Do changes in primary care service use over time differ by neighbourhood income? Population-based longitudinal study in British Columbia, Canada.

BACKGROUND: Strong primary care systems have been associated with improved health equity. Primary care system reforms in Canada may have had equity implications, but these have not been evaluated. We sought to determine if changes in primary care service use between 1999/2000 and 2017/2018 differ by neighbourhood income in British Columbia. METHODS: We used linked administrative databases to track annual primary care visits, continuity of care, emergency department (ED) visits, specialist referrals, and prescriptions dispensed over time. We use generalized estimating equations to examine differences in the magnitude of change by neighbourhood income quintile, adjusting for age, sex/gender, and comorbidity, and stratified by urban/rural location of residence. We also compared the characteristics of physicians providing care to people living in low- and high-income neighbourhoods at two points in time. RESULTS: Between 1999/2000 and 2017/8 the average number of primary care visits per person, specialist referrals, and continuity of care fell in both urban and rural settings, while ED visits and prescriptions dispensed increased. Over this period in urban settings, primary care visits, continuity, and specialist referrals fell more rapidly in low vs. high income neighbourhoods (relative change in primary care visits: Incidence Rate Ratio (IRR) 0.881, 95% CI: 0.872, 0.890; continuity: partial regression coefficient -0.92, 95% CI: -1.18, -0.66; specialist referrals: IRR 0.711, 95%CI: 0.696, 0.726), while ED visits increased more rapidly (IRR 1.06, 95% CI: 1.03, 1.09). The percentage of physicians who provide the majority of visits to patients in neighbourhoods in the lower two income quintiles declined from 30.6% to 26.3%. CONCLUSION: Results raise concerns that equity in access to primary care has deteriorated in BC. Reforms to primary care that fail to attend to the multidimensional needs of low-income communities may entrench existing inequities. Policies that tailor patterns of funding and allocation of resources in accordance with population needs, and that align accountability measures with equity objectives are needed as part of further reform efforts.

[New treatments for renal cell carcinoma: hope and limits]. / Nouveautés thérapeutiques dans le cancer du rein: espoirs et questions.

Metastatic renal cell carcinoma remains a main therapeutic challenge in oncology. Interferon-alpha and Interleukin-2 have been the sole available drugs for decades. Allogeneic bone marrow transplantation is an interesting but experimental therapeutic approach. The von Hippel-Lindau disease is a rare genetic disorder predisposing to the development of renal cell carcinoma. Its molecular elucidation paves the way for novel therapeutic approaches based, mainly but not exclusively, on the inhibition of angiogenesis.

Liver transplantation in maple syrup urine disease.

UNLABELLED: Maple syrup urine disease (MSUD) is an autosomal recessive disorder. Impaired activity of the branched-chain 2-oxoacid dehydrogenase complex (BCOA-DH) causes accumulation of branched-chain L-amino (BCAA) and 2-oxoacids (BCOA) which may exert neurotoxic effects. Treatment comprises dietary management with strictly reduced quantities of protein and BCAA as well as aggressive intervention during acute neonatal and subsequent metabolic complications. MSUD is regarded as a metabolic disorder with potentially favourable outcome when the patients are kept on a carefully supervised long-term therapy. Up to now, three MSUD patients, exhibiting the classical form of the disease, have received orthotopic whole liver transplantation (OLT). Liver replacement resulted in a clear increase in whole body BCOA-DH activity to at least the level of very mild MSUD variants. These patients no longer require protein restricted diets and the risk of metabolic decompensation during catabolic events is apparently abolished. CONCLUSION: Considering the overall expenses, risks, and outcome, however, the benefit of OLT, even in the most severe form of MSUD, may not be significantly different from that of a classical strict dietary management. Thus, OLT appears not to represent a specific option in the treatment in MSUD.

[The anti-inflammatory action of an oral sustained-release theophylline preparation. Results of a clinical pilot study with low dosages]. / Untersuchungen zur antiinflammatorischen Wirkung eines oralen retardierten Theophyllin-Präparates. Ergebnisse einer Klinischen Pilotstudie mit niedriger Dosierung.

