Delivering reform in English healthcare: an ideational perspective

A variety of perspectives has been put forward to understand reform across healthcare systems. Recently, some have called for these perspectives to give greater recognition to the role of ideational processes. The purpose of this article is to present an ideational approach to understanding the delivery of healthcare reform. It draws on a case of English healthcare reform – the Next Stage Review led by Lord Darzi – to show how the delivery of its reform proposals was associated with four ideational frames. These frames built on the idea of “progress” in responding to existing problems; the idea of “prevailing policy” in forming part of a bricolage of ideas within institutional contexts; the idea of “prescription” as top-down structural change at odds with local contexts; and the idea of “professional disputes” in challenging the notion of clinical engagement across professional groups. The article discusses the implications of these ideas in furthering our understanding of policy change, conflict and continuity across healthcare settings

IUPHAR-DB: updated database content and new features

The International Union of Basic and Clinical Pharmacology (IUPHAR) database, IUPHAR-DB (http://www.iuphar-db.org) is an open access, online database providing detailed, expert-driven annotation of the primary literature on human and rodent receptors and other drug targets, together with the substances that act on them. The present release includes information on the products of 646 genes from four major protein classes (G protein-coupled receptors, nuclear hormone receptors, voltage- and ligand-gated ion channels) and ∼3180 bioactive molecules (endogenous ligands, licensed drugs and key pharmacological tools) that interact with them. We have described previously the classification and curation of data for small molecule ligands in the database; in this update we have annotated 366 endogenous peptide ligands with their amino acid sequences, post-translational modifications, links to precursor genes, species differences and relationships with other molecules in the database (e.g. those derived from the same precursor). We have also matched targets with their endogenous ligands (peptides and small molecules), with particular attention paid to identifying bioactive peptide ligands generated by post-translational modification of precursor proteins. Other improvements to the database include enhanced information on the clinical relevance of targets and ligands in the database, more extensive links to other databases and a pilot project for the curation of enzymes as drug targets

Comparison of long-term mortality risk following normal exercise vs adenosine myocardial perfusion SPECT

A higher frequency of clinical events has been observed in patients undergoing pharmacological vs exercise myocardial perfusion single-photon emission computed tomography (SPECT). While this difference is attributed to greater age and co-morbidities, it is not known whether these tests also differ in prognostic ability among patients with similar clinical profiles. We assessed all-cause mortality rates in 6,069 patients, followed for 10.2 ± 1.7 years after undergoing exercise or adenosine SPECT. We employed propensity analysis to match exercise and adenosine subgroups by age, gender, symptoms, and coronary risk factors. Within our propensity-matched cohorts, adenosine patients had an annualized mortality rate event rates that was more than twice that of exercise patients (3.9% vs 1.6%, P < .0001). Differences in mortality persisted among age groups, including those <55 years old. In the exercise cohort, mortality was inversely related to exercise duration, with comparable mortality noted for patients exercising <3 min and those undergoing adenosine testing. Among patients with normal stress SPECT tests, those undergoing adenosine testing manifest a mortality rate that is substantially higher than that observed among adequately exercising patients, but comparable to that observed among very poorly exercising patients. This elevated risk underscores an important challenge for managing patients undergoing pharmacological stress testing

Non-Disruptive Tactics of Suppression Are Superior in Countering Terrorism, Insurgency, and Financial Panics

BACKGROUND: Suppressing damaging aggregate behaviors such as insurgency, terrorism, and financial panics are important tasks of the state. Each outcome of these aggregate behaviors is an emergent property of a system in which each individual's action depends on a subset of others' actions, given by each individual's network of interactions. Yet there are few explicit comparisons of strategies for suppression, and none that fully incorporate the interdependence of individual behavior. METHODS AND FINDINGS: Here I show that suppression tactics that do not require the removal of individuals from networks of interactions are nearly always more effective than those that do. I find using simulation analysis of a general model of interdependent behavior that the degree to which such less disruptive suppression tactics are superior to more disruptive ones increases in the propensity of individuals to engage in the behavior in question. CONCLUSIONS: Thus, hearts-and-minds approaches are generally more effective than force in counterterrorism and counterinsurgency, and partial insurance is usually a better tactic than gag rules in quelling financial panics. Differences between suppression tactics are greater when individual incentives to support terrorist or insurgent groups, or susceptibilities to financial panic, are higher. These conclusions have utility for policy-makers seeking to end bloody conflicts and prevent financial panics. As the model also applies to mass protest, its conclusions provide insight as well into the likely effects of different suppression strategies undertaken by authoritarian regimes seeking to hold on to power in the face of mass movements seeking to end them

Factors associated with herbal use among urban multiethnic primary care patients: a cross-sectional survey

