Quality of life in the first year after breast cancer surgery: rehabilitation needs and patterns of recovery.

BACKGROUND: Although mortality rates from breast cancer are declining, many breast cancer survivors will experience physical and psychological sequelae that affect their everyday lives. Few prospective studies have examined the rehabilitation needs of newly diagnosed breast cancer patients, and little is known about the predictors of health-related quality of life (QOL) in this population. METHODS: Between 1987 and 1990, 227 women with early stage breast cancer participated in a prospective longitudinal study in which detailed information was collected through interviews, standardized measures of QOL and psychological distress, and clinical evaluation. Comparisons of physical and treatment-related problems were made according to type of surgical treatment. Multivariate regression analysis was performed to examine the predictors of QOL at one year after surgery. RESULTS: Physical and treatment-related problems were reported frequently one month after breast cancer surgery, and occurred with equal frequency in women receiving modified radical mastectomy or breast conservation treatment. There were no significant differences in problems reported at one year by type of surgery; however, frequently reported problems include 'numbness in the chest wall or axilla,' 'tightness, pulling or stretching in the arm or axilla,' 'less energy or fatigue,' 'difficulty in sleeping,' and 'hot flashes'. There was no relationship between the type of surgery and mood or QOL. Poorer QOL one year after surgery was significantly associated with greater mood disturbance and body image discomfort one month after surgery, as well as positive lymph node involvement. Although the majority of patients experienced substantial disruptions in the physical and psychosocial dimensions of QOL post-operatively, most women recovered during the year after surgery, with only a minority (<10%) significantly worsening during that time. CONCLUSIONS: At one year after surgery, most women report high levels of functioning and QOL, with no relationship between the type of surgery and QOL. Women who reported lower levels of QOL at one year after diagnosis had greater mood disturbance and poorer body image one month after surgery, as well as lower income and positive axillary nodes.

Exact and asymptotic tests for homogeneity in several 2 x 2 tables.

This paper presents the results of a Monte Carlo study comparing the performance, in terms of size and power, of six exact and six asymptotic tests for the homogeneity of odds ratios in several 2 x 2 contingency tables. With a small sample size or sparse data structure, the exact tests performed better than the asymptotic tests because they maintained the nominal size and, in some situations, had slightly higher power. Among the exact tests, we recommend the Zelen, Pearson chi-square and scores tests. Among the asymptotic tests, the Breslow-Day and Pearson chi-square tests were slightly better in some situations than the unconditional and conditional score tests. However, both exact and asymptotic tests had low power for small strata sizes, even with moderate to large heterogeneity of odds ratios. Corroborating previous findings, the asymptotic unconditional likelihood ratio test was too liberal in terms of size.

Major expansions of select CD8+ subsets in acute Epstein-Barr virus infection: comparison with chronic human immunodeficiency virus disease.

CD8+ lymphocyte phenotypes were characterized during acute Epstein-Barr virus (EBV) infection, and a comparison was made to previous studies of human immunodeficiency virus (HIV). This was of interest because CD8+ cells contribute to immunologic control of both infections, but the usual outcome of EBV infection is benign, whereas untreated HIV infection is fatal. During acute EBV infection, CD8+ cells expressed elevated levels of the activation antigens CD38 and HLA-DR, similar to that during chronic HIV infection. Within 16 weeks, when EBV latency is established, CD8+ cell activation had resolved. In contrast, activation persists in HIV infection. Expression of CD38 and HLA-DR on CD8+ cells could be a marker for ongoing viral replication in both infections. Other CD8+ cell alterations observed in this study of acute EBV infection included increases in both CD62L- and CD62L+ CD8+ cells and unique kinetics in the expansion of the CD57+CD8+ cell subset.

Shortened telomeres in the expanded CD28-CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis.