A pilot study in 14 patients with mild asthma was performed to study the anti-inflammatory efficacy of theophylline (CAS 58-55-9). At the start, during and at the end of a 3 months' treatment with oral sustained release theophylline and during 1 week thereafter, the influence on airway hyperreactivity and ECP (eosinophil cationic protein) serum levels was investigated. Airway responsiveness was expressed as the cumulative provocative dose of methacholine necessary to decrease FEV1 by 20% (PD20-FEV1). Data of 8 patients were suitable for evaluation. At a mean predose serum concentration of 6.5 mg/l, theophylline increased the mean PD20-FEV1 for methacholine from 151 micrograms (at start) to 332 micrograms (at the end of medication), and reduced the mean ECP serum concentration from 34.6 to 24.5 micrograms/l. Up to 1 week after theophylline treatment, the improvement of airway hyperreactivity compared to the baseline was maintained, whereas ECP-serum levels tended to increase. Thus, theophylline markedly attenuated airway hyperreactivity in patients with bronchial asthma at "subtherapeutic" serum theophylline concentrations as well as ECP serum concentrations, suggesting the anti-inflammatory efficacy of theophylline. These observations may have therapeutic implications in the treatment of patients with mild asthma. A slight improvement of lung function and dyspnoea, and a reduction of additional beta 2-bronchodilator use was also observed. Two patients only complained of slight nausea, tremor and restlessness.

Assessment of whole body L-leucine oxidation by noninvasive L-[1-13C]leucine breath tests: a reappraisal in patients with maple syrup urine disease, obligate heterozygotes, and healthy subjects.

Suitability of a recently proposed noninvasive L-[13C]leucine breath test for assessment of whole body leucine oxidation in maple syrup urine disease (MSUD) was examined. Oral L-[1-13C]leucine loads (38 micromol/kg body weight) were performed in overnight fasted MSUD patients (n = 6, classical form), obligate heterozygote parents (n = 6), and control subjects (n = 10). Three-hour 13CO2 exhalation kinetics were evaluated using curve fitting procedures. Venous blood was obtained in most cases and analyzed for 13C-labeled plasma metabolites. In control subjects, maximal 13CO2 exhalation was reached at tmax = 55 +/- 18 min. Cumulative 13CO2 output at 3 h amounted to 4.7 +/- 0.7 micromol x (kg body weight)(-1). Estimated total 3CO2 exhalation was 7.2 +/- 1.4 micromol x (kg body weight)(-1) (19.0 +/- 3.6% of the dose). Half of this amount was expired at t1/2 = 130 +/- 18 min. The data show a considerable degree of intersubject variability. Intraindividual variability was comparable, however, when checked in two volunteers. In obligate heterozygotes, 13CO2 kinetics were similar to controls (tmax = 35 +/- 8 min, t1/2 = 95 +/- 16 min). Total 13CO2 output [5.7 +/- 1.4 micromol x (kg body weight)(-1)] tended to be in the lower control range. None of the MSUD patients under study exhibited a significant increase in 13CO2 output after load. Maximal increase of label in plasma 4-methyl-2-oxopentanoate, the physiologic precursor of 13CO2, was 16.1 +/- 3.5 MPE in control subjects. In MSUD, label dilution was increased and correlated with the patients' leucine/4-methyl-2-oxopentanoate plasma levels. Considering the generally high variability of 13CO2 output and the unstable substrate pools in MSUD, we discuss the limitations of whole body leucine oxidation measurements by noninvasive approaches.

Compartmental approach for evaluation of plasma kinetics and (13)co(2)-exhalation after oral loading with L-[1-(13)c]leucine.

Abstract A seven compartment model was applied for evaluation of oral L-[1-(13)C]leucine loading tests (38 µmol/kg body wt.) in healthy volunteers. The model comprises transport and absorption in stomach and gut into a central L-leucine-compartment which is connected to a protein compartment and to the compartment of the corresponding 2-oxo acid. CO(2) release from the latter occurs in a fast and a slow compartment into the central CO(2) compartment for exhalation. Using the fmins routine of MATLAB for parameter estimation, a good agreement was obtained between calculated and actually measured kinetics of (13)C-labelled metabolites and a mean in vivo L-leucine oxidation of 0.365 ± 0.071 µmol/kg per min (n = 5) was computed. Plausibility of the model was checked by predicting in vivo leucine oxidation rates from primed continuous infusion tests (priming: L-[1-(13)C]leucine, 5 µmol/kg; NaH(13)CO(2), 1.2 µmol/kg; infusion: L-[1-(13)C]leucine, 5 µmol/kg per h). In 5 tested volunteers, the experimental L-leucine oxidation rate amounted to 0.358 ± 0.105 µmol/kg per min versus predicted 0.324±0.099 µmol/kg per min. Possible causes for some observed intraindividual variations are discussed.

Frequency of adult T-cell leukaemia/lymphoma and HTLV-I in Ibadan, Nigeria.

