Quality of life gains in frail and intermediate-fit patients with multiple Myeloma: Findings from the prospective HOVON123 clinical trial.

BACKGROUND: Frailty in newly-diagnosed multiple myeloma (NDMM) patients is associated with treatment-related toxicity, which negatively affects health-related quality of life (HRQoL). Currently, data on changes in HRQoL of frail and intermediate-fit MM patients during active treatment and post-treatment follow-up are absent. METHODS: The HOVON123 study (NTR4244) was a phase II trial in which NDMM patients ≥ 75 years were treated with nine dose-adjusted cycles of Melphalan-Prednisone-Bortezomib (MPV). Two HRQoL instruments (EORTC QLQ-C30 and -MY20) were obtained before start of treatment, after 3 and 9 months of treatment and 6 and 12 months after treatment for patients who did not yet start second-line treatment. HRQoL changes and/or differences in frail and intermediate-fit patients (IMWG frailty score) were reported only when both statistically significant (p < 0.005) and clinically relevant (>MID). RESULTS: 137 frail and 71 intermediate-fit patients were included in the analysis. Compliance was high and comparable in both groups. At baseline, frail patients reported lower global health status, lower physical functioning scores and more fatigue and pain compared to intermediate-fit patients. Both groups improved in global health status and future perspective; polyneuropathy complaints worsened over time. Frail patients improved over time in physical functioning, fatigue and pain. Improvement in global health status occurred earlier than in intermediate-fit patients. CONCLUSION: HRQoL improved during anti-myeloma treatment in both intermediate-fit and frail MM patients. In frail patients, improvement occurred faster and, in more domains, which was retained during follow-up. This implies that physicians should not withhold safe and effective therapies from frail patients in fear of HRQoL deterioration.

Stepping from traditional to integrative medicine: perspectives of Israeli-Arab patients on complementary medicine's role in cancer care.

BACKGROUND: Limited research is available on the perspectives of patients with cancer regarding integration of complementary medicine (CM) in conventional supportive cancer care. The purpose of this study was to explore patients' perspectives concerning CM integration within conventional oncology settings. PATIENTS AND METHODS: A 27-item questionnaire was constructed and administered to a convenient sample of Arab patients receiving cancer care in three oncology centers in northern Israel. RESULTS: Of the 324 respondents (94.7% response rate), 124 of 313 (39.6%) reported the use of CM for cancer-related outcomes. A logistic regression model indicated that CM was used with active chemo- or radiotherapy treatment [EXP [B], 2.926, 95% confidence interval (CI) 1.276-6.708; P=0.011] and a higher degree of spiritual quest (EXP [B], 3.425, 95% CI 1.042-11.253; P=0.043). Herbal medicine was the leading CM modality (87.9% of CM users), which included the use of 28 plants and traditional remedies, of which 17 were used to improve QOL, with 5 of the herbs having potential interactions with chemotherapy. 83.1% of respondents stated that they would consult with a CM provider if CM were to be integrated into the oncology department. Patients' expectation of CM consultation was clearly associated with expectations of QOL improvement, coping with cancer, and alleviating chemotherapy's side-effects when compared with expectations of cancer cure (P<0.0001). The three leading concerns which patients expected to be improved by integrative CM treatment were gastrointestinal symptoms (63.2%), fatigue (51.9%), and pain (40.5%). CONCLUSIONS: Integrative CM consultations should focus on the improvement of QOL concomitant with safety concerns regarding potential drug-herb interactions. The need to integrate a nonjudgmental yet evidence-based CM consultation service may also be applicable to oncology institutions challenged with culturally diverse populations with a high prevalence of traditional medicine use.

Formulary availability and regulatory barriers to accessibility of opioids for cancer pain in the Middle East: a report from the Global Opioid Policy Initiative (GOPI).

The Middle East is a heterogeneous region with substantial variability in social development, wealth and palliative care development. The region has few democracies, strong but diverse religious affiliations, and many of the region's counties are involved in political upheavals or regional conflicts. While the global consumption of opioids has increased throughout the last 30 years, there has been little increase in opioid consumption in the Middle East. This is the first comprehensive study of opioid availability and accessibility of opioids in the Middle East. Data are reported on the availability and accessibility of opioids for the management of cancer pain in 16 of 24 countries. The data are relevant to 329 million of the region's 403 million people (82%). The survey found that with the exception of Israel, opioid availability continues to be low throughout most of the Middle East. Formulary deficiencies are severe in several countries in particular Afghanistan, Iraq, Lebanon, Libya, Palestine and Tunisia. Even when opioids are on formulary, they are often unavailable, particularly in these same countries. Access is also significantly impaired by widespread over-regulation that is pervasive across the region.