OBJECTIVE: To test the hypothesis that the expanded population of non-proliferative CD28-CD8+ T cells in HIV disease have shortened telomeres, thereby providing evidence that increased rounds of CD8+ cell division occur during HIV disease, possibly leading to replicative senescence and exhaustion of CD8+ T-cell responses. DESIGN: CD8+ cells play a central role in control of HIV infection. In late HIV disease, an expanded population of CD28-CD8+ cells with reduced proliferative potential has been documented. A similar population of CD28-CD8+ cells has been identified in ageing humans, where telomere length measurements have suggested that these cells have reached the irreversible state of replicative senescence. METHODS: CD8+ cells from HIV-infected and control subjects were sorted by flow cytometry into CD28+ and CD28- fractions. Telomere lengths were determined as mean terminal restriction fragment (TRF) lengths by Southern hybridization. RESULTS: The TRF lengths of sorted CD28-CD8+ cells in HIV-infected subjects ranged between 5 and 7 kilobases (kb) and were significantly shorter than TRF lengths of CD28-CD8+ cells in uninfected subjects (P = 0.003). The TRF length in CD28-CD8+ cells from HIV-infected subjects was the same as that observed for centenarian peripheral blood mononuclear cells and is compatible with a state of replicative senescence. CONCLUSIONS: The shortened telomeres in the CD28-CD8+ cells in HIV-infected subjects and the poor proliferative potential of these cells identifies CD8+ cell replicative senescence as a newly described feature of HIV disease. Our results provide a mechanism for the loss of CD8+ cell control of viral replication that accompanies advanced HIV disease. Replicative senescence may contribute to exhaustion of the T-cell response as a result of chronic HIV disease. Whether this phenomenon occurs in other chronic viral infections is unknown.

Persistently seronegative men from whom HIV-1 has been isolated are genetically and immunologically distinct.

Studies in both monkeys and humans have suggested that transient infection with HIV-1 can occur without provoking a measurable humoral immune response. The objective of this study was to look for genetic and immunologic correlates of transient HIV-1 infection in antibody-negative men from whom HIV-1 had been isolated. The distributions of MHC class I, class II, and TAP (transporter protein associated with antigen processing) region genes were compared between 23 persistently seronegative men from whom HIV-1 was isolated at least once (isol+/Ab-) and 137 men who seroconverted. A subset of 13 of the 23 isol+/Ab- men were compared to 27 seronegative men for distribution of CD25+CD4+ and CD25+CD8+ cells in the absence of exogenous immunologic stimulation. The prevalences of the TAP1.4, and a combination of TAP1.4, and TAP2.3 variants were significantly higher in the isol+/Ab- men. The proportion of CD8+ cells that expressed CD25+ antigen was also significantly higher in the isol+/Ab- men than in the seronegative men. We conclude that isol+/Ab- men may be genetically and immunologically distinct from HIV-1 susceptible men. We hypothesize that activated CD8+ cells may have cleared HIV-1 infection in these men through genetically mediated influences of the TAP genes on the presentation of peptides by HLA class I molecules.

Natural killer cell immunodeficiency in HIV disease is manifest by profoundly decreased numbers of CD16+CD56+ cells and expansion of a population of CD16dimCD56- cells with low lytic activity.

Natural killer (NK) cells were enumerated by three-color immunofluorescence in 255 uninfected and 399 human immunodeficiency virus-infected adults. Several dramatic alterations were observed. First, the median number and percentage of CD16+CD56+ NK cells, the subset that comprises > 90% of the NK cells in healthy adults, were severely decreased (median, 175/mm3 in uninfected controls; 63/mm3 in HIV-infected non-AIDS subjects). Even subjects with > 800 CD4+ cells/mm3 had decreased CD16+CD56+ NK cell levels (97/mm3). Second, the number of CD16+CD56- cells, an NK population that is rare in healthy adults, was elevated (median, 20/mm3 in uninfected controls; 64/mm3 in HIV-seropositive non-AIDS subjects). Third, the expression of CD16 on the NK cells was markedly reduced; some CD56+ cells and virtually all CD56- cells were CD16dim. Fourth, fluorescence-activated cell-sorting studies revealed little NK- or antibody-dependent cellular cytotoxic activity in the CD16dimCD56- cell population. These results indicate that the pathogenesis of HIV disease includes numerical alterations in subpopulations of NK cells. A better understanding of how HIV infection causes this aspect of pathogenesis is needed.

