Parental trust in health care--a prospective study from the Children's Cancer Hospital in Egypt.

OBJECTIVE: Patient-physician communication and patient satisfaction are important elements of cancer care. Trust is considered to be crucial for the patient-physician relationship, yet little is to be found in the literature regarding what factors may influence trust. METHODS: We assessed predictors of trust in health-care professionals and in the medical care by administering two questionnaires, one at start of chemotherapy treatment and one at the time of the third chemotherapy cycle, to 304 parents of children with newly diagnosed cancer at the Children's Cancer Hospital in Cairo, Egypt. RESULTS: Parents' trust in the medical care at the time of the child's third chemotherapy cycle was significantly associated with the following at the start of treatment: having received at least moderate information about the disease (relative risk (RR) 13.2; 95% CI 7.8-22.3) and the treatment (RR 17.2; 95% CI 9.5-31.4), having the opportunity to communicate with the child's physicians (RR 21.3; 95% CI 11.7-38.8), being satisfied with the physicians conversation style (RR 30.6; 95% CI 14.4-64.9), having the emotional needs met (RR 22.2; 95% CI 11.8-41.9), and being met with care by the child's physicians (RR 32.0; 95% CI 15.2-67.7). After multivariable model selection, the strongest predictor of trust at the time of the third chemotherapy cycle was to be met with care at the start of treatment. CONCLUSION: Parents being met with care by the child's physicians at the beginning of the child's chemotherapy treatment develop an increased trust in the medical care.

Prospective study of human papillomavirus and risk of cervical adenocarcinoma.

Human papillomaviruses (HPV) are established as a major cause of cervical carcinoma. However, causality inference is dependent on prospective evidence showing that exposure predicts risk for future disease. Such evidence is available for squamous cell carcinoma, but not for cervical adenocarcinoma. We followed a population-based cohort of 994,120 women who participated in cytological screening in Sweden for a median of 6.7 years. Baseline smears from women who developed adenocarcinoma during follow-up (118 women with in situ disease and 164 with invasive disease) and their individually matched controls (1,434 smears) were analyzed for HPV using PCR. Conditional logistic regression was used to estimate odds ratios (OR) of future adenocarcinoma with 95% confidence intervals (CI). Being positive for HPV 16 in the first cytologically normal smear was associated with increased risks for both future adenocarcinoma in situ (OR: 11.0, 95% CI: 2.6-46.8) and invasive adenocarcinoma (OR: 16.0, 95% CI: 3.8-66.7), compared to being negative for HPV 16. Similarly, an HPV 18 positive smear was associated with increased risks for adenocarcinoma in situ (OR: 26.0, 95% CI: 3.5-192) and invasive adenocarcinoma (OR: 28.0, 95% CI: 3.8-206), compared to an HPV 18 negative smear. Being positive for HPV 16/18 in 2 subsequent smears was associated with an infinite risk of both in situ and invasive adenocarcinoma. In conclusion, infections with HPV 16 and 18 are detectable up to at least 14 years before diagnosis of cervical adenocarcinoma. Our data provide prospective evidence that the association of HPV 16/18 with cervical adenocarcinoma is strong and causal.

Guilt after the loss of a husband to cancer: is there a relation with the health care provided?

BACKGROUND: Feelings of guilt are common after bereavement. We investigated whether feelings of guilt after the loss of a husband to cancer are associated with the health care provided at the time close to and at the moment of death. MATERIALS AND METHODS: The study population consisted of 506 widows of men who died of prostate cancer in 1995 or of urinary bladder cancer in 1995 or 1996 at the ages 45-74 years. We collected information on the received health care at the time of the husband's death from the widows, through a postal questionnaire. RESULTS: Widows who perceived that their husbands did not get enough pain relief had an increased relative risk of 1.7 (95% CI 1.1-2.8), for guilt feelings, compared to widows who felt that their husbands had adequate pain relief. If a widow considered her husband being exposed to less satisfactory care or treatment, she had an almost two-fold increased relative risk, 1.9 (95% CI 1.2-3.1), for guilt feelings after the husband's death, compared to a widow who thought that satisfactory care or treatment was provided. DISCUSSION: Feelings of guilt after bereavement may occur in response to the perception of inadequate health care during the last months and at the actual moment of death of the significant other.

