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Tobacco abuse and its treatment. Turning old and new issues into opportunities for the occupational health nurse.

1. Tobacco use is linked to excessive rates of cardiovascular disease, lung disease, and many fatal neoplasms. In the United States it is the number one cause of illness and premature death. Cigarettes and other combusted forms of tobacco generate environmental tobacco smoke, a major contributor to asthma attacks, heart attacks, and lung cancer among nonsmokers. 2. Cigarettes are the most prevalent and abused form of tobacco, but other forms, such as cigars and smokeless tobacco, also contain nicotine and may cause dependency in high risk groups that consume these products. 3. The addictiveness of tobacco products, especially cigarettes, is particularly detrimental to vulnerable groups such as youth, women, blue collar workers, and other high risk and economically disadvantaged populations. 4. Effective treatment programs (e.g., individual and group counseling, close monitoring, drug treatment) are available to treat nicotine dependency, but many health care providers have been reluctant to educate their patients and clients about these programs. 5. Workplace tobacco use treatment programs, along with policies to restrict tobacco use, have special merit for employers concerned with worker health and safety, productivity, and profitability. Even the more successful tobacco treatment programs perform better when combined with additional efforts to reduce worker health risks and promote well being.

Adolescent↗

Pain and palliative care for people living with HIV/AIDS in Asia.

Millions of people living with HIV/AIDS (PLHA) in Asia need access to palliative care as part of a comprehensive response to their support needs. There are many causes of pain in HIV/AIDS, and its prevalence is as high if not higher than in cancer, but it is frequently undertreated. Access to adequate pain relief and palliative care is impeded by the barriers which face PLHA in Asia. These include few care and support services, lack of recognition and acknowledgement of pain in HIV/AIDS by health care professionals, widespread stigma and discrimination especially towards vulnerable groups such as injecting drug users, government regulatory mechanisms which make access to opioids even more difficult for the care services which have developed and a lack of understanding of or advocacy for pain relief and palliative care in the literature on HIV/AIDS care and support. During the growth of palliative care in Asia, there is opportunity for advocates of palliative care and care for PLHA to collaborate to influence national policy.

Analgesics, Opioid↗

Clinical and epidemiologic trends in HIV/AIDS patients in a hospital setting of Yaoundé, Cameroon: a 6-year perspective.

OBJECTIVES: In order to appreciate the impact of the HIV/AID pandemic in Yaound , Cameroon, an evaluation of the clinical and epidemiologic trends in HIV/AIDS patients was undertaken in a hospital setting. METHODS: A rapid assessment method was used to collect data. Patient record examination, interviews and direct observation were employed. RESULTS: Of 875 cases studied in the hospital during a 6-year period, 43.7% were males and 56.3% females. A total of 5.4% of all the cases were seen in 1993 compared to 30.5% in 1998. The number of admissions per patient ranged from 0 to 4, with a median duration of admission of 14 days (range 0-343 days). The 25-44-year age group was mostly affected (63.4% cases) and 10.1% were in the 0-14-year age group. About 27% of cases died in hospital, mainly between 1996 and 1997. The predominant clinical manifestations included persistent fever and diarrhea, excessive weight loss, chronic cough and profound asthenia. Opportunistic infections and cancers also formed part of the picture. CONCLUSIONS: The increasing clinical and epidemiologic trends of the HIV/AIDS pandemic within the hospital show the devastation and socio-economic impact, especially on the Cameroonian youth and women. Intense public health measures must be put in place to educate and cater for the vulnerable groups in society.

AIDS-Related Opportunistic Infections↗

Five-year-survey of invasive aspergillosis in a paediatric cancer centre. Epidemiology, management and long-term survival.

