Pretreatment prognostic factors for survival in small-cell lung cancer: A new prognostic index and validation of three known prognostic indices on 341 patients

Aims: a) To identify which pretreatment clinical or blood parameters werepredictive of patient survival in small-cell lung cancer (SCLC) in aretrospective analysis. b) To validate three known prognostic indices: RoyalMarsden Model (index 1), London Group (index 2) and Manchester Score (index3).Patients and methods: From 1981 to 1993, 341 SCLC patients were treatedwith chemotherapy with or without surgery or radiotherapy. Univariate andmultiple regression analyses of survival were performed and the feasibilityof these models was explored, index 1: Karnofsky index, albumin, sodium andalkaline phosphatase; index 2: ECOG performance status (PS), albumin andalanine transaminase; and index 3: lactate dehydrogenase (LDH), diseaseextent, sodium, Karnofsky index, alkaline phosphatase and bicarbonate.Results: Significant prognostic factors for survival after univariate andmultiple regression analysis were: disease extent, PS, creatine kinase,neutrophilia, LDH, hypoalbuminemia, hyperglycemia and bicarbonate. A newprognostic index was performed that included LDH, hypoalbuminemia,neutrophilia, disease extent and PS. It defined three prognostic groups (PG).Median survival and two-year survival for these PG were 12.3, 8 and 3.4 monthsand 16.5%, 2.3% and 0%, respectively. The following PGwere identified after application of the three models proposed: Index 1identified two PG with 0% and 16.6% two-year survival (P <0.001); index 2 detected three PG with 0%, 5% and 15.7%two-year survival (P < 0.001) and index 3 detected three PG with 0%,2.5% and 16.2% two-year survivals, respectively (P < 0.001).Conclusion: A new prognostic index is proposed allowing identification ofthree different PG. The feasibility of three known prognostic models wasvalidated and demonstrated. Variables other than disease extent or PS (albuminor LDH) should be taken into account in designing future clinical trials.     

A comparison of perinatal mortality between ethnic Chinese and ethnic whites: Why the Chinese rate was lower

Objectives. To confirm the observation that has been occasionally reported in the literature that perinatal mortality rate is lower in ethnic Chinese than in ethnic whites, and to assess the reasons for this lower perinatal mortality rate.

Methods. Secondary‐analysis based on published data.

Results. This exercise demonstrates that the perinatal mortality rate was lower in ethnic Chinese than in ethnic whites. The birth weight distribution in ethnic Chinese was more favourable with reduced births at two extremes of the distribution, and the exposure to risk factors for perinatal death by their mothers was also lower.

Conclusion: Perinatal mortality rate is lower in ethnic Chinese than in ethnic whites, and the lower perinatal mortality rate in ethnic Chinese is probably caused by their favourable birth weight distribution and lower exposure to risk factors of perinatal death by their mothers.     

Age as a prognostic factor in the malignant melanoma population

Background: The incidence of malignant melanoma is increasing faster than any other cancer, and the state of Florida has one of the highest incidence of melanoma in the United States. This increased incidence is thought to be due to the intense sunlight exposure and ultraviolet radiation exposure in the elderly population. With the increased emphasis on issues of aging, it is appropriate to study the role of age as a prognostic factor for malignant melanoma in the Florida population. Methods: A retrospective, computer-aided search identified 442 consecutively registered patients with malignant melanoma at the Cutaneous Oncology Program. All patients had stage 1 or 2 disease (cutaneous disease only) at diagnosis. Prognostic variables analyzed included the most powerful factors for stage 1 and 2 melanoma, tumor thickness, ulceration, and Clark level of invasion. Other prognostic variables included in the analysis were the clinical variables of sex and primary site (axial vs. extremity). The population was divided into patients 65 and >65 years of age. Results: Significant disease-free survival differences were encountered in the older population, with only 55% of the elderly population being disease free at 5 years compared with 65% for the younger population (p=0.0073). However, a greater percentage of patients with melanoma who were >65 years of age had ulcerated lesions (17.5% vs. 12.9%) and a greater percentage of thick lesions at diagnosis (67.2% vs. 62.7%). Both of these prognostic factors would bias the older population with a poorer survival. A stepwise regression analysis of the entire population was performed, treating age as a continuous variable. Surprisingly, increasing age along with tumor thickness were the only significant predictors for disease-free survival. After inclusion of these two prognostic variables, none of the other prognostic factors, including Clark level, ulceration, sex, and primary site, added to the prognostic model. Conclusions: From this analysis, it is apparent that geriatric patients with melanoma have a worse prognosis than a younger control population, even after the correction for the more commonly cited prognostic factors. This information should be used in mathematical modeling to identify high-risk populations who are candidates for perhaps more aggressive primary or adjuvant therapies.Presented at the 46th Annual Cancer Symposium of The Society of Surgical Oncology, Los Angeles, California, March 18–21, 1993.     

