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PubMed1995

A study of five variable number tandem repeat (VNTR) loci in the Greek population.

The use of hypervariable tandem repeat loci for population genetic studies, genetic analysis of inherited disease and individual identification purposes requires establishment of a genetic database for each reference population. In the present study we have analysed variability at five tandem repeat loci (D1S80, D17S5, 3'-hvr/apoB, F8vWF and D6S89)in a representative sample (88 to 156 individuals of greek ancestry), using polymerase chain reaction amplification. Between nine and 19 alleles were resolved throughout the five polymorphic loci. Heterozygosity indices for these loci in the greek population ranged from 0.68 to 0.85. Allele frequencies follow a bimodal discrimination (pd) and allelic diversity (h) values ranged from 0.84 to 0.94 and 0.85 to 0.91, respectively, and indicated that these loci are highly informative and can be used for population studies, forensic purposes and parentage and family testing. Comparison of observed and expected genotype frequencies by the conventional chi-square test indicated conformity to Hardy-Weinberg predictions.

Alleles↗

PubMed2002

Progression-free rate as the principal end-point for phase II trials in soft-tissue sarcomas.

We have estimated progression-free rates (PFR) for various groups of soft-tissue sarcoma patients from our clinical trials database, to provide reference values for conducting phase II studies with PFR as the principal end-point. In 146 pretreated patients receiving an active agent, the PFR estimates were 39 and 14% at 3 and 6 months; with inactive regimens (234 patients), those estimates were 21 and 8% respectively. In 1154-non-pretreated patients, PFR estimates varied from 77% (synovial sarcoma) to 57% (malignant fibrous histiocytoma (MFH)) at 3 months, and from 56% (synovial sarcoma) to 38% (MFH) at 6 months. In 61 leiomyosarcomas from gastrointestinal origin, the corresponding figures were 44 and 30%, respectively. Consequently, for first-line therapy, a 6-month PFR of > or = 30-56% (depending on histology) can be considered as a reference value to suggest drug activity; for second-line therapy, a 3-month PFR of > or = 40% would suggest a drug activity, and < or = 20% would suggest inactivity.

Adolescent↗

PubMed1999

Tools, methods, and strategies. Do innovative models of health care delivery improve quality of care for selected vulnerable populations? A systematic review.

BACKGROUND: A criticism of conventional office or clinic-based models of care is that they focus on patients' urgent problems and do not provide the comprehensive assessments, education, and psychosocial support that vulnerable patients also need. Innovative models have emerged to address these needs. A systematic review of prospective studies involving searches of computerized databases, reviews of reference lists, and contacts with authors, was conducted to determine whether multidisciplinary teams, outreach or home care, and case management improve the quality of the care in two vulnerable populations-the terminally ill and the mentally ill. RESULTS: Literature searches identified 730 citations. 52 original articles met screening standards, and 24 studies fulfilled all criteria. Patient and caregiver satisfaction was consistently higher with innovative models. In no study was satisfaction lower. Functional, clinical, or psychological improvements were not consistently demonstrated. For mentally ill patients, multidisciplinary outreach strategies were effective in reducing inpatient hospitalizations. Costs were inadequately assessed in the studies to draw a summary conclusion. DISCUSSION: Like other interventions, health care delivery models can be assessed from an evidence-based perspective. More needs to be learned about the costs and health improvements of innovative models before we can determine whether the increased patient and caregiver satisfaction found justifies widespread use of these models. Development of a uniform set of quality outcome measures and encouragement to evaluate efforts and disseminate results will help accomplish this goal.

Humans↗

PubMed1999

Heart failure disease management: a critical review.

