Capecitabine and vinorelbine as first-line treatment in elderly patients (> or =65 years) with metastatic breast cancer. A phase II trial (SAKK 25/99)

BACKGROUND: We evaluated previously established regimens of capecitabine plus vinorelbine in older patients with advanced breast cancer stratified for presence versus absence of bone metastases. PATIENTS AND METHODS: Patients > or =65 years who had received no prior chemotherapy for advanced breast cancer received up to six 21-day cycles of vinorelbine 20 mg/m(2) i.v. on days 1 + 8 with oral capecitabine on days 1-14 (1,000 vs. 1,250 mg/m(2) daily in patients with vs. without bone involvement). RESULTS: Median age was 72 years in patients with bone metastases (n = 47) and 75 years in patients without bone metastases (n = 23). Response rates were 43% (95% confidence interval, CI, 28.3-58.8) and 57% (95% CI = 34.5-76.8), respectively. Median time to progression was 4.3 (95% CI = 3.5-6.0 months) and 7.0 months (CI = 4.1-8.3), respectively. Neutropenia was the most common toxicity, with grade 3/4 occurring in 43 and 39%, respectively. Pulmonary embolism was seen in 5 and grade 3 thrombosis in 3 patients. Other toxicities were mild to moderate. CONCLUSIONS: These regimens of capecitabine and vinorelbine are active and well tolerated in patients with advanced breast cancer > or =65 years. Response rates were comparable to published results. The lower capecitabine doses appeared appropriate given the advanced age, bone involvement and prior radiotherapy.

Adapting health-risk communication to the specific cultural contexts of diverse populations : an assessment of malaria-treatment programs in Liberia

Drawing on theories of technical communication, rhetoric, literacy, language and culture, and medical anthropology, this dissertation explores how local culture and traditions can be incorporated into health-risk-communication-program design and implementation, including the design and dissemination of health-risk messages. In a modern world with increasing global economic partnerships, mounting health and environmental risks, and cross-cultural collaborations, those who interact with people of different cultures have “a moral obligation to take those cultures seriously, including their social organization and values” (Hahn and Inhorn 10). Paradoxically, at the same time as we must carefully adapt health, safety, and environmental-risk messages to diverse cultures and populations, we must also recognize the increasing extent to which we are all becoming part of one, vast, interrelated global village. This, too, has a significant impact on the ways in which healthcare plans should be designed, communicated, and implemented. Because communicating across diverse cultures requires a system for “bridging the gap between individual differences and negotiating individual realities” (Kim and Gudykunst 50), both administrators and beneficiaries of malaria-treatment-and-control programs (MTCPs) in Liberia were targeted to participate in this study. A total of 105 people participated in this study: 21 MTCP administrators (including designers and implementers) completed survey questionnaires on program design, implementation, and outcomes; and 84 MTCP beneficiaries (e.g., traditional leaders and young adults) were interviewed about their knowledge of malaria and methods for communicating health risks in their tribe or culture. All participants showed a tremendous sense of courage, commitment, resilience, and pragmatism, especially in light of the fact that many of them live and work under dire socioeconomic conditions (e.g., no electricity and poor communication networks). Although many MTCP beneficiaries interviewed for this study had bed nets in their homes, a majority (46.34 percent) used a combination of traditional herbal medicine and Western medicine to treat malaria. MTCP administrators who participated in this study rated the impacts of their programs on reducing malaria in Liberia as moderately successful (61.90 percent) or greatly successful (38.10 percent), and they offered a variety of insights on what they might do differently in the future to incorporate local culture and traditions into program design and implementation. Participating MTCP administrators and beneficiaries differed in their understanding of what “cultural incorporation” meant, but they agreed that using local indigenous languages to communicate health-risk messages was essential for effective health-risk communication. They also suggested that understanding the literacy practices and linguistic cultures of the local people is essential to communicating health risks across diverse cultures and populations.

