Success Of Current Treatments Research Articles

Exploring Diet-Based Treatments for Atrial Fibrillation: Patient Empowerment and Citizen Science as a Model for Quality-of-Life-Centered Solutions.

Atrial fibrillation (AF) is the most common heart rhythm disorder in the Western world. Between the years 2010 and 2019, the global prevalence of AF rose from 33.5 million to 59 million, highlighting the importance of developing equitable treatments for patients. The disease is associated with symptoms such as palpitations, dizziness, fatigue, shortness of breath, and cognitive dysfunction. In addition, AF increases the risk of developing a stroke and heart failure. Despite new insights into risk factors that can lead to the development of AF, the success of current treatments is suboptimal. Numerous risk factors, such as hypertension, diabetes, and obesity, have been associated with the development and progression of AF. As these can be lifestyle-related risk factors, lifestyle modification may be a solution to reduce AF-related symptoms as well as episodes. Research results show that certain dietary changes can reduce AF and numerous risk factors for AF. Increasing attention is being given to Mediterranean and whole, plant-based eating patterns, which emphasize eating grains, legumes, vegetables, fruits, and nuts, while excluding most-or all-animal products. Hence, what are the beneficial aspects of a Mediterranean and plant-based diet which consists mainly of unprocessed foods? In the current review, we discuss the outcomes of diet-based treatments. Moreover, other diet-related treatments, brought up by patient initiatives, are highlighted. These patient-initiated studies include L-glutamine and electrolytes as options to manage AF. Also, we highlight the emerging importance of valuing patient needs and a quality-of-life-centered approach to medicine. As indicated by recent studies and patient experiences, citizen science can create inclusive solutions that lead to patient empowerment and a holistic approach for AF management.

Colorectal Liver Metastasis: Can Cytokines Make the Difference?

Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. Metastasis is the prime driver of CRC-related mortality, and the liver is the organ most frequently involved. Despite the overall success of current treatments, colorectal liver metastasis (CRLM) is associated with poor prognoses and a survival rate of only 14%. Recent studies have highlighted the importance of the tumor microenvironment (TME) and the crosstalk within it in determining the invasion of distant organs by circulating cancer cells. In the TME, cellular communication is mediated via soluble molecules, among which cytokines have recently emerged as key regulators, involved in every aspect of tumor progression and the metastatic cascade. Indeed, in the serum of CRC patients elevated levels of several cytokines are associated with cancer development and progression. The current review evaluates the role of different cytokines during CRLM development. Additionally, considering the increasing amount of data concerning the importance of cytokine complex networks, we outline the potential of combination treatments using targeted cytokines together with other well-established therapies, such as immune checkpoint blockades, chemotherapy, or gene therapy, to improve therapeutic outcomes.

Long-term health and economic benefits of switching to tenofovir alafenamide versus continuing on entecavir in chronic hepatitis B patients with low-level viremia in Saudi Arabia.

Despite the success of current treatments, many chronic hepatitis B (CHB) patients still live with low-level viremia [LLV] resulting in liver disease progression. This study evaluated the long-term health and economic impact of switching to tenofovir alafenamide (TAF) from entecavir (ETV) in Saudi Arabia (SA) in chronic hepatitis B (CHB) LLV patients. A hybrid decision tree Markov state-transition model was developed to simulate a cohort of patients with CHB LLV treated with ETV and switched to TAF over a lifetime horizon in SA. While on treatment, patients either achieved complete virologic response (CVR) or maintained LLV. CVR patients experienced slower progression to advanced liver disease stages as compared to LLV patients. Demographic data, transition probabilities, treatment efficacy, health state costs, and utilities were sourced from published literature. Treatment costs were sourced from publicly available databases. Base case analysis found that over a lifetime horizon, switching to TAF versus remaining on ETV increased the proportion of patients achieving CVR (76% versus 14%, respectively). Switching to TAF versus remaining on ETV resulted in a reduction in cases of compensated cirrhosis (-52%), decompensated cirrhosis (-5%), hepatocellular carcinoma (-22%), liver transplants (-12%), and a 37% reduction in liver-related deaths. Switching to TAF was cost-effective with an incremental cost-effectiveness ratio of $57,222, assuming a willingness-to-pay threshold of three times gross national income per capita [$65,790/QALY]. This model found that switching to TAF versus remaining on ETV in SA CHB LLV patients substantially reduced long-term CHB-related morbidity and mortality and was a cost-effective treatment strategy.

Healthcare Provider Perspectives on HIV Cure Research in Ghana.