BACKGROUND: Despite major advances in the pharmacotherapy of heart failure, hospitalization rates remain high, owing in large part to a multitude of psychosocial, behavioral, and financial factors that serve as barriers to effective compliance with prescribed treatment. To deal with these issues, many centers have adopted a multidisciplinary approach to heart failure disease management. METHODS AND RESULTS: A systematic review of the literature was conducted using the Medline database supplemented by reference lists from published articles. From 1983 to 1998, 16 studies describing multidisciplinary heart failure disease management programs were published in the English language literature. Of these, 10 were nonrandomized, observational studies and 6 were randomized clinical trials. All studies reported significant benefits in terms of reducing hospital utilization, and several studies reported improved quality of life, functional capacity, patient satisfaction, and compliance with diet and medications. In all studies in which a cost analysis was performed, heart failure disease management programs were found to be cost-effective. The limitations of the current data include concerns about the generalizability of published findings to the large and heterogenous population of patients with heart failure in the community, the feasibility of translating specific disease management programs into diverse practice environments, uncertainty about how to design and implement a maximally cost-effective heart failure disease management strategy, and how to best tailor the treatment program to the needs of each individual patient. The impact of heart failure disease management programs on survival is also unknown. CONCLUSION: Based on currently available data, heart failure disease management programs appear to be a cost-effective approach to reducing morbidity and enhancing quality of life in selected patients with heart failure. However, additional study is needed involving larger and more diverse populations to define the optimal approach to heart failure disease management.

Cost-Benefit Analysis↗

PubMed1997

Distant metastases in terminal head and neck cancer patients.

With improved control of cancer above the clavicles, distant metastases (DM) are frequently more seen and are becoming a more common cause of morbidity and mortality. The present study defined the incidence of distant metastases in a cohort of terminal head and neck cancer patients (HNCP) and compared it to current reported data. The incidence of distant metastases in relation to the primary tumour was evaluated and their impact on survival was assessed. A retrospective survey of patient charts was made, based on the hospice database and original referring hospital charts. Data of 59 patients admitted to the hospice were evaluated. The incidence and location of locoregional and distant disease were studied and effects on survival analyzed. The overall survival from diagnosis to demise was 42.7 months. Thyroid cancer was seen in 20.3 per cent of cases and squamous cell cancer was seen in 59.3 per cent. Distant metastases were found in 83 per cent and 48.6 per cent of patients respectively. Laryngeal cancer patients had a 54.5 per cent incidence of distant metastases. Locoregional disease was seen in 47 per cent of cases and 35.7 per cent of them had distant metastases while a 64.3 per cent incidence of distant metastases was found in cases without locoregional disease. Mean survival was 47.3 months with distant metastases vs 36.5 months without metastases. The difference was not statistically significant. The incidence of distant metastases in squamous cell cancer in terminal HNCP was 48.6 per cent. This is the highest reported incidence of metastases in a clinical series. Patients without locoregional disease had almost a two-fold incidence of metastases. Survival was not affected by metastases in this series.

Aged↗

PubMedDate not supplied

A hierarchical clustering approach for large compound libraries.

A modified version of the k-means clustering algorithm was developed that is able to analyze large compound libraries. A distance threshold determined by plotting the sum of radii of leaf clusters was used as a termination criterion for the clustering process. Hierarchical trees were constructed that can be used to obtain an overview of the data distribution and inherent cluster structure. The approach is also applicable to ligand-based virtual screening with the aim to generate preferred screening collections or focused compound libraries. Retrospective analysis of two activity classes was performed: inhibitors of caspase 1 [interleukin 1 (IL1) cleaving enzyme, ICE] and glucocorticoid receptor ligands. The MDL Drug Data Report (MDDR) and Collection of Bioactive Reference Analogues (COBRA) databases served as the compound pool, for which binary trees were produced. Molecules were encoded by all Molecular Operating Environment 2D descriptors and topological pharmacophore atom types. Individual clusters were assessed for their purity and enrichment of actives belonging to the two ligand classes. Significant enrichment was observed in individual branches of the cluster tree. After clustering a combined database of MDDR, COBRA, and the SPECS catalog, it was possible to retrieve MDDR ICE inhibitors with new scaffolds using COBRA ICE inhibitors as seeds. A Java implementation of the clustering method is available via the Internet (http://www.modlab.de).

Algorithms↗

PubMed2006

Difference in folate content of green and red sweet peppers (Capsicum annuum) determined by liquid chromatography-mass spectrometry.

