Assessing the potential for improvement of primary care in 34?countries: a cross-sectional survey

Objective

To investigate patients’ perceptions of improvement potential in primary care in 34 countries.

Methods

We did a cross-sectional survey of 69 201 patients who had just visited general practitioners at primary-care facilities. Patients rated five features of person-focused primary care – accessibility/availability, continuity, comprehensiveness, patient involvement and doctor–patient communication. One tenth of the patients ranked the importance of each feature on a scale of one to four, and nine tenths of patients scored their experiences of care received. We calculated the potential for improvement by multiplying the proportion of negative patient experiences with the mean importance score in each country. Scores were divided into low, medium and high improvement potential. Pair-wise correlations were made between improvement scores and three dimensions of the structure of primary care – governance, economic conditions and workforce development.

Findings

In 26 countries, one or more features of primary care had medium or high improvement potentials. Comprehensiveness of care had medium to high improvement potential in 23 of 34 countries. In all countries, doctor–patient communication had low improvement potential. An overall stronger structure of primary care was correlated with a lower potential for improvement of continuity and comprehensiveness of care. In countries with stronger primary care governance patients perceived less potential to improve the continuity of care. Countries with better economic conditions for primary care had less potential for improvement of all features of person-focused care.

Conclusion

In countries with a stronger primary care structure, patients perceived that primary care had less potential for improvement.     

UT2 Practical Applications of the Health Utilities Index

The Health Utilities Index is designed to describe and to quantify the health status and the health-related quality-of-life (HRQOL) of subjects. This validated and reliable instrument has been employed by over 100 research groups worldwide and exists in three formats (face-to-face interview, telephone interview and self-administration). Translations into several languages are also available. As a generic preference-weighted system, the Health Utilities Index not only measures and describes health status, but also provides a quantitative measure of HRQOL as a single summary score based on community preferences for health status. The score, founded on utility theory and anchored to the conventional 0–1 (dead–healthy) scale, is appropriate as a quality-weight in the calculation of quality-adjusted life-years (QALY's). Given that QALYs have been recognized as a universal measure for use in cost-effectiveness/cost-utility analyses and are recommended in the reporting and monitoring of population health, this instrument has wide ranging applications in outcomes and health economic research. This workshop will provide an introduction to the Health Utilities Index and focus on its practical application. We will describe our experiences as they relate to issues such as frequency and mode of administration, patient recall, compliance, sample size considerations, data analysis and interpretation. Citing previous studies, this workshop will demonstrate how the Health Utilities Index can be utilized in prospective clinical research, patient surveys and as a means for developing utility estimates in retrospective health economic models. Researchers and analysts involved in quality-of-life and health economic evaluations will gain a working knowledge of the Health Utilities Index and an appreciation of its diversified use as a generic HRQOL instruments.     

Dose-dependent localization of TCDD in isolated centrilobular and periportal hepatocytes

Dose-response relationships for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suggest a differential sensitivity of liver cell types to the induction of cytochrome P450 gene expression, and that the induction of hepatic protein CYP1A2 causes sequestration of TCDD. In addition, immunolocalization of hepatic CYP1A1/1B1/1A2 proteins is not uniform after exposure to TCDD. The mechanism for the regio-specific induction of hepatic P450s by TCDD is unknown, but may involve the differential distribution of participants in the AhR-mediated pathway and/or regional P450 isozymes, as well as, non-uniform distribution/sequestration of TCDD. Therefore, this study examined the effects of TCDD in unfractionated, centrilobular and periportal hepatocytes isolated from female Sprague-Dawley rats acutely exposed (3 days) to a single oral dose of 0.01-10.0 microg [3H]TCDD/kg. A dose- dependent increase in concentration of TCDD was accompanied by a dose- dependent increase in CYP1A1, CYP1A2, and CYP1B1 mRNA expression and associated enzymes in all liver-cell populations. Centrilobular hepatocytes showed a 2.7- to 4.5-fold higher concentration of TCDD as compared to the periportal hepatocytes at doses up to 0.3 microg TCDD/kg. Centrilobular hepatocytes also exhibited an elevated MROD activity as compared to the periportal hepatocytes at doses up to 0.3 microg TCDD/kg. Furthermore, centrilobular hepatocytes showed an elevated concentration of induced CYP1A2 and CYP1B1 mRNA as compared to periportal hepatocytes within the 0.01- and 0.3-microg TCDD/kg- treatment groups. This is the first study to demonstrate that a dose- dependent difference in distribution of TCDD exists between centrilobular and periportal cells that might be related to regional differences in P450 induction.      

