Active symptom monitoring for premenopausal women with breast cancer initiating adjuvant endocrine therapy: Protocol for the SWOG S2010 randomized controlled efficacy trial.

BACKGROUND: Premenopausal women with early stage, high risk hormone receptor positive breast cancer are at risk of early discontinuation of adjuvant endocrine therapy (ET), primarily because of toxicity, which can increase the risk of disease recurrence and death. We hypothesize that identification of bothersome symptoms between clinic visits, and automated notification of clinicians about symptoms, will result in improved persistence with ET. METHODS: Pre- and perimenopausal women planning to receive adjuvant treatment with tamoxifen or an aromatase inhibitor plus ovarian function suppression or ablation for treatment of breast cancer are eligible. A total of 540 participants will be enrolled and randomized 1:1 to patient education with or without Active Symptom Monitoring (ASM). The ASM intervention includes 6 symptom questions (hot flashes, sadness, anxiety, insomnia, vaginal dryness, joint pain) that will be completed via text, email, or telephone weekly for 24 weeks, then every 4 weeks for 48 weeks. All participants will complete a battery of questionnaires every 12 weeks to examine symptoms, beliefs about medicine, self-efficacy, and ET adherence. Optional blood draws will be collected at baseline and after 12, 48, and 72 weeks of therapy to examine estradiol and ET concentrations. The primary endpoint is time to nonpersistence with initially prescribed ET within the first 72 weeks, evaluated using Kaplan-Meier plots and multivariable Cox regression. CONCLUSION: We expect early identification and management of ET-related toxicities to improve persistence with breast cancer therapy, breast cancer outcomes, and quality of life for premenopausal women at high risk of breast cancer recurrence. CLINICALTRIALS: govNCT05568472.

Relationship between platinum-DNA adducts in leukocytes of patients with advanced germ cell cancer and survival.

Platinum-DNA adducts can be measured in peripheral blood leukocytes during platinum-based chemotherapy, and high adduct levels have been correlated with favorable clinical response in patients with germ cell cancer. Twenty-five patients with advanced germ cell cancer were treated with platinum-based chemotherapy regimens using the same dose and schedule of cisplatin. Platinum-DNA adducts were measured by atomic absorption spectrometry on the first and fifth days of the first cycle of cisplatin-based therapy. The patients were followed prospectively for 6-35 months (median, 26 months). Twenty-two patients had adduct levels measured 24 h after the first dose of cisplatin. There was no difference in the mean adduct levels of those who were alive and without progression of disease compared to those who were dead or progressing (P = 0.65). Twenty-three patients had day 5 adduct levels measured. The mean day 5 adduct level in the 15 patients who were alive and without progression was 62.133 fmol/microgram compared to 153.50 fmol/microgram in the patients who were dead or progressing (two-sided P = 0.02). Contrary to previous reports, these data indicate that high platinum-DNA adduct levels do not correlate with favorable outcome in patients with advanced germ cell cancer.

Preventing pneumococcal bacteremia in patients at risk. Results of a matched case-control study.

BACKGROUND: Three randomized controlled trials of the effectiveness of pneumococcal vaccine in elderly and chronically ill adults in the United States have failed to show significant protective efficacy during 44,213 person-years of follow-up. Case-control studies have greater statistical power to detect significant prevention of rare diseases such as pneumococcal bacteremia, but they also have a greater susceptibility to bias, necessitating consistent results from multiple studies. Three case-control studies at two different universities have shown prevention of systemic infection, but another study found no benefit. METHODS: Patients with pneumococcal bacteremia who were at least 2 years old and had chronic illness indicating the need for pneumococcal vaccine, or who were at least 65 years old were compared with matched control subjects for frequency of prior vaccination. Matching variables included date of admission, age, sex, race, type and duration of chronic illness serving as the major vaccine indication, number of vaccine indications and number of medical hospitalizations since licensure of the pneumococcal vaccine in 1978, and type of primary medical care. RESULTS: Pneumococcal vaccination was documented in the records of six (7%) of 85 cases and 26 (17%) of 152 control subjects, suggesting 81% efficacy in conditional logistical regression analysis (95% confidence interval, 34% to 94%, P = .008). CONCLUSIONS: Four case-control studies at three universities have now demonstrated significant protective efficacy of pneumococcal vaccine for preventing pneumococcal bacteremia. The development of antibiotic-resistant Streptococcus pneumoniae indicates an urgent need for an increased rate of vaccination among high-risk patients and for the development of more immunogenic conjugate vaccines that may enhance efficacy among elderly and immunocompromised patients as well as infants.

