Introduction: A recently emerging respiratory disease named coronavirus disease 2019 (COVID-19) has quickly spread across the world. This disease is initiated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and uncontrolled cytokine storm, but it remains unknown as to whether a robust antibody response is related to clinical deterioration and poor outcome in COVID-19 patients. Methods: Anti-SARS-CoV-2 IgG and IgM antibodies were determined by chemiluminescence analysis (CLIA) in COVID-19 patients at a single center in Wuhan. Median IgG and IgM levels in acute and convalescent-phase sera (within 35 days) for all included patients were calculated and compared between severe and non-severe patients. Immune response phenotyping based on the late IgG levels and neutrophil-to-lymphocyte ratio (NLR) was characterized to stratified patients into different disease severities and outcomes. Results: A total of 222 patients were included in this study. IgG was first detected on day 4 of illness, and its peak levels occurred in the fourth week. Severe cases were more frequently found in patients with high IgG levels, compared to those with low IgG levels (51.8 vs. 32.3%; p = 0.008). Severity rates for patients with NLR^hiIgG^hi, NLR^hiIgG^lo, NLR^loIgG^hi, and NLR^loIgG^lo phenotype were 72.3, 48.5, 33.3, and 15.6%, respectively (p < 0.0001). Furthermore, severe patients with NLR^hiIgG^hi, NLR^hiIgG^lo had higher inflammatory cytokines levels including IL-2, IL-6 and IL-10, and decreased CD4+ T cell count compared to those with NLR^loIgG^lo phenotype (p < 0.05). Recovery rates for severe patients with NLR^hiIgG^hi, NLR^hiIgG^lo, NLR^loIgG^hi, and NLR^loIgG^lo phenotype were 58.8% (20/34), 68.8% (11/16), 80.0% (4/5), and 100% (12/12), respectively (p = 0.0592). Dead cases only occurred in NLR^hiIgG^hi and NLR^hiIgG^lo phenotypes. Conclusions: COVID-19 severity is associated with increased IgG response, and an immune response phenotyping based on the late IgG response and NLR could act as a simple complementary tool to discriminate between severe and non-severe COVID-19 patients, and further predict their clinical outcome.

Keywords: COVID-19; IgG; clinical outcome; disease severity; neutrophil-to-lymphocyte ratio.

Stage-specific differentiation markers were used to evaluate the cellular composition and the origin of nonimmortalized (PrEC) and immortalized (PZ-HPV7, CA-HPV10, RWPE-1, and 957E/hTERT) human prostate cell lines. These studies documented that immortalized and nonimmortalized prostate epithelial cells established and maintained in low (i.e., <300 micromol/L) Ca(2+) serum-free defined (SFD) medium were all derived from normal nonmalignant prostate tissues and contain CD133(+)/ABCG2(+)/alpha(2)beta(1)(Hi)/p63(-)/PSCA(-)/AR(-)/PSA(-) prostate stem cells. In these cultures, prostate stem cells are able to self-renew and generate two distinct cell lineages: the minor proliferatively quiescent neuroendocrine lineage and the major transit-amplifying cell lineage. Subsequently, CD133(-)/ABCG2(-)/alpha(2)beta(1)(Hi)/p63(+)/PSCA(-)/AR(-)/PSA(-) transit-amplifying cells proliferate frequently and eventually mature into proliferatively quiescent CD133(-)/ABCG2(-)/alpha(2)beta(1)(Lo)/p63(-)/PSCA(+)/AR(-)/PSA(-) intermediate cells. Such proliferatively quiescent intermediate cells, however, do not complete their full maturation into CD133(-)/ABCG2(-)/alpha(2)beta(1)(Lo)/p63(-)/PSCA(-)/AR(+)/PSA(+) luminal-secretory cells in low Ca(2+) SFD medium. Addition of universal type I IFN and synthetic androgen (R1881) to culture medium resulted in up-regulation of androgen receptor protein expression. However, it failed to induce full differentiation of intermediate cells into AR(+)/PSA(+) luminal-secretory cells. Our results indicate that such inability of prostate epithelial cells to complete their differentiation is due to continuous expression of Notch-1 receptor and its downstream effector, Hey-1 protein, which actively suppresses differentiation via its ability to transcriptionally repress a series of genes, including the GATA family of transcription factors.

BACKGROUND

Underrepresentation of ethnic minority communities limits the generalizability of HIV vaccine trial results. We explored perceived barriers and motivators regarding HIV vaccine trial participation among low-socioeconomic ethnic minority respondents at risk for HIV.

METHODS

Six focus group interviews were conducted using a semistructured interview guide. Participants (N = 58, mean age = 36 years, 37% female, and 56% Latino/a and 35% African American) were recruited using venue-based sampling in Los Angeles. Data were analyzed using narrative thematic analysis and Ethnograph qualitative software.