Contribution of genetic and nutritional factors to DNA damage in heavy smokers

Prior epidemiological evidence suggests that genes controlling the metabolism of carcinogens and antioxidant/nutritional status are associated with lung cancer risk, possibly through their ability to modulate DNA damage by carcinogens. We performed a cross-sectional analysis of 159 heavy smokers from a cohort of subjects enrolled in a smoking cessation program. A total of 159 blood samples were analyzed to determine the relative contributions of genetic polymorphisms [CYP1A1 MspI and exon 7 and glutathione S-transferase M1 (GSTM1)] and plasma micronutrients to polycyclic aromatic hydrocarbon-DNA (PAH-DNA) adduct levels. DNA damage in smokers was affected by genetic polymorphisms and nutritional status. Smokers with the CYP1A1 exon 7 valine polymorphism had significantly higher (2-fold, P < or = 0.03) levels of DNA damage than those without. In parallel models, PAH-DNA adducts were inversely associated with plasma levels of retinol (beta = -0.93, P = 0.01), beta-carotene (beta = -0.18, P = 0.09), and alpha- tocopherol (beta = -0.28, P = 0.21) in 159 subjects. The association between smoking-adjusted plasma beta-carotene levels and DNA damage was only significant in those subjects lacking the GSTM1 detoxification gene (beta = -0.30, P = 0.05, n = 75). There was a statistical interaction between beta-carotene and alpha-tocopherol; when beta- carotene was low, alpha-tocopherol had a significant protective effect (beta = -0.78, P = 0.04) on adducts, but not when beta-carotene was high (beta = -0.16, P = 0.57). Plasma alpha-tocopherol was significantly correlated with beta-carotene (r = 0.36, P = 0.0005) and less strongly with retinol (r = 0.20, P = 0.0005). These results suggest that several micronutrients may act in concert to protect against DNA damage and highlight the importance of assessing overall antioxidant status. In conclusion, a subset of smokers may be at increased risk of DNA damage and possibly lung cancer due to the combined effect of low plasma micronutrients and genetic susceptibility factors. The use of biological markers to assess efficacy of interventions and to study mechanisms of micronutrients is timely given the current debate regarding the use of chemopreventive agents in high risk populations.      

药物在室内自然光照射下的贮存期预测方法研究

以己酸孕酮注射液为例,研究了药物在自然光和不同灯光照射下的含量变化规律,预测了药物在室内自然光照射下的贮存期。找出了不同光源对药物稳定性影响的等效数量关系,使在今后的研究中可以用灯光为光源预测药物在室内自然光照射下的贮存期。己酸孕酮注射液在光照试验中含量变化服从零级反应规律:C=C₀-K(Et),在室内自然光照射下的贮存期约为1.9年。     

γ－去氢骆驼蓬碱等咔啉类生物碱的辐射防护作用

γ－去氢骆驼蓬碱等咔啉类生物碱的辐射防护作用利国威，桑培根，潘国英（中山医科大学肿瘤防治中心广州５１００６０）从新疆产蒺藜科植物骆驼蓬（ＰｅｈａｎｕｍｈａｒｍａｌａＬ．）的种子中分离得到３个化合物，其中γ－去氢骆驼蓬碱（γ－ｈａｒｍｉｎｅ，Ⅰ）为新化...     