The epidemiology, management, and long-term survival of invasive aspergillosis was assessed in a prospective, 5-year observational study in 346 unselected paediatric cancer patients receiving dose-intensive chemotherapy for newly diagnosed or recurrent malignancies. Invasive aspergillosis occurred exclusively in the context of haematological malignancies, where it accounted for an incidence of 6.8% (n = 13 of 189). The lung was the primary site in 12 cases, and dissemination was present in three of those. Prior to diagnosis, the overwhelming majority of patients had been profoundly neutropenic for at least 14 days (n = 11 of 13) and were receiving systemic antifungal agents (n = 10 of 13). Clinical signs and symptoms were nonspecific but always included fever. All 11 patients who were diagnosed and treated during lifetime for a minimum of 10 days responded to either medical or combined medical and surgical treatment, and seven were cured (64%). Nevertheless, the overall long-term survival was merely 31% after a median follow-up of 5.68 years after diagnosis. Apart from refractory or recurrent cancer, the main obstacles to successful outcome were failure to diagnose IA during lifetime and bleeding complications in patients with established diagnosis. The frequency of invasive aspergillosis of greater than 15% in paediatric patients with acute myeloblastic leukaemia and recurrent leukaemias warrants the systematic investigation of preventive strategies in these highly vulnerable subgroups.

Adolescent↗

Lifestyle intervention development study to improve physical function in older adults with cancer: outcomes from Project LEAD.

PURPOSE: Declines in physical functioning (PF) among elderly cancer patients threaten quality of life and the ability to maintain independence. Adherence to healthy lifestyle behaviors may prevent functional decline. PATIENTS AND METHODS: Project Leading the Way in Exercise and Diet (LEAD), an intervention development study of the Pepper Older Americans Independence Center, aimed to determine whether breast and prostate cancer survivors (age 65+ years) assigned to a 6-month home-based diet and exercise intervention experienced improvements in PF when compared with an attention control arm receiving general health information. An accrual target was set at 420, and PF (Short Form-36 subscale), physical activity (Community Healthy Activities Models Program for Seniors), and diet quality (index from 3-day recalls) were assessed at baseline and at 6 and 12 months (6 months after intervention). RESULTS: This developmental project did not achieve its accrual target (N = 182); however, PF change scores were in the direction and of the magnitude projected. Baseline to 6-month change scores in the intervention versus the control arms were as follows: PF, +3.1 v -0.5 (P = .23); physical activity energy expenditure, +111 kcal/wk v -400 kcal/wk (P = .13); and diet quality index, +2.2 v -2.9 (P = .003), respectively. Differences between arms diminished during the postintervention period. CONCLUSION: These findings suggest that home-based diet and exercise interventions hold promise in improving lifestyle behaviors among older cancer survivors, changes that trend toward improved PF. Future studies should incorporate larger sample sizes and interventions that sustain long-term effects and also take into account secular trends; these efforts will require adequate planning and resources to overcome the numerous barriers to intervening in this difficult to reach yet vulnerable population.

Activities of Daily Living↗

TNF-alpha induced DNA damage in primary murine hepatocytes.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, usually arising from a background of chronic inflammatory disease. Tumor necrosis factor alpha (TNF-alpha) is a pro-inflammatory cytokine produced in response to tissue injury, endotoxin exposure or infection and TNF-alpha signalling in hepatocytes is associated with an increase in oxidative stress. DNA is vulnerable to reactive oxygen species (ROS)-induced damage, which is highly mutagenic. Cells respond to DNA damage through the stabilisation of the tumor suppressor p53, which maintains genomic fidelity through induction of a cell cycle arrest in order to allow repair or elimination of the damaged cell through apoptosis. This study was carried out to determine if TNF-alpha caused oxidative DNA damage in primary cultures of murine hepatocytes and whether any damage would result in the induction of the tumor suppressor p53 and cell-cycle arrest. Using a modified Comet assay, to measure DNA damage we have demonstrated that TNF-alpha causes the formation of 8-oxo-deoxyguanosine (8-oxodG), an established marker of oxidative DNA damage, and a lesion associated with chronic hepatitis in human livers. In addition, the increase in DNA damage did not result in p53 stabilisation and TNF-alpha caused an increase in cell-cycle progression. We believe that this study indicates a possible putative role for TNF-alpha in the early stages of malignant transformation of hepatocytes.