RESULTS

Perceived barriers to HIV vaccine trial participation, in rank order, were (1) vaccine-induced HIV infection, (2) physical side effects, (3) uncertainty about vaccine efficacy, (4) uncertainty about other vaccine characteristics, (5) mistrust, (6) low perceived HIV risk, (7) study demands, (8) stigma, and (9) vaccine-induced HIV seropositivity. Motivators were (1) protection against HIV infection, (2) free insurance and/or medical care, (3) altruism, and (4) monetary incentives.

CONCLUSIONS

Population-specific HIV vaccine trial recruitment and implementation strategies should address trial risks from a family perspective, cultural gender norms, mistrust, low perceived HIV risk, the importance of African-American and Latino/a community participation in HIV vaccine trials, and misconceptions about gaining protection against HIV infection. Increasing the cultural relevance of trial recruitment and implementation should facilitate the participation of Latinos/as and African Americans in HIV vaccine trials.

BACKGROUND

An important aspect of a new surgical technique is whether it can be performed by other surgeons in other institutions. The authors report the first 297 cases in a multi-institutional and multinational review of laparoscopic cholecystectomy performed via a single portal of entry.

METHODS

Data were collected retrospectively for the initial patients undergoing single-port cholecystectomy by 13 surgeons who performed these procedures in their institutions after training by the authors. The review included operative time, blood loss, incision length, length of hospital stay (LOS), necessary additional trocars, and other parameters important to cholecystectomy. A database of all the single-port-access (SPA) surgeries performed by the surgeons included demographic and procedural details, LOS, complications, and initial follow-up data.

RESULTS

To date, 297 single-port cholecystectomies have been performed for a variety of diagnoses, primarily cholelithiasis. The average operative time was 71 min, and the average LOS was 1-2 days. The average blood loss was minimal. The use of additional port sites outside the umbilicus occurred in 34 of the cases. Of the 35 intraoperative cholangiograms performed, 34 were successful. No significant complications occurred except for seromas and minor postoperative wound infections. These results are comparable with those for standard multiport cholecystectomy. In addition, no access site hernias (ASH) occurred.

CONCLUSIONS

The findings demonstrate that SPA surgery is an alternative to multiport laparoscopy with fewer scars and better cosmesis. One factor affecting the rate for adoption of SPA surgery among other surgeons is the reproducibility of this new procedure. Although this study had insufficient data to determine fully the benefits of SPA surgery, the feasibility of this procedure with safe, acceptable results was demonstrated in this initial large series across multinational institutions.

BACKGROUND

Anterior shoulder instability associated with severe glenoid bone loss is rare, and little has been reported on this problem. Recent biomechanical and anatomical studies have suggested guidelines for bony reconstruction of the glenoid.

OBJECTIVE

Anatomical glenoid reconstruction will restore stability in shoulders with recurrent anterior instability owing to glenoid bone loss.

METHODS

Case series; Level of evidence, 4.

METHODS

Eleven cases of traumatic recurrent anterior instability that required bony reconstruction for severe anterior glenoid bone loss were reviewed. In all cases, the length of the anterior glenoid defect exceeded the maximum anteroposterior radius of the glenoid based on preoperative assessment by 3-dimensional CT scan. Surgical reconstruction was performed using an intra-articular tricortical iliac crest bone graft contoured to reestablish the concavity and width of the glenoid. The graft was fixed with cannulated screws in combination with an anterior-inferior capsular repair.

RESULTS

At mean follow-up of 33 months, the mean American Shoulder and Elbow Surgeons score was 94, compared with a preoperative score of 65. The University of California, Los Angeles score improved to 33 from 18. The Rowe score improved to 94 from a preoperative score of 28. The mean motion loss compared with the contralateral, normal shoulder was 7 degrees of flexion, 14 degrees of external rotation in abduction, and one spinous process level for internal rotation. All patients returned to preinjury levels of sport, and only 2 complained of mild pain with overhead sports activities. No patients reported any recurrent instability (dislocation or subluxation). The CT scans with 3-dimensional reconstructions obtained 4 to 6 months postoperatively demonstrated union of the bone graft with incorporation along the anterior glenoid rim and preservation of joint space.

CONCLUSIONS

Anatomical reconstruction of the glenoid with autogenous iliac crest bone graft for recurrent glenohumeral instability in the setting of bone deficiency is an effective form of treatment for this problem.