Exact power computation for dose-response studies.

The toxicity of an agent or the therapeutic effect of a drug may be assessed by a dose-response study. We present a method for computing the exact power of exact and large sample statistical tests employed for binary response data from such a study. This method, based on recursive polynomial multiplications, enables fast computation of exact power for studies with up to a moderately large sample size. We demonstrate the efficiency of our method using three examples. The method is suitable for the design and power analysis of dose-response studies in which the usual asymptotic approximations are suspect.

Effects of a program to train radiologic technologists to identify abnormalities on mammograms.

PURPOSE: To assess whether radiologic technologists could be successfully trained to identify abnormalities on mammograms. MATERIALS AND METHODS: Eight radiologic technologists from two different institutions took a pretest, underwent an 8-hour training course followed by a period of preceptorship, and then took a posttest. Seven radiologists also took the pretest and posttest, which consisted of evaluating 1,238 two-view screening examinations, including 318 biopsy-proved cancers. RESULTS: Overall, technologists at institution 1 had lower sensitivity (78%) at the pretest, which improved at the posttest (90%). Technologists at institution 2 had lower specificity at the pretest (44%), which improved on the posttest (64%). Hypothetical pairing of radiologists and technologists with use of posttest results revealed an increase in sensitivity (median increase, 12% at institution 1 and 19% at institution 2). CONCLUSION: Formalized training successfully modified the technologists' skills. Radiologic technologists could be used to increase the number of breast cancers detected at screening mammography.

Exact analysis for paired binary data.

This paper provides an efficient algorithm to generate exact distributions for the bivariate logistic model with common and sub-unit-specific covariates. The algorithm can be used to analyze correlated paired binary response data from studies lacking a large sample size. Possible applications include a clinical trial with two distinct binary outcomes, a binary outcome cross-over or two-time point cohort study, and a pair-matched prospective study with binary outcome. Analysis of data from an ophthalmologic study is provided to illustrate the method. Extension to three or more correlated binary responses is also outlined.

CD8+ lymphocyte activation at human immunodeficiency virus type 1 seroconversion: development of HLA-DR+ CD38- CD8+ cells is associated with subsequent stable CD4+ cell levels. The Multicenter AIDS Cohort Study Group.

Subsets of activated CD8+ lymphocytes defined by membrane expression of the activation antigens HLA-DR and CD38 were counted by three-color flow cytometry in homosexual men who subsequently became seropositive for human immunodeficiency virus type 1 (HIV). Profound CD8+ cell activation was seen in all subjects at seroconversion and 6 and 12 months later. The HLA-DR+ CD38+ CD8+ cell population, which has potent direct HIV cytotoxic T cell activity, was markedly elevated at seroconversion in all subjects. In some men, these levels remained elevated throughout the first year of infection. During the next 5 years, these men had stable CD4+ cell levels, whereas the others did not. Long-term survivors (seropositive for 9 years, > 800 CD4+ cells/mm3) also had elevated levels of this subset, despite few other activated CD8+ cells. Thus, selective elevation of HLA-DR+ CD38- CD8+ cells was a marker of subsequent stable HIV disease.

Efficient power computation for exact and mid-P tests for the common odds ratio in several 2 x 2 tables.

When designing a study that may generate a set of sparse 2 x 2 tables, or when confronted with 'negative' results upon exact analysis of such tables, we need to compute the power of exact tests. In this paper we provide an efficient approach for computing exact unconditional power for four exact tests on the common odds ratio in a series of 2 x 2 tables. These tests are the traditional exact test; a test based on a probability ordering of the sample space; and two tests based on ordering the sample space according to distance from the mean, or median. For each test, we consider both a conservative version and a mid-P adjusted version. We explore three computational options for power determination: exact power computation, calculation of exact upper and lower bounds for power, and Monte Carlo confidence bounds for power. We present an interactive program implementing these options. For study design, the program may be run several times to arrive at a sample configuration with adequate power.