Antiretroviral therapy (ART) has reduced mortality and improved life expectancy among HIV patients but does not provide a cure. Patients must remain on lifelong medications and deal with drug resistance and side effects. This underscores the need for HIV cure research. However, participation in HIV cure research has risks without guaranteed benefits. We determined what HIV healthcare providers know about HIV cure research trials, the risks involved, and what kind of cure interventions they are likely to recommend for their patients. We conducted in-depth qualitative interviews with 39 HIV care providers consisting of 12 physicians, 8 counsellors, 14 nurses, 2 pharmacists, 2 laboratory scientists, and 1 community advocate from three hospitals. Interviews were transcribed verbatim and coded, and thematic analysis was performed independently by two investigators. Participants were happy about the success of current treatments and hopeful that an HIV cure will be found in the near future, just as ART was discovered through research. They described cure as total eradication of the virus from the body and inability to test positive for HIV or transmit the virus. In terms of risk tolerance, respondents would recommend to their patients' studies with mild to moderate risks like what patients on antiretroviral therapy experience. Participants were reluctant to recommend treatment interruption to patients as part of a cure study and wished trials could be performed without stopping treatment. Healthcare providers categorically rejected death or permanent disability as an acceptable risk. The possibility of finding a cure that will benefit the individual or future generations was strong motivations for providers to recommend cure trials to their patients, as was transparency and adequate information on proposed trials. Overall, the participants were not actively seeking knowledge on cure research and lacked information on the various cure modalities under investigation. While hopeful for an HIV cure, healthcare providers in Ghana expect a cure to be definitive and pose minimal risk to their patients.

In Vitro Efficacy of Extracts and Isolated Bioactive Compounds from Ascomycota Fungi in the Treatment of Colorectal Cancer: A Systematic Review.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Despite the advances and success of current treatments (e.g., chemotherapy), there are multiple serious side effects which require the development of new treatment strategies. In recent years, fungi have gained considerable attention as a source of extracts and bioactive compounds with antitumor capabilities because of their antimicrobial and antioxidant properties and even their anti-inflammatory and antiviral activities. In the present review, a systematic search of the existing literature in four electronic databases was carried out in which the antitumor activity against CRC cells of Ascomycota fungi extracts or compounds was tested. The systematical research in the four databases resulted in a total of 883 articles. After applying exclusion and inclusion criteria, a total of 75 articles were finally studied. The order Eurotiales was the most studied (46% of the articles), and the ethyl acetate extraction was the most used method (49% of the papers). Penicillium extracts and gliotoxin and acetylgliotoxin G bioactive compounds showed the highest cytotoxic activity. This review also focuses on the action mechanisms of the extracts and bioactive compounds of fungi against CRC, which were mediated by apoptosis induction and the arrest of the cell cycle, which induces a notable reduction in the CRC cell proliferation capacity, and by the reduction in cell migration that limits their ability to produce metastasis. Thus, the ability of fungi to induce the death of cancer cells through different mechanisms may be the basis for the development of new therapies that improve the current results, especially in the more advanced stages of the CCR.

The psychological, psychosocial and emotional wellbeing of children and young people with leukaemia

Leukaemia is the most common childhood cancer, and with the success of current treatment, it has an overall survival rate of up to 92%. Despite this, treatment does not come without consequences. As a result, it is no surprise that recent research has examined the long-term implications of this treatment. An integrative review was conducted to capture a broad range of primary research studies from both quantitative and qualitative perspectives. Four electronic databases were searched, displaying 3239 articles, of which nine met all the inclusion criteria. This integrative review explores these studies, using thematic analysis, with the purpose of identifying the impact this disease has on the psychological, psychosocial and emotional wellbeing of children and young people (CYP) diagnosed with leukaemia. The review highlighted the vast impact that a leukaemia diagnosis can have on CYP and five main trends emerged: experienced emotions; relationships with peers; relationships with family; academic challenges; and differentiating factors. As a result of the findings, it is recommended that CYP receive psychological support from diagnosis, with a regular reassessment throughout treatment. Parents and carers require support to enable them to efficiently care for their children. It is evident from this review that further research in this area would be beneficial to address some gaps in the literature.

The Global Fund in China: Multidrug-resistant tuberculosis nationwide programmatic scale-up and challenges to transition to full country ownership.

China has the world’s second largest burden of multidrug-resistant tuberculosis (MDR-TB; resistance to at least isoniazid and rifampicin), with an estimated 57,000 cases (range, 48,000–67,000) among notified pulmonary TB patients in 2015. During October 1, 2006–June 30, 2014, China expanded MDR-TB care through a partnership with the Global Fund to Fight AIDS, Tuberculosis, and Malaria (Global Fund). We analyzed data on site expansion, patient enrolment, treatment outcomes, cost per patient, and overall programme expenditure. China expanded MDR-TB diagnostic and treatment services from 2 prefectures in 2006 to 92 prefectures, covering 921 of the country’s 3,000 counties by June 2014. A total of 130,910 patients were tested for MDR-TB, resulting in 13,744 laboratory-confirmed cases, and 9,183 patients started on MDR-TB treatment. Treatment success was 48.4% (2011 cohort). The partnership between China and the Global Fund resulted in enormous gains. However, changes to health system TB delivery and financing coincided with the completion of the Global Fund Programme, and could potentially impact TB and MDR-TB control. Transition to full country financial ownership is proving difficult, with a decline in enrollment and insufficient financial coverage. Given needed improvement to the current treatment success rates, these factors jeopardise investments made for MDR-TB control and care. China now has a chance to cement its status in TB control by strengthening future financing and ensuring ongoing commitment to quality service delivery.