Following an acute T cell response, most activated effector cells die, while some survive and become memory cells. The pro-apoptotic Bcl-2 family member, Bcl-2 interacting mediator of death (Bim) is critical for eliminating most effector T cells, while expression of CD127 (IL-7Ralpha) has been proposed to mark effector cells destined to become memory cells. Here, we examined the effects of Bim on the death of effector T cells in relationship to CD127 expression and on development of T cell memory following lymphocytic choriomeningitis virus (LCMV) infection. We found that large numbers of CD127(lo) LCMV-specific CD4(+) and CD8(+) T cells were lost in wild-type mice, but were spared in Bim(-/-) mice. Further, while the numbers of CD127(hi) T cells declined only slightly during contraction of the response in wild-type mice, they increased significantly in Bim(-/-) mice due to re-expression of CD127 on CD127(lo) T cells that had avoided apoptosis. Functional memory T cells were significantly increased in Bim(-/-) mice; however, they underwent a slow attrition due to decreased proliferative renewal. Taken together, these data suggest that the absence of Bim-mediated death of LCMV-specific CD4(+) and CD8(+) T cells in vivo can increase T cell memory, but other homeostatic mechanisms control the long-term maintenance of memory cells.

We carried out 2 functional magnetic resonance imaging experiments to investigate the cortical mechanisms underlying the contribution of form and surface properties to object recognition. In experiment 1, participants performed same-different judgments in separate blocks of trials on pairs of unfamiliar "nonsense" objects on the basis of their form, surface properties (i.e., both color and texture), or orientation. Attention to form activated the lateral occipital (LO) area, whereas attention to surface properties activated the collateral sulcus (CoS) and the inferior occipital gyrus (IOG). In experiment 2, participants were required to make same-different judgments on the basis of texture, color, or form. Again attention to form activated area LO, whereas attention to texture activated regions in the IOG and the CoS, as well as regions in the lingual sulcus and the inferior temporal sulcus. Within these last 4 regions, activation associated with texture was higher than activation associated with color. No color-specific cortical areas were identified in these regions, although parts of V1 and the cuneus yielded higher activation for color as opposed to texture. These results suggest that there are separate form and surface-property pathways in extrastriate cortex. The extraction of information about an object's color seems to occur relatively early in visual analysis as compared with the extraction of surface texture, perhaps because the latter requires more complex computations.

Few data exist on the extent to which the differences in breast cancer risk between "racial-ethnic" groups in the United States (US) are "explained" by differences in their distribution of risk factors. We have determined this for African-American (AA), native Hawaiian (NH), Japanese-American (JA), Latina-US-born (L-US), Latina-non-US-born (L-NUS), and white (W) women using prospective incidence data on 88,712 postmenopausal women recruited in 1993-1996. We identified 1,757 incident breast cancer cases through 1999 among these women (1,116 cases after excluding women with a simple hysterectomy or missing risk factor data). Data were available on seven "known" risk factors: ages at menarche and first birth; parity; age at and type of menopause; weight; hormone replacement therapy use; and alcohol consumption. The relative risks (RRs) of breast cancer (with the RR in Ws set to 1.0) for the groups were as follows: W = 1.0; AA = 0.78; NH = 1.33; JA = 0.99; L-US = 0.77; and L-NUS = 0.60. After adjustment for the risk factors, the RRs were as follows: W = 1.0; AA = 0.98; NH = 1.65; JA = 1.11; L-US = 0.95; and L-NUSB = 0.84. The slightly greater risk of the JAs compared with the Ws is in sharp contrast to the very low breast cancer rates that were observed in "traditional" Japanese women and in early Japanese migrants. The adjusted RR of NHs is 65% greater than that of Ws, and that of migrant Latinas is 16% lower than that of Ws. Elucidating the causes of the high rates in NHs is now a major focus of our efforts.

Background: The COVID-19 pandemic has placed an unprecedented strain on health systems, with rapidly increasing demand for healthcare in hospitals and intensive care units (ICUs) worldwide. As the pandemic escalates, determining the resulting needs for healthcare resources (beds, staff, equipment) has become a key priority for many countries. Projecting future demand requires estimates of how long patients with COVID-19 need different levels of hospital care.

Methods: We performed a systematic review of early evidence on length of stay (LoS) of patients with COVID-19 in hospital and in ICU. We subsequently developed a method to generate LoS distributions which combines summary statistics reported in multiple studies, accounting for differences in sample sizes. Applying this approach, we provide distributions for total hospital and ICU LoS from studies in China and elsewhere, for use by the community.

Results: We identified 52 studies, the majority from China (46/52). Median hospital LoS ranged from 4 to 53 days within China, and 4 to 21 days outside of China, across 45 studies. ICU LoS was reported by eight studies-four each within and outside China-with median values ranging from 6 to 12 and 4 to 19 days, respectively. Our summary distributions have a median hospital LoS of 14 (IQR 10-19) days for China, compared with 5 (IQR 3-9) days outside of China. For ICU, the summary distributions are more similar (median (IQR) of 8 (5-13) days for China and 7 (4-11) days outside of China). There was a visible difference by discharge status, with patients who were discharged alive having longer LoS than those who died during their admission, but no trend associated with study date.

Conclusion: Patients with COVID-19 in China appeared to remain in hospital for longer than elsewhere. This may be explained by differences in criteria for admission and discharge between countries, and different timing within the pandemic. In the absence of local data, the combined summary LoS distributions provided here can be used to model bed demands for contingency planning and then updated, with the novel method presented here, as more studies with aggregated statistics emerge outside China.

