‘No‐one has listened to anything I’ve got to say before’: Co‐design with people who are sleeping rough

BackgroundDespite policies and programmes aimed at housing people who are homeless, there are still people who live and sleep rough. This project used the skills and knowledge of people in this situation to identify a strategy to mitigate some of the risks.ObjectiveTo describe the development and conduct of a co‐design project involving people who are homeless.Setting/Group MembersA Working Group of 11 was formed following a careful recruitment process from people who had volunteered after consultation by the project team. The co‐design approach was guided by a set of principles.MethodsEight members of the Working Group were interviewed by an external researcher (RM). The approach was primarily deductive, with the principles adopted by the project team used as a framework for data collection and analysis. The co‐design process was captured by the project leaders (BK, PC) supplemented with documentation review and team discussions.ResultsThe group met weekly for 12 weeks, with 8‐10 members present on average. They reviewed information from the survey, contributed ideas for solutions and ultimately decided to provide information via print, a website and an event. Important factors in on‐going involvement were carefully selecting group members and making participation rewarding for them.Discussion/ConclusionsVulnerable people such as those experiencing homelessness can be excluded from decision‐making processes affecting them, as they can be perceived as hard to reach and unable to make a meaningful contribution. This project demonstrated that a carefully managed project, with sufficient resources and commitment, it was possible to involve people who are homeless and maintain involvement over an extended time period.Public ContributionThe Working Group reviewed survey findings and developed an intervention to minimize the health, social and legal harms of sleeping rough. Several members reviewe this paper.     

Resolution of Diabetes Following Vertical Gastroplasty in Morbidly Obese Patients

Case reports are presented on three patients treated for morbid obesity by vertical gastroplasty. Prior to surgery the patients had diabetes which required insulin, up to 200 units per day, or oral hypoglycaemics for its control. Six months after surgery the diabetes had been resolved in all three patients, and they were no longer dependent on medication. Subjective reports from the patients suggests that their quality of life improved significantly.     

Biochemical Changes after Vertical Banded Gastroplasty for Morbid Obesity

A prospective study of biochemical changes after vertical banded gastroplasty for morbid obesity, in 94 patients (10 males and 84 females, ages ranging from 18 to 59 years) has been carried out. Liver function tests and electrolyte estimations were performed preoperatively, during hospitalisation for surgery, at 6 weeks and at 6 months postoperatively, and demonstrated no significant changes in liver function in these patients 6 months after surgery. The study concludes that there is no increase in the risk of liver damage or electrolyte disturbance after vertical gastroplasty, but that there may be subtle hepatic changes present as gall bladder disease developed in 18 patients postoperation (19%).     

Vinflunine (20′,20′-difluoro- 3′,4′-dihydrovinorelbine), a novel Vinca alkaloid, which participates in P-glycoprotein (Pgp)-mediated multidrug resistance in vivo and in vitro

Vinflunine (VFL) is a novel derivative of vinorelbine (NVB, Navelbine®), which has shown markedly superior antitumor activity to NVB, in various experimental animal models. To establish whether this new Vinca alkaloid participates in P-glycoprotein (Pgp)-mediated multidrug resistance (MDR), VFL-resistant murine P388 cells (P388/VFL) were established in vivo and used in conjunction with the well established MDR P388/ADR subline, to define the in vivo resistance profile for VFL. P388/VFL cells proved cross-resistant to drugs implicated in MDR (other Vinca alkaloids, doxorubicin, etoposide), but not to campothecin or cisplatin and showed an increased expression of Pgp, without any detectable alterations in topoisomerase II or in glutathione metabolism. The P388/ADR cells proved cross-resistant to VFL both in vivo and in vitro, and this VFL resistance was efficiently modulated by verapamil in vitro. Cellular transport experiments with tritiated-VFL revealed differential uptake by P388 sensitive and P388/ADR resistant cells, comparable with data obtained using tritiated-NVB. In various in vitro models of human MDR tumor cells, whilst full sensitivity was retained in cells expressing alternative non-Pgp-mediated MDR mechanisms, cross resistance was identified in Pgp-overexpressing cells. Differences were, however, noted in terms of the drug resistance profiles relative to the other Vincas, with tumor cell lines proving generally least cross-resistant to VFL. Overall, these results suggest that VFL, like other Vinca alkaloids, participates in Pgp-mediated MDR, with tumor cells selected for resistance to VFL overexpressing Pgp, yet MDR tumor cell lines proved generally less cross resistant to VFL relative to the other Vinca alkaloids.     