In utero nucleoside reverse transcriptase inhibitor exposure and signs of possible mitochondrial dysfunction in HIV-uninfected children.

BACKGROUND: There is equivocal evidence of in utero nucleoside reverse transcriptase inhibitor (NRTI) exposure and the occurrence of mitochondrial dysfunction (MD) in HIV-uninfected children born of HIV-infected women. METHODS: The primary analysis included 1037 HIV-uninfected children born in 1991-2002 and enrolled in Pediatric AIDS Clinical Trials Group protocols 219/219C. Possible cases with unexplained signs of MD according to the Enquête Périnatale Française criteria were identified through retrospective review. Associations between overall in utero NRTI exposure, and trimester of first in utero NRTI exposure and possible MD were estimated with exact logistic regression. RESULTS: Cases (n = 20) were significantly more likely to be male and to be born in earlier years than non-cases (n = 1017). There was no association between overall in utero NRTI exposure and MD. In unadjusted models there were higher odds of first in utero exposure in the third trimester to lamivudine (3TC) [odds ratio (OR), 3.76 versus 3TC unexposed; 95% confidence interval (CI), 1.09-11.78] and to zidovudine (ZDV) and 3TC in combination (ZDV/3TC) (OR, 3.29 vs. ZDV/3TC unexposed; 95% CI, 0.96-10.25) among cases than noncases. When adjusted for year of birth the odds of first exposure in the third trimester to 3TC (OR, 10.57; 95% CI, 1.93-75.61) and ZDV/3TC (OR, 9.84; 95% CI, 1.77-71.68) were significantly higher among cases than non-cases. Incomplete data precluded control of possible confounding by maternal viral load and psychoactive drug use. CONCLUSIONS: Our study suggests that first exposure to 3TC or ZDV/3TC in the third trimester may be associated with the occurrence of possible MD. Further studies that rigorously assess MD and better control confounding are needed.

A longitudinal Swedish study on screening for squamous cell carcinoma and adenocarcinoma: evidence of effectiveness and overtreatment.

BACKGROUND: Organized Papanicolaou (Pap) screening has markedly reduced the incidence of cervical squamous cell carcinoma (SCC). However, the potential for overtreatment of precursor lesions is quite high for SCC, and the effectiveness of Pap screening for prevention of cervical adenocarcinoma is questionable. METHODS: Using the nationwide, virtually complete Swedish Cancer Register, we analyzed standardized incidence rates for SCC in situ (CIS), SCC, adenocarcinoma in situ (AIS) and adenocarcinoma, between 1968 and 2002. For each county, we calculated Spearman correlations between incidence of in situ lesions and incidence of invasive cancer, 5, 10, and 15 years later. We also used generalized estimating equation (GEE) models to compare adjusted estimates for associations between in situ incidences and invasive carcinomas over counties. RESULTS: The overall decrease in SCC incidence in Sweden following the introduction of cervical screening confirms the beneficial nature of cervical screening on SCC incidence over the last 30 years. A similar benefit was not apparent for adenocarcinoma. GEE estimates for the relative change in SCC for an increase of 100 CIS cases per 100,000 women-years were 1.05 for the 5-year and 1.02 for the 10-year lag periods. For adenocarcinoma and AIS, similar analyses gave corresponding estimates of 1.17 for the 5-year and 1.08 for the 10-year lag periods. The lack of an inverse correlation suggests that increased reported incidence of CIS in certain counties did not forecast a reduction in SCC for those counties. CONCLUSION: Our data confirm the effectiveness of Pap smear screening in reducing the incidence of SCC, but suggest no clear benefit on adenocarcinoma. Our data also suggest that relaxed histopathologic criteria for diagnosis of cervical CIS may increase its recorded incidence with no measurable benefit in the reduction of invasive cancer.

Reproductive health of adolescent girls perinatally infected with HIV.