Roman ophthalmology. A glimpse of our distant past

Ophthalmic artifacts from a house destroyed in 275 A.D. and recently excavated in Schwarzenacker, W. Germany, are described and illustrated. The reconstructed house of ophthalmologist, Sextus Ajacius Launus, and its contents provides a fascinating glimpse of ophthalmology as practiced nearly 17 centuries ago in the Roman Empire.     

Congenital pupillary-iris-lens membrane with goniodysgenesis (a new entity)

We encountered two clinically similar but genetically unrelated cases of a disorder characterized by an unusual white pupillary-iris-lens membrane with extension to a prominent Schwalbe's line, the membranes were vascularized and their appearance changed over time. In both cases the abnormality was unilateral. Anomalous chamber angles were seen on gonioscopy. The clinical appearance is similar to a combination of iridogoniodysgenesis and pupillary membrane. However, our two cases are unique and fit into neither category. We postulate that this is a new entity consisting of an anomalous chamber angle and iris-lens membrane resulting from a localized iris (pupillary membrane), infarct with secondary neovascularization, during formation of the chamber angle.     

Combining Viral Vectored and Protein-in-adjuvant Vaccines Against the Blood-stage Malaria Antigen AMA1: Report on a Phase 1a Clinical Trial

The development of effective vaccines against difficult disease targets will require the identification of new subunit vaccination strategies that can induce and maintain effective immune responses in humans. Here we report on a phase 1a clinical trial using the AMA1 antigen from the blood-stage Plasmodium falciparum malaria parasite delivered either as recombinant protein formulated with Alhydrogel adjuvant with and without CPG 7909, or using recombinant vectored vaccines—chimpanzee adenovirus ChAd63 and the orthopoxvirus MVA. A variety of promising “mixed-modality” regimens were tested. All volunteers were primed with ChAd63, and then subsequently boosted with MVA and/or protein-in-adjuvant using either an 8- or 16-week prime-boost interval. We report on the safety of these regimens, as well as the T cell, B cell, and serum antibody responses. Notably, IgG antibody responses primed by ChAd63 were comparably boosted by AMA1 protein vaccine, irrespective of whether CPG 7909 was included in the Alhydrogel adjuvant. The ability to improve the potency of a relatively weak aluminium-based adjuvant in humans, by previously priming with an adenoviral vaccine vector encoding the same antigen, thus offers a novel vaccination strategy for difficult or neglected disease targets when access to more potent adjuvants is not possible.     

CFU-GM content of bone marrow graft correlates with time to hematologic reconstitution following autologous bone marrow transplantation with 4- hydroperoxycyclophosphamide-purged bone marrow

Autologous bone marrow transplants (BMTs) can repopulate the hematologic system of patients treated with marrow-ablative chemotherapy and/or radiotherapy. However, treatment of the bone marrow graft to eliminate residual tumor cells prior to reinfusion can delay the return of peripheral blood elements, presumably from damage to or loss of hematopoietic stem cells responsible for hematologic recovery. To develop a model predictive of hematologic recovery, we studied the progenitor cell contents of 4-hydroperoxycyclophosphamide (100 micrograms/mL)-purged bone marrow grafts of 40 consecutive patients undergoing autologous BMT at this center. Granulocyte-macrophage colonies (CFU-GM) were grown from all grafts after treatment with this chemotherapeutic agent, but erythroid (BFU-E) and mixed (CFU-GEMM) colonies were grown from only 44% and 33% of the grafts respectively. The recovery of CFU-GM after purging ranged from 0.07% to 23%. The logarithm of CFU-GM content of the treated grafts was linearly correlated with the time to recovery of peripheral blood leukocytes (r = -0.80), neutrophils (r = -0.79), reticulocytes (r = -0.60), and platelets (r = -0.66). The CFU-GM content of purged autologous bone marrow grafts may reflect the hematopoietic stem cell content of the grafts and thus predict the rate of hematologic recovery in patients undergoing autologous BMT.