Folic acid (pteroylmonoglutamic acid) is used in enriched foods; however, very little folic acid occurs naturally in fruits and vegetables. For the U.S. Department of Agriculture's National Food and Nutrient Analysis Program, a number of fruits and vegetables have been assayed for endogenous folates, by a liquid chromatography-mass spectrometry method, to evaluate the accuracy of existing data for total folate determined by standard microbiological analysis. Folate in red and green sweet peppers (Capsicum annuum) differed notably (70.2 and 20.7 microg/100 g, respectively) and exceeded existing values determined by microbiological assay (18 and 11 microg/100 g, respectively). 5-Methyltetrahydrofolate was the predominant vitamer, but a significant amount of 5-formyltetrahydrolfolate and some 10-formylfolate were present. These findings may assist in making dietary recommendations or developing research diets related to folate. The data from this study have been used to update the folate values in release 19 of the USDA Nutrient Database for Standard Reference.

Capsicum↗

PubMed1997

Chemotherapy for symptom control in recurrent squamous cell carcinoma of the head and neck.

BACKGROUND: The role of chemotherapy in patients with recurrent squamous cell carcinomas of the head and neck (SCCHN) is unclear. The aim of this study was to assess the ability of combination chemotherapy to control symptoms in this setting. PATIENTS AND METHODS: Using a prospectively accrued database all patients referred for chemotherapy with symptomatic relapse following surgery were identified. Objective response was recorded using standard criteria and maximum symptom response was assessed retrospectively from case notes using a published scoring scale. RESULTS: A total of 57 (median age 56, range 37-85) patients were studied who had received mainly cisplatin/5-fluorouracil combinations. Thirty-seven had previously received radiotherapy. Fifty-two patients had evaluable disease; 18 (35%) had objective responses (14 PRs and 4 CRs). There were a total of 103 symptoms recorded with eight different individual symptoms. Forty-four (43%) symptoms improved on treatment, 52 (50%) were unchanged and 7 (7%) worsened. The number of patients with improvement in the most frequently recorded symptoms were as follows: pain 11/28 (39%), swelling 12/23 (52%) and dysphagia 6/18 (33%). Sixty-seven percent of patients with objective response also had an improvement in their symptoms but a significant proportion (33%) of non-responders had a symptomatic response. Lack of objective response was not correlated with worsening symptoms. Grade 3/4 toxicity was uncommon (6%-17%) and there were no toxic deaths. A majority of patients (82%) experienced either no change or an improvement in performance status. CONCLUSION: These results demonstrate that chemotherapy improves many of the symptoms associated with recurrent SCCHN, without deterioration in performance status. Symptomatic improvement is more likely if there is evidence of significant tumour shrinkage, but even non-responding patients can benefit.

Adult↗

PubMed1999

Systematic review and meta-analysis of corticosteroids for the resolution of malignant bowel obstruction in advanced gynaecological and gastrointestinal cancers. Systematic Review Steering Committee.

BACKGROUND: The objective was to locate, appraise and summarise evidence from scientific studies on intestinal obstruction due to advanced gynaecological and gastrointestinal cancers, in order to assess the efficacy of corticosteroids. MATERIALS AND METHODS. DATA SOURCES: A comprehensive list of studies was provided by an extensive search of electronic databases, relevant journals, bibliographic databases, conference proceedings, reference lists, the grey literature, personal contact and the world wide web. DATA SYNTHESIS: Two researchers extracted the data independently. A qualitative analysis was performed of the dichotomous data of resolution of obstruction and death at one month. Both fixed and random effect models were used. Number needed to treat (with corticosteroids to resolve one episode of bowel obstruction) was derived from the odds ratio. Kaplan-Meier survival curves from individual patient data were also analysed. Studies of lower methodological quality were assessed in a qualitative manner. RESULTS: There is a trend towards resolution of bowel obstruction using corticosteroids but this result does not achieve statistical significance. There is no statistically significant difference in mortality at one month, nor in the Kaplan Meier survival curves. Number needed to treat is 6, though with wide confidence intervals (3-infinity). The results are robust to fixed and random effects models and to 'best' and 'worst case' scenarios on the data from missing patients. The morbidity associated with corticosteroids appears to be very low. CONCLUSIONS: The role of corticosteroids needs further elucidation. More patients need to be recruited in order to obtain more precise results. Further trials should include quality of life measures as primary outcomes as well as most effective type of corticosteroid, dose or dosing regime, route of administration and morbidity.

