indolocarbazole series of antitumor agents targeting topoisomerase I.     

Comparison of intravenous or epidural patient-controlled analgesia in the elderly after major abdominal surgery

BACKGROUND: Patient-controlled analgesia (PCA) with intravenous morphine and patient-controlled epidural analgesia (PCEA), using an opioid either alone or in combination with a local anesthetic, are two major advances in the management of pain after major surgery. However, these techniques have been evaluated poorly in elderly people. This prospective, randomized study compared the effectiveness on postoperative pain and safety of PCEA and PCA after major abdominal surgery in the elderly patient. METHODS: Seventy patients older than 70 yr of age and undergoing major abdominal surgery were assigned randomly to receive either combined epidural analgesia and general anesthesia followed by postoperative PCEA, using a mixture of 0.125% bupivacaine and sufentanil (PCEA group), or general anesthesia followed by PCA with intravenous morphine (PCA group). Pain intensity was tested three times daily using a visual analog scale. Postoperative evaluation included mental status, cardiorespiratory and gastrointestinal functions, and patient satisfaction scores. RESULTS: Pain relief was better at rest (P = 0.001) and after coughing (P = 0.002) in the PCEA group during the 5 postoperative days. Satisfaction scores were better in the PCEA group. Although incidence of delirium was comparable in the PCA and PCEA groups (24% vs. 26%, respectively), mental status was improved on the fourth and fifth postoperative days in the PCEA group. The PCEA group recovered bowel function more quickly than did the PCA group. Cardiopulmonary complications were similar in the two groups. CONCLUSION: After major abdominal surgery in the elderly patient, patient-controlled analgesia, regardless of the route (epidural or parenteral), is effective. The epidural route using local anesthetics and an opioid provides better pain relief and improves mental status and bowel activity.