Prevalence of aging population in the Middle East and its implications on cancer incidence and care.

The Middle Eastern population is aging rapidly, and as aging is the main risk factor for cancer, the incidence and prevalence of that disease are increasing among all the populations in the region. These developments represent huge challenges to national and community-based health services. At the current state of affairs, most Middle Eastern countries require the cooperation of international agencies in order to cope with such new challenges to their health systems. The focus and emphasis in facing these changing circumstances lie in the education and training of professionals, mainly physicians and nurses, at the primary, secondary and tertiary levels of health services. It is imperative that these training initiatives include clinical practice, with priority given to the creation of multidisciplinary teams both at the cancer centers and for home-based services.

Multidisciplinary care team for cancer patients and its implementation in several Middle Eastern countries.

This article introduces palliative care to cancer patients in Middle Eastern countries. It considers the importance of the multidisciplinary team in providing an adequate service to the patient and his/her family. It provides views of professionals from the various countries with regard to the role of the nurse in such teams; whereby the three elements of palliative care nursing entail: 1. Working directly with patients and families; 2. Working with other health and social care professionals to network and co-ordinate services; and 3. working at an organizational level to plan, develop and manage service provision in local, regional and national settings. This article also details the challenges that nurses face in the Middle East and outlines the preferable ways to overcome such challenges. The latter include more focused educational activities at the undergraduate and graduate levels and continuous clinical training throughout their work as palliative care nurse specialists.

Promoting new approaches for cancer care in the Middle East.

Cancer is now the fastest growing killing disease in the Middle East. Accordingly, there is an urgent need to train local health professionals: oncologists, palliative care experts, oncology nurses, psychologists, along with social workers, physiotherapists and spiritual counselors on strategies for early detection, curative therapies and palliation. Professionals in the region, along with the public, need to convince medical administrators, regulators and policymakers about investing in education and training of YOUNG professionals, as well as those with already proven experience in cancer care. Training is the basis for any future cancer care program, which aims at the integration of palliative care practices into standard oncology care across the trajectory of the illness.

Guideline adherence for empirical treatment of pneumonia and patient outcome. Treating pneumonia in the Netherlands.

INTRODUCTION: According to the Dutch guidelines, severity of community acquired pneumonia (CAP) (mild, moderate-severe, severe) should be based on either PSI, CURB65 or a 'pragmatic' classification. In the last mentioned, the type of ward of admission, as decided by the treating physician, is used as classifier: no hospital admission is mild, admission to a general ward is moderate-severe and admission to an intensive care unit (ICU) is severe CAP. Empiric antibiotic recommendations for each severity class are uniform. We investigated, in 23 hospitals, which of the three classification systems empirical treatment of CAP best adhered to, and whether a too narrow spectrum coverage (according to each of the systems) was associated with a poor patient outcome (in-hospital mortality or need for ICU admission). PATIENTS AND METHODS: Prospective observational study in 23 hospitals. RESULTS: 271 (26%) of 1047 patients with CAP confirmed by X-ray were categorised in the same severity class with all three classification methods. Proportions of patients receiving guideline-adherent antibiotics were 62.9% (95% CI 60.0-65.8%) for the pragmatic, 43.1% (95% CI 40.1-46.1%) for PSI and 30.5% (95% CI 27.8-33.3%) for CURB65 classification. 'Under-treatment' based on the pragmatic classification was associated with a trend towards poor clinical outcome, but no such trend was apparent for the other two scoring systems. CONCLUSIONS: Concordance between three CAP severity classification systems was low, implying large heterogeneity in antibiotic treatment for CAP patients. Empirical treatment appeared most adherent to the pragmatic classification. Non-adherence to treatment recommendations based on the PSI and CURB65 was not associated with a poor clinical outcome.

Palliative cancer care in Middle Eastern countries: accomplishments and challenges.