Preclinical in vivo antitumor activity of vinflunine, a novel fluorinated Vinca alkaloid

Vinflunine, or 20′,20′-difluoro-3′,4′-dihydrovino‐relbine, is a novel Vinca alkaloid obtained by hemisynthesis using superacidic chemistry. The most impressive structural modification of this vinorelbine derivative was the selective introduction of two fluorine atoms at the 20′ position, a part of the molecule previously inaccessible by classic chemistry. The antitumor activity of vinflunine was evaluated against a range of transplantable murine and human tumors. Vinflunine exhibited marked activity against murine P388 leukemia grafted i.v. when given i.p. in single or multiple doses according to various schedules or in single i.v. or p.o. doses. Increases in life span achieved with vinflunine, as assessed by T/C ratios, ranged from 200% to 457% and proved markedly superior to those of 129–186% obtained with the other Vinca alkaloids tested. Against s.c.-implanted B16 melanoma, multiple i.p. administration of vinflunine proved active in terms of both survival prolongation and tumor growth inhibition, with optimal T/C values and relative areas under the tumor growth curves (rAUC) being 24% and 36%, respectively. The extent of this activity was superior to that noted for vinorelbine under the same experimental conditions. Growth inhibition of human tumor xenografts LX-1 (lung) and MX-1 (breast) was also observed following four weekly i.p. injections of vinflunine as reflected by optimal T/C values of 23% and 26%, respectively, and significant differences in the rAUCs noted for treated versus control animals. It was also noticeable that vinflunine induced considerably more prolonged inhibitory effects on tumor growth than did vinorelbine. These results demonstrate that vinflunine is well tolerated and is definitively active against a range of experimental animal tumor models. Vinflunine activity has been documented in terms of both survival prolongation and tumor growth inhibition, with definite superiority over vinorelbine being shown in each tumor model evaluated. Received: 13 July 1997 / Accepted: 21 October 1997     

The association between women’s health information use and health care visits

OBJECTIVE: To determine the effect of the type of information sources used on health services use. METHODS: Population-based random-digit dialing survey of 498 women, between December 1999 and January 2000, on use of health information sources and health visits. RESULTS: After adjustment for sociodemographic and medical factors, use of print health media and computer-based resources was associated with 1.9 and 1.6 more visits, respectively compared to non-use (Regression coefficients 1.9; [95% confidence interval {CI} 0.1, 3.7] and 1.6; [95% CI 0.3, 3.0]). CONCLUSIONS: Print health media and computer-based sources are associated with a higher number of health care visits.     

Development of a diabetes care management curriculum in a family practice residency program.

Improving the quality of care for patients with chronic illness has become a high priority. Implementing training programs in disease management (DM) so the next generation of physicians can manage chronic illness more effectively is challenging. Residency training programs have no specific mandate to implement DM training. Additional barriers at the training facility include: 1) lack of a population-based perspective for service delivery; 2) weak support for self-management of illness; 3) incomplete implementation due to physician resistance or inertia; and 4) few incentives to change practices and behaviors. In order to overcome these barriers, training programs must take the initiative to implement DM training that addresses each of these issues. We report the implementation of a chronic illness management curriculum based on the Improving Chronic Illness Care (ICIC) Model. Features of this process included both patient care and learner objectives. These were: development of a multidisciplinary diabetes DM team; development of a patient registry; development of diabetes teaching clinics in the family practice center (nutrition, general management classes, and one-on-one teaching); development of a group visit model; and training the residents in the elements of the ICIC Model, ie, the community, the health system, self-management support, delivery system design, decision support, and clinical information systems. Barriers to implementing these curricular changes were: the development of a patient registry; buy-in from faculty, residents, clinic leadership, staff, and patients for the chronic care model; the ability to bill for services and maintain clinical productivity; and support from the health system key stakeholders for sustainability. Unique features of each training site will dictate differences in emphasis and structure; however, the core principles of the ICIC Model in enhancing self-management may be generalized to all sites.     