Animals↗

Multi-Omics Biomarker Signatures for Precision Diagnosis and Prognosis in Primary Liver Cancer: A Literature Review.

Primary liver cancer (PLC) is a biologically heterogeneous group of malignancies dominated by hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and a smaller subset of combined hepatocellular-cholangiocarcinoma (cHCC-CCA), and its clinical burden remains high because current diagnostic and prognostic tools do not adequately capture molecular diversity. Conventional imaging, serum markers, and histopathological assessment remain insufficient for precise early diagnosis, subtype-resolved classification, and outcome stratification, while tissue and liquid biopsy approaches have expanded the range of analytes available for clinical assessment. Recent studies have identified candidate biomarker signatures across genomic, epigenomic, transcriptomic, proteomic, metabolomic, and circulating layers, suggesting that integrated multi-omics profiling may better represent tumor lineage, clonal evolution, immune context, and therapeutic vulnerability than isolated molecular readouts. However, these layers are not equally mature for clinical use: genomic testing is closest to routine therapeutic application in iCCA, plasma methylation assays are advancing for HCC surveillance augmentation, and many proteomic or metabolomic panels remain validation-stage tools. Their clinical value remains constrained by sampling bias, biospecimen-dependent signal loss, assay standardization, cost, and the need for prospective validation across clinically diverse populations. This narrative review critically synthesizes current evidence on multi-omics biomarker signatures for precision diagnosis and prognosis in primary liver cancer and argues that clinically useful signatures should be question-specific, stage-aware, and specimen-aware rather than universal multi-analyte panels.

Humans↗

Contemporary chemotherapy issues for children with brainstem gliomas.

Radiotherapy has remained the mainstay of treatment for children with intrinsic, diffuse pontine tumors in spite of over 20 years of clinical trials attempting to validate the additional role of chemotherapy. Conventional phase II clinical trials conducted in patients with recurrent or progressive brainstem gliomas using single chemotherapy agents such as cyclophosphamide, carboplatin, cisplatin, etoposide and thiotepa or combinations of chemotherapy agents have produced low response rates in the range of 15-20%. Preradiotherapy chemotherapy phase II trials in newly diagnosed patients have yielded similar results with a therapeutic window as long as 4 months. Preliminary data from protocols employing high-dose chemotherapy with stem cell support have also met with disappointment. The one published phase III trial conducted by the Children's Cancer Study Group comparing radiotherapy with radiotherapy plus chemotherapy (CCNU, vincristine and prednisone) failed to establish a benefit to multimodality therapy. Current studies include the use of radiosensitizing chemotherapy (carboplatin, estramustine and cisplatin) in newly diagnosed patients and more intensive neoadjuvant chemotherapy trials. Major advances in our management await insights into molecular vulnerability of high-grade gliomas.

Antineoplastic Agents↗

Radioprotectants: pharmacology and clinical applications of amifostine.

Amifostine (Ethyol, ALZA Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) is a phosphorylated cysteamine derivative that was originally developed by the US Army Walter Reed Institute (Washington, DC) as a radioprotectant. Amifostine, a prodrug, is metabolized by the enzyme alkaline phosphatase to an active sulfhydryl compound (WR-1065) capable of scavenging radiation-generated free radicals and preventing cell damage. The disulfides of WR-1065 are structurally analogous to endogenous polyamines, which can bind to DNA molecules and stabilize them in a compact form less vulnerable to damage by cytotoxic agents. Preclinical and clinical studies show that amifostine is a selective radioprotectant that reduces both early and late radiation-induced toxicities to normal tissues while leaving tumor cells exposed to the cytotoxic effects of radiation. Preclinical data indicate that amifostine could reduce the risk of secondary cancers caused by radiation and certain forms of chemotherapy.

Alkaline Phosphatase↗

Reactive oxygen species in cancer cells: live by the sword, die by the sword.