BACKGROUND: The use of herbal supplements in the United States has become increasingly popular. The prevalence of herbal use among primary care patients varies in previous studies; the pattern of herbal use among urban racially/ethnically diverse primary care patients has not been widely studied. The primary objectives of this study were to describe the use of herbs by ethnically diverse primary care patients in a large metropolitan area and to examine factors associated with such use. The secondary objective was to investigate perceptions about and patterns of herbal use. METHODS: Data for a cross-sectional survey were collected at primary care practices affiliated with the Southern Primary-care Urban Research Network (SPUR-Net) in Houston, Texas, from September 2002 to March 2003. To participate in the study, patients had to be at least 18 years of age and visiting one of the SPUR-Net clinics for routine, nonacute care. Survey questions were available in both English and Spanish. RESULTS: A total of 322 patients who had complete information on race/ethnicity were included in the analysis. Overall, 36% of the surveyed patients (n = 322) indicated use of herbs, with wide variability among ethnic groups: 50% of Hispanics, 50% of Asians, 41% of Whites, and 22% of African-Americans. Significant factors associated with an individual's herbal use were ethnicity other than African-American, having an immigrant family history, and reporting herbal use by other family members. About 40% of survey respondents believed that taking prescription medications and herbal medicines together was more effective than taking either alone. One-third of herbal users reported using herbs on a daily basis. More Whites (67%) disclosed their herbal use to their health-care providers than did African-Americans (45%), Hispanics (31%), or Asians (31%). CONCLUSIONS: Racial/ethnic differences in herbal use were apparent among this sample of urban multiethnic adult primary care patients. Associated factors of herbal use were non-African-American ethnicity, immigrant family history, and herbal use among family members. Whereas Hispanics and Asians reported the highest rates of herbal use, they were the least likely to disclose their use to health-care professionals. These findings are important for ensuring medication safety in primary care practices

Is Paromomycin an Effective and Safe Treatment against Cutaneous Leishmaniasis? A Meta-Analysis of 14 Randomized Controlled Trials

Millions of people worldwide are suffering from cutaneous leishmaniasis that is caused by parasites of the genus Leishmania. Although pentavalent antimony compounds are the treatment of choice, their use is limited by high cost, poor compliance, and systemic toxicity. Paromomycin was developed to overcome such limitations. However, there is no consensus on its efficacy. This meta-analysis assessed the efficacy and safety of paromomycin compared with placebo and pentavalent antimony compounds. Fourteen randomized controlled trials, including 1,221 patients, met our selection criteria. Topical paromomycin appeared to have therapeutic activity against the old world and new world cutaneous leishmaniasis, with increased local reactions, when combined with methylbenzethonium chloride. Topical paromomycin was not significantly different from intralesional pentavalent antimony compounds in treating the old world form, whereas it was inferior to parenteral pentavalent antimony compounds in treating the new world form. However, a similar efficacy was found between parenteral paromomycin and pentavalent antimony compounds in treating the new world form. Fewer systemic side effects were observed with topical and parenteral paromomycin than pentavalent antimony compounds. These results suggest that topical paromomycin with methylbenzethonium chloride could be a therapeutic alternative to pentavalent antimony compounds for selected cases of the old world cutaneous leishmaniasis

Photodynamic therapy for multi-resistant cutaneous Langerhans cell histiocytosis

Langerhans cell histiocytosis is a rare group of proliferative disorders. Beside cutaneous involvement, other internal organs can be affected. The treatment of cutaneous lesions is difficult and relies on topical corticosteroids, carmustine, nitrogen mustard, and photochemotherapy. Systemic steroids and vinblastine are used for recalcitrant skin lesions. However, some cases fail to respond. An 18-month old boy presented a CD1a+, S100a+ Langerhans cell histocytosis with cutaneous and severe scalp involvement. Topical corticosteroids and nitrogen mustard failed to improve the skin lesions. Systemic corticosteroids and vinblastine improved the truncal involvement but had no effect on the scalp lesions. Methylaminolevulinate (MAL) based photodynamic therapy (PDT) resulted in a significant regression of the scalp lesions. Control histology revealed an almost complete clearance of the tumor infiltrate. Clinical follow-up after six months showed no recurrence

Use of dietary supplements by female seniors in a large Northern California health plan