Keywords: Bed demand; COVID-19; Hospitalisation; ICU capacity; Length of stay; SARS-CoV-2.

Factors accounting for long-term nonprogression may include infection with an attenuated strain of human immunodeficiency virus type 1 (HIV-1), genetic polymorphisms in the host, and virus-specific immune responses. In this study, we examined eight individuals with nonprogressing or slowly progressing HIV-1 infection, none of whom were homozygous for host-specific polymorphisms (CCR5-Delta32, CCR2-64I, and SDF-1-3'A) which have been associated with slower disease progression. HIV-1 was recovered from seven of the eight, and recovered virus was used for sequencing the full-length HIV-1 genome; full-length HIV-1 genome sequences from the eighth were determined following amplification of viral sequences directly from peripheral blood mononuclear cells (PBMC). Longitudinal studies of one individual with HIV-1 that consistently exhibited a slow/low growth phenotype revealed a single amino acid deletion in a conserved region of the gp41 transmembrane protein that was not seen in any of 131 envelope sequences in the Los Alamos HIV-1 sequence database. Genetic analysis also revealed that five of the eight individuals harbored HIV-1 with unusual 1- or 2-amino-acid deletions in the Gag sequence compared to subgroup B Gag consensus sequences. These deletions in Gag have either never been observed previously or are extremely rare in the database. Three individuals had deletions in Nef, and one had a 4-amino-acid insertion in Vpu. The unusual polymorphisms in Gag, Env, and Nef described here were also found in stored PBMC samples taken 3 to 11 years prior to, or in one case 4 years subsequent to, the time of sampling for the original sequencing. In all, seven of the eight individuals exhibited one or more unusual polymorphisms; a total of 13 unusual polymorphisms were documented in these seven individuals. These polymorphisms may have been present from the time of initial infection or may have appeared in response to immune surveillance or other selective pressures. Our results indicate that unusual, difficult-to-revert polymorphisms in HIV-1 can be found associated with slow progression or nonprogression in a majority of such cases.

The molecular basis for the resistance of serogroup B Neisseria meningitidis to the bactericidal activity of normal human sera (NHS) was examined with a NHS-resistant, invasive serogroup B meningococcal isolate and genetically and structurally defined capsule-, lipooligosaccharide (LOS)-, and sialylation-altered mutants of the wild-type strain. Expression of the (alpha2-->8)-linked polysialic acid serogroup B capsule was essential for meningococcal resistance to NHS. The very NHS-sensitive phenotype of acapsular mutants (99.9 to 100% killed in 10, 25, and 50% NHS) was not rescued by complete LOS sialylation or changes in LOS structure. However, expression of the capsule was necessary but not sufficient for a fully NHS-resistant phenotype. In an encapsulated background, loss of LOS sialylation by interrupting the alpha2,3 sialyltransferase gene, lst, increased sensitivity to 50% NHS. In contrast, replacement of the lacto-N-neotetraose alpha-chain (Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc) with glucose extensions (GlcN) in a galE mutant resulted in a strain resistant to killing by 50% NHS at all time points. Encapsulated meningococci expressing a Hep2(GlcNAc)->>KDO2->>lipid A LOS without an alpha-chain demonstrated enhanced sensitivity to 50% NHS (98% killed at 30 min) mediated through the antibody-dependent classical complement pathway. Encapsulated LOS mutants expressing truncated Hep2->>KDO2->>lipid A and KDO2->>lipid A structures were also sensitive to 50% NHS (98 to 100% killed at 30 min) but, unlike the wild-type strain and mutants with larger oligosaccharide structures, they were killed by hypogammaglobulinemic sera. These data indicate that encapsulation is essential but that the LOS structure contributes to the ability of serogroup B N. meningitidis to resist the bactericidal activity of NHS.

OBJECTIVE

Most patients with colorectal liver metastases present to general surgeons and oncologists without a specialist interest in their management. Since treatment strategy is frequently dependent on the response to earlier treatments, our aim was to create a therapeutic decision model identifying appropriate procedure sequences.

METHODS

We used the RAND Corporation/University of California, Los Angeles Appropriateness Method (RAM) assessing strategies of resection, local ablation and chemotherapy. After a comprehensive literature review, an expert panel rated appropriateness of each treatment option for a total of 1,872 ratings decisions in 252 cases. A decision model was constructed, consensus measured and results validated using 48 virtual cases, and 34 real cases with known outcomes.

