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.     

Phylogenetic reconstruction of Mycobacterium tuberculosis within four settings of the Caribbean region: tree comparative analyse and first appraisal on their phylogeography.

In order to compare phylogenetic methods and to reconstruct the evolutionary history of the tubercle bacilli, a set of macro-array-based genotyping data of Mycobacterium tuberculosis clinical isolates (called spoligotyping for spacer oligonucleotide typing, which assays the variability of the Direct Repeat -DR- locus), was analyzed in four settings of the Caribbean region (Guadeloupe, Martinique, Cuba and Haiti). A set of 47 alleles, split into 26 shared and 21 unique alleles) representative of 321 individual M. tuberculosis clinical isolates from patients residing in the above regions was studied. The following methods (and software in brackets) were investigated: numerical taxonomy distance methods (TAXOTRON), maximum parsimony procedure (PAUP), median-joining networks (NETWORK), and nested clade analysis (GEODIS). Results using these methods were analyzed, compared and discussed. The latter method (GEODIS) was investigated in detail by introducing geographical data together with genetic variability results to detect a link between population structure and population history, and to test the null hypothesis of no association between geography and genotypes. Irrespective of the methods used, our findings demonstrate that a core structure of four families (or clades) of M. tuberculosis strains is highly prevalent within the islands studied, indirectly reflecting passed colonization history of these different settings. Specificity of M. tuberculosis genotypes in each of the islands is discussed in the light of their respective colonial and contemporary histories.     

Retrospective analysis of selective lymphadenectomy in apparent early-stage endometrial cancer.

PURPOSE: Selective lymphadenectomy is widely accepted in the management of endometrial cancer. Purported benefits are individualization of adjuvant therapy based on extent of disease and resection of occult metastases. Our goal was to assess effects of the extent of selective lymphadenectomy on outcomes in women with apparent stage I endometrial cancer at laparotomy. PATIENTS AND METHODS: Patients with endometrial cancer who received primary surgical treatment between 1973 and 2002 were identified through an institutional tumor registry. Inclusion criteria were clinical stage I/IIA disease and procedure including hysterectomy and selective lymphadenectomy (pelvic or pelvic + aortic). Exclusion criteria included presurgical radiation, grossly positive lymph nodes, or extrauterine metastases at laparotomy. Recurrence and survival were analyzed using Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: Among 509 patients, the median number of lymph nodes removed was 15 (median pelvic, 11; median aortic, three). Pelvic and aortic node metastases were found in 24 (5%) of 509 patients and 11 (3%) of 373 patients, respectively. Patients with poorly differentiated cancers having more than 11 pelvic nodes removed had improved overall survival (hazard ratio [HR], 0.25; P < .0001) and progression-free survival (HR, 0.26; P < .0001) compared with patients having poorly differentiated cancers with 11 or fewer nodes removed. Number of nodes removed was not predictive of survival among patients with cancers of grade 1 to 2. Performance of aortic selective lymphadenectomy was not associated with survival. Three (27%) of 11 patients with microscopic aortic nodal metastasis are alive without recurrence. CONCLUSION: These data add to the literature documenting the possible therapeutic benefit of selective lymphadenectomy in management of patients with apparent early-stage endometrial cancer.     

In vitro and in vivo targeting properties of iodine-123- or iodine-131-labeled monoclonal antibody 14C5 in a non-small cell lung cancer and colon carcinoma model.

PURPOSE: The monoclonal antibody (mAb) 14C5 is a murine IgG1 directed against a yet undefined molecule involved in cell substrate adhesion found on the surface of malignant breast cancer tissue. mAb 14C5 is able to inhibit cell substrate adhesion and invasion of breast cancer cells in vitro. In normal tissues as well as in the stroma surrounding in situ carcinomas of the breast, no expression of the antigen 14C5 occurs. The aim of this study was to investigate the in vitro and in vivo targeting properties of 123I- and 131I-labeled mAb 14C5 as a novel agent for radioimmunodetection and radioimmunotherapy. EXPERIMENTAL DESIGN: Internalization of mAb 14C5 was investigated with 125I-labeled mAb 14C5 and by confocal laser scanning microscopy. Biodistribution studies of 131I-labeled mAb 14C5 and planar gamma imaging were done in nude mice bearing an A549 (non-small cell lung carcinoma) or a LoVo (colon carcinoma) tumor. RESULTS: Internalization studies with both A549 and LoVo cells showed that 125I-labeled mAb 14C5 is slowly internalized with approximately 30% of the initially bound mAb 14C5 internalized after 2 hours at 37 degrees C. Internalization of mAb 14C5 could be visualized with confocal laser scanning microscopy. In vivo, radioisotope uptake peaked at 24 hours for both tumor models (n = 5) with no significant difference in percentage of injected dose/g tissue (A549 10.4 +/- 0.8 and LoVo 9.3 +/- 0.8). Via planar gamma camera imaging, A549 lung tumors as well as LoVo colon tumors could be clearly visualized. CONCLUSIONS: The in vitro and in vivo targeting properties of 123I- and 131I-labeled mAb 14C5 are promising and could provide a new antibody-based agent for radioimmunodetection and radioimmunotherapy of patients bearing antigen 14C5-expressing tumors.     