An assessment of the use of anthropometric measures for predicting low birth weight.

We report results of an evaluation of two anthropometric surrogates, viz chest circumference and mid-arm circumference, of birth weight. Optimal criteria for predicting birth weight below 2000 g and below 2500 g were provided by use of chest circumference alone. However, even the best criterion was not very sensitive indicating that use of anthropometric surrogates may have a limited practical value.

Predicting psychosocial risk in patients with breast cancer.

Breast cancer is the most common neoplasm in North American women. The psychosocial impact of breast cancer has been extensively studied, and a number of investigators have attempted to characterize women who are at high risk for increased psychosocial morbidity. Although a detailed interview performed by a professional is the clinical standard for psychosocial assessment, such interviews are usually time-consuming and expensive, and thus are rarely performed. This study was designed to develop a strategy for the rapid identification of newly-diagnosed breast cancer patients at risk for psychosocial morbidity. A sample of 227 newly diagnosed breast cancer patients were interviewed systematically by a clinical social worker and were subsequently classified for risk of psychosocial distress in the year after diagnosis. In addition, these women completed a battery of standardized instruments designed to assess quality of life, rehabilitation needs and psychological distress. A logistic regression procedure was used to examine a wide range of variables for their ability to correctly classify the risk of psychosocial distress in this sample. The final model included the Cancer Rehabilitation Evaluation System (CARES) Psychosocial Summary Scale, the Karnofsky Performance Status score and age as the best predictors of psychosocial risk. Subsequently these three variables were used to construct a clinically usable risk prediction model. Additional research should be performed to validate this predictive model.

Describing the health-related quality of life impact of HIV infection: findings from a study using the HIV Overview of Problems--Evaluation System (HOPES).

This study aimed to describe the results of findings from data collected with an HIV-specific health-related quality of life tool, and to examine the relationship between clinical and biological factors and health-related quality of life (HRQL). Data were collected as a cross-sectional, patient-completed assessment of health-related quality of life. Laboratory data were abstracted from the medical chart. Patients (n = 318) with HIV infection including asymptomatic (37%), ARC (20%), AIDS (25%), and AIDS with cancer (18%) were receiving health services at one of the medical centres serving HIV-infected patients in the Los Angeles community, including UCLA, community physicians, Veterans Affairs Medical Centers, and a county hospital. Additional data were contributed by the Johns Hopkins University Medical Center CMV Retinitis Clinic. Symptomatic patients and patients with the lowest CD4 counts reported poorer HRQL than asymptomatic patients and patients with higher CD4 counts. However, medical and demographic variables explained only 35% of the variability of HRQL ratings in this sample of HIV-infected patients. While clinical status and Karnofsky performance status may be used to estimate the impact of HIV infection on HRQL, they are not a substitute for independent assessment of HRQL by the patient.

Characteristics of women at risk for psychosocial distress in the year after breast cancer.

PURPOSE: To provide a detailed description of rehabilitation problems of women, considered to be low risk and at risk for psychosocial morbidity, diagnosed with stage I and II breast cancer 1 month and 1 year after primary treatment. PATIENTS AND METHODS: A sample of 227 newly diagnosed breast cancer patients were systematically interviewed by a clinical social worker and classified for risk of psychosocial distress in the year after diagnosis. They completed a battery of standardized instruments to assess quality of life (QL), rehabilitation needs, and psychologic distress. The primary QL instrument, the Cancer Rehabilitation Evaluation System (CARES), provides a detailed listing of rehabilitation needs. Descriptive CARES data are presented with comparisons between the two groups. RESULTS: The at-risk women had significantly more problems with greater severity than the low-risk women in all areas (physical, psychosocial, medical interaction, sexual, and marital). While both groups showed improvement over the year following diagnosis, the at-risk group had significantly more problems 1 year later. Many physical problems subside, but problems at the local surgical site, psychologic distress, communication with marital partners, and negative body image are more persistent in the at-risk group 1 year later, while half of both groups continue to have sexual dysfunction. CONCLUSION: The detailed listing of problems provided by the CARES may be helpful to clinicians in their interactions with patients. The need for preventive and early intervention for the at-risk patients is underscored.

