Comparing Medications in a Therapeutic Area Using an NNT Model

OBJECTIVES: Clinicians are told to use the number needed to treat (NNT) to compare the benefits of therapeutic strategies, and researchers are asked to report results this way, generally without considering differences among the studies from which these were derived. METHODS: The crude NNT currently advocated is compared to the NNT standardized for a common outcome, follow-up time, study population and comparator. An NNT model for cardiovascular disease is described as an example that addresses differences among studies of secondary prevention of cardiovascular disease. Crude NNTs are compared to those obtained from the model. RESULTS: Follow-up in the 18 trials identified varied from 1.0 to 6.2 years; rates of cardiovascular events in the untreated subgroups ranged from 4.8% to 45.9%. The crude NNTs were more variable (9.1-163.7) than those obtained from the model (9.1-75.2). The effect of standardization was substantial in some cases, with proportional changes ranging from a 91% decrease to a 223% increase. CONCLUSION: Using an NNT model to account for differences in study design allows for more meaningful comparisons.     

Complexity of Family Life Among the Low‐Income and Working Poor: Introduction to the Special Issue

Like all families, low‐income and working‐poor families need economic stability, safety, good health, and engagement in the larger community. However, the complexity of their lives is greatly impacted by limited economic resources. Three primary themes are explored by the 12 articles in this special issue: competing stressors and tensions, effective parenting, and economic stability and financial decision making. Key findings and program and policy implications identified by each set of authors are discussed. This body of work provides research‐based practice and policy suggestions to guide future efforts in partnering with families to strengthen their families and communities for successful enhancement of child well‐being.     

Don’t Have No Time: Daily Rhythms and the Organization of Time for Low‐Income Families*

Using ethnographic data from Welfare, Children, and Families: A Three‐City Study, we examined time obligations and resource coordination of low‐income mothers. Longitudinal data from 75 African American, Hispanic, and non‐Hispanic White families residing in Chicago, including information on daily routines, perceptions of time, and access to resources, were gathered via participant observation and intensive semistructured interviews over 4 years. Results indicated that families constantly improvised daily rhythms to obtain and sustain resources, including child care, transportation, and social services. Participants were proactive in identifying and coordinating resources to transition from welfare to work or to maintain paid employment. Strategies used to coordinate resources and the cost associated with the inability to do so are discussed. Policy and social service recommendations are offered.     

α‐crystallin: a review of its structure and function

α‐crystallin, the major protein of the mammalian lens in most species, is an aggregate assembled from two polypeptides, each with a molecular weight around 20,000 Da. It is polydisperse and can be isolated in a variety of forms, including spherical particles with molecular weights ranging upwards from about 200 kDa. Sequence comparisons reveal that it is a member of the small heat shock protein (shsp) family. These proteins are aggregates assembled from polypeptides of 10 to 25 kDa that share a common central domain of about 90 residues (the ‘α‐crystallin domain’) with variable N‐ and Gterminal extensions. α‐crystallin has been intensively studied for more than 50 years but its three‐dimensional structure remains unknown because it has not been possible to obtain crystals for X‐ray studies and it is too large for NMR measurements. Structural information has been derived from a variety of solution studies. Because of the protein's polydispersity, interpretation of data has been difficult. This led to different viewpoints and vigorous debate on its structure and properties. Recently, the crystal structures of two closely‐related small heat shock proteins have been determined. These have provided some insight into the structure of α‐crystallin and explanations of previous observations. Like many other heat shock proteins, α‐crystallin exhibits chaperone‐like properties, including the ability to prevent the precipitation of denatured proteins and to increase cellular tolerance to stress. It has been suggested that these functions are important for the maintenance of lens transparency and the prevention of cataract.     

High-dose methotrexate therapy of childhood acute lymphoblastic leukemia: lack of relation between serum methotrexate concentration and creatinine clearance.

BACKGROUND: The objectives of this study were: (1) to analyze the relation of serum methotrexate (MTX) concentration with creatinine clearance, (2) to compare the leucovorin rescue dose administered to the patients based on creatinine clearance, with the one calculated according to serum MTX levels, and (3) to determine MTX-related toxicity. PROCEDURE: Thirty children with high-risk non-B acute lymphoblastic leukemia (ALL) treated according to the national protocol (PINDA 92) based on ALL BFM 90, were randomized to receive consolidation with four doses of either 1 or 2 g/m(2) MTX as a 24-hr infusion, at 2-week intervals (group M1 and M2, respectively). Serum MTX concentrations were measured at 24, 42, and 48 hr after beginning the infusion and were analyzed retrospectively. The creatinine clearance was calculated after 12-hr intravenous hydration prior to each MTX dose. Leucovorin dosage was adjusted according to creatinine clearance. RESULTS: Serum MTX concentrations at 24, 42, and 48 hr after starting the infusion were not related to creatinine clearance in both treatment groups. Leucovorin rescue administered according to creatinine clearance was excessive in 43% in group M1 and in 51% in group M2, as compared to the dose calculated according to serum MTX levels. No serious clinical complications were observed. CONCLUSIONS: These results suggest that creatinine clearance is not a good parameter to calculate leucovorin rescue. MTX-related toxicity in this group of patients receiving a dose of 1 or 2 g/m(2) and rescued with leucovorin without monitoring serum MTX levels was acceptable.     