Seroepidemiology of hepatitis D (delta agent) and hepatitis B among Virginia State prisoners.

A serosurvey of hepatitis D (HDV) and hepatitis B (HBV) was conducted in an asymptomatic population of newly incarcerated prison inmates in Virginia. Of 459 men entering the prison, 445 provided both sera and demographic and personal information. Six (1.3%) had antibody to HDV (anti-HDV). Evidence of past infection with HBV was found in 146 (32.8%); 9 (2.0%) were positive for HBV surface antigen (HBsAg). HBV seropositivity correlated with intravenous drug abuse, nonwhite race, and tattoos acquired in prison. Sera obtained after an interval of seven to ten months revealed seroconversion to anti-HDV in one of two HBsAg-positive men who admitted to parenteral drug use while incarcerated. Because he had been incarcerated elsewhere for more than one year before entering this prison, it is concluded that HDV transmission occurred in prison. The association of HDV infection with progression to chronic active and fulminant hepatitis suggests that serologic surveillance of HBsAg-positive inmates may be indicated for identification of possible HDV index cases.

Employment outcomes among survivors of common cancers: the Symptom Outcomes and Practice Patterns (SOAPP) study.

INTRODUCTION: Risk factors for employment difficulties after cancer diagnosis are incompletely understood, and interventions to improve post-cancer employment remain few. New targets for intervention are needed. METHODS: We assessed a cohort of 530 nonmetastatic cancer patients (aged ≤ 65 years, >6 months from diagnosis, off chemo- or radiotherapy) from the observational multi-site Symptom Outcomes and Practice Patterns study. Participants reported employment change, current employment, and symptoms. Groups were based on employment at survey (working full- or part-time versus not working) and whether there had been a change due to illness (yes versus no). The predictive power of symptom interference with work was evaluated for employment group (working stably versus no longer working). Race/ethnicity, gender, cancer type, therapy, and time since diagnosis were also assessed. Association between employment group and specific symptoms was examined. RESULTS: The cohort was largely non-Hispanic white (76 %), female (85 %), and diagnosed with breast cancer (75 %); 24 % reported a change in employment. On multivariable analysis, participants with at least moderate symptom interference were more likely to report no longer working than their less effected counterparts (odds ratio (OR) = 8.0, 95 % CI, 4.2-15.4), as were minority participants compared with their non-Hispanic white counterparts (OR = 3.2, 95 % CI, 1.8-5.6). Results from the multiple regression model indicated the combination of fatigue (OR = 2.3, 95 % CI, 1.1-4.7), distress (OR = 3.9, 95 % CI, 1.7-9.0), and dry mouth (OR = 2.6, 95 % CI, 1.1-6.2) together with race/ethnicity and time since diagnosis adequately accounted for employment group. CONCLUSIONS: Our findings support the hypothesis that residual symptom burden is related to post-cancer employment: Residual symptoms may be targets for intervention to improve work outcomes among cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: This analysis examines whether increased symptom burden is associated with a change to not working following a cancer diagnosis. We also examined individual symptoms to assess which symptoms were most strongly associated with not working after a cancer diagnosis. Our hope is that we will be able to use this information to both screen survivors post-active treatment as well as target high-risk symptoms for further and more aggressive intervention, in an attempt to improve post-cancer work outcomes.

Predicting death in patients hospitalized for community-acquired pneumonia.

OBJECTIVE: To validate a previously reported discriminant rule for predicting mortality in adult patients with primary community-acquired pneumonia and to determine which factors available at hospital admission predict a fatal outcome among such patients. DESIGN: Historical cohort study. SETTING: University hospital. PATIENTS: Adults admitted to the hospital for community-acquired pneumonia. MEASUREMENTS: Using stepwise logistic regression, we analyzed prognostic factors (data available at admission and recorded in the medical record) that showed a univariate association with mortality. The predictive values of three discriminant rules were measured to validate the results of a previous study. MAIN RESULTS: Of 245 patients, 20 (8.2%) died. Of 42 prognostic factors identified in previous studies, 8 were associated with mortality, but only a respiratory rate of 30/min or more, a diastolic blood pressure of 60 mm Hg or less, and a blood urea nitrogen of more than 7 mmol/L remained predictive in the multivariate analysis. A discriminant rule composed of these three variables was 70% sensitive and 84% specific in predicting mortality, yielding an overall accuracy of 82%. CONCLUSION: Tachypnea, diastolic hypotension, and an elevated blood urea nitrogen were independently associated with death from pneumonia in our study, confirming the value of a previously reported discriminant rule from the British Thoracic Society. This rule may be useful in triage decisions because it identifies high-risk patients who may benefit from special medical attention.