Distal Roux-en-Y gastric bypass for the treatment of morbid obesity

Background: Classical Roux-en-Y gastric bypass (cRYGB) is a combined restrictive and slightly malabsorptive operation. Excess-BMI-loss (EBMIL) in cRYGB is ~60%, but is diminished for super obese patients (BMI > 50 kg/m2). We therefore designed a modified, mainly malabsorptive distal RYGB (dRYGB). Methods: We report mid-term results after 77 consecutive dRYGB in which malabsorption is inversely related to the length of the common channel. The common channel was 100–150 cm long depending on preoperative BMI, the biliopancreatic limb was 100 cm long, which left >>250 cm for the alimentary channel. To avoid the potentially dangerous combination of malabsorption with sustained restriction the pouch size was increased to ~50ml and a 25 mm circular stapler was used for the gastro-jejunostomy. Results: 33 open and later on 44 laparoscopic interventions have been performed. Median preoperative BMI was 50.2 kg/m 2. No severe intraoperative complications have been observed and no anastomotic leakage was noted in the postoperative period. 5 patients needed balloon dilation of an anastomotic stricture. 3 marginal ulcers occurred at the gastrojejunostomy. The 54 patients with a follow-up time of over 12 months (median 24 months) showed an overall median BMI-reduction of 17 to an actual median BMI of 31.6 kg/m2, corresponding to a EBMIL of 74.5%. Obesity-related comorbid conditions were significantly reduced or cured. Intermittent diarrhea or steatorrhea in 12 patients was easily treated by pancreatic enzyme supplementation. Conclusion: dRYGB is technically more demanding than cRYGB, but shows excellent results in terms of weight-loss and therefore also in reduction of comorbidity especially in super-obese patients. Measuring all three limb lengths allows for a calibration of the malabsorption. The quality of food-intake being important to (super-) obese patients in terms of quality of life, a less restrictive pouch seems more adapted to them. Lifelong multidisciplinary follow-up is mandatory.

Antiretroviral treatment during pregnancy

OBJECTIVE: Virologic failure of HIV-positive patients is of special concern during pregnancy. We compared virologic failure and the frequency of treatment changes in pregnant and non-pregnant women of the Swiss HIV Cohort Study. METHODS: Using data on 372 pregnancies in 324 women we describe antiretroviral therapy during pregnancy. Pregnant women on HAART at conception (n = 131) were matched to 228 non-pregnant women (interindividual comparison) and to a time period of equal length before and after pregnancy (intraindividual comparison). Women starting HAART during pregnancy (n = 145) were compared with 578 non-pregnant women starting HAART. FINDINGS: The median age at conception was 31 years, 16% (n = 50) were infected through injecting drug use and the median CD4 cell count was 489 cells/microl. In the majority of pregnancies (n = 220, 59%), women had started ART before conception. When ART was started during pregnancy (n = 145, 39%), it was mainly during the second trimester (n = 100, 69%). Two thirds (n = 26) of 35 women starting in the third trimester were diagnosed with HIV during pregnancy. The risk of virologic failure tended to be lower in pregnant than in non-pregnant women [adjusted odds ratio 0.52 (95% confidence interval 0.25-1.09, P = 0.08)], but was similar in the intraindividual comparison (adjusted odds ratio 1.04, 95% confidence interval 0.48-2.28). Women starting HAART during pregnancy changed the treatment less often than non-pregnant women. CONCLUSION: Despite the physiological changes occurring during pregnancy, HIV infected pregnant women are not at higher risk of virologic failure.

Antiretroviral therapy in resource-limited settings 1996 to 2006: patient characteristics, treatment regimens and monitoring in sub-Saharan Africa, Asia and Latin America