Cytochrome P450 epoxygenases as EDHF synthase(s)

The metabolism of arachidonic acid by cytochrome P450 (CYP) epoxygenases generates epoxyeicosatrienoic acids (EETs) which affect numerous cellular process including Ca(2+) signaling and the activity of Ca(2+)-dependent K(+) channels. The expression of the CYP epoxygenase(s) that generate EETs in endothelial cells is not constitutive but is determined by a number of physical (fluid shear stress and cyclic stretch) and pharmacological stimuli which also affect responses attributed to an endothelium-derived hyperpolarizing factor (EDHF). This review summarizes the role played by EETs, and the enzymes that generate and metabolize them, in EDHF-mediated responses.     

Food effects on tablet disintegration.

The aims of the present study was to investigate if food components, as represented by a multi-component nutritional drink for tube feeding, could affect tablet disintegration of standard tablets in vitro as well as in vivo and propose a mechanism for potential food effects on tablet disintegration. The tablet disintegration was delayed between 5 min and more than 1h in the simulated gastric fed medium compared to a simple buffer. This effect was dependent on the tablet composition. A similar delay in tablet disintegration was also found in vivo after administration of the nutritional drink to three Labradors as observed by removing the tablet from the stomach at different times through a gastric fistula. The delay in tablet disintegration appeared to be caused by precipitation of a film, mainly consisting of protein, on the tablet surface as indicated by disintegration studies with pure nutrients, identification by IR spectroscopy of contents of precipitates obtained in a model study were the nutrients were incubated with different tablet excipients and visual observations of tablets exposed to the simulated fed medium. The drug dissolution of a soluble compound, metoprolol tartrate, from a standard tablet was also strongly delayed in the simulated fed medium. In conclusion, food, could significantly delay tablet disintegration and drug dissolution in the stomach by formation of a film around the tablets. This effect could be monitored by a simple in vitro disintegration test using a test medium based on a nutritional drink. More studies are needed to investigate the significance of the slow tablet disintegrations on bioavailability and for which types of food the present effect occurs.     

Dental care utilization: a study of 50- to 75-year-olds in Southern Sweden

This study investigates dental care utilization in an adult population in Southern Sweden in relation to dental and social conditions, attitudes to costs, and perceived need to obtain dental services. The study was based on responses to a questionnaire sent in 1998 to a random sample, 1974 persons, aged 50-75 years. The response rate was 66%. A significantly higher probability of dental care utilization less than once a year was found for men, for those with few remaining teeth, and for those with removable dentures. A higher probability of dental care utilization less than once a year was found for those who stated perceived need to obtain dental care with no possibility because of the cost and for those who stated that the cost had influenced their attendance for dental care. The results showed that there were differences for sex and dental conditions in dental care utilization and that dental care utilization was related to attitudes towards costs of dental care.     

When people with dementia are perceived as witches. Consequences for patients and nurse education in South Africa

Aims and Objectives

To explore and describe the link between culture and dementia care with the focus on the influence of the belief in dementia as witchcraft and people with dementia as witches.

Background

In South Africa, especially in townships and rural areas, dementia is often perceived as connected to witchcraft rather than to disease. Persons labelled as witches—mostly older women—may be bullied, ostracised, beaten, stoned, burned, even killed.

Method

One strand of findings from a larger international study is presented with in‐depth qualitative interviews of one close family member and seven nurses caring for patients with severe dementia in nursing homes in Tshwane in South Africa. A hermeneutic analytic approach was used.

Results

Two main themes are found, namely “Belief in witchcraft causing fear of persons with dementia” and “Need of knowledge and education.” Fear of and violence towards people with dementia are based on the belief that they are witches. Some of the nurses had also held this belief until they started working with patients with dementia. There is a great need for education both among healthcare workers and the populace.

Discussion

The “witch” belief prevents seeking professional help. As nursing homes tend to be private and expensive, professional dementia care is virtually unattainable for the poor. Dementia needs a more prominent place in nursing curricula. Nurses as educators need to know the local culture and language to be accepted in the various communities. They need to visit families affected by dementia, give awareness talks in churches, schools and clinics and facilitate support groups for carers of people with dementia in the local language.

Conclusion

Improved nurses’ education in gerontology and geriatric care is needed. Trained specialist nurses may work as mediators and help eradicate the witchcraft beliefs connected to severe dementia.