The seroprevalence of cytomegalovirus among Virginia State prisoners.

A prevalence serosurvey of adult male prisoners entering the Virginia State Prison was conducted to evaluate the epidemiology of cytomegalovirus within this population. Four hundred and forty-five (97%) of 459 male inmates provided serum for analysis and 427 completed a detailed demographic questionnaire. Sera were tested for cytomegalovirus by passive latex agglutination and 64% were reactive. Multivariate discriminant analysis showed an independent association of seropositivity with age, non-white race, and a history of gonorrhea. There was no apparent contribution from admitted homosexual contact though this may have been under-reported. There was no correlation of seropositivity with intravenous drug use or with the length or number of prior incarcerations. Prisoners possess the same correlates for cytomegalovirus seropositivity as the general adult population; past imprisonment did not independently contribute to cytomegalovirus seropositivity.

Enterobacter endocarditis.

Endocarditis due to Enterobacter species is very rare. We recently cared for a patient who developed E. cloacae endocarditis following mitral valve replacement with a porcine heterograft, and was successfully treated with antibiotic therapy alone. A review of the literature disclosed an additional 17 well-described cases of enterobacter endocarditis. Two-thirds of the patients had underlying cardiac disease. The mitral valve was most frequently involved (10/16 cases) with 4 of the patients having concomitant aortic valve involvement. The overall mortality rate was 44.4%. Antibiotic therapy of enterobacter endocarditis should consist of the combination of a beta-lactam antibiotic and an aminoglycoside with careful monitoring of blood cultures to assure the adequacy of therapy. Resistance of enterobacter to previously susceptible antibiotics may occur during therapy due to induction of a chromosomally-mediated beta-lactamase, necessitating a change in antimicrobial therapy. Valvular surgery is indicated for patients failing medical management.

Use of the aromatase inhibitor anastrozole in the treatment of patients with advanced prostate carcinoma.

BACKGROUND: Men with prostate carcinoma initially respond to therapies designed to inhibit androgen secretion or block its action. Later, the tumors in these patients become refractory to androgen-related therapies. Therefore, additional hormonal maneuvers that would benefit these men currently are needed. Reports of androgen receptor mutations and historic clinical observations raised the hypothesis that estrogens might be involved in the proliferation of androgen-refractory prostate carcinoma. METHODS: To explore this hypothesis, 14 men with advanced prostate carcinoma that was refractory to medical or surgical orchiectomy and antiandrogens were entered into a clinical Phase II trial involving suppression of estrogens. After complete evaluation, each patient received 1 mg daily of the third-generation aromatase inhibitor anastrozole until disease progression. Follow-up included serial determinations of prostate specific antigen (PSA), measurements of evaluable lesions, and assessment of intensity of pain. RESULTS: No patient experienced an objective response or disease stabilization as measured by PSA level or the greatest dimension of the lesion. Minimal improvement of bone pain was reported in two patients receiving intensive analgesic medication. CONCLUSIONS: It was concluded that the dependence of androgen-insensitive prostate carcinoma on estrogens for proliferation is uncommon and that aromatase inhibitors may not have a place in the treatment of prostate carcinoma at this stage of the disease.

Efficacy of an attachable subcutaneous cuff for the prevention of intravascular catheter-related infection. A randomized, controlled trial.

We performed a randomized controlled trial of an attachable subcutaneous cuff for the prevention of central vascular catheter-related infection among patients receiving intensive care. Catheters were placed percutaneously into new sites with or without a cuff and were dressed with polyantibiotic ointment containing polymyxin, neomycin, and bacitracin. Microbial colonization developed in 34.5% of 29 control and 7.7% of 26 cuffed catheters. Catheter-related bloodstream infection occurred with 13.8% of control vs 0% of cuffed catheters. The cuff was not associated with adverse effects. An unexpectedly large proportion (75%) of catheter infections were due to Candida albicans. This may have been due, in part, to the use of polyantibiotic ointment, as suggested by a pooled analysis of previous trials that demonstrated increased Candida colonization of catheters with the ointment, which is not fungicidal. These data suggest that the cuff can reduce the incidence of catheter-related infection among high-risk patients receiving catheter site care with an antibacterial ointment.