OBJECTIVES: To describe temporal trends in baseline clinical characteristics, initial treatment regimens and monitoring of patients starting antiretroviral therapy (ART) in resource-limited settings. METHODS: We analysed data from 17 ART programmes in 12 countries in sub-Saharan Africa, South America and Asia. Patients aged 16 years or older with documented date of start of highly active ART (HAART) were included. Data were analysed by calculating medians, interquartile ranges (IQR) and percentages by regions and time periods. Not all centres provided data for 2006 and 2005 and 2006 were therefore combined. RESULTS: A total of 36,715 patients who started ART 1996-2006 were included in the analysis. Patient numbers increased substantially in sub-Saharan Africa and Asia, and the number of initial regimens declined, to four and five, respectively, in 2005-2006. In South America 20 regimes were used in 2005-2006. A combination of 3TC/D4T/NVP was used for 56% of African patients and 42% of Asian patients; AZT/3TC/EFV was used in 33% of patients in South America. The median baseline CD4 count increased in recent years, to 122 cells/microl (IQR 53-194) in 2005-2006 in Africa, 134 cells/microl (IQR 72-191) in Asia, and 197 cells/microl (IQR 61-277) in South America, but 77%, 78% and 51%, respectively, started with <200 cells/microl in 2005-2006. In all regions baseline CD4 cell counts were higher in women than men: differences were 22cells/microl in Africa, 65 cells/microl in Asia and 10 cells/microl in South America. In 2005-2006 a viral load at 6 months was available in 21% of patients Africa, 8% of Asian patients and 73% of patients in South America. Corresponding figures for 6-month CD4 cell counts were 74%, 77% and 81%. CONCLUSIONS: The public health approach to providing ART proposed by the World Health Organization has been implemented in sub-Saharan Africa and Asia. Although CD4 cell counts at the start of ART have increased in recent years, most patients continue to start with counts well below the recommended threshold. Particular attention should be paid to more timely initiation of ART in HIV-infected men.

Effects of forest management and time on herbaceous species dynamics in the western Upper Peninsula of Michigan

The herbaceous layer is a dynamic layer in a forest ecosystem which often contains the highest species richness in northern temperate forests. Few long-term studies exist in northern hardwood forests with consistent management practices to observe herbaceous species dynamics. The Ford Forest (Michigan Technological University) reached its 50th year of management during the winter of 2008-2009. Herbaceous species were sampled during the summers pre- and post-harvest. Distinct herbaceous communities developed in the 13-cm diameter-limit treatment and the uncut control. After the harvest, the diameter-limit treatments had herbaceous communities more similar to the 13-cm diameter-limit treatment than the uncut control; the herbaceous layer contained more exotic and early successional species. Fifty years of continuous management changed the herbaceous community especially in the diameter-limit treatments. Sites used in the development of habitat classification systems based on the presence and absence of certain herbaceous species can also be used to monitor vegetation change over time. The Guide to Forest Communities and Habitat Types of Michigan was developed to aid forest managers in understanding the potential productivity of a stand, and often aid in the development of ecologically-based forest management practices. Subsets of plots used to create the Western Upper Peninsula Guide were resampled after 10 years. During the resampling, both spring and summer vegetation were sampled and earthworm populations were estimated through liquid extraction. Spring sampling observed important spring ephemerals missed during summer sampling. More exotic species were present during the summer 2010 sampling than the summer 2000 sampling. Invasive European earthworms were also observed at all sample locations in all habitat types; earthworm densities increased with increasing habitat richness. To ensure the accuracy of the guide book, plots should be monitored to see how herbaceous communities are changing. These plots also offer unique opportunities to monitor for invasive species and the effects of a changing climate.

Using PSA to guide timing of androgen deprivation in patients with T0-4 N0-2 M0 prostate cancer not suitable for local curative treatment (EORTC 30891)

OBJECTIVE: EORTC trial 30891 compared immediate versus deferred androgen-deprivation therapy (ADT) in T0-4 N0-2 M0 prostate cancer (PCa). Many patients randomly assigned to deferred ADT did not require ADT because they died before becoming symptomatic. The question arises whether serum prostate-specific antigen (PSA) levels may be used to decide when to initiate ADT in PCa not suitable for local curative treatment. METHODS: PSA data at baseline, PSA doubling time (PSADT) in patients receiving no ADT, and time to PSA relapse (>2 ng/ml) in patients whose PSA declined to <2 ng/ml within the first year after immediate ADT were analyzed in 939 eligible patients randomly assigned to immediate (n=468) or deferred ADT (n=471). RESULTS: In both arms, patients with a baseline PSA>50 ng/ml were at a>3.5-fold higher risk to die of PCa than patients with a baseline PSA12 mo. Time to PSA relapse after response to immediate ADT correlated significantly with baseline PSA, suggesting that baseline PSA may also reflect disease aggressiveness. CONCLUSIONS: Patients with a baseline PSA>50 ng/ml and/or a PSADT<12 mo were at increased risk to die from PCa and might have benefited from immediate ADT, whereas patients with a baseline PSA<50 ng/ml and a slow PSADT (>12 mo) were likely to die of causes unrelated to PCa, and thus could be spared the burden of immediate ADT.

