PROMISE: Working with the CF community to understand emerging clinical and research needs for those treated with highly effective CFTR modulator therapy

Highly effective CFTR modulator drug therapy is increasingly available to those with cystic fibrosis. Multiple observational research studies are now being conducted to better understand the impacts of this important therapeutic milestone on long-term outcomes, patient care needs, and future research priorities. PROMISE is a large, multi-disciplinary academic study focused on the broad impacts of starting elexacaftor/tezacaftor/ivacaftor in the US population age 6 years and older. The many areas of investigation and rationale for each are discussed by organ systems, along with recognition of remaining important questions that will not be addressed by this study alone. Knowledge gained through this and multiple complementary studies around the world will help to understand important health outcomes, clinical care priorities, and research needs for a large majority of people treated with these or similarly effective medications targeting the primary cellular impairment in cystic fibrosis.     

Diagnosis of tuberculosis: urgent need to strengthen laboratory services

Tuberculosis (TB) is of great public health concern globally, and the impact is most felt in developing countries of Asia and Africa, where 95% of cases and 98% of deaths are attributable to the disease, The disease is poverty-driven and the situation is further worsened by absence of rapid diagnostic tools to facilitate early diagnosis of the illness, thus leading to widespread of the disease. While attention is being focused on the HIV/AIDS pandemic, little is being heard of TB, especially in the areas of laboratory diagnosis despite the fact that the disease is the commonest cause of death in people living with HIV/AIDS. The importance of a diagnostic laboratory in a TB control program cannot be overemphasized. Smear microscopy, which is the cornerstone of World Health Organization (WHO) 'DOTS' strategy for the treatment of TB, has many drawbacks among which is its inability to detect latent infection and the dependency of its sensitivity on a trained and motivated microscopist. Therefore, there is a need for a more reliable, sensitive and rapid diagnostic test to facilitate early diagnosis of cases and prompt initiation of therapy for a TB control program to have a meaningful impact in the community.     

Exocrine ductalpCO2 in the rabbit pancreas

An improvedpCO₂ microelectrode has been evaluated and used to investigate whether a significant barrier to diffusion of CO₂ exists in the rabbit pancreas. The results of this study show the improved Carter and CaflischpCO₂ microelectrode to be an accurate and reliable tool for measuring pancreatic venous and ductalpCO₂. The similarities betweenpCO₂ values from the pancreatic ducts and small pancreatic veins suggest that there is no barrier to CO₂ diffusion between small veins and exocrine ducts in the rabbit pancreas, and that ductalpCO₂ is probably strongly influenced by the CO₂ tension of the small pancreatic blood vessels.     

Epicoccum allergy: skin reaction patterns and spore/mycelium disparities recognized by IgG and IgE ELISA inhibition

Comparable degrees of skin reactivity were observed towards spore and mycelium extracts from two isolates of Epicoccum and to one preparation of Alternaria in 35 rural and 120 university patients. The best experimental extracts detected Epicoccum sensitivity in 70% of the group tested while the commercial extract detected sensitivity in only 6%. Skin reaction correlations were greatest within isolates (eg, spore-A/mycelium-A), then for specific fungus parts (eg, spore-A/spore-B), then between isolates and parts (spore-A/mycelium-B). High correlations were found between individual IgG and IgE ELISA values for all antigens using serum from Epicoccum skin-reactive patients. ELISA inhibition results suggested that significant cross-reactivity exists between Epicoccum and Alternaria antigens recognized by IgG but not by IgE. ELISA inhibition cross-reaction patterns among Epicoccum antigens were comparable to skin reactions while IgG patterns showed little variability. Further characterization of spore/mycelium and interstrain recognition patterns among different immunoglobulin isotypes will be necessary before complete standardization of extracts from different parts of fungi will be possible. The use of spore material for skin testing and treatment of Epicoccum sensitivity appears to be both premature and unnecessary at this time.     

The impact of drug therapy on quality of life in headache and migraine

Although headache is among the most common and costly disorders in primary care, our understanding of its direct impact on the quality of life of affected individuals is incomplete. While studies evaluating the role of headache on health-related quality of life and healthcare economics are starting to appear in the medical literature, the effect of pharmacotherapy in improving quality of life is only beginning to be studied. At present, studies evaluating health-related quality of life in patients with migraine who are undergoing treatment are limited to 3 agents: sumatriptan, flurbiprofen and diclofenac. Several studies have consistently indicated that these drugs benefit patients by improving key dimensions of health-related quality of life or patients' sense of well-being to a significant extent. Given the magnitude of functional and emotional impairment associated with chronic headache disorders, assessing patients' perceptions of their quality of life makes a useful contribution to the evaluation of therapeutic interventions and should supplement traditional clinical endpoints in determining the effectiveness of new drugs.     

Comparison of topoisomerase I and II expression in primary brain tumor and lung cancer

Topoisomerase I (TOP I) and II (TOP II) activities and their corresponding levels were analyzed in 27 primary brain tumors and 32 lung cancers (28 NSCLC, 4 SCLC). The TOP I and II activities in primary brain tumors varied from 500-2,000 units/mg and 100-3,000 units/mg respectively. Their corresponding levels varied from <0.01-3.30 (TOP I) and 0.24-8.30 (TOP II) arbitrary units. In lung cancer, the TOP I and II activities ranged from 1,000-4,000 and 500-4,000 units/mg respectively with their levels ranging from 0.30-61.60 and 0.2-14.2 arbitrary units respectively. These parameters were compared in both tumors using the Wilcoxon rank sums test, the difference were statically significance for all four parameters with a p<0.0001 for TOP I and II activities and TOP I levels and p<0.09 for TOP II levels. Using linear regression analysis, there was no correlation between TOP I and II activities and their corresponding levels in primary brain tumor. However, in lung cancer, the relationship between TOP I activities and levels were linear with r(2)=0.2 and p<0.0094, but not for TOP II activity and their levels. There was no relationship between TOP I and TOP II levels in the same tumor for both types of cancer. The future clinical implication of these findings are discussed.     

Reproductive rights and wrongs

Notions of racial superiority created population control policies. White men defined overpopulation as the root of development problems (e.g., from poverty to political instability) in developing countries and decided to solve it themselves. This notion was accepted without resistance. Governments decided to persuade or coerce women to have fewer children instead of improving living conditions. Since no basic health care system existed in these countries, decision makers delivered Western contraceptive technologies. Hormonal contraceptives and IUDs were heavily promoted, but inadequate back-up services to treat side effects or monitor use existed. Barrier methods, which prevent sexually transmitted diseases, were not promoted. Pregnancy prevention was more important than safety. Women had no control over their own fertility. Views of Margaret Sanger, a pioneer of the birth control movement, formed the foundation for more aggressive laws based on eugenics. The American Birth Control League advocated racial progress and sterilization. Large organizations initiated contraceptive research. Later public institutions took over contraceptive research that focused on female methods because the field was dominated by males. Developing countries depend on the US Food and Drug Administration (FDA) rulings to develop their own guidelines on contraceptives. The pharmaceutical industry weakens FDA'S resolve. It considers developing countries to be a huge expanding market. The Western attitude that family planning is much safer than childbearing punishes the poor for their poverty and disregards long-term risks to women. Providers do not always inform women about risks of contraceptives. The sterilization program in India was based on restricted choice, coercion, targets, and incentives. Success stories include Cuba, South Korea, Sri Lanka, and Kerala State in India. Expansion of basic health care and improvement of the general condition of people's lives are needed.