Purpose

To examine the effects of the occurrence and co-occurrence of comorbidities (COM), functional limitations (FL), and geriatric syndromes (GS) on treatment and outcomes in older cancer patients.

Materials and Methods

We used records from the Ohio Cancer Incidence Surveillance System linked with Medicare data, clinical assessment data from the home health care Outcomes and Assessment Information Set, and death certificate data. Our patient population included fee-for-service HHC Medicare beneficiaries diagnosed with incident loco-regional breast or colorectal cancer in years 1999–2001 (n=1236). We grouped patients according to the presence of multimorbidity: (0): none of COM, FL, or GS; (1): occurrence – but no co-occurrence – of COM, FL, or GS; (2): co-occurrence of any two of COM, FL, and GS; and (3): co-occurrence of all three of COM, FL, and GS. Our outcomes were receipt of standard treatment, as well as overall survival (OS) and disease-specific survival (DSS) through 2005. Multivariable regression models were developed to analyze the independent association between multimorbidity and the outcomes, before and after adjusting for age.

Results

The effect of multimorbidity on our outcomes was attenuated considerably by age. Adjusting for age and compared with no multimorbidity (0), high multimorbidity (3) remained significantly and negatively associated with receipt of standard treatment (adjusted odds ratio: 0.57, 95% Confidence Interval (CI): 0.33, 0.97). Furthermore, high multimorbidity (3) was associated with increased hazard for OS, but not for DSS (adjusted hazard ratio and 95% CI: 2.15 (1.58, 2.93) for three entities).

Conclusion

Multimorbidity is significantly and independently associated with cancer treatment and OS, but not DSS.

HIV-infected infants may have CXCR4-using (X4-tropic) HIV, CCR5-using (R5-tropic) HIV, or a mixture of R5-tropic and X4-tropic HIV (dual/mixed, DM HIV). The level of infectivity for R5 virus (R5-RLU) varies among HIV-infected infants. HIV tropism and R5-RLU were measured in samples from HIV-infected Ugandan infants using a commercial assay. DM HIV was detected in 7/72 (9.7%) infants at the time of HIV diagnosis (birth or 6–8 weeks of age, 4/15 (26.7%) with subtype D, 3/57 (5.3 %) with other subtypes, P=0.013). A transition from R5-tropic to DM HIV was observed in only two (6.7%) of 30 infants over 6–12 months. Six (85.7%) of seven infants with DM HIV died, compared to 21/67 (31.3%) infants with R5-tropic HIV (p=0.09). Higher R5-RLU at 6–8 weeks was not associated with decreased survival. Infants with in utero infection had a higher median R5-RLU than infants who were HIV-uninfected at birth (p=0.025).

Background

The Vulnerable Elders Survey (VES-13) has been validated for screening older cancer patients for a Comprehensive Geriatric Assessment (CGA). To identify a widely acceptable approach that encourages oncologists to screen older cancer patients for a CGA, we examined the Eastern Cooperative Oncology Group Performance Status (ECOG-PS) and Karnofsky Index of Performance Status (KPS) scales’ ability to identify abnormalities on a CGA and compared the performance of the two instruments with the VES-13.

Methods

We enrolled 117 participants, ≥65 years with stage I–IV cancer into this cross-sectional study. Our primary outcome variable was ≥two abnormalities on the CGA, (Yes or No). We employed receiver operating characteristic curve analysis to compare the discriminatory abilities of the three instruments to identify ≥two abnormalities on the CGA.

Results

Of the 117 participants, 43% had ≥two abnormalities on the CGA. The VES-13 was predictive of ≥two abnormalities on the CGA, area under the curve (AUC)=0.85 [(95% CI: 0.78–0.92); sensitivity=88%, specificity=69%, at cut-off ≥3]. The ECOG-PS and KPS showed similar discriminatory powers, AUC=0.88 [(95% CI: 0.83–0.94); sensitivity=94%, specificity=55%, at cut-off ≥1]; and AUC=0.90 [(95% CI: 0.84–0.96); sensitivity=78%, specificity=91%, at cut-off ≤80%], respectively.