Sera from a small sample of adult blood donors, healthy school children and patients with lymphoma, leukaemia, non-haematologic cancer, congenital and inflammatory disorders from Ibadan, Nigeria were screened for HTLV-I antibody by an enzyme-linked immunoabsorbent assay and confirmed by investigational Western blot. Seventy-nine of 236 positively screened samples could not be tested for confirmation. Seropositive reactivity was observed in nine of 123 blood donors, and 3 of 46 healthy school children but banding patterns on Western blot were often sparse. Among non-Burkitt's non Hodgkin's lymphoma patients six of 30 were HTLV-I positive including four of four with clinical features of adult T-cell leukaemia (ATL). Other clinical conditions had a frequency of positivity indistinguishable from healthy donors. Western blot patterns ranged from strong with multiple bands, which were uncommon, to those with only p24 and p21 envelope positive which were frequent. Given the relative paucity of clinical ATL and the unusual Western blot patterns the true rate of HTLV-I infection may be lower than estimated. It is possible that a cross-reactive HTLV-I-like virus accounts for this pattern.

Transcultural nursing care values, beliefs, and practices of American (USA) Gypsies.

This ethnonursing qualitative investigation was focused on the domain of culture care values, expression and meanings of selected American Gypsies. The purpose of the study was to explicate culture care American Gypsy lifeways in order to help nurses understand this largely unknown culture, and to offer guidelines for providing culturally congruent nursing care. Leininger's theory of Culture Care Diversity and Universality was the appropriate theory to use for this study, along with the ethnonursing research method to generate emic and etic grounded data. Findings substantiated that the world view, ethnohistory, religion (moral code), kinship and cultural values, and generic folk practices were powerful influences of Gypsy lifeways and supported culture congruent nursing care. Ethnohistorical facts strongly buttressed the cultural values, norms, and moral codes for culture specific care practices. Several Gypsy culture specific and dominant care meanings, expressions, and actions were confirmed and made credible from raw data and thematic analysis. They were: 1) protective in-group caring; 2) watching over and guarding against Gadje; 3) facilitating care rituals; 4) respecting Gypsy values; 5) alleviating Gadje harassment; 6) remaining suspicious of outsiders; and 7) dealing with purity and impurity moral codes and rules. Culture specific and congruent care generated from Leininger's theory with the three predicted modes were identified to guide nursing decisions and actions.

Human T-lymphotropic virus type I (HTLV-I) seroprevalence in Jamaica. I. Demographic determinants.

During 1985 and 1986, the authors measured antibodies to human T-lymphotropic virus type I (HTLV-I) in a cohort of 13,260 Jamaicans from all parts of the island who applied for food-handling licenses. HTLV-I seroprevalence was strongly age and sex dependent, rising from 1.7% (10-19 years) to 9.1% (greater than or equal to 70 years) in men and from 1.9% (10-19 years) to 17.4% (greater than or equal to 70 years) in women. In a logistic regression analysis, women were more likely to be seropositive than were men, and farmers, laborers, and the unemployed were more likely to be HTLV-I seropositive than were those reporting student or professional occupations. In men, African ethnicity was associated with HTLV-I seropositivity in the univariate analysis but was not a risk factor after adjustment for age and sex. There was a trend toward higher age-stratified HTLV-I seroprevalence among younger women who reported more pregnancies, but older multigravidas had lower rates of HTLV-I seropositivity. Persons born outside Jamaica had significantly lower seroprevalence than did those born in Jamaica, but they were of slightly different ethnic and occupational compositions than those born in Jamaica.

Anti-AIDS agents, 3. Inhibitory effects of colchicine derivatives on HIV replication in H9 lymphocyte cells.

A series of colchicine and isocolchicine derivatives were evaluated as inhibitors of HIV replication in H9 lymphocytes. Colchicine showed only very slight inhibition in the absence of toxicity, as measured by the therapeutic index (IC50/EC50). None of the derivatives inhibited HIV replication in the absence of toxicity.

Anti-AIDS agents, 2: Inhibitory effects of tannins on HIV reverse transcriptase and HIV replication in H9 lymphocyte cells.