Phase I trial of 17-allylamino-17-demethoxygeldanamycin in patients with advanced cancer.

PURPOSE: We determined the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLT) of 17-allylamino-17-demethoxygeldanamycin (17-AAG) when infused on days 1, 8, and 15 of a 28-day cycle in advanced solid tumor patients. We also characterized the pharmacokinetics of 17-AAG, its effect on chaperone and client proteins, and whether cytochrome P450 (CYP) 3A5 and NAD(P)H:quinone oxidoreductase 1 (NQO1) polymorphisms affected 17-AAG disposition or toxicity. PATIENTS AND METHODS: An accelerated titration design was used. Biomarkers were measured in peripheral-blood mononuclear cells (PBMCs) at baseline and on days 1 and 15, and pharmacokinetic analysis was performed on day 1 of cycle 1. CYP3A5*3 and NQO1*2 genotypes were determined and correlated with pharmacokinetics and toxicity. RESULTS: Twenty-one patients received 52 courses at 11 dose levels. DLTs at 431 mg/m(2) were grade 3 bilirubin (n = 1), AST (n = 1), anemia (n = 1), nausea (n = 1), vomiting (n = 1), and myalgias (n = 1). No tumor responses were seen. 17-AAG consistently increased heat shock protein (Hsp) 70 levels in PBMCs. At the MTD, the clearance and half-life (t(1/2)) of 17-AAG were 11.6 L/h/m(2) and 4.15 hours, respectively; whereas the active metabolite 17-aminogeldanamycin had a t(1/2) of 7.63 hours. The CYP3A5*3 and NQO1*2 polymorphisms were not associated with 17-AAG toxicity. The CYP3A5*3 polymorphism was associated with higher 17-AAG clearance. CONCLUSION: The MTD of weekly 17-AAG is 308 mg/m(2). 17-AAG induced Hsp70 in PBMCs, indicating that Hsp90 has been affected. Further evaluation of 17-AAG is ongoing using a twice-weekly regimen, and this schedule of 17-AAG is being tested in combination with chemotherapy.     

Comparative preclinical and clinical pharmacokinetics of a cremophor-free, nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel formulated in Cremophor (Taxol).

PURPOSE: To compare the preclinical and clinical pharmacokinetic properties of paclitaxel formulated as a Cremophor-free, albumin-bound nanoparticle (ABI-007) and formulated in Cremophor-ethanol (Taxol). EXPERIMENTAL DESIGN: ABI-007 and Taxol were given i.v. to Harlan Sprague-Dawley male rats to determine pharmacokinetic and drug disposition. Paclitaxel pharmacokinetic properties also were assessed in 27 patients with advanced solid tumors who were randomly assigned to treatment with ABI-007 (260 mg/m(2), 30 minutes; n = 14) or Taxol (175 mg/m(2), 3 hours; n = 13), with cycles repeated every 3 weeks. RESULTS: The volume of distribution at steady state and clearance for paclitaxel formulated as Cremophor-free nanoparticle ABI-007 were significantly greater than those for paclitaxel formulated with Cremophor (Taxol) in rats. Fecal excretion was the main elimination pathway with both formulations. Consistent with the preclinical data, paclitaxel clearance and volume of distribution were significantly higher for ABI-007 than for Taxol in humans [21.13 versus 14.76 L/h/m(2) (P = 0.048) and 663.8 versus 433.4 L/m(2) (P = 0.040), respectively]. CONCLUSIONS: Paclitaxel formulated as ABI-007 differs from paclitaxel formulated as Taxol, with a higher plasma clearance and a larger volume of distribution. This finding is consistent with the absence of paclitaxel-sequestering Cremophor micelles after administration of ABI-007. This unique property of ABI-007 could be important for its therapeutic effectiveness.