Adrenal Cortex Hormones↗

PubMed2001

Childhood sun exposure as a risk factor for melanoma: a systematic review of epidemiologic studies.

OBJECTIVE: To review the evidence that childhood is a period of particular susceptibility to the carcinogenic effects of solar radiation. METHODS: Studies were identified through searches of computerized bibliographic databases and article reference lists. Eligible studies were those that reported risks of melanoma associated with sun exposure during two or more age-periods. RESULTS: The measurement of childhood sun exposure varied across studies, preventing formal meta-analysis for most measures. We found that the way in which sun exposure was measured led to strikingly different conclusions regarding the association between age-specific sun exposure and risk of melanoma. Ecological studies assessing ambient sun exposure consistently reported lower risks of melanoma among people who resided in a low ultraviolet (UV) environment in childhood compared with those who resided in a high UV environment. In contrast, case-control studies differed widely in their findings, and no consistent associations with childhood sun exposure were observed. CONCLUSIONS: Ecological studies provided better-quality evidence than case-control studies for examining the effects of exposure to sunlight during specific age periods. Exposure to high levels of sunlight in childhood is a strong determinant of melanoma risk, but sun exposure in adulthood also plays a role.

Adult↗

PubMed2003

Physical therapy for pregnancy-related low back and pelvic pain: a systematic review.

BACKGROUND: A systematic review of prospective controlled clinical trials was performed to assess the effectiveness of physical therapy interventions for the prevention and treatment of pregnancy-related back and pelvic pain. Pregnancy-related low back and pelvic pain has an impact on daily life for many women. Prevention and treatment of back and pelvic pain is therefore an important issue for all those concerned with women's health. METHODS: All prospective controlled clinical trials retrieved by systematic searching of electronic databases, checking of reference lists and contacting of authors were examined. Two reviewers independently selected trials for inclusion and independently assessed the internal validity of the included trials. Authors were contacted to obtain missing information. RESULTS: Nine trials with a total of 1350 patients were reviewed. Except for three high-quality studies, the validity of the trials was moderate to low. Two high-quality studies showed no difference in pain intensity and functional status between the exercise groups and the control groups. In the third high-quality study significant reduction in sick leave was found in favor of water gymnastics compared with no intervention. Because the included trials were considered heterogeneous with regard to study design, population intervention and outcome, no meta-analysis was performed. CONCLUSIONS: Because of heterogeneity and the varying quality of the studies no strong evidence exists concerning the effect of physical therapy interventions on the prevention and treatment of back and pelvic pain related to pregnancy. Future studies should meet current methodological standards, and interventions to be evaluated should be based on established theoretical framework.

Female↗

PubMed1993

Chromosomal distribution of 320 genes from a brain cDNA library.

We have determined the chromosomal assignment of 320 brain expressed genes by studying the segregation of polymerase chain reaction (PCR) products in human rodent somatic cell hybrids and by genetically mapping polymorphic cDNAs using the CEPH (Centre d'Etude du Polymophisme Humaine) reference pedigrees and database. These mapped genes can function as markers on the physical map of the human genome, as well as serve as candidate disease gene loci. Distribution of these genes to the human chromosomes correlates well with the GC content of the chromosomes. However, the distribution of these genes does not correlate well with the cytogenetic length of each chromosome.

Animals↗

PubMed2000

Interventions to prevent weight gain: a systematic review of psychological models and behaviour change methods.

