Departures from cost-effectiveness recommendations: The impact of health system constraints on priority setting

The methods and application of cost-effectiveness analysis have reached an advanced stage of development. Many decision makers consider cost-effectiveness analysis to be a valid and feasible approach towards setting health priorities, and it has been extensively applied in evaluating interventions and developing evidence based clinical guidelines. However, the recommendations arising from cost-effectiveness analysis are often not implemented as intended. A fundamental reason for the failure to implement is that CEA assumes a single constraint, in the form of the budget constraint, whilst in reality decision-makers may be faced with numerous other constraints. The objective of this paper is to develop a typology of constraints that may act as barriers to implementation of cost-effectiveness recommendations. Six categories of constraints are considered: the design of the health system; costs of implementing change; system interactions between interventions; uncertainty in estimates of costs and benefits; weak governance; and political constraints. Where possible -and if applicable- for each class of constraint, the paper discusses ways in which these constraints can be taken into account by a decision maker wishing to pursue the principles of cost-effectiveness

The economics of infectious diseases

Economics can make immensely valuable contributions to our understanding of infectious disease transmission and the design of effective policy responses. The one unique characteristic of infectious diseases makes it also particularly complicated to analyze: the fact that it is transmitted from person to person. It explains why individuals’ behavior and externalities are a central topic for the economics of infectious diseases. Many public health interventions are built on the assumption that individuals are altruistic and consider the benefits and costs of their actions to others. This would imply that even infected individuals demand prevention, which stands in conflict with the economic theory of rational behavior. Empirical evidence is conflicting for infected individuals. For healthy individuals, evidence suggests that the demand for prevention is affected by real or perceived risk of infection. However, studies are plagued by underreporting of preventive behavior and non-random selection into testing. Some empirical studies have shown that the impact of prevention interventions could be far greater than one case prevented, resulting in significant externalities. Therefore, economic evaluations need to build on dynamic transmission models in order to correctly estimate these externalities. Future research needs are significant. Economic research needs to improve our understanding of the role of human behavior in disease transmission; support the better integration of economic and epidemiological modeling, evaluation of large-scale public health interventions with quasi-experimental methods, design of optimal subsidies for tackling the global threat of antimicrobial resistance, refocusing the research agenda toward underresearched diseases; and most importantly to assure that progress translates into saved lives on the ground by advising on effective health system strengthening

National trends in emergency readmission rates: A longitudinal analysis of administrative data for England between 2006 and 2016

Objective To assess trends in 30-day emergency readmission rates across England over one decade. Design Retrospective study design. Setting 150 non-specialist hospital trusts in England. Participants 23 069 134 patients above 18 years of age who were readmitted following an initial admission (n=62 584 297) between April 2006 and February 2016. Primary and secondary outcomes We examined emergency admissions that occurred within 30 days of discharge from hospital (‘emergency readmissions’) as a measure of healthcare quality. Presented are overall readmission rates, and disaggregated by the nature of the indexed admission, including whether it was elective or emergency, and by clinical health condition recorded. All rates were risk-adjusted for patient age, gender, ethnicity, socioeconomic status, comorbidities and length of stay. Results The average risk-adjusted, 30-day readmission rate increased from 6.56% in 2006/2007 to 6.76% (P<0.01) in 2012/2013, followed by a small decrease to 6.64% (P<0.01) in 2015/2016. Emergency readmissions for patients discharged following elective procedures decreased by 0.13% (P<0.05), whereas those following emergency admission increased by 1.27% (P<0.001). Readmission rates for hip or knee replacements decreased (−1.29%; P<0.001); for acute myocardial infarction (−0.04%; P<0.49), stroke (+0.62%; P<0.05), chronic obstructive pulmonary disease (+0.41%; P<0.05) and heart failure (+0.15%; P<0.05) remained stable; and for pneumonia (+2.72%; P<0.001), diabetes (+7.09%; P<0.001), cholecystectomy (+1.86%; P<0.001) and hysterectomy (+2.54%; P<0.001) increased. Conclusions Overall, emergency readmission rates in England remained relatively stable across the observation period, with trends of slight increases contained post 2012/2013. However, there were large variations in trends across clinical areas, with some experiencing marked increases in readmission rates. This highlights the need to better understand variations in outcomes across clinical subgroups to allow for targeted interventions that will ensure highest standards of care provided for all patients

