Further characterization of morphologically defined typical and atypical CLL: a clinical, immunophenotypic, cytogenetic and prognostic study on 390 cases

We analysed a group of 390 patients, diagnosed with chronic lymphocytic leukaemia (CLL). Cases were subclassified as morphologically typical and atypical CLL according to the criteria of the FAB proposal. Typical CLL cases were mostly diagnosed at a low-risk stage (Binet A/Rai 0), required no immediate treatment and expected a long survival; atypical CLL cases mostly presented at a more advanced risk stage (Binet B/Rai I–II), usually required immediate treatment and their survival was shorter. Moreover, clinical staging was of prognostic significance in typical but not in atypical cases.   In typical CLL, del(11q) was the most common chromosomal abnormality (21%) whereas in atypical CLL trisomy 12 was found in about 65% of the cases documented with an abnormal karyotype. Although chromosomal abnormalities were associated with a poor survival in typical CLL, they are of no prognostic significance in atypical CLL.   Based on these data, we conclude that subtyping CLL by morphology enables the identification of two groups of cases, each characterized by a specific clinical presentation, different cytogenetic abnormalities and prognostic parameters. We speculate that these two groups may represent two related, but different, diseases with different prognostic parameters and a different survival.     

CD34-related coexpression of <Emphasis Type="Italic">MDR1 and BCRP</Emphasis> indicates a clinically resistant phenotype in patients with acute myeloid leukemia (AML) of older age

Clinical resistance to chemotherapy in acute myeloid leukemia (AML) is associated with the expression of the multidrug resistance (MDR) proteins P-glycoprotein, encoded by the MDR1/ABCB1 gene, multidrug resistant-related protein (MRP/ABCC1), the lung resistance-related protein (LRP), or major vault protein (MVP), and the breast cancer resistance protein (BCRP/ABCG2). The clinical value of MDR1, MRP1, LRP/MVP, and BCRP messenger RNA (mRNA) expression was prospectively studied in 154 newly diagnosed AML patients ≥60 years who were treated in a multicenter, randomized phase 3 trial. Expression of MDR1 and BCRP showed a negative whereas MRP1 and LRP showed a positive correlation with high white blood cell count (respectively, p < 0.05, p < 0.001, p < 0.001 and p < 0.001). Higher BCRP mRNA was associated with secondary AML (p < 0.05). MDR1 and BCRP mRNA were highly significantly associated (p < 0.001), as were MRP1 and LRP mRNA (p < 0.001) expression. Univariate regression analyses revealed that CD34 expression, increasing MDR1 mRNA as well as MDR1/BCRP coexpression, were associated with a lower complete response (CR) rate and with worse event-free survival and overall survival. When adjusted for other prognostic actors, only CD34-related MDR1/BCRP coexpression remained significantly associated with a lower CR rate (p = 0.03), thereby identifying a clinically resistant subgroup of elderly AML patients.     

Failure to control an outbreak of qnrA1-positive multidrug-resistant Enterobacter cloacae infection despite adequate implementation of recommended infection control measures

A large outbreak with an aminoglycoside-resistant Enterobacter cloacae (AREC) clone occurred at the University Medical Center Utrecht beginning in 2001 and continued up through the time that this study was completed. This clone (genotype I) contains a conjugative R plasmid carrying the qnrA1, bla(CTX-M-9), and aadB genes, encoding resistance to quinolones, extended-spectrum beta-lactamases, and aminoglycosides, respectively. The aim of this study was to determine whether this clone was more transmissible than other AREC strains. Therefore, the dissemination of this genotype and of other E. cloacae strains was studied. In addition, infection control measures taken were evaluated. Pulsed-field gel electrophoresis analysis divided the 191 AREC strains into 42 different genotypes, of which 5 (12%) involved at least three patients. Aside from this outbreak (133 patients), only two other small outbreaks occurred, showing that the infection control measures were successful for all strains but one. Among 324 aminoglycoside-susceptible E. cloacae strains, 34/166 (20%) genotypes were identified from at least three patients, but only 4 involved small outbreaks. The outbreak strain was also detected in 11 of 15 other Dutch hospitals and caused outbreaks in at least 4. Evaluation of infection control measures showed that the outbreak strain disseminated throughout the hospital despite adequate implementation of internationally accepted guidelines on the control of multidrug-resistant Enterobacteriaceae (MRE). In conclusion, some MRE strains are better able to spread than others, and these strains may not be controlled by the current infection control guidelines. Strategies to identify such strains in an early phase and adapted guidelines for such "superbugs" are needed to prevent these clones from becoming endemic.     