OBJECTIVES: We sought to describe the reproductive health of adolescent girls perinatally infected with HIV. METHODS: We estimated the incidence of first pregnancy, genital infections, and abnormal cervical cytology for 638 girls aged 13 years and older in the Pediatric AIDS Clinical Trials Group protocol 219C. RESULTS: Thirty-eight girls became pregnant, for a first pregnancy rate of 18.8/1000 person-years; 7 of these girls had additional pregnancies (95% confidence interval [CI]=13.3, 25.7). Thirty-two pregnancies resulted in live births. All girls received antiretroviral therapy during pregnancy. One infant was HIV infected, 29 were uninfected, and 2 had unknown infection status, for a rate of mother-to-child transmission of HIV in infants with known infection status of 3.3% (95% CI=0.1, 18.6). Condylomata and trichomoniasis were the most frequent genital infections. Forty-eight (47.5%) of 101 girls with Papanicolaou test examinations had abnormal cervical cytology, including atypical cells of undetermined significance (n=18), low-grade squamous intraepithelial lesions (SIL; n=27), and high-grade SIL (n=3). Many abnormalities persisted despite intervention. CONCLUSIONS: Pregnancy rates were lower and cervical abnormalities were higher than among non-HIV-infected adolescents. These findings underscore the importance of Papanicolaou tests and promotion of safer sexual practices in this population.

Synergy between cigarette smoking and human papillomavirus type 16 in cervical cancer in situ development.

BACKGROUND: A majority of studies have implicated the involvement of cigarette smoking in cervical cancer development, although its mechanism of action remains unclear. We conducted a large population-based case-control study to address the potential interaction between smoking and human papillomavirus type 16 (HPV-16) in development of cervical cancer in situ (CIS). METHODS: Information on risk factors for CIS was collected via interview, and archival cervical smears were tested for HPV-16 DNA presence in cases (n = 375) and controls (n = 363). Adjusted odds ratios (OR) for the effects of smoking, HPV-16 presence/absence, and load at first smear (taken, on average, 9 years before diagnosis) were calculated. RESULTS: The risk for CIS among current smokers who were HPV-16 positive at time of first smear was >14-fold [adjusted OR, 14.4; confidence interval (95% CI), 5.6-36.8] compared with HPV-16-negative current smokers. In contrast, the risk for CIS among HPV-16-positive nonsmokers was only 6-fold (adjusted OR, 5.6; 95% CI, 2.7-11.5), compared with HPV-16-negative nonsmokers. HPV-16-positive smokers with high viral load at time of first smear exhibited a high risk for CIS (adjusted OR, 27.0; 95% CI, 6.5-114.2) compared with HPV-16-negative smokers. Within nonsmokers, however, high HPV-16 load contributed only a 6-fold increased risk compared with HPV-16-negative nonsmokers (adjusted OR, 5.9; 95% CI, 2.4-14.6). Interaction was observed (P = 0.03) between duration of smoking and HPV-16 presence in CIS development. CONCLUSION: Results suggest a synergistic effect between smoking and both HPV-16 status and HPV-16 viral load, which may occur almost a decade before CIS detection.

Risk factors for opportunistic illnesses in children with human immunodeficiency virus in the era of highly active antiretroviral therapy.

OBJECTIVE: To examine the relationship between the use of highly active antiretroviral treatment (HAART) and the occurrence of opportunistic illnesses (OIs) among children perinatally infected with human immunodeficiency virus. DESIGN: Prospective cohort study. SETTING: Pediatric AIDS Clinical Trials Group 219C cohort. PARTICIPANTS: From September 15, 2000, to August 31, 2003, 1927 children perinatally infected with human immunodeficiency virus and receiving HAART were followed up. Main Exposures Age at initiating HAART, duration of HAART use, CD4+ T-lymphocyte percentage, and human immunodeficiency virus 1 viral load. MAIN OUTCOME MEASURES: Incidence rates for Centers for Disease Control and Prevention OI category B and OI category C events were calculated. The association between main exposures and OI occurrence was estimated using proportional hazards regression. RESULTS: Of 1927 subjects, 226 (12.7%) developed OIs during follow-up. Incidence rates were 4.99 per 100 person-years (95% confidence interval, 4.30-5.76) for first OI category B events and 1.47 per 100 person-years (95% confidence interval, 1.12-1.91) for first OI category C events. Duration of HAART use was not related to OI risk. Older age (age >10 years) at HAART initiation was associated with increased risk of a first OI (hazard ratio, 2.48; 95% confidence interval, 1.23-5.00) compared with initiating HAART in children younger than 2 years. This increased risk diminished after adjusting for CD4+ T-lymphocyte percentage and Centers for Disease Control and Prevention disease category at HAART initiation. More children with OIs than without OIs had a CD4+ T-lymphocyte percentage of less than 15% at HAART initiation (49.6% of children with OIs vs 23.7% of children without OIs), at enrollment (41.2% of children with OIs vs 7.7% of children without OIs), and at the end of follow-up (41.2% of children with OIs vs 8.3% of children without OIs). CONCLUSIONS: Opportunistic illnesses are occurring in the pediatric human immunodeficiency virus population in the HAART era, mainly in children with persistently low CD4+ T-lymphocyte percentages. Lack of a sustained response to HAART rather than age at or duration of HAART use is predictive of OI risk.