Anti- Helicobacter pylori activity of crude acetonic extracts of Streptomyces sp. H7372

IntroductionHelicobacter pylori is a gram negative bacterium and a gastric pathogen that infects approximately 50% of the world's populations. Prolonged H. pylori infection causes chronic inflammation and significantly increases the risk of developing gastric cancer, making it a serious global health issue. Recent studies have showed that the success of current treatment, the standard triple therapy, using a wide range of antibiotics (amoxicillin, metronidazole, tetracycline etc.), has declined to unacceptable rates of 80% or less due to antibiotic resistance. New perspectives at current anti- Helicobacter pylori therapy and strategies as well as novel drug alternatives are essentially needed to eradicate H. pylori infection. ObjectiveWe reported a new strain Streptomyces sp. H7372, a gram-positive aerobic bacterium isolated from mangrove soil in Sabah, Malaysia that has shown anti-Helicobacter pylori activities. MethodsStreptomyces sp. H7372 was extracted once with acetone and dried at 40°C. The dried extract was dissolved in distilled water and was examined in vitro. Broth microdilution method was used to determine minimum inhibitory concentration of Streptomyces sp. H7372 against H. pylori ATCC 700824 strain. For disc assay, both ATCC and some clinical strains of H. pylori were grown on TSA blood agar with varying extract concentrations to study zone of inhibition. ResultsThe acetonic extract was found to be fairly inhibitory to Helicobacter pylori ATCC 700824 strain (MIC: 0.0625 ug/ul) as compared to Amoxicillin (MIC: 1×10−5 ug/ul). Disc assay showed concentration dependent inhibitory effect. ConclusionThe present study shows that the acetone extracts from Streptomyces sp. H7372 displayed a strong potential alternative against H. pylori. In the future, extract will be successively fractioned into different chemical portions and will be examined in vitro. Anti-inflammation and anti-adhesion assays will be performed in human gastric mucosal cell line infected with H. pylori to understand the mechanisms of anti-H.pylori activity of H7372.

Effect of altering fibroblast integrin associated protein expression on the growth and protein expression of pancreas cancer cells.

251 Background: The lack of success of current treatments for pancreatic ductal adenocarcinoma (PDA) may be due in part to the presence of the dense surrounding stromal response and the interactions between the stroma and cancer cells. We have shown that integrin associated proteins, in particular PINCH, are expressed to a higher degree in the stroma adjacent to the tumor cells and PINCH expression is positively correlated with poorer PDA patient outcomes. We hypothesize that decreasing PINCH protein expression in the tumor associated stroma will decrease the growth and expression of growth promoting proteins in PDA cells. Methods: Red fluorescent protein (RFP) stably expressing MiaPaCa-2 cells were co-cultured with WI38 fibroblasts, or WI38 fibroblasts with shRNA knockdown of PINCH protein (PINCH KD). Cell growth of the PDA cells alone and upon exposure to WI38 and PINCH KD fibroblasts was determined using RFP at 48 hours. PINCH, Akt, and pAKt protein expression in cultured PDA cells, exposed to media, WI38, or WI38 PINCH KD cells via a transwell system, were determined by western blot with values normalized to GAPDH protein expression at 48 hours. Results: MiaPaCa-2 cells grown in co-culture with WI38 cells had a 70%±5% increase in RFP, while those grown in co-culture with WI38 PINCH KD cells had a 40%±3% increase relative to MiaPaCa2 cells grown alone. In terms of relative PINCH protein expression there was an increase in MiaPaCa-2 (20%±5%) cells grown in co-culture with WI38 cells compared to alone but not when grown with PINCH KD (6%±3%). MiaPaCa-2 cells had a greater increase in AKT (47%±6% compared with 19%±4%) and pAKT (36%±5 and 22%±4%) in the cells grown with WI38 cells compared to PDA cells grown with WI38 PINCH KD. Conclusions: Reductions in fibroblast PINCH protein expression are associated with reductions in the growth of adjacent PDA cells, as well as the expression of growth enhancing proteins (PINCH, AKT, and pAKT). Since greater PINCH expression within PDA stromal cells is associated with poorer patient outcomes, understanding the mechanisms associated with this tumor-stromal interaction may provide intervention opportunities.