Age-related differences in breast cancer treatment

Background: More than half of the cases of breast cancer treated in the United States occur in women over age 65. This study investigates age-related differences in breast cancer therapy. Methods: A retrospective review of all women with primary operable invasive breast cancer treated at the University of Michigan Breast Care Center over a 30-month period showed a total of 77 older patients aged 65 years (median, 71; oldest patient, 92) for whom full information was available regarding comorbidity, tumor stage and histology, and details of surgery, radiation, and chemohormonal therapy and complications. Fifty-one similar younger patients aged 55–64 years (median, 59) were identified for comparison. Patients were classified as either having received standard treatment or nonstandard treatment. Standard therapy was prospectively defined as follows: local/regional—lumpectomy and axillary lymph node dissection plus radiation therapy or modified radical mastectomy; systemic—chemotherapy and/or tamoxifen for stage II disease. A comorbidity score calculated for each patient assigned one point each for nursing home residence, nonambulatory status, recent surgery, and each medical problem requiring drug therapy. Results: When overall treatment (local/regional plus systemic) was assessed, proportionately fewer older patients (55 of 77 versus 47 of 51;p<0.01) received standard treatment. Fewer older than younger patients (62 of 77 versus 50 of 51;p<0.01) received surgical therapy that included an axillary dissection. A smaller proportion of older patients received radiation therapy following lumpectomy and axillary lymph node dissection (26 of 29 versus 19 of 19; N.S.). Overall, only 59 of 77 older patients versus 50 of 51 younger patients (p<0.001) received standard local/regional care. Similar proportions of younger and older patients (19 of 22 and 24 of 30, respectively) received standard systemic therapy for stage II breast cancer, but older patients were less likely to receive chemotherapy than younger patients (7% versus 50%;p<0.001). Treatment-related complications were not age-related but were more frequent in patients receiving standard treatment than in patients receiving nonstandard treatment (45 of 102 versus two of 26;p<0.001). Comorbidity score correlated with the use of nonstandard therapy but not with age. The scores for both older and younger patients receiving overall standard treatment were 0.8 versus 1.5 and 1.4, respectively, in patients receiving nonstandard treatment. Interestingly, explanations for decisions to deviate from standard treatment guidelines were often not identified. Comorbidity was explicitly noted in only one of four younger patients who received nonstandard treatment therapy. In 22 older patients who received nonstandard treatment, comorbidity was cited in eight cases, patient age was cited in six cases, and patient choice was cited in four cases. Follow-up (median, 34 months) did not show that disease-free or overall survival differences were related to age or to treatment (standard versus nonstandard). Conclusions: These data demonstrate age-related variations in breast cancer treatment in a multidisciplinary breast care unit. Lower complication rates and equivalent short-term outcomes in women who received nonstandard therapy suggest good clinical judgment may have played a role in these differences. Although age-related patient preferences and comorbidity are relevant, the age-related attitudes of caregivers must also be taken into account to fully explain these variations.Presented at the 46th Annual Cancer Symposium of the Society of Surgical Oncology, Los Angeles, March 18–21, 1993.     

Influence of age and human papillomavirus-infection on reliability of cervical cytopathology

The aim of the present study was to evaluate the effect of age and human papillomavirus (HPV) infection associated cellular changes on the predictive value of cervical cytology. In a group of 671 women with Papanicolaou smears suggesting low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL) or invasive cervical cancer, cervical cytology was correlated with the histological finding. Predictive values were calculated and related to severity of the lesion, age and HPV associated changes. The predictive values of Papanicolaou (cervical) smears suggesting LSIL, HSIL and invasive carcinoma were 40%, 86%, and 78%, respectively. A poor predictive value of smears suggesting LSIL was found among older women. HPV associated changes were diagnosed in 80% of women 25 years of age, 66% in the age group 26 to 35 years, 51% in the age group 36 to 45 years and 38% in women aged 46 years (P = 0.03). The presence of HPV associated cellular changes led to a significantly higher number of overdiagnoses (9% with HPV infection compared to 4% without HPV infection) and HPV negative cases were more frequently associated with underdiagnosis (15% without HPV infection compared to 8% with HPV infection,P = 0.0011). This result remained significant after adjustment for age (P = 0.004). Cellular changes associated with HPV infection most frequently occurred in young women. HPV infection should therefore be acknowledged as source of overdiagnosis in the cytological evaluation of SIL especially in woung women.Supported by the Research Grant of the Mayor of Vienna (no. 1045 [to Dr. Kainz])     

