Molecular basis of protein S deficiency in three families also showing independent inheritance of factor V leiden

The molecular basis of type I or III Protein S deficiency has been investigated in three kindred also showing independent inheritance of factor V (FV) Leiden. A T to C transition in codon 570 (Met-->Thr) was identified in the propositi and shown to segregate with protein S deficiency in all but one of the affected members of two kindred. This individual was heterozygous for a second transition (C to T) causing substitution of serine 624 by leucine. A second member of the same family, with markedly reduced free protein S levels when compared with affected relatives, was heterozygous for both mutations. Haplotype analysis of individuals with the mutated ATG570ACG allele in the two kindred suggested they may have been related by a common ancestor. A G to A transition resulting in substitution of cysteine 145 by tyrosine was detected in the third kindred. All mutations are believed to interfere with protein S binding to C4b-binding protein resulting in reduced free protein S levels. Of the five individuals studied who had experienced thrombotic events, three had combined protein S deficiency and FV Leiden reemphasising the importance of FV Leiden as an additional risk factor for thrombosis in protein S deficiency.     

Exploring doctor and patient views about risk communication and shared decision-making in the consultation

Background There have been significant conceptual developments regarding shared decision‐making (SDM) and assessments of people's hypothetical preferences for involvement in treatment or care decisions. There are few data on the perceptions of patients and professionals about SDM in actual practice. Objective To explore, from paired doctor–patient interviews, participants’ perceptions of SDM in the consultation and the level of consensus between the participants in the consultation process. Design Qualitative analysis of semi‐structured interview data. Setting and participants Twenty general practitioners received training packages in ‘risk communication’ (RC) and ‘SDM’ to use as tools within the consultation. Forty patients with one of four conditions, for which a range of treatment options is available, were selected. Patient/doctor pairs were interviewed separately following consultations at four stages –‘baseline’ [general practitioner's (GP) usual consultation style], SDM training, RC alone, and both RC and SDM training. Interviews were transcribed and analysed using NVivo software. Results Risk communication interventions by doctors appeared to result in a greater perception of decisions being made in the consultation. High levels of satisfaction with consultations were evident before application of the interventions and did not change after the interventions. Doctors’ and patients’ perceptions of the consultations were highly congruent at all phases of the study. Conclusion Shared decision‐making and RC approaches were helpful in selected consultations and showed no detrimental effects to patients. However, the use of RC and SDM made only small differences to decision‐making in consultations within the population studied. Increasing patient participation may be seen as more ethically justifiable than the traditional paternalistic approach but this needs to be set against the additional training costs incurred.     

Clinical utility of N-terminal pro-B-type natriuretic peptide for risk stratification of patients with acute decompensated heart failure. Derivation and validation of the ADHF/NT-proBNP risk score

Background

NT-proBNP has been associated with prognosis in acute decompensated heart failure (ADHF). Whether NT-proBNP provides additional prognostic information beyond that obtained from standard clinical variables is uncertain. We sought to assess whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) determination improves risk reclassification of patients with ADHF and to develop and validate a point-based NT-proBNP risk score.

Methods

This study included 824 patients with ADHF (453 in the derivation cohort, 371 in the validation cohort). We compared two multivariable models predicting 1-year all-cause mortality, including clinical variables and clinical variables plus NT-proBNP. We calculated the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI). Then, we developed and externally validated the NT-proBNP risk score.

Results

One-year mortalities for the derivation and validation cohorts were 28.3% and 23.4%, respectively. Multivariable predictors of mortality included chronic obstructive pulmonary disease, estimated glomerular filtration rate, sodium, hemoglobin, left ventricular ejection fraction, and moderate to severe tricuspid regurgitation. Adding NT-proBNP to the clinical variables only model significantly improved the NRI (0.129; p = 0.0027) and the IDI (0.037; p = 0.0005). In the derivation cohort, the NT-proBNP risk score had a C index of 0.839 (95% CI: 0.798–0.880) and the Hosmer–Lemeshow statistic was 1.23 (p = 0.542), indicating good calibration. In the validation cohort, the risk score had a C index of 0.768 (95% CI: 0.711–0.817); the Hosmer–Lemeshow statistic was 2.76 (p = 0.251), after recalibration.

Conclusions

The NT-proBNP risk score provides clinicians with a contemporary, accurate, easy-to-use, and validated predictive tool. Further validation in other datasets is advisable.     

Cervical cancer staging

The "International Classification of the Stages of Carcinoma of the Uterine Cervix" dates back to 1950; since then, seven changes have been made to the staging system for cervical cancer (almost all were made to Stage I), the most recent being in 1995. The FIGO system of classification of cervical cancer is originally based on the results of clinical examination, essentially of the anatomical extent of disease, and is determined at the time of primary diagnosis. Only if the rules for clinical staging are strictly observed is it possible to compare results using different modalities of treatment. Cervical cancer remains a clinically staged malignancy according to the FIGO staging system. Surgical-pathologic staging would not be feasible for advanced-stage disease or in early-stage patients treated primarily with radiation, especially in nations that do not routinely offer surgical extirpation due to different or limited health care resources. However, surgical and pathological data are important for precise analysis of survival and prognostic risk factors.