Reactive oxygen species and tumor biology are intertwined in a complex web, making it difficult to understand which came first, whether oxidants are required for tumor cell growth, and whether oxidant stress can be exploited therapeutically. Evidence suggests that transformed cells use ROS signals to drive proliferation and other events required for tumor progression. This confers a state of increased basal oxidative stress, making them vulnerable to chemotherapeutic agents that further augment ROS generation or that weaken antioxidant defenses of the cell. In this respect, it appears that tumor cells may die by the same systems they require.

Antineoplastic Agents↗

Shock as a complication of cancer.

Shock is a syndrome in which multiple etiologies converge on a pathway of response which, although preservative and compensatory early on, rapidly becomes irreversible and fatal. The mechanisms of this response are under intense investigation, though little therapeutic improvement has accompanied our understanding. The patient with malignancy is at risk for developing shock both as a result of his disease and therapy for his disease, yet he is by no means alone in his vulnerability. Technologic advances may still bring more effective support to the shock patient, while immunologic advances may ultimately provide support to the shock patient, while immunologic advances may ultimately provide answers and cure.

Critical Care↗

Current status of short synthetic peptides as vaccines.

Preventative medicine in the form of vaccination had a huge impact on human health in the 20th Century. Vaccines are now recognized as the most effective line of defence against infectious agents that cause disease and death, and in some cases vaccines have enabled complete eradication of disease from the globe (e.g. smallpox). Nevertheless there are still many human diseases (e.g. viral and parasitic infections, cancers) for which there are no effective vaccines. Current vaccines are mainly live and attenuated viruses or viral, bacterial or recombinant proteins and polypeptides. By virtue of their natural amino acid composition, polypeptides and proteins are relatively safe materials for vaccination, but they are expensive to manufacture making them inaccessible to the most vulnerable and needy human populations that cannot afford such medicines. This review will focus on shorter synthetic peptides that are cheaper to manufacture, conceivably even safer for human use because of increased specificity, but they also suffer from problems that have presumably resulted in their lack of progress in clinical trials. Since 1990, over 100 chemically synthesized short peptide vaccines have entered Phase I clinical trials, less than 20 have progressed into Phase II, but none have entered Phase III clinical trials. In this review we discuss reasons why vaccines based on short peptides may not have succeeded in the clinic, identify problems such as insufficient immunogenicity, structural/conformational instability, chemical instability due to degradation, and describe possible solutions to some of these problems that have been investigated in recent years.

Clinical Trials as Topic↗

Suboptimal antidepressant use in the elderly.

Ongoing changes in available agents and health care delivery systems have made it imperative to study the quality of antidepressant use in vulnerable and traditionally underserved elderly. We conducted a retrospective cohort study among 12,130 new antidepressant users aged > or =65 years with a recent diagnosis of depression in the Pennsylvania Pharmaceutical Assistance Contract for the Elderly Program from January 1, 1994, to December 31, 1999. Additional use information was available through Medicare data. Potentially hazardous antidepressant regimens were defined as use of highly anticholinergic agents or daily dosages in excess of geriatric prescribing guidelines. Low-intensity regimens were defined by lower than recommended daily dosages, too-short durations of therapy, or lack of follow-up. Of all elderly antidepressant users, 43.3% were taking suboptimal regimens. Potentially hazardous regimens were used by 11.9%, including 7.3% taking highly anticholinergic agents and 5.3% using excessively high daily dosages. Low-intensity regimens were used by 34.8% of patients, including 7.6% with excessively low daily dosages, 19.3% with short durations of therapy, and 14.8% with inadequate follow-up. Potentially hazardous regimens were associated with ages 65 to 74 years, nursing home residence, cancer diagnoses, less comorbidity, use of other psychiatric medications, making more physician visits, and earlier calendar years. Low-intensity regimens were associated with ages > or =85 years, nonwhite race, greater comorbidity, fewer physician visits or inpatient days in the baseline 6 months, and not using other psychiatric medications. Suboptimal antidepressant use remains common in the elderly, especially the use of inadequately intensive regimens. Interventions are needed to improve the quality and outcomes of antidepressant use in this vulnerable population.