Pulmonary hypertension in Switzerland: treatment and clinical course

BACKGROUND: The prognosis of pulmonary hypertension (PH), especially idiopathic pulmonary arterial hypertension (IPAH), has improved during the recent years. The Swiss Registry for PH represents the collaboration of the various centres in Switzerland dealing with PH and serves as an important tool in quality control. The objective of the study was to describe the treatment and clinical course of this orphan disease in Switzerland. METHODS: We analyzed data from 222 of 252 adult patients, who were included in the registry between January 1999 and December 2004 and suffered from either PAH, PH associated with lung diseases or chronic thromboembolic PH (CTEPH) with respect to the following data: NYHA class, six-minute walking distance (6-MWD), haemodynamics, treatments and survival. RESULTS: If compared with the calculated expected figures the one, two and three year mean survivals in IPAH increased from 67% to 89%, from 55% to 78% and from 46% to 73%, respectively. Most patients (90%) were on oral or inhaled therapy and only 10 patients necessitated lung transplantation. Even though pulmonary endarterectomy (PEA) was performed in only 7 patients during this time, the survival in our CTEPH cohort improved compared with literature data and seems to approach outcomes usually seen after PEA. The 6-MWD increased maximally by 52 m and 59 m in IPAH and CTEPH, respectively, but in the long term returned to or below baseline values, despite the increasing use of multiple specific drugs (overall in 51% of IPAH and 29% of CTEPH). CONCLUSION: Our national registry data indicate that the overall survival of IPAH and presumably CTEPH seems to have improved in Switzerland. Although the 6-MWD improved transiently, it decreased in the long term despite specific and increasingly combined drug treatment. Our findings herewith underscore the progressive nature of the diseases and the need for further intense research in the field.

Prenatal diagnosis and treatment planning of congenital heart defects-possibilities and limits

BACKGROUND: Newborns with hypoplastic left heart syndrome (HLHS) or right heart syndrome or other malformations with a single ventricle physiology and associated hypoplasia of the great arteries continue to be a challenge in terms of survival. The vast majority of these forms of congenital heart defects relate to abnormal morphogenesis during early intrauterine development and can be diagnosed accurately by fetal echocardiography. Early knowledge of these conditions not only permits a better understanding of the progression of these malformations but encourages some researchers to explore new minimally invasive therapeutic options with a view to early pre- and postnatal cardiac palliation. DATA SOURCES: PubMed database was searched with terms of "congenital heart defects", "fetal echocardiography" and "neonatal cardiac surgery". RESULTS: At present, early prenatal detection has been applied for monitoring pregnancy to avoid intrauterine cardiac decompensation. In principle, the majority of congenital heart defects can be diagnosed by prenatal echocardiography and the detection rate is 85%-95% at tertiary perinatal centers. The majority, particularly of complex congenital lesions, show a steadily progressive course including subsequent secondary phenomena such as arrhythmias or myocardial insufficiency. So prenatal treatment of an abnormal fetus is an area of perinatal medicine that is undergoing a very dynamic development. Early postnatal treatment is established for some time, and prenatal intervention or palliation is at its best experimental stage in individual cases. CONCLUSION: The upcoming expansion of fetal cardiac intervention to ameliorate critically progressive fetal lesions intensifies the need to address issues about the adequacy of technological assessment and patient selection as well as the morbidity of those who undergo these procedures.