RESULTS

Consensus was achieved with overall agreement rates of 93.4 to 99.1%. Absolute resection contraindications included unresectable extrahepatic disease, more than 70% liver involvement, liver failure, and being surgically unfit. Factors not influencing treatment strategy were age, primary tumor stage, timing of metastases detection, past blood transfusion, liver resection type, pre-resection carcinoembryonic antigen (CEA), and previous hepatectomy. Immediate resection was appropriate with adequate radiologically-defined resection margins and no portal adenopathy; other factors included presence of < or = 4 or>> 4 metastases and unilobar or bilobar involvement. Resection was appropriate postchemotherapy, independent of tumor response in the case of < or = 4 metastases and unilobar liver involvement. Resection was appropriate only for>> 4 metastases or bilobar liver involvement, after tumor shrinkage with chemotherapy. When possible, resection was preferred to local ablation.

CONCLUSIONS

The results were incorporated into a decision matrix, creating a computer program (OncoSurge). This model identifies individual patient resectability, recommending optimal treatment strategies. It may also be used for medical education.

BACKGROUND

Elements of malnutrition-inflammation complex syndrome (MICS) may blunt the responsiveness of anemia of end-stage renal disease (ESRD) to recombinant human erythropoietin (EPO).

METHODS

The authors examined cross-sectional associations between the required dose of EPO within a 13-week interval as prescribed by practicing nephrologists who were blind to the study and several laboratory values known to be related to nutrition and/or inflammation, as well as the malnutrition-inflammation score (MIS), which is a fully quantitative assessment tool based on the subjective global assessment of nutrition.

RESULTS

A total of 339 maintenance hemodialysis (MHD) outpatients, including 181 men, who were aged 54.7 +/- 14.5 years (mean +/- SD), who had undergone dialysis for 36.3 +/- 33.2 months, were selected randomly from 7 DaVita dialysis units in Los Angeles South/East Bay area. The average weekly dose of administered recombinant human EPO within a 13-week interval was 217 +/- 187 U/kg. Patients were receiving intravenous iron supplementation (iron gluconate or dextran) averaging 39.5 +/- 47.5 mg/wk. The MIS and serum concentrations of high-sensitivity C-reactive protein, interleukin 6 (IL-6), tumor necrosis factor-alpha, and lactate dehydrogenase had positive correlation with required EPO dose and EPO responsiveness index (EPO divided by hemoglobin), whereas serum total iron binding capacity (TIBC), prealbumin and total cholesterol, as well as blood lymphocyte count had statistically significant but negative correlations with indices of refractory anemia. Most correlations remained significant even after multivariate adjustment for case-mix and anemia factors and other relevant covariates. Similar associations were noticed across EPO per body weight tertiles via analysis of variance and after estimating odds ratio for higher versus lower tertile via logistic regression after same case-mix adjustment.

CONCLUSIONS

The existence of elements of MICS as indicated by a high MIS and increased levels of proinflammatory cytokines such as IL-6 as well as decreased nutritional values such as low serum concentrations of total cholesterol, prealbumin, and TIBC correlates with EPO hyporesponsiveness in MHD patients.

Renal tubulointerstitial damage is the final common pathway leading from chronic kidney disease to end-stage renal disease. Inflammation is clearly involved in tubulointerstitial injury, but it remains unclear how the inflammatory processes are initiated and regulated. Here, we have shown that in the mouse kidney, the transcription factor Krüppel-like factor-5 (KLF5) is mainly expressed in collecting duct epithelial cells and that Klf5 haploinsufficient mice (Klf5+/- mice) exhibit ameliorated renal injury in the unilateral ureteral obstruction (UUO) model of tubulointerstitial disease. Additionally, Klf5 haploinsufficiency reduced accumulation of CD11b+ F4/80(lo) cells, which expressed proinflammatory cytokines and induced apoptosis among renal epithelial cells, phenotypes indicative of M1-type macrophages. By contrast, it increased accumulation of CD11b+ F4/80(hi) macrophages, which expressed CD206 and CD301 and contributed to fibrosis, in part via TGF-β production--phenotypes indicative of M2-type macrophages. Interestingly, KLF5, in concert with C/EBPα, was found to induce expression of the chemotactic proteins S100A8 and S100A9, which recruited inflammatory monocytes to the kidneys and promoted their activation into M1-type macrophages. Finally, assessing the effects of bone marrow-specific Klf5 haploinsufficiency or collecting duct- or myeloid cell-specific Klf5 deletion confirmed that collecting duct expression of Klf5 is essential for inflammatory responses to UUO. Taken together, our results demonstrate that the renal collecting duct plays a pivotal role in the initiation and progression of tubulointerstitial inflammation.

BACKGROUND

Opioid analgesics remain a mainstay in the treatment of pain associated with surgical procedures. Such use is associated with adverse drug events (ADEs).

OBJECTIVE

To investigate the impact of opioid-related ADEs on total hospital costs and length of stay (LOS) in adult surgical patients.

METHODS

This was a retrospective matched cohort study using data from computerized medical records. ADE cases were prospectively detected using computerized surveillance and verified by pharmacists. Surgical patients treated at LDS Hospital in Salt Lake City from January 1, 1998, to December 31, 2003, were included. The primary outcomes were costs and hospital LOS associated with opioid-related ADEs and the relationship of opioid dose to ADE events.