Discriminative power of visual evoked potential characteristics in multiple sclerosis

To investigate the discriminative power of pattern-reversal visual evoked potential characteristics (peak latencies and amplitude) and to test whether the addition of visual evoked potential amplitude can increase the power of the visual evoked potential in the diagnosis of multiple sclerosis, we retrospectively studied visual evoked potentials in 59 patients with definite multiple sclerosis and 126 control subjects. Two check sizes (17 and 10) were used. Females had significantly higher amplitudes and shorter latencies than males. N80 latency showed a gradual increase and P100 amplitude a decrease with age. P100 latency was stable between the ages of 20 and 55 years but was increased in childhood and the elderly. The significance of visual evoked potential peak latencies and amplitude in separating the two groups was investigated by means of a (multivariate) discriminant analysis. The visual evoked potential with a pattern of 10 could be measured in 58% of patients with multiple sclerosis. The exclusive use of the P100 amplitude in the discriminant analysis resulted in a percentage of correctly classified cases of 84%, whereas for P100 and N80 latency it was 85% and 90%, respectively. With the 17 pattern, the N80 latency yielded also a higher correct percentage than did the P100 latency. Although N80 latency is, to a greater extent than P100 latency, influenced by age, sex and size of stimulus pattern, when these influences are accounted for, the N80 latency is a more sensitive measure than P100 latency in the classification of multiple sclerosis. Combined use of latency and amplitude for discriminant analysis yielded no significant improvement of the percentage of correctly classified cases.Abbreviations MS multiple sclerosis - SD standard deviation     

The most immature infants: Is evidence-based practice possible?

IntroductionAt extremely low gestational ages, preterm infants are markedly physiologically immature, thus their responses to common clinical interventions may differ from more mature preterm babies. This study was performed to describe the evidence base which is available to make care decisions for such infants.MethodsA literature search of recent large neonatal randomized controlled trials (RCTs) was performed to determine the representation of infants <25 weeks of gestation, and whether it is clear if the overall results applied to the most immature infants.ResultsAmong 30 multi-centre RCTs in neonatology from the last 5 years, many excluded the most immature infants, and those that included them rarely presented the impacts of the intervention on the most at-risk group. Over 25,000 infants of under 32 weeks gestational age (GA) were included in these trials. Eight trials presented results of the primary outcome for infants of <26 weeks GA (n = 2,152) and a further four trials for infants <25 weeks, n = 711.ConclusionThe evidence base for treatment decisions for the highest risk infants in the NICU is severely limited. RCTs in extremely preterm infants should not exclude the highest risk group, and lower limits of gestational age (or body weight) should be avoided, any infant receiving intensive care should be eligible regardless of how immature. The results among the most immature infants should be presented separately, or be easily available, in order to build a database of effective treatments among infants of 22,23, and 24 weeks GA.     

Periventricular- intraventricular hemorrhage in the premature infant- A historical perspective

The objective of this chapter is to trace the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood flow changes in the genesis of hemorrhage, clinical factors that increase the bleeding risk, and potential preventative strategies. In 1976, neuropathological studies demonstrated capillary rupture within the germinal matrix as the precursor of hemorrhage. In 1980, introduction of cranial ultrasound facilitated diagnosis of intraventricular hemorrhage. In 1979, loss of cerebral autoregulation in sick newborn infants was demonstrated. In the 1980’s, studies demonstrated the importance of intravascular factors in provoking hemorrhage. In 1983, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. In 1994, antenatal steroids use to accelerate lung development was recommended. This was associated with an unanticipated reduction in hemorrhage. In the mid 1990’s early indomethacin administration was associated with a reduction of severe hemorrhage.     

原子转移自由基聚合法合成含羟基星状共聚物

以２－溴异丁酸季戊四醇四酯为引发剂在ＣｕＢｒ／ｂｐｙ催化下实施苯乙烯和丙烯酸β－羟丙酯原子转移自由基共聚合,结果表明聚合物的分子量与理论分子量接近,聚合反应具有活性聚合的特征。进一步对聚合产物进行ＧＰＣ,Ｈ－ＮＭＲ,ＩＲ和羟值滴定分析,表明合成的星状共聚合物中同时具有苯乙烯和丙烯酸β－羟丙酯结构单元,而且羟基在聚合物中近似均匀分布。