BACKGROUND: Women aged ≥ 65 years are high utilizers of prescription and over-the-counter medications, and many of these women are also taking dietary supplements. Dietary supplement use by older women is a concern because of possible side effects and drug-supplement interactions. The primary aim of this study was to provide a comprehensive picture of dietary supplement use among older women in a large health plan in Northern California, USA, to raise awareness among health care providers and pharmacists about the need for implementing structural and educational interventions to minimize adverse consequences of self-directed supplement use. A secondary aim was to raise awareness about how the focus on use of herbals and megavitamins that has occurred in most surveys of complementary and alternative therapy use results in a significant underestimate of the proportion of older women who are using all types of dietary supplements for the same purposes. METHODS: We used data about use of different vitamin/mineral (VM) supplements and nonvitamin, nonmineral (NVNM) supplements, including herbals, from a 1999 general health survey mailed to a random sample of adult members of a large Northern California health plan to estimate prevalence of and characteristics associated with supplement use among women aged 65–84 (n = 3,109). RESULTS: Based on weighted data, 84% had in the past 12 months used >1 dietary supplement, 82% a VM, 59% a supplement other than just multivitamin or calcium, 32% an NVNM, and 25% an herbal. Compared to white, nonHispanic women, African-Americans and Latinas were significantly less likely to use VM and NVNM supplements and Asian/Pacific Islanders were less likely to use NVNM supplements. Higher education was strongly associated with use of an NVNM supplement. Prevalence did not differ by number of prescription medications taken. Among white, nonHispanic women, multiple logistic regression models showed that college education, good health, belief that health practices have at least a moderate effect on health, and having arthritis or depression significantly increased likelihood of NVNM use, while having diabetes decreased likelihood. CONCLUSIONS: An extremely high proportion of older women are using dietary supplements other than multivitamins and calcium, many in combination with multiple prescription medications. Increased resources should be devoted to helping clinicians, pharmacists, supplement vendors, and consumers become more aware of the safety, effectiveness, and potential side effects of dietary supplements

Different rates of cognitive decline in autosomal dominant and late-onset Alzheimer disease

As prevention trials advance with autosomal dominant Alzheimer disease (ADAD) participants, understanding the similarities and differences between ADAD and "sporadic" late-onset AD (LOAD) is critical to determine generalizability of findings between these cohorts. Cognitive trajectories of ADAD mutation carriers (MCs) and autopsy-confirmed LOAD individuals were compared to address this question. Longitudinal rates of change on cognitive measures were compared in ADAD MCs (n = 310) and autopsy-confirmed LOAD participants (n = 163) before and after symptom onset (estimated/observed). LOAD participants declined more rapidly in the presymptomatic (preclinical) period and performed more poorly at symptom onset than ADAD participants on a cognitive composite. After symptom onset, however, the younger ADAD MCs declined more rapidly. The similar but not identical cognitive trajectories (declining but at different rates) for ADAD and LOAD suggest common AD pathologies but with some differences

Variant-dependent heterogeneity in amyloid β burden in autosomal dominant Alzheimer's disease: cross-sectional and longitudinal analyses of an observational study

Background: Insights gained from studying individuals with autosomal dominant Alzheimer's disease have broadly influenced mechanistic hypotheses, biomarker development, and clinical trials in both sporadic and dominantly inherited Alzheimer's disease. Although pathogenic variants causing autosomal dominant Alzheimer's disease are highly penetrant, there is substantial heterogeneity in levels of amyloid β (Aβ) between individuals. We aimed to examine whether this heterogeneity is related to disease progression and to investigate the association with mutation location within PSEN1, PSEN2, or APP. Methods: We did cross-sectional and longitudinal analyses of data from the Dominantly Inherited Alzheimer's Network (DIAN) observational study, which enrols individuals from families affected by autosomal dominant Alzheimer's disease. 340 participants in the DIAN study who were aged 18 years or older, had a history of autosomal dominant Alzheimer's disease in their family, and who were enrolled between September, 2008, and June, 2019, were included in our analysis. 206 participants were carriers of pathogenic mutations in PSEN1, PSEN2, or APP, and 134 were non-carriers. 62 unique pathogenic variants were identified in the cohort and were grouped in two ways. First, we sorted variants in PSEN1, PSEN2, or APP by the affected protein domain. Second, we divided PSEN1 variants according to position before or after codon 200. We examined variant-dependent variability in Aβ biomarkers, specifically Pittsburgh-Compound-B PET (PiB-PET) signal, levels of CSF Aβ1-42 (Aβ42), and levels of Aβ1-40 (Aβ40). Findings: Cortical and striatal PiB-PET signal showed striking variant-dependent variability using both grouping approaches (p0·7), and CSF Aβ42 levels (codon-based grouping: p=0·49; domain-based grouping: p=0·095). Longitudinal PiB-PET signal also varied across codon-based groups, mirroring cross-sectional analyses. Interpretation: Autosomal dominant Alzheimer's disease pathogenic variants showed highly differential temporal and regional patterns of PiB-PET signal, despite similar functional progression. These findings suggest that although increased PiB-PET signal is generally seen in autosomal dominant Alzheimer's disease, higher levels of PiB-PET signal at an individual level might not reflect more severe or more advanced disease. Our results have high relevance for ongoing clinical trials in autosomal dominant Alzheimer's disease, including those using Aβ PET as a surrogate marker of disease progression. Additionally, and pertinent to both sporadic and autosomal dominant Alzheimer's disease, our results suggest that CSF and PET measures of Aβ levels are not interchangeable and might reflect different Aβ-driven pathobiological processes. Funding: National Institute on Aging, Doris Duke Charitable Foundation, German Center for Neurodegenerative Diseases, Japanese Agency for Medical Research and Development