RESULTS

Patients experiencing opioid-related ADEs had significantly increased median total hospital costs (7.4% increase; 95% CI 3.83 to 10.96; p < 0.001) and increased median LOS (10.3% increase; 95% CI 6.5 to 14.2; p < 0.001) compared with matched non-ADE controls. The increased costs attributable to ADEs, by surgery type, were general surgery ($676.51; 95% CI 351.50 to 1001.50), orthopedics ($861.50; 95% CI 448.20 to 1274.80), and obstetrics/gynecology ($540.90; 95% CI 281.40 to 800.40). Similarly, increased LOS attributable to ADEs, by surgery type, were general surgery (0.64 days; 95% CI 0.40 to 0.88), orthopedics (0.52 days; 95% CI 0.33 to 0.71), and obstetrics/gynecology (0.53 days; 95% CI 0.33 to 0.72). Higher doses of opioids were associated with increased risk of experiencing ADEs (OR 1.3; 95% CI 1.07 to 1.60; p = 0.01).

CONCLUSIONS

Opioid-related ADEs following surgery were associated with significantly increased LOS and hospitalization costs. These ADEs occurred more frequently in patients receiving higher doses of opioids.

OBJECTIVE

To evaluate the prognostic significance for AIDS occurrence of plasma levels of immune activation markers in comparison with and in conjunction with HIV viral load and CD4 T-cell measurements.

METHODS

A retrospective analysis was conducted of three plasma activation markers, the soluble tumor necrosis factor (TNF) receptor II (TNF-RII), neopterin and soluble interleukin-2 receptor levels, and of CD4 T-cell levels and plasma HIV viral load.

METHODS

The participants were 659 men taking part in the University of California Los Angeles Multicenter AIDS Cohort Study who were HIV-seropositive but AIDS-free in 1985.

METHODS

Clinically defined AIDS within 3 years. Failure time statistical regression models for the time to development of AIDS were used to assess prognostic capacity of the parameters alone and in combination.

RESULTS

All the markers had prognostic capability. The levels of the three plasma activation markers correlated well with each other (median r = 0.61). They related less well with HIV RNA plasma levels (median r = 0.50) and least well with CD4 cell levels (median r = 0.36). Furthermore, plasma marker levels were shown to be able to stratify patients for prognosis within all the major categories of CD4 T-cell and HIV RNA levels.

CONCLUSIONS

Plasma levels of soluble TNF-RII and other soluble markers of immune activation have prognostic capabilities which are different from HIV and CD4 T-cell levels. Combination of a single plasma activation marker measurement (such as soluble TNF-RII) with CD4 T-cell levels improved the prognostic capability of each. A new graphic technique for presenting prognostic capability indicated that plasma soluble TNF-RII and CD4 cell levels are better prognostic factors than HIV plasma level with CD4 cells < 200 x 10(6)/l. Inexpensive tests for one of the plasma activation markers, such as soluble TNF-RII or neopterin, can be useful for evaluations of HIV disease course, especially when expensive equipment, technical expertise and funding required for flow cytometry and for HIV load measurements are not readily available.

OBJECTIVE

To determine the current values and estimate the projected values (to the year 2041) for annual number of proximal femoral fractures (PFFs), age-adjusted rates of fracture, rates of death in the acute care setting, associated length of stay (LOS) in hospital, and seasonal variation by sex and age in elderly Canadians.

METHODS

Hospital discharge data for fiscal year 1993-94 from the Canadian Institute for Health Information were used to determine PFF incidence, and Statistics Canada population projections were used to estimate the rate and number of PFFs to 2041.

METHODS

Canada.

METHODS

Canadian patients 65 years of age or older who underwent hip arthroplasty.

METHODS

PFF rates, death rates and LOS by age, sex and province.

RESULTS

In 1993-94 the incidence of PFF increased exponentially with increasing age. The age-adjusted rates were 479 per 100,000 for women and 187 per 100,000 for men. The number of PFFs was estimated at 23,375 (17,823 in women and 5552 in men), with a projected increase to 88,124 in 2041. The rate of death during the acute care stay increased exponentially with increasing age. The death rates for men were twice those for women. In 1993-94 an estimated 1570 deaths occurred in the acute care setting, and 7000 deaths were projected for 2041. LOS in the acute care setting increased with advancing age, as did variability in LOS, which suggests a more heterogeneous case mix with advancing age. The LOS for 1993-94 and 2041 was estimated at 465,000 and 1.8 million patient-days respectively. Seasonal variability in the incidence of PFFs by sex was not significant. Significant season-province interactions were seen (p < 0.05); however, the differences in incidence were small (on the order of 2% to 3%) and were not considered to have a large effect on resource use in the acute care setting.

CONCLUSIONS

On the assumption that current conditions contributing to hip fractures will remain constant, the number of PFFs will rise exponentially over the next 40 years. The results of this study highlight the serious implications for Canadians if incidence rates are not reduced by some form of intervention.