OBJECTIVE: To identify and review published interventions aimed at the prevention of weight gain. DESIGN: A systematic review of published interventions aimed at the prevention of weight gain. METHODS: Search strategies-we searched eight databases, manually checked reference lists and contacted authors. Inclusion and exclusion criteria-studies of any design, in which participants were selected regardless of weight or age, were included. Interventions targeting a specific subgroup, multifactorial interventions, interventions aimed at weight loss, and those with an ambiguous aim were excluded. Data extraction-data were extracted on behaviours targeted for change, psychological model, behaviour change methods and modes of delivery, methodological quality, characteristics of participants, and outcomes related to body weight and self-reported diet and physical activity. Classification and validation-a taxonomy of behaviour change programmes was developed and used for classification of underlying model, behaviour change methods, and modes of delivery. The data extraction and subsequent classification were independently validated. RESULTS: Eleven publications were included, describing five distinct interventions in schools and four in the wider community. Where diet and physical activity were described, positive effects were usually obtained, but all were measured by self-report. Effects on weight were mixed but follow-up was generally short. Smaller effects on weight gain were found among low-income participants, students and smokers. Many participants in the community-based studies were overweight or obese. Study dropout was higher among thinner and lower-income subjects. CONCLUSION: Interventions to prevent weight gain exhibited various degrees of effectiveness. Definite statements about the elements of the interventions that were associated with increased effect size cannot be made as only one of the five studies that involved an RCT design reported a significant effect on weight. This intervention involved a correspondence programme and a mix of behaviour change methods including goal setting, self-monitoring and contingencies. Future interventions might be more effective if they were explicitly based on methods of behaviour change that have been shown to work in other contexts. Effective interventions would be more easily replicated if they were explicitly described. Effectiveness might be more precisely demonstrated if more objective measures of physical activity and diet were used, and if the follow-up was over a longer period. International Journal of Obesity (2000) 24, 131-143

Behavior Therapy↗

PubMed2002

Intensive exercise may preserve bone mass of the upper limbs in spinal cord injured males but does not retard demineralisation of the lower body.

STUDY DESIGN: Cross-sectional study comparing a group of active spinal cord injured (SCI) males carefully matched for age, height, and weight with active able-bodied male controls. OBJECTIVES: To compare bone mass of the total body, upper and lower limbs, hip, and spine regions in active SCI and able-bodied individuals. SETTING: Outpatient study undertaken in two centres in New Zealand. METHODS: Dual energy X-ray absorptiometry (DEXA) scanning was used to determine bone mass. Questionnaires were used to ascertain total time spent in weekly physical activity for each individual. The criterion for entry into the study was regular participation in physical activity of more than 60 min per week, over and above that required for rehabilitation. RESULTS: Seventeen SCI and their able-bodied controls met our required activity criterion. Bone mineral density (BMD) values of the total body and hip regions were significantly lower in the SCI group than in their controls (P=0.0001). Leg BMD and bone mineral content (BMC) were also significantly lower in the SCI group (P=0.0001). By contrast, lumbar spine BMD and arm BMD and BMC did not differ between the SCI and control groups. Arm BMD and BMC were greater (not significant) than the reference norms (LUNAR database) for both groups. CONCLUSION: Intensive exercise regimens may contribute to preservation of arm bone mass in SCI males, but does not prevent demineralisation in the lower body.

Absorptiometry, Photon↗

PubMed2002

Systematic review: herbal medicinal products for non-ulcer dyspepsia.

BACKGROUND: Non-ulcer dyspepsia is predominantly a self-managed condition, although it accounts for a significant number of general practitioner consultations and hospital referrals. Herbal medicinal products are often used for the relief of dyspeptic symptoms. AIMS: : To critically assess the evidence for and against herbal medicinal products for the treatment of non-ulcer dyspepsia. METHODS: Systematic searches were performed in six electronic databases and the reference lists located were checked for further relevant publications. No language restrictions were imposed. Experts in the field and manufacturers of identified herbal extracts were also contacted. All randomized clinical trials of herbal medicinal products administered as supplements to human subjects were included. RESULTS: Seventeen randomized clinical trials were identified, nine of which involved peppermint and caraway as constituents of combination preparations. Symptoms were reduced by all treatments (60-95% of patients reported improvements in symptoms). The mechanism of any anti-dyspeptic action is difficult to define, as the causes of non-ulcer dyspepsia are unclear. There appear to be few adverse effects associated with these remedies, although, in many cases, comprehensive safety data were not available. CONCLUSIONS: There are several herbal medicinal products with anti-dyspeptic activity and encouraging safety profiles. Further research is warranted to establish their therapeutic value in the treatment of non-ulcer dyspepsia.

Carum↗

PubMed2000

Fournier's gangrene: a review of 1726 cases.