Priorities for antibiotic resistance surveillance in Europe

Antibiotic resistance is an increasing global problem. Surveillance studies are needed to monitor resistance development, to guide local empirical therapy, and to implement timely and adequate countermeasures. To achieve this, surveillance studies must have standardised methodologies, be longitudinal, and cover a sufficiently large and representative population. However, many fall short of these requirements that define good surveillance studies. Moreover, current efforts are dispersed among many, mostly small, initiatives with different objectives. These studies must be tailored to the various reservoirs of antibiotic-resistant bacteria, such as hospitalised patients, nursing homes, the community, animals and food. Two studies that could serve as examples of tailored programmes are the European Antimicrobial Resistance Surveillance System (EARSS), which collects resistance data during the diagnosis of hospitalised patients, and the DANMAP programme, which collects data in the veterinary sector. As already noted by the WHO, genetic studies that include both the typing of isolates and the characterisation of resistance determinants are necessary to understand fully the spread and development of antibiotic resistance.     

Social Media and Rating Sites as Tools to Understanding Quality of Care: A Scoping Review

Background

Insight into the quality of health care is important for any stakeholder including patients, professionals, and governments. In light of a patient-centered approach, it is essential to assess the quality of health care from a patient’s perspective, which is commonly done with surveys or focus groups. Unfortunately, these “traditional” methods have significant limitations that include social desirability bias, a time lag between experience and measurement, and difficulty reaching large groups of people. Information on social media could be of value to overcoming these limitations, since these new media are easy to use and are used by the majority of the population. Furthermore, an increasing number of people share health care experiences online or rate the quality of their health care provider on physician rating sites. The question is whether this information is relevant to determining or predicting the quality of health care.

Objective

The goal of our research was to systematically analyze the relation between information shared on social media and quality of care.

Methods

We performed a scoping review with the following goals: (1) to map the literature on the association between social media and quality of care, (2) to identify different mechanisms of this relationship, and (3) to determine a more detailed agenda for this relatively new research area. A recognized scoping review methodology was used. We developed a search strategy based on four themes: social media, patient experience, quality, and health care. Four online scientific databases were searched, articles were screened, and data extracted. Results related to the research question were described and categorized according to type of social media. Furthermore, national and international stakeholders were consulted throughout the study, to discuss and interpret results.

Results

Twenty-nine articles were included, of which 21 were concerned with health care rating sites. Several studies indicate a relationship between information on social media and quality of health care. However, some drawbacks exist, especially regarding the use of rating sites. For example, since rating is anonymous, rating values are not risk adjusted and therefore vulnerable to fraud. Also, ratings are often based on only a few reviews and are predominantly positive. Furthermore, people providing feedback on health care via social media are presumably not always representative for the patient population.

Conclusions

Social media and particularly rating sites are an interesting new source of information about quality of care from the patient’s perspective. This new source should be used to complement traditional methods, since measuring quality of care via social media has other, but not less serious, limitations. Future research should explore whether social media are suitable in practice for patients, health insurers, and governments to help them judge the quality performance of professionals and organizations.     

Morbidity and prognosis after therapeutic lymph node dissections for malignant melanoma.

Melanoma patients with clinically evident regional lymph node metastases are treated with therapeutic lymph node dissections (TLNDs). The aim of this study was to evaluate morbidity and mortality following TLND in our institution. Moreover, disease-free (DFS) and overall (OS) survival were evaluated and factors that influence prognosis after TLND were assessed. Between 1982 and 2005, 236 patients underwent a TLND. Patients, who received a palliative LND or a sentinel node procedure, were not included. The median Breslow thickness was 2.4mm. Ulceration was present in 23% of patients and unknown in 66%. 37 patients had unknown primary tumors. There were 129 ilio-inguinal, 50 axillary and 61 cervical dissections performed. 37% of the patients experienced at least one operation related complication. The most frequently seen complications were wound infections/necrosis and chronic lymph edema. Ilio-inguinal dissection patients experienced significantly more complications and a longer duration of hospitalization compared to axillary or cervical patients. The duration of hospitalization has been reduced in recent years from 12 to 5days. The mean follow-up was 29months. Kaplan-Meier estimated 5-year regional control was 79%, 5-year DFS was 19% and 5-year OS was 26%. The number of positive lymph nodes, the site of the primary tumor and extra capsular extension (ECE) were independent prognostic factors for DFS and only site and ECE for OS. In conclusion, TLND for stage III melanoma is accompanied with considerable short-term complications, and can achieve regional control and potential curation in approximately one in every four patients.     