Conclusion

The ECOG-PS and KPS were equivalent to the VES-13 in identifying older cancer patients with at least two abnormalities on the CGA. Given that oncologists are already conversant with the KPS and ECOG-PS, these two instruments offer medical oncologists a widely acceptable approach for screening older patients for a CGA.

OBJECTIVE

Single-dose nevirapine (sdNVP) can reduce the risk of HIV vertical transmission. We assessed risk factors for NVP resistance in plasma and breast milk from sdNVP-exposed Ugandan women.

METHODS

Samples were analyzed using the Roche AMPLICOR HIV-1 Monitor Test Kit, v1.5, and the ViroSeq HIV-1 Genotyping System. NVP concentrations were determined by liquid chromatography with tandem mass spectroscopy.

RESULTS

HIV genotypes (plasma and breast milk) were obtained for 30 women 4 weeks after sdNVP (HIV subtypes: 15A, 1C, 12D, 2 recombinant). NVP resistance was detected in 12 (40%) of 30 breast milk samples. There was a non-significant trend between detection of NVP resistance in breast milk and plasma (p=0.06). There was no association of HIV resistance in breast milk with median maternal pre-NVP viral load or CD4 cell count, median breast milk viral load at 4 weeks, breast milk sodium >10 mmol/L, HIV subtype, or concentration of NVP in breast milk or plasma.

CONCLUSIONS

NVP resistance was frequently detected in breast milk 4 weeks after sdNVP exposure. In this study, we were unable to identify specific factors associated with breast milk NVP resistance.

Purpose

To examine patterns of colorectal cancer (CRC) treatment and survival in relation to comorbidities (COM), functional limitations (FL), and geriatric syndromes (GS).

Methods

Our study population consisted of Ohio elders diagnosed with incident invasive CRC in the period August 1999 to November 2001 and admitted to home health care (HHC) in the 30 days before or after cancer diagnosis (n = 1009). We used data from the Ohio Cancer Incidence Surveillance System, vital records, and Medicare administrative data, including the HHC Outcome and Assessment Information Set (OASIS), which includes detailed clinical data for HHC patients. Counts of COM, FL, and GS at baseline were retrieved from the OASIS. Multivariable logistic and survival models were developed to examine the association between clinical attributes and outcomes, adjusting for demographic covariates and cancer stage.

Results

Comorbidities were associated with increased likelihood of surgery-only, but not with surgery + chemotherapy. Both FL and GS were associated with lower likelihood to undergo surgery-only or surgery + chemotherapy. Two or more GS was associated with disease-specific mortality (adjusted hazard ratio [AHR]: 2.71; 95% confidence interval [CI]: 1.80–4.07) and overall mortality (AHR: 2.34; 95% CI: 1.74–3.15). Two or more FL was associated with overall mortality (AHR: 1.33; 95% CI: 1.10–1.62), but not with disease-specific mortality. COM was not associated with overall mortality, but was negatively associated with disease-specific mortality at borderline level of significance (AHR: 0.78; 95% CI: 0.61–1.00).

Conclusion

Our findings demonstrate the importance of accounting for FL and GS, in addition to COM, when studying cancer-related outcomes in elders.