BACKGROUND: Although there is much consensus, certain controversies exist regarding the management of Fournier's gangrene. METHOD: Publications in English on Fournier's gangrene from January 1950 to September 1999 were obtained through the Medline database and relevant reference lists in publications. It was possible to identify 1726 cases for study. Data extracted for review included country of reported cases, number of patients in each report and relevant clinical features. RESULTS: Fournier's gangrene occurs worldwide. However, its definition has generated considerable controversy as efforts are made to refine the original description in the light of increasingly understood aetiological factors. Attempts to classify the disease into primary and secondary forms have not been successful. The basic pathological process, necrotizing fasciitis, has been identified in the perineum of women and children, although the disease afflicts the male more often than the female. Most reported cases have occurred in the USA and Canada. The major sources of sepsis are the local skin, colon, anus and rectum, and the lower urinary tract. Colonic, anal and rectal sources carry the worst prognosis. Diabetes mellitus is important in aetiological terms. Rare causes include vasectomy and circumcision. Investigations are essential to define the cause of an episode but not for the diagnosis of the disease. Early aggressive treatment of Fournier's gangrene and underlying conditions is essential. Hyperbaric oxygen and honey are treatment modalities yet to be universally adopted. Risk of death, 16 per cent overall in this series, is related to the patient's condition at presentation. CONCLUSION: Controversies over the definition of Fournier's gangrene persist but these do not affect the treatment options. The diagnosis is made on clinical grounds. The occurrence of the disease in women is under-reported and may go unrecognized by some clinicians. Some treatment options, such as hyperbaric oxygenation and radical excision, remain controversial.

Age Distribution↗

PubMed2002

A review of physical restraint minimization in the acute and residential care settings.

OBJECTIVES: The objective of this review was to investigate physical restraint minimization in acute and residential care settings. The first aim was to determine the effectiveness of attempts to minimize the use of physical restraint, and the second was to generate a description of the characteristics of restraint minimization programmes. METHOD: A comprehensive search was undertaken involving all major databases and the reference lists of all relevant papers. To be included in the review studies had to be an evaluation of restraint minimization in an acute or residential care setting. As only a single randomized controlled trial (RCT) was identified, it was not possible statistically to pool the findings of different studies on the effectiveness of restraint minimization. To generate a description of the characteristics of restraint minimization programmes, the reported components of these programmes were identified and categorized. RESULTS: A total of 16 studies evaluating restraint minimization were identified: three in acute care and 13 in residential care. Of these, only one was an RCT, with the most common approach being the before and after study design. Based on the findings of the single RCT, education supported by expert consultation effectively reduced the use of restraint in residential care. There has been little evaluation of restraint minimization in acute care settings. The common approach to restraint minimization has involved a programme of multiple activities, with restraint education being the characteristic common to most programmes. DISCUSSION: Evidence suggests that physical restraint can be safely reduced in residential care settings through a combination of education and expert clinical consultation. There is little information on restraint minimization in acute care settings. The major finding of this review is the need for further investigation into all aspects of restraint minimization.

Accidental Falls↗

PubMed2003

Patient injury and physical restraint devices: a systematic review.

OBJECTIVE: To investigate physical restraint-related injuries. Areas of interest were the prevalence of injury, types of injuries, risk of sustaining an injury and specific restraint devices associated with injury. DEFINITIONS: Injury in the context of this review was considered to be either direct injury, such as lacerations and strangulation, or indirect injury considered to be an adverse outcome such as increased mortality rates or duration of hospitalization. METHOD: A comprehensive search was undertaken that involved all major databases and the reference list of all relevant papers. To be included in the review studies had to involve people in acute or residential care settings and report data related to injury caused by restraint devices. A number of different types of research designs were included in the review. The findings of studies were pooled using odds ratio and narrative discussion. RESULTS: The search identified 11 papers reporting the findings of 12 observational studies. These studies were supplemented with the findings of a number of other types of studies that reported restraint-related data. The review highlights the potential danger of using physical restraint in acute and residential health care facilities. Observational studies suggest that physical restraint may increase the risk of death, falls, serious injury and increased duration of hospitalization. However, there is little information to enable the magnitude of the problem to be determined. DISCUSSIONS: Many of the findings highlight the urgent need for further investigation into the use of physical restraint in health care facilities. Further research should investigate the magnitude of the problem and specific restraint devices associated with injury. However, given the limited nature of the evidence, this association should be investigated further using rigorous research methods.

Asphyxia↗