Aged↗

A magical dream: a pilot project in animal-assisted therapy in pediatric oncology.

For children with cancer, being hospitalized represents a great source of stress. Hospitalized children are not only deprived of their familiar and comforting world, but they must also face various and often painful treatments. They must quickly adapt to new people and to an environment that is very different from that of their homes. They have greater safety needs. Thus, it is important to offer these children concrete ways to better adapt to the stresses of hospitalization. Animal-assisted therapy, considered within this project as a novel approach to care, constitutes an interesting solution. It involves using the privileged relation between children and animals to foster the process of adaptation to illness and the hospital environment. The experience described in this article is a one-year pilot project completed on a pediatric oncology unit. A priori, an already very heavy workload, the vulnerability of the patients, and many constraints added to the concerns related to the presence of animals on a tertiary care unit. A postiori, the rigorous design and implementation process of the pilot project, the strong involvement and engagement of volunteers and professionals, the quality of the participating "therapeutic" dogs, the originality of the entire process, and the satisfaction of the patients and nursing staff contributed to its success and to establishing the basis for a permanent implementation of this special care program for children hospitalized with cancer.

Adaptation, Psychological↗

Measuring quality in nurse-managed centers using HEDIS measures.

Nurse-managed centers (NMCs) provide viable options for primary healthcare and contribute substantially to filling access gaps for vulnerable populations. The purposes of this paper are to (a) describe a pilot application and adaptation of eight Health Plan Employer Data and Information Set (HEDIS) measures to six NMCs, (b) report the findings from the quality assessments, and (c) compare findings to national HEDIS data. The eight quality assessment areas are asthma, cervical cancer screening, childhood immunizations, depression, diabetes, hypertension, mammography screening, and smoking cessation. The NMCs achieved or exceeded HEDIS 50th percentile levels in a number of important clinical areas, but did not attain the 50th percentile level in others. Thus, HEDIS measures are relevant for the assessment of care quality and provide useful data for quality improvement in NMCs.

Benchmarking↗

New therapeutic strategies and drug candidates for neurodegenerative diseases: p53 and TNF-alpha inhibitors, and GLP-1 receptor agonists.

Owing to improving preventative, diagnostic, and therapeutic measures for cardiovascular disease and a variety of cancers, the average ages of North Americans and Europeans continue to rise. Regrettably, accompanying this increase in life span, there has been an increase in the number of individuals afflicted with age-related neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and stroke. Although different cell types and brain areas are vulnerable among these, each disorder likely develops from activation of a common final cascade of biochemical and cellular events that eventually lead to neuronal dysfunction and death. In this regard, different triggers, including oxidative damage to DNA, the overactivation of glutamate receptors, and disruption of cellular calcium homeostasis, albeit initiated by different genetic and/or environmental factors, can instigate a cascade of intracellular events that induce apoptosis. To forestall the neurodegenerative process, we have chosen specific targets to inhibit that are at pivotal rate-limiting steps within the pathological cascade. Such targets include TNF-alpha, p53, and GLP-1 receptor. The cytokine TNF-alpha is elevated in Alzheimer's disease, Parkinson's disease, stroke, and amyotrophic lateral sclerosis. Its synthesis can be reduced via posttranscriptional mechanisms with novel analogues of the classic drug, thalidomide. The intracellular protein and transcription factor, p53, is activated by the Alzheimer's disease toxic peptide, Abeta, as well as by excess glutamate and hypoxia to trigger neural cell death. It is inactivated by novel tetrahydrobenzothiazole and -oxazole analogues to rescue cells from lethal insults. Stimulation of the glucagon-like peptide-1 receptor (GLP-1R) in brain is associated with neurotrophic functions that, additionally, can protect cells against excess glutamate and other toxic insults.

Animals↗