Nontypeable Haemophilus influenzae (NTHi) is a leading causative agent of otitis media. Much of the inflammation occurring during NTHi disease is initiated by lipooligosaccharides (LOS) on the bacterial surface. Phosphorylcholine (PCho) is added to some LOS forms in a phase-variable manner, and these PCho(+) variants predominate in vivo. Thus, we asked whether this modification confers some advantage during infection. Virulence of an otitis media isolate (NTHi strain 86-028NP) was compared with that of an isogenic PCho transferase (licD) mutant using a chinchilla (Chinchilla lanigera) model of otitis media. Animals infected with NTHi 86-028NP licD demonstrated increased early inflammation and a delayed increase in bacterial counts compared to animals infected with NTHi 86-028NP. LOS purified from chinchilla-passed NTHi 86-028NP had increased PCho content compared to LOS purified from the inoculum. Both strains were recovered from middle ear fluids as long as 14 days postinfection. Biofilms were macroscopically visible in the middle ears of euthanized animals infected with NTHi 86-028NP 7 days and 14 days postchallenge. Conversely, less dense biofilms were observed in animals infected with NTHi 86-028NP licD 7 days postinfection, and none of the animals infected with NTHi 86-028NP licD had a visible biofilm by 14 days. Fluorescent antibody staining revealed PCho(+) variants within biofilms, similar to our prior results with tissue culture cells in vitro (S. L. West-Barnette, A. Rockel, and W. E. Swords, Infect. Immun. 74:1828-1836, 2006). Animals coinfected with equal proportions of both strains had equal persistence of each strain and somewhat greater severity of disease. We thus conclude that PCho promotes NTHi infection and persistence by reducing the host inflammatory response and by promoting formation of stable biofilm communities.

OBJECTIVE

To compare the outcomes of patients with hypertension and non-insulin-dependent diabetes mellitus (NIDDM) who were cared for in three different systems of care and by generalist and subspecialist physicians.

METHODS

An observational study with follow-up at three periods: (1) a 2-year study of 532 patients with hypertension and 170 patients with NIDDM who had entrance and exit histories, physical examinations, and laboratory tests; (2) a 4-year follow-up of 1044 patients with hypertension and 317 patients with NIDDM based on patient-reported functional status; and (3) 7-year mortality for 1296 patients with hypertension and 424 patients with NIDDM.

METHODS

Patients sampled from health maintenance organizations, large multispecialty groups, and solo or single-specialty group practices in Boston, Mass, Los Angeles, Calif, and Chicago, Ill. Patients were designated as belonging to one of three systems of care: fee for service; prepaid patients in solo or small single-specialty groups or in large multispecialty group practices, referred to as independent practice associations; and staff-model health maintenance organizations. The principal providers were family practitioners, general internists, cardiologists, or endocrinologists.

METHODS

Physiological, functional, and mortality. For hypertension, we measured blood pressure and stroke incidence. For NIDDM, we measured blood pressure, glycosylated hemoglobin level, visual function, vibration sense, ulcers and infections in the feet, and albumin excretion rate. Functional outcomes were assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Mortality was assessed for the 7 years following the entrance examination.

RESULTS

We found no evidence that any one system of care or physician specialty achieved consistently better 2-year or 4-year outcomes than others for patients with NIDDM or hypertension. Endocrinologists appeared to achieve better foot-ulcer and infection outcomes for patients with NIDDM, particularly when compared with family practitioners. However, no other specialist differences were found in any individual measures for either condition. Moreover, no adjusted mortality differences among systems or among physicians specialties were observed in the 7-year follow-up period.

CONCLUSIONS

No meaningful differences were found in the mean health outcomes for patients with hypertension or NIDDM, whether they were treated by different care systems or by different physician specialists. Although prepaid medicine relies more heavily on generalist physicians than does fee for service, there is no evidence from these analyses that the quality of care of moderately ill patients with these two common disease was adversely affected. These findings must be viewed in light of the historically higher costs of fee-for-service medicine and of subspecialty physician practice.

We have undertaken a series of experiments to examine the behavior of individual components of cell membranes. Here we report an initial stage of these experiments, in which the properties of a chemically simple lipid mixture are carefully mapped onto a phase diagram. Four different experimental methods were used to establish the phase behavior of the 3-component mixture DSPC/DOPC/chol: (1) confocal fluorescence microscopy observation of giant unilamellar vesicles, GUVs; (2) FRET from perylene to C20:0-DiI; (3) fluorescence of dilute dyes C18:2-DiO and C20:0-DiI; and (4) wide angle X-ray diffraction. This particular 3-component mixture was chosen, in part, for a high level of immiscibility of the components in order to facilitate solving the phase behavior at all compositions. At 23 degrees C, a large fraction of the possible compositions for this mixture give rise to a solid phase. A region of 3-phase coexistence of {Lalpha+Lbeta+Lo} was detected and defined based on a combination of fluorescence microscopy of GUVs, FRET, and dilute C20:0-DiI fluorescence. At very low cholesterol concentrations, the solid phase is the tilted-chain phase Lbeta'. Most of the phase boundaries have been determined to be within a few percent of the composition. Measurements of the perturbations of the boundaries of this accurate phase diagram could serve as a means to understand the behaviors of a range of added lipids and proteins.

