Symptom-relieving Drugs Research Articles

A Comprehensive Update of Anti-COVID-19 Activity of Heterocyclic Compounds.

The Coronavirus disease 2019 (COVID-19) pandemic is one of the most considerable health problems across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the major causative agent of COVID-19. The severe symptoms of this deadly disease include shortness of breath, fever, cough, loss of smell, and a broad spectrum of other health issues such as diarrhea, pneumonia, bronchitis, septic shock, and multiple organ failure. Currently, there are no medications available for coronavirus patients, except symptom-relieving drugs. Therefore, SARS-CoV-2 requires the development of effective drugs and specific treatments. Heterocycles are important constituents of more than 85% of the physiologically active pharmaceutical drugs on the market now. Several FDA-approved drugs have been reported including molnupiravir, remdesivir, ritonavir, oseltamivir, favipiravir, chloroquine, and hydroxychloroquine for the cure of COVID-19. In this study, we discuss potent anti-SARS-CoV-2 heterocyclic compounds that have been synthesized over the past few years. These compounds included; indole, piperidine, pyrazine, pyrimidine, pyrrole, piperazine, quinazoline, oxazole, quinoline, isoxazole, thiazole, quinoxaline, pyrazole, azafluorene, imidazole, thiadiazole, triazole, coumarin, chromene, and benzodioxole. Both in vitro and in silico studies were performed to determine the potential of these heterocyclic compounds in the fight against various SARS-CoV-2 proteins.

Current understanding of pollen allergy: Its origin, impacting factors, treatment regime, and monitoring methods

Pollen allergy is currently evolving into a major aspect regarding allergic bronchial asthma and allergic rhinitis, which are significant global health issues over the past decades. More pollen allergens are being recognized as the changing patterns of pollen exposures trigger increasing numbers of suffering patients. Impacting factors such as human-induced activities and climate change can lengthen pollen seasons as well as heighten pollen production in general. Allergen Immunotherapy (AIT) is an advancing therapeutic vaccine for pollen allergy that can modify the disease and the sensitization of allergens in patients which are less common than symptom-relieving drugs. Monitoring methods contribute greatly to the necessary observation of pollen exposure for treatment processes and the well-being of patients. Automatic monitors are being developed using technologies of different fields based on the traditional methods of pollen counting.

Allergic Diseases: A Comprehensive Review on Risk Factors, Immunological Mechanisms, Link with COVID-19, Potential Treatments, and Role of Allergen Bioinformatics.

The prevalence of allergic diseases is regarded as one of the key challenges in health worldwide. Although the precise mechanisms underlying this rapid increase in prevalence are unknown, emerging evidence suggests that genetic and environmental factors play a significant role. The immune system, microbiota, viruses, and bacteria have all been linked to the onset of allergy disorders in recent years. Avoiding allergen exposure is the best treatment option; however, steroids, antihistamines, and other symptom-relieving drugs are also used. Allergen bioinformatics encompasses both computational tools/methods and allergen-related data resources for managing, archiving, and analyzing allergological data. This study highlights allergy-promoting mechanisms, algorithms, and concepts in allergen bioinformatics, as well as major areas for future research in the field of allergology.

Randomized Controlled Immunotherapy Clinical Trials for GBM Challenged.