BACKGROUND: In larger parts of the Middle East palliative care is still misunderstood among health professionals, cancer patients and the public at large. One reason to that is because the term does not obviously communicate the intent of this clinical discipline, which is lending better quality of life while combating cancer. Further, culture, tradition and religion have contributed to this misgiving and confusion especially at the terminal stage of the disease. METHODS: The Middle East Cancer Consortium jointly with the American Society of Clinical Oncology, the American Oncology Nursing Society, the San Diego Hospice Center for Palliative Medicine and the Children's Hospital & Clinics of Minnesota initiated a series of training courses and workshops in the Middle East to provide updated training to physicians, nurses, social workers and psychologists from throughout the region with basic concepts of palliative care and pain managements in adults and children cancers. RESULTS: During the past 6 years hundreds of professionals took part in these educational and training activities, thereby creating the core of trained caregivers who start to make the change in their individual countries. CONCLUSIONS: The outcome of consecutive training activities can overcome geopolitical instabilities, and yield a genuine change in approach of both regulators, medical administrators, medical staff and the public; as to the important contribution of palliative care services to the welfare of the patient and his/her family.

Integrative oncology in the Middle East: from traditional herbal knowledge to contemporary cancer care.

BACKGROUND: Based on traditional, historical, ethnobotanical, laboratory, and clinical findings, we present research framework aiming to identify Middle Eastern herbs that are worthy of further research for their anticancer potential. METHODS: A comprehensive research project was developed by a multinational team comprising family physicians, medicine specialists, oncologists, an Islamic medicine history specialist, a traditional medicine ethnobotanist, and a basic research scientist. The project followed two consecutive phases: (i) historical and ethnobotanical search for cancer-related keywords and (ii) Medline search for in vitro and in vivo studies. RESULTS: This search yielded 44 herbs associated with cancer care. The Medline search yielded 34 herbs of which 9 herbs were reported in various clinical studies. CONCLUSIONS: This multidisciplinary survey was found to be a valuable way to identify herbs with potential clinical significance in cancer care. Based on this pilot study, it is suggested that the Middle East can serve as a valuable region for future multicultural-oriented cancer research.

Characterization of mammary epithelial cell line HC11 using the NIA 15k gene array reveals potential regulators of the undifferentiated and differentiated phenotypes.

Differentiation of undifferentiated mammary epithelial stem and/or progenitor cells results in the production of luminal-ductal and myoepithelial cells in the young animal and upon pregnancy, the production of luminal alveolar cells. A few key regulators of differentiation have been identified, though it is not known yet how these proteins function together to achieve their well-orchestrated products. In an effort to identify regulators of early differentiation, we screened the NIA 15k gene array of 15,247 developmentally expressed genes using mouse mammary epithelial HC11 cells as a model of differentiation. We have confirmed a number of genes preferentially expressed in the undifferentiated cells (Lgals1, Ran, Jam-A and Bmpr1a) and in those induced to undergo differentiation (Id1, Nfkbiz, Trib1, Rps21, Ier3). Using antibodies to the proteins encoded by Lgals1, and Jam-A, we confirmed that their proteins levels were higher in the undifferentiated cells. Although the amounts of bone morphogenetic protein receptor-1A (BMPR1A) protein were present at all stages, we found the activity of its downstream signal transduction pathway, as measured by the presence of phosphorylated-SMAD1, -SMAD5, and -SMAD8, is elevated in undifferentiated cells and decreases in fully differentiated cells. This evidence supports that the BMPR1A pathway functions primarily in undifferentiated mammary epithelial cells. We have identified a number of genes, of known and unknown function, that are candidates for the maintenance of the undifferentiated phenotype and for early regulators of mammary alveolar cell differentiation.

[Systematic diagnosis of erythrocytosis]. / Systematische diagnostiek van erytrocytose.

Erythrocytosis is a phenomenon with life-threatening complications and a broad differential diagnosis. Erythrocytosis is usually secondary to a cardiopulmonary condition leading to a low arterial oxygen tension. A probable diagnosis can often be made on the basis of the history, physical examination, a measurement of the peripheral oxygen saturation, and simple laboratory tests. The differential diagnosis can be narrowed down by a determination of the erythropoietin concentration and the JAK2 mutation. If the erythrocytosis is found to be non-physiological, then reduction of the haematocrit via bloodletting and, depending on the diagnosis, treatment with acetylsalicylic acid are indicated.

Epidemiology of classic Kaposi's sarcoma in the Israeli Jewish population between 1960 and 1998.