The Sexual Acquisition and Transmission of HIV Cooperative Agreement Program (SATHCAP) examined the role of drug use in the sexual transmission of the human immunodeficiency virus (HIV) from traditional high-risk groups, such as men who have sex with men (MSM) and drug users (DU), to lower risk groups in three US cities and in St. Petersburg, Russia. SATHCAP employed respondent-driven sampling (RDS) and a dual high-risk group sampling approach that relied on peer recruitment for a combined, overlapping sample of MSM and DU. The goal of the sampling approach was to recruit an RDS sample of MSM, DU, and individuals who were both MSM and DU (MSM/DU), as well as a sample of sex partners of MSM, DU, and MSM/DU and sex partners of sex partners. The approach efficiently yielded a sample of 8,355 participants, including sex partners, across all four sites. At the US sites-Los Angeles, Chicago, and Raleigh-Durham-the sample consisted of older (mean age = 41 years), primarily black MSM and DU (both injecting and non-injecting); in St. Petersburg, the sample consisted of primarily younger (mean age = 28 years) MSM and DU (injecting). The US sites recruited a large proportion of men who have sex with men and with women, an important group with high potential for establishing a generalized HIV epidemic involving women. The advantage of using the dual high-risk group approach and RDS was, for the most part, the large, efficiently recruited samples of MSM, DU, and MSM/DU. The disadvantages were a recruitment bias by race/ethnicity and income status (at the US sites) and under-enrollment of MSM samples because of short recruitment chains (at the Russian site).

A case-control study was conducted in Los Angeles County, California, of 163 very young breast-cancer cases (all aged 32 or less at diagnosis) to investigate the role, if any, of oral contraceptives (OC) in the development of the disease. OC use before first full-term pregnancy (FFTP) was associated with an elevated risk, which increased with duration of OC use (relative risk approximately 2.2 at 6 years of use, P < 0.01). This increased risk could not be explained by other risk factors. OC use after FFTP was not associated with any change in risk. A first-trimester abortion before FFTP, whether spontaneous or induced, was associated with a 2.4-fold increase in breast-cancer risk (P < 0.005).

Compared with findings in Western countries, the prevalence of reflux esophagitis in Oriental countries is estimated to be low. In this prospective study, we aimed to examine the proportion of reflux esophagitis in Japanese adults, as evaluated by endoscopy. Endoscopists were prospectively directed to grade esophageal mucosal breaks with esophagitis according to the Los Angeles Classification of Esophagitis in all subjects that underwent endoscopic examination. In total, 6010 subjects underwent endoscopic examination for evaluation of esophagitis grading from December 1996 to February 1998. The subjects included 4394 outpatients who were not receiving medication for gastrointestinal disease and 1616 subjects who visited the hospital for routine physical examinations. The overall proportion of esophagitis was 16.3%. Most of the subjects with esophagitis were classified as having grade A or B (proportion of grades A and B, 9.6% and 4.6%, respectively). The age-related proportion of esophagitis and of severe esophagitis (i.e., grades C and D) increased in females aged over 70 and in males aged over 80. Increased body mass index (partly due to decreased height caused by osteoporosis), and/or hiatal herniation, were related to the proportion of esophagitis in females aged over 70. These data indicated that reflux esophagitis is a common disease in Japan. However, severe esophagitis (grades C and D) is not common.

OBJECTIVE

To determine the usefulness of the 6-minute walk test as an integrated measure of mobility in older adults.

METHODS

Observational study.

METHODS

Community centers and retirement homes in the Los Angeles area.

METHODS

Eighty-six older adults without significant disease.

METHODS

None.

METHODS

Assessments included the 6-minute walk, chair stands, standing balance, gait speed, body mass index, and self-reported physical functioning and general health perceptions.

RESULTS

One-week test-retest reliability of the 6-minute walk was .95. As hypothesized, the 6-minute walk distance was significantly greater for active than for inactive older adults (p < .0001), moderately correlated with chair stands (r = .67), standing balance (r = .52), and gait speed (r = -.73). It had a low correlation with body mass index (r = -.07). The correlation of the 6-minute walk with self-reported physical functioning was .55, and its correlation with general health perceptions was .39. Self-report and performance measures explained 69% of the variance in 6-minute walk scores.

CONCLUSIONS

The 6-minute walk test is reliable and is valid in relation to the performance and self-reported indicators of physical functioning tested in this study. It could serve as a useful integrated measure of mobility.