Simple SummaryAlthough multiple meta-analyses on active specific immunotherapy treatment for glioblastoma multiforme (GBM) have demonstrated a significant prolongation of overall survival, no single research group has succeeded in demonstrating the efficacy of this type of treatment in a prospective, double-blind, placebo-controlled, randomized clinical trial. In this paper, we explain how the complexity of the tumor biology and tumor–host interactions make proper stratification of a control group impossible. The individualized characteristics of advanced therapy medicinal products for immunotherapy contribute to heterogeneity within an experimental group. The dynamics of each tumor and in each patient aggravate comparative stable patient groups. Finally, combinations of immunotherapy strategies should be integrated with first-line treatment. We illustrate the complexity of a combined first-line treatment with individualized multimodal immunotherapy in a group of 70 adults with GBM and demonstrate that the integration of immunogenic cell death treatment within maintenance chemotherapy followed by dendritic cell vaccines and maintenance immunotherapy might provide a step towards improving the overall survival rate of GBM patients.Immunotherapies represent a promising strategy for glioblastoma multiforme (GBM) treatment. Different immunotherapies include the use of checkpoint inhibitors, adoptive cell therapies such as chimeric antigen receptor (CAR) T cells, and vaccines such as dendritic cell vaccines. Antibodies have also been used as toxin or radioactive particle delivery vehicles to eliminate target cells in the treatment of GBM. Oncolytic viral therapy and other immunogenic cell death-inducing treatments bridge the antitumor strategy with immunization and installation of immune control over the disease. These strategies should be included in the standard treatment protocol for GBM. Some immunotherapies are individualized in terms of the medicinal product, the immune target, and the immune tumor–host contact. Current individualized immunotherapy strategies focus on combinations of approaches. Standardization appears to be impossible in the face of complex controlled trial designs. To define appropriate control groups, stratification according to the Recursive Partitioning Analysis classification, MGMT promotor methylation, epigenetic GBM sub-typing, tumor microenvironment, systemic immune functioning before and after radiochemotherapy, and the need for/type of symptom-relieving drugs is required. Moreover, maintenance of a fixed treatment protocol for a dynamic, deadly cancer disease in a permanently changing tumor–host immune context might be inappropriate. This complexity is illustrated using our own data on individualized multimodal immunotherapies for GBM. Individualized medicines, including multimodal immunotherapies, are a rational and optimal yet also flexible approach to induce long-term tumor control. However, innovative methods are needed to assess the efficacy of complex individualized treatments and implement them more quickly into the general health system.

Paroxysmal Nocturnal Hemoglobinuria in Patients with Aplastic Anemia: Challenges, Characteristics, and Analysis of Clinical Experience

Background & Aims. Paroxysmal nocturnal hemoglobinuria (PNH) is a disease caused by an acquired clonal disorder of hematopoietic stem cells with clone cell membrane hypersensitivity to the complement. PNH can exist as an independent disease and can also be associated with other pathological conditions characterized by bone marrow deficiency, first of all with aplastic anemia (AA). In PNH-associated AA (AA/PNH) pathological clones may be initially of different size. In some patients a gradual growth of PNH clone is observed together with occurring signs of intravascular hemolysis and transformation into classical hemolytic PNH. In this case it is important to assess the clinical situation and determine eligibility for complement inhibitor therapy. During targeted therapy it is necessary to assess the efficacy of treatment based on monitoring of complement-mediated hemolysis and to identify probable reasons for insufficient effect. Materials & Methods. The paper deals with 1 clinical case. A female patient born in 1964, with initial diagnosis of AA was followed-up from 1989 till present at the Russian Research Institute of Hematology and Transfusiology. Her treatment included blood-component therapy, the use of antilymphocyte immunoglobulin, cyclosporine, plasmapheresis, eculizumab, and symptom-relieving drugs. Results. The study deals with the case of transformation of non-severe AA with remission after immune-suppressive therapy into classical hemolytic PNH. The case report describes the characteristic features, AA/PNH diagnosis and treatment issues at different stages of the disease, and the reasons for incomplete effect of targeted therapy. Conclusion. The case under discussion confirms the relevance of current methods of detecting PNH clone at early stages of AA diagnosis and dynamic follow-up with respect to a probable growth of clone with PNH phenotype, especially at the stage of hematopoietic recovery. Determination of PNH clone size and lactate dehydrogenase serum level is required for timely amendment of treatment strategy with a switch to long-term targeted monitoring of hemolysis which allows to prevent irreversible visceral changes and severe complications. In case of insufficient effect of targeted therapy with ongoing anemia Coombs test is recommended because of probability of C3-mediated extravascular hemolysis.

Determinants of non-adherence to adjuvant endocrine treatment in women with breast cancer: the role of comorbidity