关于"惠民"医疗服务的实践与思考

惠民医疗是指对民政部门认定核准,缺乏经济支持的最低生活保障待遇家庭中没有享受政府、社会、单位医疗保障待遇的,并确有病需治疗的人员实行五免五减半医疗服务。南京市儿童医院针对惠民医疗服务中问题,对惠民医疗服务界定、服务模式、补偿机制和服务远景做出了思考。     

A novel brain receptor is expressed in a distinct population of olfactory sensory neurons

Three novel G-protein-coupled receptor genes related to the previously described RA1c gene have been isolated from the mouse genome. Expression of these genes has been detected in distinct areas of the brain and also in the olfactory epithelium of the nose. Developmental studies revealed a differential onset of expression: in the brain at embryonic stage 17, in the olfactory system at stage E12. In order to determine which cell type in the olfactory epithelium expresses this unique receptor type, a transgenic approach was employed which allowed a coexpression of histological markers together with the receptor and thus visualization of the appropriate cell population. It was found that the receptor-expressing cells were located very close to the basal membrane of the epithelium; however, the cells extended a dendritic process to the epithelial surface and their axons projected into the main olfactory bulb where they converged onto two or three glomeruli in the dorsal and posterior region of the bulb. Thus, these data provide evidence that this unique type of receptor is expressed in mature olfactory neurons and suggests that it may be involved in the detection of special odour molecules.     

Oxytocin receptor agonists enhance inhibitory synaptic transmission in the rat hippocampus by activating interneurons in stratum pyramidale

Oxytocin probably plays a role as a neurotransmitter/neuromodulator in the hippocampus of the rat. Oxytocin binding sites are present in the subiculum and CA1 region and oxytocin can excite a class of CA1 nonpyramidal neurons. In the present work we characterized the effect of oxytocin on hippocampal synaptic transmission. Whole-cell recordings were obtained from pyramidal neurons, in conditions of nearly symmetrical chloride concentrations. The selective oxytocin receptor agonist, [Thr4,Gly7]-oxytocin (TGOT), caused an increase in the frequency and amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) in virtually all neurons. These peptide-enhanced IPSCs were blocked by bicuculline, but not by strychnine, and reversed near 0 mV, indicating that they were mediated by gamma-aminobutyric acid (GABA)A receptors. On average, TGOT caused a nearly threefold increase in the frequency and almost a doubling in the amplitude of spontaneous IPSCs. TGOT did not influence the frequency and the amplitude of miniature IPSCs or spontaneous excitatory postsynaptic currents (EPSCs), and had no effect on evoked IPSCs. The peptide did not affect the basic membrane properties of pyramidal neurons or their GABA sensitivity. Thus, TGOT facilitated inhibitory transmission by exerting an excitatory action on the soma and/or dendrites of GABAergic interneurons. Extracellular recordings were performed in interneurons located in various hippocampal strata. Their sensitivity to TGOT was compared to that of substance P (SP). Interneurons in stratum pyramidale were excited both by TGOT and by SP. By contrast, stratum radiatum interneurons responded to SP but not to TGOT. In stratum oriens, half of the interneurons responded to SP, but only a minority to TGOT. Thus, oxytocin-responsive interneurons appear to be preferentially located in close vicinity of pyramidal neurons.     

Heme oxygenase1 (HSP-32) is induced in myelin-phagocytosing Schwann cells of injured sciatic nerves in the rat

Schwann cells participate in myelin phagocytosis in the early stage of Wallerian degeneration, prior to the recruitment of macrophages. This is the first report that Schwann cells induce heme oxygenase-1 (HO-1), a 32-kDa heat shock protein, only when they have transformed into myelin-phagocytosing cells from myelinating cells (days 2-3) immediately after crush injury of rat sciatic nerves. Double immunofluorescent labelling for HO-1 and transferrin receptors revealed that HO-1-immunoreactive Schwann cells also expressed transferrin receptors suggesting activation of iron metabolism. The transient induction of HO-1 in Schwann cells may contribute to the adaptive function in an altered environment when the cells have lost contact with axons, and may play a crucial role in the ensuing regeneration.     

Recovery from a recurrent major depressive episode

Episode-related factors and antidepressant treatment adequacy may be important determinants of recovery from a major depressive episode (MDE). We compared recovered and nonrecovered patients on baseline sociodemographic, clinical and episode-related measurements. Twenty-five inpatients with recurrent major depressive disorder diagnosed by SADS-L participated in this naturalistic, prospective, longitudinal study. Recovery, which was defined as a sustained return to non-depressed status lasting > or = 8 consecutive weeks, was assessed at 6- and 12-month follow-up with the Streamlined Longitudinal Interval Continuation Evaluation (SLICE). Thirteen (52%) patients met recovery criteria. The cumulative proportion remaining depressed for at least 52 weeks was 42.5%. Recovered patients had shorter episodes preceding the index hospitalization (P = .01). Despite adequate antidepressant pharmacotherapy, the length of the current episode remains the most important correlate of recovery from MDE recurrence. Our small sample size and the uncontrolled nature of treatment may limit the generalizability of these findings.