Self-reported non-adherence to antiretroviral therapy repeatedly assessed by two questions predicts treatment failure in virologically suppressed patients

BACKGROUND: The aim of this study was to explore the predictive value of longitudinal self-reported adherence data on viral rebound. METHODS: Individuals in the Swiss HIV Cohort Study on combined antiretroviral therapy (cART) with RNA <50 copies/ml over the previous 3 months and who were interviewed about adherence at least once prior to 1 March 2007 were eligible. Adherence was defined in terms of missed doses of cART (0, 1, 2 or >2) in the previous 28 days. Viral rebound was defined as RNA >500 copies/ml. Cox regression models with time-independent and -dependent covariates were used to evaluate time to viral rebound. RESULTS: A total of 2,664 individuals and 15,530 visits were included. Across all visits, missing doses were reported as follows: 1 dose 14.7%, 2 doses 5.1%, >2 doses 3.8% taking <95% of doses 4.5% and missing > or =2 consecutive doses 3.2%. In total, 308 (11.6%) patients experienced viral rebound. After controlling for confounding variables, self-reported non-adherence remained significantly associated with the rate of occurrence of viral rebound (compared with zero missed doses: 1 dose, hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.72-1.48; 2 doses, HR 2.17, 95% CI 1.46-3.25; >2 doses, HR 3.66, 95% CI 2.50-5.34). Several variables significantly associated with an increased risk of viral rebound irrespective of adherence were identified: being on a protease inhibitor or triple nucleoside regimen (compared with a non-nucleoside reverse transcriptase inhibitor), >5 previous cART regimens, seeing a less-experienced physician, taking co-medication, and a shorter time virally suppressed. CONCLUSIONS: A simple self-report adherence questionnaire repeatedly administered provides a sensitive measure of non-adherence that predicts viral rebound.

[Treatment of lymphangiomas with picibanil in the first year of life]

BACKGROUND: The therapeutic gold standard of cystic hygroma is its complete resection. Because of its growth pattern and its main location in the head and neck region complete resection is not always possible. An alternative is the local injection of Picibanil, but only few cases have been published about its use in infants. PATIENTS/METHOD: We retrospectively analyzed the data of 8 infants (age: 2 weeks-12 months) who got Picibanil therapy because of cystic hygroma in the time period 2002 until 2006. Follow up ranged from 3 months up to 3 years. RESULTS: During the postoperative period all patients had local swelling, in 4 cases accompanied with local inflammation and fever. Tumor reduction of >50% was obtained in 7 of 8 patients. CONCLUSIONS: Local injection of Picibanil in infants with cystic hygroma seems to be a safe alternative to surgical therapy, especially when complete tumor resection means damage of important neighbouring structures. Prospective trials are necessary to confirm the better outcome after therapy with Picibanil compare to primary surgery.

Percutaneous transluminal angioplasty and stent placement in acute vessel occlusion: evaluation of new methods for interventional stroke treatment

BACKGROUND AND PURPOSE: The major goal of acute ischemic stroke treatment is fast and sufficient recanalization. Percutaneous transluminal balloon angioplasty (PTA) and/or placement of a stent might achieve both by compressing the thrombus at the occlusion site. This study assesses the feasibility, recanalization rate, and complications of the 2 techniques in an animal model. MATERIALS AND METHODS: Thirty cranial vessels of 7 swine were occluded by injection of radiopaque thrombi. Fifteen vessel occlusions were treated by PTA alone and 15, by placement of a stent and postdilation. Recanalization was documented immediately after treatment and after 1, 2, and 3 hours. Thromboembolic events and dissections were documented. RESULTS: PTA was significantly faster to perform (mean, 16.6 minutes versus 33.0 minutes for stent placement; P < .001), but the mean recanalization rate after 1 hour was significantly better after stent placement compared with PTA alone (67.5% versus 14.6%, P < .001). Due to the self-expanding force of the stent, vessel diameter further increased with time, whereas the recanalization result after PTA was prone to reocclusion. Besides thromboembolic events related to the passing maneuvers at the occlusion site, no thrombus fragmentation and embolization occurred during balloon inflation or stent deployment. Flow to side branches could also be restored at the occlusion site because it was possible to direct thrombus compression. CONCLUSIONS: Stent placement and postdilation proved to be much more efficient in terms of acute and short-term vessel recanalization compared with PTA alone.