PurposeTo examine factors associated with non-adherence during 5 years of endocrine treatment, including the possible influence of comorbidity burden and specific medical conditions.MethodsFrom all women diagnosed with stage I–III, ER-positive breast cancer in Stockholm-Gotland, Uppsala–Örebro and Northern Sweden between 2006 and 2009, we included 4645 women who had at least one dispensation of tamoxifen or aromatase inhibitors (AIs) and 5 years of follow-up without distant recurrence. A medical possession ratio of < 80% was used to define non-adherence. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of non-adherence.ResultsDuring follow-up, 977 (21%) women became non-adherents. Non-adherence was associated with greater comorbidity burden assessed by Charlson comorbidity index (CCI) during follow-up (OR 1.43; 95% CI 1.08–1.88 for ≥ 2 additional scores compared to 0), pre-diagnostic HRT use (OR 1.99; 1.58–2.49), not married (OR 1.42; 1.23–1.64), high educational level (OR 1.25; 1.02–1.53 compared to lowest level), and use of symptom-relieving drugs. HER-2 positivity (OR 0.61; 0.45–0.81) and adjuvant chemotherapy (OR 0.42; 0.35–0.52) were associated with lower odds of non-adherence. Similar patterns were observed for the presence of lymph node metastasis, higher tumour grade, and use of AIs compared to tamoxifen. Myocardial infarction and chronic pulmonary disease was suggested as leading conditions associated with non-adherence in women with increasing CCI.ConclusionWe identified subgroups of women with breast cancer at increased risk of non-adherence. Our findings related to comorbidity suggest the importance of focusing on the presence of specific co-existing conditions when monitoring adherence.

62O_PR Non-adherence to adjuvant endocrine treatment and its determinants among early stage breast cancer patients

Background Non-adherence to adjuvant endocrine treatment (ET) among breast cancer patients has been associated with worse prognosis. We sought to identify factors affecting non-adherence to ET, taking into account determinants at baseline and followup. Methods From linkage between Swedish national registers, we identified all women diagnosed with stage I-III, ER-positive breast cancer in Stockholm-Gotland, Uppsala- O€rebroand NorthernSwedenbetween 2006 and 2009.A total of 4,413 women who had at least one dispensation of tamoxifen or aromatase inhibitors (AIs) and 5 years of follow-up were included in the analysis. A medical possession ratio (MPR) of < 80% was used to define non-adherents. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of non-adherence to ET. Results During follow-up, 1,131 (25.6%) women became non-adherents. The following determinants of non-adherence were identified: age, marital status, region of diagnosis, private hospital, tumour size, lymph node metastasis, tumour grade, HER2 status, type of surgery, adjuvant chemotherapy, type of ET, pre-diagnostic hormone replacement therapy, the use of symptom-relieving drugs at baseline and during follow-up, baseline scores and any increase in Charlson co-morbidity index (CCI). In multivariable analysis, non-adherence was only associated with younger age (OR: 0.67; 95%CI: 0.50- 0.90and0.66; 0.48-0.92 forage50-65 and65+ comparedto < 50, respectively), marital status(OR:1.40;95%CI:1.23-1.60forsingle/divorced/widowedcomparedtomarried women),socioeconomicstatus(OR:1.17;95%CI:1.00-1.37and1.60;1.16-2.21for white collar and being unemployed compared to blue collar workers, respectively), and pre-diagnostic use ofhormone replacementtherapy(OR: 1.57; 95%CI: 1.28-1.93). Conclusions Our study identifies socioeconomic subgroups with increased risk ofnon- adherence that may be of use when measures for improving adherence are tested. Women with pre-diagnosticuseofHRT mayrepresentabiologicalsubsetwith a disposition for side effects from ET. Legal entity responsible for the study King's College London Funding King's College London Disclosure All authors have declared no conflicts ofinterest.

Use of symptom-relieving drugs before and after surgery for urinary incontinence in women: a cohort study

ObjectiveTo describe the use of symptom-relieving drugs (antimuscarinic drugs or duloxetine) before and after surgery for urinary incontinence (UI); and for those with use of antimuscarinic drugs or duloxetine before...

Provision of Pain- and Symptom-Relieving Drugs for HIV/AIDS in Sub-Saharan Africa

Provision of Pain- and Symptom-Relieving Drugs for HIV/AIDS in Sub-Saharan Africa

Provision of Pain- and Symptom-Relieving Drugs for HIV/AIDS in Sub-Saharan Africa