Intestinal absorption of human insulin in pigs using delivery systems based on superporous hydrogel polymers

The interaction of 8-methoxypsoralen (8-MOP) with calf thymus DNA was studied in darkness at 25 degrees C and pH 7.4. The enthalpy curve for 8-MOP-DNA interaction was obtained by isothermal titration calorimetry and showed a two-step process for the interaction. According to the spectrophotometric data, it was suggested that some compaction may occur in the DNA structure at higher [8-MOP](t)/[DNA] ratio. Using the fluorescence quenching data, the Scatchard analysis was performed for 8-MOP-DNA interaction at the extended ranges of drug concentration. The results indicated that the first set of binding sites was occupied by 1 mol of drug bound per near eight base pairs of DNA. Also 8-MOP caused the quenching of the fluorescence emission of DNA-ethidium bromide complex. The Scatchard analysis of these data indicated the non-competitive manner for quenching. A non-displacement based quenching mechanism has been suggested for this behavior. The circular dichroism spectra also confirmed the non-intercalative binding of 8-MOP at higher concentrations accompanied by some conformational changes in DNA structure. It has been suggested that at low drug load, 8-MOP binds to DNA as an intercalator, which is an endothermic process, whereas at higher ratios of [8-MOP](t)/[DNA], it binds to the outside of DNA, probably in the minor groove and causes some compaction in DNA, which is the exothermic process.     

MTHFR 677C-->T polymorphism and risk of coronary heart disease: a meta-analysis

Context  In observational studies, individuals with elevated levels of plasma homocysteine tend to have moderately increased risk of coronary heart disease (CHD). The MTHFR 677CT polymorphism is a genetic alteration in an enzyme involved in folate metabolism that causes elevated homocysteine concentrations, but its relevance to risk of CHD is uncertain. Objective  To assess the relation of MTHFR 677CT polymorphism and risk of CHD by conducting a meta-analysis of individual participant data from all case-control observational studies with data on this polymorphism and risk of CHD. Data Sources  Studies were identified by searches of the electronic literature (MEDLINE and Current Contents) for relevant reports published before June 2001 (using the search terms MTHFR and coronary heart disease), hand searches of reference lists of original studies and review articles (including meta-analyses) on this topic, and contact with investigators in the field. Study Selection  Studies were included if they had data on the MTHFR 677CT genotype and a case-control design (retrospective or nested case-control) and involved CHD as an end point. Data were obtained from 40 (34 published and 6 unpublished) observational studies involving a total of 11 162 cases and 12 758 controls. Data Extraction  Data were collected on MTHFR 677CT genotype, case-control status, and plasma levels of homocysteine, folate, and other cardiovascular risk factors. Data were checked for consistency with the published article or with information provided by the investigators and converted into a standard format for incorporation into a central database. Combined odds ratios (ORs) for the association between the MTHFR 677CT polymorphism and CHD were assessed by logistic regression. Data Synthesis  Individuals with the MTHFR 677 TT genotype had a 16% (OR, 1.16; 95% confidence interval [CI], 1.05-1.28) higher odds of CHD compared with individuals with the CC genotype. There was significant heterogeneity between the results obtained in European populations (OR, 1.14; 95% CI, 1.01-1.28) compared with North American populations (OR, 0.87; 95% CI, 0.73-1.05), which might largely be explained by interaction between the MTHFR 677CT polymorphism and folate status. Conclusions  Individuals with the MTHFR 677 TT genotype had a significantly higher risk of CHD, particularly in the setting of low folate status. These results support the hypothesis that impaired folate metabolism, resulting in high homocysteine levels, is causally related to increased risk of CHD.