Trends in the incidence of classic Kaposi's sarcoma in the Jewish population in Israel for the period between 1960 and 1998 were analysed. World standardised incidence rates of 20.7 and 7.5 per million among men and women, respectively, were calculated. The highest incidence rates were displayed by men originated from Africa and by Asian-born women.

A comparison of population-based cancer incidence rates in Israel and Jordan.

Reliable information about comparative cancer incidence in the Middle East has been lacking. The Middle East Cancer Consortium (MECC) has formed a network of population-based registries with standardized basic data. Here the age-adjusted cancer incidences are compared for four populations: Israeli Jews, Israeli non-Jews, Jordanians and the US Surveillance Epidemiology and End Results (SEER) population, for the years 1996-1997 (Israel) and 1996-1998 (other populations). The all-sites rate of cancer is approximately twice as high in Israeli Jews and SEER, compared with Israeli non-Jews and Jordanians. Rates of lung cancer are similar among Israeli Jews and non-Jews and about twice as high as in Jordanians. Childhood leukaemia rates in Jordan are higher than in Israeli Jews, but lower than SEER. Hodgkin lymphoma rates in Israeli non-Jews and Jordanians are similar to SEER, but non-Hodgkin lymphoma rates are lower than SEER. The previous suspicion of higher overall leukaemia and lymphoma rates in Jordan is thus not confirmed.

Fighting colorectal cancer: molecular epidemiology differences among Ashkenazi and Sephardic Jews and Palestinians.

BACKGROUND: To evaluate and compare differences in the molecular genetics among high-risk (Ashkenazi Jews), intermediate-risk (Sephardic Jews) and low-risk (Palestinians) groups for colorectal cancer who live in the same geographical region. PATIENTS AND METHODS: The 1995-1996 records from the Tel Aviv Medical Center and Muqased hospital (East Jerusalem) randomly identified patients with colorectal cancer. There were 25 patients from each ethnic group. Epidemiological data were obtained from interviews with the patients and from their hospital charts. The levels of cyclin D1, beta-catenine, p27, p53, Ki-67 and Her-2/neu proteins were determined by immunohistochemistry. The main outcome measures were the association between gene expression and colorectal incidence in the different ethnic groups. RESULTS: Ashkenazi Jews have the highest rate of colorectal cancer, and are diagnosed at an early stage compared with Palestinians (72% and 33% of the cases are in Dukes' A and B, respectively), and, hence, this may explain the better 5-year survival rate among this group. Sephardic Jews are diagnosed at a more advanced stage, the tumors are poorly differentiated and they lack p27. Palestinians have significantly higher cyclin D1 levels. There was a statistically significant inverse correlation between the expression of beta-catenine and cyclin D1, as well as p53 and p27 (P <0.05). CONCLUSIONS: Increased expression of cyclin D1, p53, Ki-67, beta-catenine and Her-2/neu, and decreased expression of p27 may be important events in the three ethnic groups with colorectal cancer. The lower mortality rate among Ashkenazi Jews may be partially explained by their better molecular biology profile.

Age-related changes in upper airway muscles morphological and oxidative properties.

Obstructive sleep apnea (OSA) is a common disorder of the middle aged and elderly. It results from the decrease in upper airway muscle (UAM) tone that occurs during sleep. It is unclear whether age-related changes in UAM could constitute a contributory mechanism to the increased prevalence of OSA with increasing age, and previous papers evaluating the effects of aging on UAM in rats reported conflicting results. In the present study, we compared, in four age groups of Wistar rats (6-24 months), fiber-type distribution, mean cross-sectional fiber area and succinate dehydrogenase optical density of dilating and non-dilating UAM, and the diaphragm. Succinate dehydrogenase optical density, a marker of oxidative capacity, decreased significantly after the age of 6 months in all muscles (except for the sternohyoid), particularly in the genioglossus, the main tongue protrudor. In this muscle, we also found a significant decrease in type IIa and an increase in IIb fibers after the age of 18 months. Age-related changes in fiber-type distribution in other muscles were mostly insignificant. Dilating UAM could not be distinguished from their non-dilating neighboring muscles by their histochemical properties or aging-related changes. The aging-related changes observed in the present study may decrease UAM endurance, particularly that of the main tongue protrudor, the genioglossus.

Cancer registration in the Middle East.