Although pain and burdensome symptoms among HIV-infected persons can be effectively managed, the availability of opioids and other symptom-controlling drugs is a particular challenge in sub-Saharan Africa. This study aimed to identify current drug availability and prescribing practices in 12 sub-Saharan African countries and to examine the barriers and potential facilitators for use of opioids and other key HIV/AIDS symptom-controlling drugs. This was a cross-sectional survey, integrating data from palliative care facilities and competent authorities within ministries of health in 12 African countries. Of 62 responding facilities, problems were reported in accessing named nonopioids, with a small number of facilities unable to dispense them. Less than half the facilities were currently prescribing opioids of any strength. Further problems were identified in terms of the availability and supply continuity of named antiemetics and anxiolytics. The data identified a number of systemic problems, suggesting that opioid supply issues are similar to less controlled drugs, such as antiemetics. Among competent authorities, there was no agreement on whether further opioid expansion was possible. Integration of data from care facilities and competent authorities highlighted a disparity in the understanding of the availability of specific drugs, with competent authorities naming drugs that were not listed by any responding facility in their respective country. This study shows that opioid expansion needs to balance supply and skills: Currently there are insufficient trained clinical personnel to prescribe, and supply is unreliable. Efforts to expand supply should ensure that they do not weaken current systems.

Addition of Formoterol or Montelukast to Low-Dose Budesonide: An Efficacy Comparison in Short- and Long-Term Asthma Control

Background: Asthma is a chronic inflammatory disease of the airways. Inhaled corticosteroids are very important in anti-inflammatory treatment, but to a great extent they cannot control asthma alone. In addition to corticosteroids, long-acting β₂ agonists and leukotriene antagonists are used for asthma control. Objective: In this study, the effect of the addition of formoterol and montelukast on asthma control in patients with moderately persistent asthma who were symptomatic while using a low dose of inhaled budesonide was compared. Methods: At the beginning of the study, 40 symptomatic patients with moderately persistent asthma used 400 µg/day budesonide for a 4-week training period, and were then divided randomly into two groups, each composed of 20 persons. For the first group’s treatment regime, inhaled formoterol (9 µg) twice a day was added, and for the second group’s treatment regime, one-dose oral montelukast (10 µg) was added. These patients were followed up for 8 weeks. The patients’ peak expiratory flow (PEF) values measured in the morning and at night, changes in PEF, forced expiratory volume in 1 s, asthma symptom score and the symptom-relieving therapy used during the 12-week study period were recorded and evaluated in the clinic at the very beginning and at the end of each period. Results: Before the study, the morning PEF value of the group for whom formoterol was added to budesonide (FB) was 266.3 ± 59.3 liters/min, and in the group for whom montelukast was added to budesonide (MB), it was 262.8 ± 53.8 liters/min (p > 0.05). After the 8-week treatment period, the morning PEF values were found to be 320.5 ± 54.4 liters/min in the FB group and 293.3 ± 52.4 liters/min in the MB group; at the end of the study, it was seen that although there was an increase in morning PEF of 54.2 ± 15.2 liters/min in the FB group, there was an increase of only 30.5 ± 25.3 liters/min in the MB group (p < 0.0001). Before the study, night PEF values were 287 ± 56.6 liters/min in the FB group and 283 ± 48.5 liters/min in the MB group (p > 0.05). At the end of the treatment, the night PEF values were found to be 331.5 ± 56.1 liters/min in the FB group and 310 ± 53.1 liters/min in the MB group. At the end of the study, it was observed that although there was an increase in night PEF of 44.5 ± 23.3 liters/min in the FB group, there was an increase of only 27 ± 24.1 liters/min in the MB group (p < 0.001). Although asthma symptom scores and the use of symptom-relieving drugs showed similarities between the two groups at the beginning of the study, after treatment, the FB group had better results than the MB group with respect to these two parameters (p < 0.0001 for both). It was also seen that the two treatments are tolerated equally well. Conclusion: FB treatment, which causes a considerable improvement in lung function, showed better asthma control than MB treatment in patients with moderately persistent asthma.

Drug treatment of pain in rheumatoid disorders

The relief of pain remains a delicate balance between the potential toxicity and desired effect of currently available compounds. Physician and patient need to make the optimum use of such therapies. Control of pain and stiffness in rheumatic diseases is a dynamic process. There is a constant need for re-appraisal of aims and objectives and adjustment of treatment according to variations in disease and response. Where 'specific' therapy is available, it is clearly preferable to use it rather than employ large doses of purely symptom-relieving drugs. At present toxicity is inextricably linked to efficacy, and dissociation of these two factors seems unlikely to be achieved in the near future. More efficient 'targeting' of drugs at the site of desired action should help to minimize the adverse effects of therapy. Ultimately the most efficient way of relieving pain and stiffness will be to prevent or suppress the inflammatory disorders which give rise to the symptoms. Unfortunately this is an elusive goal at present.