Bronchial and bronchovascular sleeve resection for treatment of central lung tumors

BACKGROUND: To improve postoperative pulmonary reserve, we have employed parenchyma-sparing resections for central lung tumors irrespective of pulmonary function. The results of lobectomy, pneumonectomy, and sleeve resection were analyzed retrospectively. METHODS: From October 1995 to June 1999, 422 typical lung resections were performed for lung cancer. Of these, 301 were lobectomies (group I), 81 were sleeve resections (group II), and 40 were pneumonectomies (group III). RESULTS: Operative mortality was 2% in group I, 1.2% in group II, and 7.5% in group III (group I and II vs. group III, p<0.03). Mean time of intubation was 1.0+/-4.1 days in group I, 0.9+/-1.3 days in group II, and 3.6+/-11.2 days in group III (groups I and II vs. group III, p<0.01). The incidence of bronchial complications was 1.3% in group I, none in group II, and 7.5% in group III (group I and II vs group III, p<0.001). After 2 years, survival was 64% in group I, 61.9% in group II, and 56.1% in group III (p = NS). Freedom from local disease recurrence was 92.1% in group I, 95.7% in group II, and 90.9% in group III after 2 years (p = NS). CONCLUSIONS: Sleeve resection is a useful surgical option for the treatment of central lung tumors, thus avoiding pneumonectomy with its associated risks. Morbidity, early mortality, long-term survival, and recurrence of disease after sleeve resection are similar to those seen after lobectomy.

[Treatment of the aortic valve and ascending aorta. The significance of reconstructive methods on the aortic root]

BACKGROUND AND OBJECTIVE: The standard surgical repair of disease of the aortic valve and the ascending aorta has been combined replacement, which includes the disadvantage of inserting a mechanical valve. We have investigated an individualized approach which preserves the native valve. PATIENTS AND METHODS: Between October 1995 and October 1997, a consecutive total of 101 patients (72 men, 29 women, aged 21-83 years) underwent operations for disease of the ascending aorta: aortic dissection type A in 34 patients, aneurysmal dilatation in 67. Dilatation of the aortic arch was associated with aortic regurgitation in 58 patients. There were 11 patients with aortic valve stenosis or previously implanted aortic valve prosthesis among a total of 46 whose aortic valve was replaced (group II). Supracommissural aortic replacement with a Dacron tube was performed in 16 patients (group I) with normal valve cusps and an aortic root diameter < 3.5 cm. In 28 patients with an aortic root diameter of 3.5-5.0 cm the aortic root was remodelled (group III). Resuspension of the native aortic valve was undertaken in 11 patients with aortic root dilatation of > 5.0 cm (group IV). RESULTS: Operative intervention was electively performed in 72 patients, without any death. Of 29 patients operated as an emergency for acute type A dissection four died (14%). In 55 of the 58 patients with aortic regurgitation in proved possible to preserve native aortic valve (95%). In the early postoperative phase and after an average follow-up time of 11.8 months, transthoracic echocardiography demonstrated good aortic valve function, except in one patient each of groups III and IV who developed aortic regurgitation grades I or II. CONCLUSION: The described individualized approach makes it possible to preserve the native aortic valve in most patients with aortic regurgitation, at a low risk. Follow-up observations so far indicate good results of the reconstruction.

Use of a computerized closed-loop sodium nitroprusside titration system for antihypertensive treatment after open heart surgery

This study evaluates the clinical applicability of administering sodium nitroprusside by a closed-loop titration system compared with a manually adjusted system. The mean arterial pressure (MAP) was registered every 10 and 30 sec during the first 150 min after open heart surgery in 20 patients (group 1: computer regulation) and in ten patients (group 2: manual regulation). The results (16,343 and 2,912 data points in groups 1 and 2, respectively), were then analyzed in four time frames and five pressure ranges to indicate clinical efficacy. Sixty percent of the measured MAP in both groups was within the desired +/- 10% during the first 10 min. Thereafter until the end of observation, the MAP was maintained within +/- 10% of the desired set-point 90% of the time in group 1 vs. 60% of the time in group 2. One percent and 11% of data points were +/- 20% from the set-point in groups 1 and 2, respectively (p less than .05, chi-square test). The computer-assisted therapy provided better control of MAP, was safe to use, and helped to reduce nursing demands.