Prospective study of HPV16 viral load and risk of in situ and invasive squamous cervical cancer.

BACKGROUND: A strong association has been shown between high viral DNA load (VL) of human papillomavirus (HPV) type 16 and risk for cervical cancer in situ (CIS). However, little data is available for the significance of VL in invasive squamous cell carcinoma (SCC). METHODS: In 2 nested case-control studies among women participating in cervical screening, with a cytologically normal first smear, we collected 5,665 smears from 621 women with CIS, 457 with SCC, and individually matched controls. All smears were tested for HPV, and VLs of HPV16 positive smears were quantified using real time-PCR. The median follow-up until diagnosis of CIS or SCC was 6.1 to 7.7 years. RESULTS: Low VL's were common among both CIS and SCC case women, until 1 to 2 years before diagnosis when a surge in VL occurred. The relative risk (RR) associated with low viral load of HPV16 was around 10 for CIS, and 10 to 20 for SCC throughout 10 years before diagnosis, compared with HPV16-negative women. For women with medium to high VL, the risk for CIS was greatly increased from 5 years before diagnosis [RR, 19; 95% confidence interval (CI), 7-48]. In SCC, a high VL conferred an increased risk, but only from 3 years before diagnosis [RR, 60; 95% CI, 6-580]. CONCLUSIONS: We show differing risk functions associated with HPV16 viral load in CIS and SCC, respectively. We further show that viral loads were unexpectedly low early in the SCC disease process. IMPACT: HPV16 viral load appears highly complex which may limit its use in cervical screening.

Prospective study of human papillomavirus (HPV) types, HPV persistence, and risk of squamous cell carcinoma of the cervix.

BACKGROUND: The link between squamous cell cervical carcinoma and human papillomavirus (HPV) 16/18 is well established, but the magnitude of the risk association is uncertain and the importance of other high-risk HPV (HRHPV) types is unclear. METHODS: In two prospective nested case-control series among women participating in cytologic screening in Sweden, we collected 2,772 cervical smears from 515 women with cancer in situ (CIS), 315 with invasive squamous cell carcinoma (SCC), and individually matched controls. All smears were tested for HPV with PCR assays, and the median follow-up until diagnosis was 5 to 7 years. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (95% CI). RESULTS: The presence of HPV16/18 in the first smear was associated with 8.5-fold (95% CI, 5.3-13.7) and 18.6-fold (95% CI, 9.0-38.9) increased risks of CIS and SCC, respectively, compared with women negative for HPV. Infection with other HRHPV types in the first smear was also associated with significantly increased risks for both CIS and SCC. Persistence of HPV16 infection conferred a RR of 18.5 (95% CI, 6.5-52.9) for CIS and 19.5 (95% CI, 4.7-81.7) for SCC. The HPV16/18 attributable risk proportion was estimated at 30% to 50% for CIS, and 41% to 47% for SCC. Other HRHPV types also conferred significant proportions. CONCLUSIONS: Our large population-based study provides quantification of risks for different HPV types and prospective evidence that non-16/18 HRHPV types increase the risk for future cervical cancer. IMPACT: This study gives further insights into cervical cancer risk stratification with implications for HPV-based prevention strategies.