Nine tannins, including gallo- and ellagitannins, were evaluated as potential inhibitors of HIV replication. 1,3,4-Tri-O-galloylquinic acid [1], 3,5-di-O-galloyl-shikimic acid [2], 3,4,5-tri-O-galloylshikimic acid [3], punicalin [6], and punicalagin [7] inhibited HIV replication in infected H9 lymphocytes with little cytotoxicity. Two compounds, punicalin and punicacortein C [8], inhibited purified HIV reverse transcriptase with ID50 of 8 and 5 microM, respectively. Further studies with H9 lymphocytes indicated that chebulagic acid [5] and punicalin did not inactivate virus directly. However, 1,3,4-tri-O-galloylquinic acid and 3,5-di-O-galloylshikimic acid were more effective inhibitors under those conditions. All tannins appear to inhibit virus-cell interactions. Thus, inspite of their anti-RT activity, the mechanism by which tannins inhibit HIV may not be associated with this enzyme.

Human T-lymphotropic virus type I (HTLV-I) and tropical spastic paraparesis or HTLV-I-associated myelopathy in Hawaii.

Tropical spastic paraparesis or human T-lymphotropic virus type I (HTLV-I)-associated myelopathy is a degenerative encephalomyelopathy with pyramidal tract dysfunction affecting the lower extremities. It is associated with HTLV-I infection and found primarily in the Caribbean region and in southwestern Japan. Five cases of tropical spastic paraparesis (or HTLV-I-associated myelopathy) in Hawaii are reported. All five patients were born in Hawaii; four are women. Each of the patients has parents who were from HTLV-I-endemic areas of Japan. Two of these patients had serum antibodies to HTLV-I. Five of six of the spouses and children of the seropositive patients were also seropositive. Viral cultures of lymphocytes from both seropositive patients and two of the three seropositive children were positive for HTLV-I. None of the five patients had a history of antecedent blood transfusion, multiple sexual partners, or intravenous drug use. There is no evidence of adult T-cell leukemia or lymphoma in any of the patients or their families. Given the increasing seroprevalence of HTLV-I in the United States, clinicians need to be alert to new cases of this disorder.

Anti-AIDS agents, 1. Isolation and characterization of four new tetragalloylquinic acids as a new class of HIV reverse transcriptase inhibitors from tannic acid.

Four new tetragalloylquinic acids, 3,5-di-O-galloyl-4-O-digalloylquinic acid, 3,4-di-O-galloyl-5-O-digalloylquinic acid, 3-O-digalloyl-4,5-di-O-galloylquinic acid, and 1,3,4,5-tetra-O-galloylquinic acid, were isolated and characterized from a commercial tannic acid as a new class of human immunodeficiency virus (HIV) reverse transcriptase (RT) inhibitor. Compounds 2, 3, and 4 inhibit HIV RT activity 90, 89, and 84% at 100 microM and 73, 70, and 63% at 30 microM, respectively. Compounds 2-5 also inhibit the HIV growth in cells in the range of 61-70% with low cytotoxicity at 25 microM. The HIV cell growth inhibitory effects of these compounds at 25 microM and 6.25 microM (44-57%) are comparable to their effects against the HIV RT at 30 microM and 10 microM, respectively. The inhibitory effect of 3 against DNA polymerases indicates that the selective antiviral action of 3 is determined by more than its action with HIV RT.

Identification and some properties of a unique DNA polymerase from cells infected with human B-lymphotropic virus.

A new DNA polymerase and DNase activity were identified from cells infected with human B-lymphotropic herpesvirus (HBLV). DNA polymerase associated with HBLV infection was similar in its sensitivity to inhibition by ppi analogs as other herpesvirus-specific DNA polymerases but was dissimilar in its inhibition by certain nucleoside triphosphates.

Follicular involution in HIV lymphadenopathy. A morphometric study.

Lymph node biopsies from 75 HIV infected patients (71 homo- and bisexual men, 3 hemophiliacs and 1 woman) were studied using immunohistochemical methods with monoclonal antibodies (Mabs) against B lymphocytes, subsets of T lymphocytes, follicular dendritic cells (FDC) and HIV gag proteins p24 and p18. Histopathological changes were classified as follicular hyperplasia (FH), fragmentation (FF), atrophy (FA) and depletion (FD). Immunohistochemical stainings were quantified with the help of an Image Quantifier (IQ) and the reactivity for respective Mab-defined antigen was related quantitatively to other antigens and histopathological changes. Such measurements showed an increase in FDC in biopsies with FH and FF histology and a decrease in FA and FD cases in comparison with cases with non-HIV related lymphadenopathy. In addition it was found that the decrease in FDC was correlated with an increase in CD8+ within the follicles. Double immunostainings for p24 and various cellular markers showed that p24 was predominantly associated with follicular dendritic cells. Essentially the same findings were observed in the lymph nodes irrespective of risk group. Possible mechanisms involved in follicular involution in HIV-related lymphadenopathy are discussed.