Kaposi sarcoma-associated herpesvirus (KSHV, also called Human herpesvirus 8 or HHV8) is a γ-2 herpesvirus that causes Kaposi sarcoma. KSHV seroprevalence rates vary geographically with variable rates recorded in different sub Sahara African countries, suggesting that effects of genetic and/or environmental factors may influence the risk of infection. One study conducted in South Africa, where KSHV seroprevalence is relatively low, found that carriage of human leukocyte antigen (HLA) alleles HLA-A*6801, HLA-A*30, HLA-A*4301, and HLA-DRB1*04 was associated with increased shedding of KSHV DNA in saliva. Confirmation of those results would strengthen the hypothesis that genetic factors may influence KSHV distribution by modulating KSHV shedding in saliva. To explore these associations in another setting, we used high resolution HLA-A, B, and DRB1 typing on residual samples from the Uganda Sickle Cell Anemia KSHV study, conducted in a high KSHV seroprevalence region, to investigate associations between HLA and KSHV shedding in saliva or peripheral blood among 233 children and their mothers. HLA-A and HLA-DRB1 alleles were not associated with KSHV shedding in our study, but our study was small and was not adequately powered to exclude small associations. In exploratory analyses, we found marginal association of KSHV DNA shedding in saliva but not in peripheral blood among children carrying HLA- B*4415 and marginal association of KSHV DNA shedding in peripheral blood but not in saliva among children carrying HLA- B*0801 alleles. The contribution of individual HLA polymorphisms to KSHV shedding is important but it may vary in different populations. Larger population-based studies are needed to estimate the magnitude and direction of association of HLA with KSHV shedding and viral control.

Use of single dose nevirapine (sdNVP) to prevent HIV mother-to-child transmission is associated with the emergence of NVP resistance in many infants who are HIV infected despite prophylaxis. We combined results from four clinical trials to analyze predictors of NVP resistance in sdNVP-exposed Ugandan infants. Samples were tested with the ViroSeq HIV Genotyping System and a sensitive point mutation assay (LigAmp, for detection of K103N, Y181C, and G190A). NVP resistance was detected at 6–8 weeks in 36 (45.0%) of 80 infants using ViroSeq and 33 (45.8%) of 72 infants using LigAmp. NVP resistance was more frequent among infants who were infected in utero than among infants who were diagnosed with HIV infection after birth by 6–8 weeks of age. Detection of NVP resistance at 6–8 weeks was not associated with HIV subtype (A vs. D), pre-NVP maternal viral load or CD4 cell count, infant viral load at 6–8 weeks, or infant sex. NVP resistance was still detected in some infants 6–12 months after sdNVP exposure. In this study, in utero HIV infection was the only factor associated with detection of NVP resistance in infants 6–8 weeks after sdNVP exposure.

Abstract

Use of single dose nevirapine (sdNVP) to prevent HIV mother-to-child transmission is associated with the emergence of NVP resistance in many infants who are HIV infected despite prophylaxis. We combined results from four clinical trials to analyze predictors of NVP resistance in sdNVP-exposed Ugandan infants. Samples were tested with the ViroSeq HIV Genotyping System and a sensitive point mutation assay (LigAmp, for detection of K103N, Y181C, and G190A). NVP resistance was detected at 6–8 weeks in 36 (45.0%) of 80 infants using ViroSeq and 33 (45.8%) of 72 infants using LigAmp. NVP resistance was more frequent among infants who were infected in utero than among infants who were diagnosed with HIV infection after birth by 6–8 weeks of age. Detection of NVP resistance at 6–8 weeks was not associated with HIV subtype (A vs. D), pre-NVP maternal viral load or CD4 cell count, infant viral load at 6–8 weeks, or infant sex. NVP resistance was still detected in some infants 6–12 months after sdNVP exposure. In this study, in utero HIV infection was the only factor associated with detection of NVP resistance in infants 6–8 weeks after sdNVP exposure.

Single dose (SD) nevirapine (NVP) significantly reduces HIV mother-to-child transmission. We analyzed NVP resistance after SD NVP in 57 previously SD NVP-naїve women, 34 SD NVP-experienced women, and 17 HIV-infected infants. The proportion of women with resistance, the types of mutations detected, and the frequency and level of K103N were similar in the two groups of women at 6 weeks and 6 months post-partum. NVP resistance was detected in a similar proportion of infants born to SD NVP-naїve versus SD NVP-experienced women. Repeated use of SD NVP to prevent HIV transmission does not appear to influence NVP resistance.

In Kampala, Uganda, in 2001, hepatitis C virus antibodies were found in 27 (4%) of 603 children and in 62 (12%) of 525 of their mothers. However, only ≈10% of positive results were confirmed by reverse transcription–PCR, which suggests frequent false-positive results or viral clearance. All sequenced types were genotype 4.