Decisions at the end of life: have we come of age?

Decision making is a complex process and it is particularly challenging to make decisions with, or for, patients who are near the end of their life. Some of those challenges will not be resolved - due to our human inability to foresee the future precisely and the human proclivity to change stated preferences when faced with reality. Other challenges of the decision-making process are manageable. This commentary offers a set of approaches which may lead to progress in this field

Understanding fear of opportunism in global prize-based science contests: Evidence for gender and age differences

Global prize-based science contests have great potential for tapping into diverse knowledge on a global scale and overcoming important scientific challenges. A necessary step for knowledge to be utilized in these contests is for that knowledge to be disclosed. Knowledge disclosure, however, is paradoxical in nature: in order for the value of knowledge to be assessed, inventors must disclose their knowledge, but then the person who receives that knowledge does so at no cost and may use it opportunistically. This risk of potential opportunistic behavior in turn makes the inventor fearful of disclosing knowledge, and this is a major psychological barrier to knowledge disclosure. In this project, we investigated this fear of opportunism in global prize-based science contests by surveying 630 contest participants in the InnoCentive online platform for science contests. We found that participants in these science contests experience fear of opportunism to varying degrees, and that women and older participants have significantly less fear of disclosing their scientific knowledge. Our findings highlight the importance of taking differences in such fears into account when designing global prize-based contests so that the potential of the contests for reaching solutions to important and challenging problems can be used more effectively

Improving the coverage of the PMTCT programme through a participatory quality improvement intervention in South Africa

<p>Abstract</p> <p>Background</p> <p>Despite several years of implementation, prevention of mother-to-child transmission (PMTCT) programmes in many resource poor settings are failing to reach the majority of HIV positive women. We report on a data driven participatory quality improvement intervention implemented in a high HIV prevalence district in South Africa.</p> <p>Methods</p> <p>A participatory quality improvement intervention was implemented consisting of an initial assessment undertaken by a team of district supervisors, workshops to assess results, identify weaknesses and set improvement targets and continuous monitoring to support changes.</p> <p>Results</p> <p>The assessment highlighted weaknesses in training and supervision. Routine data revealed poor coverage of all programme indicators except HIV testing. Monthly support to all facilities took place including an orientation to the PMTCT protocol, review of local data and identification of bottlenecks to optimal coverage using a continuous quality improvement approach. One year following the intervention large improvements in programme indicators were observed. Coverage of CD4 testing increased from 40 to 97%, uptake of maternal nevirapine from 57 to 96%, uptake of infant nevirapine from 15 to 68% and six week PCR testing from 24 to 68%.</p> <p>Conclusion</p> <p>It is estimated that these improvements in coverage could avert 580 new infant infections per year in this district. This relatively simple participatory assessment and intervention process has enabled programme managers to use a data driven approach to improve the coverage of this important programme.</p

The Fitness Cost of Antibiotic Resistance in Streptococcus pneumoniae: Insight from the Field

Laboratory studies have suggested that antibiotic resistance may result in decreased fitness in the bacteria that harbor it. Observational studies have supported this, but due to ethical and practical considerations, it is rare to have experimental control over antibiotic prescription rates.We analyze data from a 54-month longitudinal trial that monitored pneumococcal drug resistance during and after biannual mass distribution of azithromycin for the elimination of the blinding eye disease, trachoma. Prescription of azithromycin and antibiotics that can create cross-resistance to it is rare in this part of the world. As a result, we were able to follow trends in resistance with minimal influence from unmeasured antibiotic use. Using these data, we fit a probabilistic disease transmission model that included two resistant strains, corresponding to the two dominant modes of resistance to macrolide antibiotics. We estimated the relative fitness of these two strains to be 0.86 (95% CI 0.80 to 0.90), and 0.88 (95% CI 0.82 to 0.93), relative to antibiotic-sensitive strains. We then used these estimates to predict that, within 5 years of the last antibiotic treatment, there would be a 95% chance of elimination of macrolide resistance by intra-species competition alone.Although it is quite possible that the fitness cost of macrolide resistance is sufficient to ensure its eventual elimination in the absence of antibiotic selection, this process takes time, and prevention is likely the best policy in the fight against resistance

The impact of disease progression on perceived health status and quality of life of long-term cancer survivors

Introduction The number of cancer survivors experiencing disease progression (DP) is increasing with the number of cancer survivors. However, little is known whether DP affects health-related quality of life (HRQL) of long-term cancer survivors. We aimed therefore to compare the health status (HS) and HRQL of DP and disease-free (DF) survivors up to 15 years after initial diagnosis. Methods 232 cancer survivors with DP identified through the Eindhoven Cancer Registry were matched with 232 DF survivors of similar demographic and clinical characteristics. Patients completed generic HS (SF-36) and cancer-specific HRQL (QOL-CS) questionnaires 5-15 years after diagnosis. Results Compared with DF survivors, DP survivors exhibited significantly lower scores on all SF-36 and QOL-CS (except spiritual well-being) dimensions. DF survivors had better scores than the normative population on all SF-36 dimensions. Among survivors with DP, those with short survival (<5 years) had significantly poorer HS scores on all dimensions except bodily pain compared with the normative population. Comparatively, the long survival (≥5 years) DP group had better HRQL than the short DP group but poorer HRQL than the normative population. In multivariate analyses, DP and DF survival time were independently associated with aspects of HS and HRQL in cancer survivors. Discussions/Conclusions DP cancer survivors have poorer long-term HS and HRQL compared with DF survivors. However, there is suggestion that HS and HRQL does improve over time following DP. Implication for Cancer Survivors Although DP survivors report poorer long-term HRQL compared with DF cancer survivors, results suggest that time can attenuate the distress of DP on HRQL. Psycho-educational programs could help to increase patients' sense of empowerment and personal control should DP occur

Impact of Selection and Demography on the Diffusion of Lactase Persistence

BACKGROUND: The lactase enzyme allows lactose digestion in fresh milk. Its activity strongly decreases after the weaning phase in most humans, but persists at a high frequency in Europe and some nomadic populations. Two hypotheses are usually proposed to explain the particular distribution of the lactase persistence phenotype. The gene-culture coevolution hypothesis supposes a nutritional advantage of lactose digestion in pastoral populations. The calcium assimilation hypothesis suggests that carriers of the lactase persistence allele(s) (LCT*P) are favoured in high-latitude regions, where sunshine is insufficient to allow accurate vitamin-D synthesis. In this work, we test the validity of these two hypotheses on a large worldwide dataset of lactase persistence frequencies by using several complementary approaches. METHODOLOGY: We first analyse the distribution of lactase persistence in various continents in relation to geographic variation, pastoralism levels, and the genetic patterns observed for other independent polymorphisms. Then we use computer simulations and a large database of archaeological dates for the introduction of domestication to explore the evolution of these frequencies in Europe according to different demographic scenarios and selection intensities. CONCLUSIONS: Our results show that gene-culture coevolution is a likely hypothesis in Africa as high LCT*P frequencies are preferentially found in pastoral populations. In Europe, we show that population history played an important role in the diffusion of lactase persistence over the continent. Moreover, selection pressure on lactase persistence has been very high in the North-western part of the continent, by contrast to the South-eastern part where genetic drift alone can explain the observed frequencies. This selection pressure increasing with latitude is highly compatible with the calcium assimilation hypothesis while the gene-culture coevolution hypothesis cannot be ruled out if a positively selected lactase gene was carried at the front of the expansion wave during the Neolithic transition in Europe

Effect of the one-child policy on influenza transmission in China: a stochastic transmission model

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Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.