This project signals an advance in cancer registration in the Middle East region. While it is too early to declare a major breakthrough, significant strides have been made toward establishing a basis for reliable information on the cancer burden at a population level and future collaborative efforts in cancer epidemiologic research and prevention.

High progesterone levels and ciliary dysfunction--a possible cause of ectopic pregnancy.

OBJECTIVES: To investigate the effects of different levels of hormones on the ciliary activity of human oviducts and, consequently, to assess their possible role in tubal implantation of the fertilized egg. DESIGN: Fallopian tube epithelial samples were incubated in media with the addition of Estradiol (E2), progesterone (P), human menopausal gonadotropin (hMG), LH, or pure FSH (Metrodin) in different concentrations. The ciliary beat frequency (CBF) was measured after 24 h of incubation. Then the media were exchanged to media without the addition of hormones and the CBF was measured again 24 h later by using the photoelectric technique. SETTING: University teaching hospital, IVF unit. RESULTS: Twenty-four hr after the addition of P to the culture medium in concentrations of 0.5 or 1 ng/ml a significant decline of the CBF down to 63% of the control level was observed (P < 0.001) and with P in concentration of 2 ng/ml or greater, 50-70% of the cilia were paralyzed. These effects of P were found to be reversible. Incubation with E2 induced a slight increase of 4% in the mean CBF (P = 0.002). Twenty-four hr incubation with Metrodin, Pergonal, or LH did not affect ciliary motility. CONCLUSIONS: Higher levels of progesterone cause ciliary dysfunction and subsequently may be a possible cause of ectopic pregnancy.

A genome-wide search for linkage to asthma. German Asthma Genetics Group.

Asthma is among the most frequent chronic diseases in childhood. Although numerous environmental risk factors have already been identified, the basis for familial occurrence of asthma remains unclear. Previous genome screens for atopy in British/Australian families and for asthma in different American populations showed inconsistent results. We report a sib pair study of a sample of 97 families, including 415 persons and 156 sib pairs. Following an extensive clinical evaluation, all participants were genotyped for 351 polymorphic dinucleotide markers. Linkage analysis for asthma identified four chromosomal regions that could to be linked to asthma: chromosome 2 (at marker D2S2298, P = 0.007), chromosome 6 (around D6S291, lowest P = 0.008), chromosome 9 (proximal to D9S1784, P = 0.007), and chromosome 12 (D12S351, P = 0.010). These linkage regions could be reproduced for all loci by analysis of total or specific immunoglobulin E (minimum P values at these regions were 0. 003, 0.001, 0.010, and 0.015, respectively).

[The principle of autogeneic rib perichondrial transplantation in the treatment of deep articular cartilage defects]. / Das Prinzip der Transplantation autogenen Rippenperichondriums zur Behandlung von tiefen Gelenkknorpeldefekten.

The purpose of this study was to examine the fate of autologous perichondrial grafts after transplantation into cartilage lesions in weight-bearing joints. Results were evaluated depending on the age of the animals and on the weight-bearing conditions. Osteochondral lesions were drilled in the articular surface of knee joints in 36 adolescent sheep. The defects were filled with autologous rib perichondrial grafts which were secured by either collagen sponges (n = 12) or fibrin glue (n = 12). Twelve animals served as controls. Following one week of immobilisation the animals were allowed to move freely. Animals were sacrificed after 4, 8, 12, and 16 weeks. The same procedure was performed in three adult animals in order to achieve hints regarding the age-dependent ingrowth of the transplants. In two of them the transplantation was done using fibrin glue for fixation; one animal served as control. Grafts were removed corresponding to the time intervals and investigated histologically. In adolescent animals grafts from weight-bearing areas and control defects did not show a regular cartilagenous differentiation. In contrast to that, hyaline-like cartilage formation could be noted in non-weight-bearing areas even after 4 weeks. In principle, the same results were found in adult sheep but a delay of cartilagenous differentiation of four weeks was observed. Depending on these results we use the procedure of perichondrial transplantation clinically for treatment of circumscript deep lesions of articular cartilage provided no osteoarthritis or any other overlying general diseases are evident. By means of the Lysholm- and Ranawat-score all six patients demonstrated postoperative improvement. Furthermore, in two patients arthroscopic controls exhibited sufficient filling of the defects and ingrowth to the surrounding cartilage. Thus, autogeneic perichondrial transplantation can be recommended for treatment of circumscript deep cartilagenous lesions of articular cartilage.