Concomitant infection of HTLV-I and HIV-1: prevalence of IgG and IgM antibodies in Washington, D.C. area.

Serum samples collected from four groups of individuals in the Washington, D.C. area were examined for the presence of IgG and IgM classes of antibody reacting against HTLV-I and HIV-1. These four groups were: (1) healthy adults with negative premarital VDRL test for syphilis (n = 113), (2) miscellaneous common disease patients (n = 155), (3) drug abusers (n = 130), and (4) homosexual men (n = 187). The former two groups are considered to be low-risk groups, and the latter two, high-risk groups. The prevalence of IgG antibody on ELISA/Western blot tests for these groups were respectively: (1) 5.3%/1.8%, (2) 5.2%/1.9%, (3) 13.9%/4.6%, and (4) 4.3%/1.6% for HTLV-I, and (1) 2.7%/0.9%, (2) 4.5%/0%, (3) 12.3%/5.4%, and (4) 8.0%/5.9% for HIV-1. Instances of possible concomitant infection as shown by the presence of antibodies against both HTLV-I and HIV-1 were found only in the latter two high-risk groups, i.e. two (1.5%) in group (3), and three (1.6%) in group (4) as confirmed by both Western blot and immunofluorescence tests. Out of 97 sera collected from drug abusers in 1985-86 which had IgG antibody by Western blot test against HIV-1, 23 (23.7%) were HTLV-I antibody positive by ELISA test (Group 5), and 8 of these were confirmed by Western blot test. Among these 8 persons, IgM antibody against HTLV-I was found in 2, while that against HIV-1 was positive in 7 persons.(ABSTRACT TRUNCATED AT 250 WORDS)

Lymphadenopathy in HIV (HTLV-III/LAV) infected subjects: the role of virus and follicular dendritic cells.

Studies of human immunodeficiency virus (HIV) associated lymphadenopathy by histopathology and immunopathology showed conspicuous changes of follicular B-cell areas from a marked hyperplasia to complete involution. Immunohistochemistry showed a corresponding increase in follicular dendritic reticulum cells (FDRC) followed by progressive destruction of these cells during involution, concomitant with invasion of follicles by T-cells. HIV gag antigens were predominantly associated with FDRC in hyperplastic follicles and diminished during involution. Virus replication was by in situ hybridization seen predominantly in follicles, presumably reflecting productive infection of CD4+ cells and/or FDRC. It is concluded that local effects of the virus play an important role in HIV lymphadenopathy. The marked cytopathogenic effects on FDRC indicate that HIV infection with lymphadenopathy represents not only a disease of CD4+ cells but also of follicular antigen presenting cells (FDRC).

Serologic, immunologic, and clinical features of parenteral drug users from contrasting populations.

We screened inpatient and outpatient parenteral drug users with no clinical evidence of AIDS for immunodeficiency and antibodies to HTLV-III by ELISA. Among 20 outpatient drug users, 5 (25%) were seropositive. Three of these (and 2 who were seronegative) had low T-cell ratios. Over 6 months, 1 seropositive patient with a low ratio developed oral thrush and weight loss. We also studied 13 parenteral drug users hospitalized for conditions other than AIDS. Eight had low T-cell ratios, and at least 6 of these developed AIDS or ARC within 4 months. Serum from 8 of 13 inpatients was available for HTLV-III testing: 6/8 were seropositive and 3 of these 6 were among those developing AIDS or ARC. Abnormal T-cell ratios among all patients were associated with abnormal HTLV-III serology (p = .02). Of the 7 patients who developed AIDS or ARC, 4 were tested for both antibodies and T-cell ratios: all 4 were seropositive and had low ratios. A low ratio (p = .0004), a positive ELISA (p = .014), and abnormalities of both tests (p = .001) were associated with the development of AIDS or ARC. Of the 26 patients without AIDS or ARC, 3 were lost to follow-up and 23 did not develop AIDS or ARC. Six of these 26 had abnormal ratios. Of the 21 patients who did not develop AIDS or ARC and who were tested for HTLV antibodies, 2 were lost to follow-up. Seven of 21 were seropositive and 2/21 were both seropositive and had a low ratio. One of these 2 seropositive patients with low ratios also had lymphadenopathy, but he was lost to follow-up. The other had no adenopathy and remained well until her death from trauma a year later. This study found two populations with very different risks. Six of 13 hospitalized parenteral drug users and only 1 of 20 healthy outpatients developed AIDS or ARC.