Data needs for integrated economic-epidemiological models of pandemic mitigation policies

The COVID-19 pandemic and the mitigation policies implemented in response to it have resulted in economic losses worldwide. Attempts to understand the relationship between economics and epidemiology has lead to a new generation of integrated mathematical models. The data needs for these models transcend those of the individual fields, especially where human interaction patterns are closely linked with economic activity. In this article, we reflect upon modelling efforts to date, discussing the data needs that they have identified, both for understanding the consequences of the pandemic and policy responses to it through analysis of historic data and for the further development of this new and exciting interdisciplinary field

The Association Between Women’s Perceptions of Professional Support and Problems Experienced on Breastfeeding Cessation: A Western Australian Study

A cross-sectional survey was used to determine the association among women’s breastfeeding problems, their perceptions of support from midwives and child health nurses, and breastfeeding cessation in the first 10 weeks postbirth in a sample of Western Australian women (N = 2669). Primiparous women (75.8%) experienced significantly more problems that multiparous women (52.6%). Although 78.8% of all women agreed or strongly agreed that staff were helpful with feeding, 53.4% confirmed that different midwives offered different feeding advice; however, receiving different advice from midwives around feeding was not associated with breastfeeding cessation. Differences in breastfeeding cessation were associated with parity. Primiparous women’s cessation was associated with experiencing any breastfeeding problems, unhelpful hospital midwives, and unhelpful information from child health nurses, whereas for multiparous women, this included 2 or more breastfeeding problems, not being able to choose when to feed, and unhelpful information from child health nurses

Outcomes of patients hospitalized for acute decompensated heart failure: does nesiritide make a difference?

<p>Abstract</p> <p>Background</p> <p>Nesiritide is indicated in the treatment of acute decompensated heart failure. However, a recent meta-analysis reported that nesiritide may be associated with an increased risk of death. Our goal was to evaluate the impact of nesiritide treatment on four outcomes among adults hospitalized for congestive heart failure (CHF) during a three-year period.</p> <p>Methods</p> <p>CHF patients discharged between 1/1/2002 and 12/31/2004 from the Adventist Health System, a national, not-for-profit hospital system, were identified. 25,330 records were included in this retrospective study. Nesiritide odds ratios (OR) were adjusted for various factors including nine medications and/or an APR-DRG severity score.</p> <p>Results</p> <p>Initially, treatment with nesiritide was found to be associated with a 59% higher odds of hospital mortality (Unadjusted OR = 1.59, 95% confidence interval [CI]: 1.31–1.93). Adjusting for race, low economic status, APR-DRG severity of illness score, and the receipt of nine medications yielded a nonsignificant nesiritide OR of 1.07 for hospital death (95% CI: 0.85–1.35). Nesiritide was positively associated with the odds of prolonged length of stay (all adjusted ORs = 1.66) and elevated pharmacy cost (all adjusted ORs > 5).</p> <p>Conclusion</p> <p>In this observational study, nesiritide therapy was associated with increased length of stay and pharmacy cost, but not hospital mortality. Randomized trials are urgently needed to better define the efficacy, if any, of nesiritide in the treatment of decompensated heart failure.</p

The Adaptor Molecule Nck Localizes the WAVE Complex to Promote Actin Polymerization during CEACAM3-Mediated Phagocytosis of Bacteria