Nosocomial bacterial infections among children with severe protein energy malnutrition.

The incidence of hospital acquired acute bacterial infections among 164 severely malnourished children admitted to the paediatric wards at the Muhimbili Medical Centre in Dar es Salaam were studied. On admission, ninety two per cent of the patients had at least one form of bacterial infection. During the subsequent two weeks hospital stay, 49% of the patients acquired a new infection. Septicaemia and urinary tract infection (UTI) were the commonest infections. Staphylococcus aureus was the commonest organism in the former, while gram negative organisms, Escherichia coli and Klebsiella species, were predominant in the latter. Pathogens similar to those found from patients were cultured from random samples taken from the floor, beds, towels, sinks and antiseptic containers in the wards. Sensitivity patterns of isolated pathogens to antimicrobial agents showed that S. aureus was highly sensitive to cloxacillin, erythromycin, and gentamicin, while the gram negative organisms were highly sensitive to gentamicin. Our study shows that the problem of nosocomial infection in paediatric wards requires urgent attention. There is a need to institute preventive measures including provision of proper nursing care, maintenance of sterile environment, and reduction of duration of hospital stay.

PIP: The incidence of hospital acquired acute bacterial infections among 164 several malnourished children admitted to the pediatric wards at the Muhimbili Medical Centre in Dar es Salaam, Tanzania, were studied. On admission, a thorough physical examination and blood and urine cultures were done on each child. Cultures from ears, throat, skin, rectum, or stools were taken. 89 (54%) were males and 75 (46%) were females with an age range of 2-59 months. 90 (55%) had marasmus, 39 (24%) had kwashiorkor, and 35 (21%) had marasmic-kwashiorkor. On admission, 32 (82%) of the kwashiorkor cases and 88 (98%) of the marasmus cases had at least 1 bacterial infection (p 0.05), a statistically significant difference. The children were followed up for 2 weeks when repeat blood and urine cultures were done for all. Antibiotic sensitivity was determined by the single disc diffusion method for antimicrobial agents used (penicillin, ampicillin, erythromycin, gentamicin, cloxacillin, chloramphenicol, contrimoxazole, nitrofurantoin, and sulphonamide). Samples were taken from randomly selected sites in the wards: 20 from floors, 20 from sinks, 20 from towels, 20 from beds, and 20 from antiseptic container. By the end of their stay in the hospital, 80 (49%) of the patients had acquired a nosocomial infection. 24 (62%) kwashiorkor cases had a nosocomial infection, while 15 (44%) of marasmus-kwashiorkor as well as 41 (45%) of the marasmus patients had such an infection. 72% of female patients were at a higher risk of acquiring an infection compared with the males (46%) (P 0.05). E. coli and Klebsiella species were the most frequently detected organisms in urine, while Staphylococcus aureus was most common in blood. Of the 100 specimens taken from the wards, 38 yielded S. aureus, 26 yielded Klebsiella species, 10 had Streptococcus faecalis, and 4 had E. coli. Erythromycin, cloxacillin, and gentamicin had a strong effect against s. aureus. Klebsiella species and E. coli were completely sensitive to gentamicin. All 10 isolates of S. faecalis from the wards were sensitive to ampicillin, erythromycin, and penicillin.

Carcinoma of the male breast in Tanzania.

This is a retrospective study of male mammary carcinoma in Tanzania based on biopsy material received from 1974 to 1987 at the Tanzania Cancer Registry. In a series of 1104 cases of breast cancer, 76 or 6.5% were male. This compares with approximately 1% in Western literature, and a similar or higher percentage in some other African countries. In Africa, medical facilities are limited, and appropriate surgical treatment, radiotherapy, and chemotherapy are difficult to procure. By the time cases reach the main hospitals, the cancer is often in a very advanced stage. Thus, there is a need to ensure early referral of cases. Further, for disseminated carcinoma, the more frequent use of orchidectomy should be considered. Orchidectomy is a simple and potentially effective procedure that can be undertaken at any hospital.