Background: CEACAM3 is a granulocyte receptor mediating the opsonin-independent recognition and phagocytosis of human-restricted CEACAM-binding bacteria. CEACAM3 function depends on an intracellular immunoreceptor tyrosine-based activation motif (ITAM)-like sequence that is tyrosine phosphorylated by Src family kinases upon receptor engagement. The phosphorylated ITAM-like sequence triggers GTP-loading of Rac by directly associating with the guanine nucleotide exchange factor (GEF) Vav. Rac stimulation in turn is critical for actin cytoskeleton rearrangements that generate lamellipodial protrusions and lead to bacterial uptake. Principal Findings: In our present study we provide biochemical and microscopic evidence that the adaptor proteins Nck1 and Nck2, but not CrkL, Grb2 or SLP-76, bind to tyrosine phosphorylated CEACAM3. The association is phosphorylation-dependent and requires the Nck SH2 domain. Overexpression of the isolated Nck1 SH2 domain, RNAi-mediated knock-down of Nck1, or genetic deletion of Nck1 and Nck2 interfere with CEACAM3-mediated bacterial internalization and with the formation of lamellipodial protrusions. Nck is constitutively associated with WAVE2 and directs the actin nucleation promoting WAVE complex to tyrosine phosphorylated CEACAM3. In turn, dominant-negative WAVE2 as well as shRNA-mediated knock-down of WAVE2 or the WAVE-complex component Nap1 reduce internalization of bacteria. Conclusions: Our results provide novel mechanistic insight into CEACAM3-initiated phagocytosis. We suggest that the CEACAM3 ITAM-like sequence is optimized to co-ordinate a minimal set of cellular factors needed to efficiently trigger actin-based lamellipodial protrusions and rapid pathogen engulfment

Global gene disruption in human cells to assign genes to phenotypes

Insertional mutagenesis in a haploid background can disrupt gene function[superscript 1]. We extend our earlier work by using a retroviral gene-trap vector to generate insertions in >98% of the genes expressed in a human cancer cell line that is haploid for all but one of its chromosomes. We apply phenotypic interrogation via tag sequencing (PhITSeq) to examine millions of mutant alleles through selection and parallel sequencing. Analysis of pools of cells, rather than individual clones[superscript 1] enables rapid assessment of the spectrum of genes involved in the phenotypes under study. This facilitates comparative screens as illustrated here for the family of cytolethal distending toxins (CDTs). CDTs are virulence factors secreted by a variety of pathogenic Gram-negative bacteria responsible for tissue damage at distinct anatomical sites[superscript 2]. We identify 743 mutations distributed over 12 human genes important for intoxication by four different CDTs. Although related CDTs may share host factors, they also exploit unique host factors to yield a profile characteristic for each CDT

Novel Association Strategy with Copy Number Variation for Identifying New Risk Loci of Human Diseases

Copy number variations (CNV) are important causal genetic variations for human disease; however, the lack of a statistical model has impeded the systematic testing of CNVs associated with disease in large-scale cohort.Here, we developed a novel integrated strategy to test CNV-association in genome-wide case-control studies. We converted the single-nucleotide polymorphism (SNP) signal to copy number states using a well-trained hidden Markov model. We mapped the susceptible CNV-loci through SNP site-specific testing to cope with the physiological complexity of CNVs. We also ensured the credibility of the associated CNVs through further window-based CNV-pattern clustering. Genome-wide data with seven diseases were used to test our strategy and, in total, we identified 36 new susceptible loci that are associated with CNVs for the seven diseases: 5 with bipolar disorder, 4 with coronary artery disease, 1 with Crohn's disease, 7 with hypertension, 9 with rheumatoid arthritis, 7 with type 1 diabetes and 3 with type 2 diabetes. Fifteen of these identified loci were validated through genotype-association and physiological function from previous studies, which provide further confidence for our results. Notably, the genes associated with bipolar disorder converged in the phosphoinositide/calcium signaling, a well-known affected pathway in bipolar disorder, which further supports that CNVs have impact on bipolar disorder.Our results demonstrated the effectiveness and robustness of our CNV-association analysis and provided an alternative avenue for discovering new associated loci of human diseases

A Randomized Controlled Study of Parent-assisted Children’s Friendship Training with Children having Autism Spectrum Disorders

This study evaluated Children’s Friendship Training (CFT), a manualized parent-assisted intervention to improve social skills among second to fifth grade children with autism spectrum disorders. Comparison was made with a delayed treatment control group (DTC). Targeted skills included conversational skills, peer entry skills, developing friendship networks, good sportsmanship, good host behavior during play dates, and handling teasing. At post-testing, the CFT group was superior to the DTC group on parent measures of social skill and play date behavior, and child measures of popularity and loneliness, At 3-month follow-up, parent measures showed significant improvement from baseline. Post-hoc analysis indicated more than 87% of children receiving CFT showed reliable change on at least one measure at post-test and 66.7% after 3 months follow-up