Biochemical and pathological correlates of cognitive and behavioural change in DLB/PDD

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are second only to Alzheimer's disease (AD) in frequency. In particular it is evident that up to 80% of people with PD will develop dementia towards the end of their life. While the neurobiology of movement disorder has been well studied in PD, much less attention has been given to mechanisms underlying the cognitive and behavioural symptoms associated with DLB and PDD. To date, the best correlate of cognitive impairment appears to be cortical Lewy bodies; however, new emphasis has been placed on small aggregates of synuclein. Furthermore, very few studies have attempted to investigate the neurochemical correlates of behavioural disorders in DLB/PDD and whether these are similar or distinct from AD. Aggregated alpha-synuclein forms the core component of Lewy bodies, a major pathological feature of Parkinson's-related conditions. The 26S proteasome is an ATP-dependent protease that catalyses the breakdown of alpha-synuclein. Previous studies have implicated alterations in the proteasome in PD. Furthermore, proteasome inhibitors have been reported to induce alpha-synuclein aggregation and Lewy body-like inclusions, resulting in neuronal loss both in vitro and in vivo. Our preliminary results indicate that selective alterations in the expression of proteosome sub-units are a feature of both DLB and PDD, while changes in activity are restricted to PDD. Depression is a common symptom in DLB/PDD, yet the evidence base for standard treatment with SSRIs is limited. In contrast to previous studies of AD, our results indicate that there is no association between depression and the 5-HT transporter, while there was a significant increase in the number of 5-HT1A receptors in those DLB/PDD patients with depression. These data may provide an insight into the lack of success of current treatments and suggest alternative approaches.

Outcome of inpatient opiate detoxification treatment in immigrants as compared to native Germans

Background Immigration is a factor with effects on the course of substance abuse and treatment response, however there is little consistent data regarding outcome of inpatient opiate detoxification treatment in immigrants as compared to native patients. Methods Patient history and the success of current detoxification treatment were systematically documented in a multicenter study in Germany which included 10 psychiatric hospitals with specialized detoxification wards. Results Out of 893 patients, 240 (27%) had a migration history. We further analyzed the three main groups (German, n = 653; Turkish, n = 58; Russian origin, n = 103). There were significant differences between groups regarding sociodemographic data, drug history, treatment experience and success of current treatment. However, considering the younger age of patients with Russian origin, analysis of younger patients (< 31 years) detected only minor group differences. In multiple logistic regressions age and center showed statistically significant associations with all outcome variables (early dropout, achievement of drug-free urine screen, regular completion of detoxification treatment, and referral to further treatment), while (Russian) origin was associated only with premature termination of treatment. Conclusion Young men were the main problem group regardless of origin. Significant center effects raise doubts regarding results from monocenter research.

Meeting report

Despite successful treatment with all- trans retinoic acid and chemotherapy, life-threatening bleeding remains a challenging complication of acute promyelocytic leukemia (APL). Indeed, bleeding and thrombosis are major complications of APL that lead to early death in approximately 10% of patients despite the success of current treatment. This condition may be attributed, in part, to the diffuse activation of coagulation, hyperfibrinolysis, and non-specific proteolytic activity that is observed in patients with APL. Therapeutic agents that induce the differentiation of leukemia cells improve outcomes compared with those observed using chemotherapy alone. They also correct the hyperactivity of the coagulation and fibrinolytic systems, thereby reducing early death from bleeding. Prophylactic therapy with newer anticoagulants may prove beneficial in patients with APL, but this must be confirmed in well-designed, randomized, controlled trials. A workshop was convened 21 January 2004 in London, England, to discuss the clinical and biological aspects of the APL-associated coagulopathy and the application of recent findings to the management of patients with APL. Eight speakers participated in the workshop: Benjamin Brenner (M.D.), Hematology Institute, Rambam Medical Center, Haifa, Israel; Anna Falanga (M.D.), Ospedali Ruiniti di Bergamo, Bergamo, Italy; Hau C. Kwaan (M.D.), Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Howard Liebman (M.D.), University of Southern California, Cancer Center, Los Angeles, CA, USA; Emmanuel Raffoux (M.D.), Department of Hematology, Hôpital Saint Louis, Paris, France; Frederick R. Rickles (M.D., F.A.C.P.), The George Washington School of Medicine, Washington, DC, USA; Javier de la Serna (M.D., Ph.D.), Servicio de Hematologia, Hospital Universitario 12 de Octubre, Madrid, Spain; and Martin S. Tallman (M.D.), Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. This meeting report provides synopses of their presentations and a summary of highlights from the meeting.

Continued inadequacies in data sources for the evaluation of cancer services.

There is a need to evaluate cancer services and provide a baseline on current treatment success and organization. This study shows that this process may be severely hindered by case note destruction or inaccessibility and incomplete information. This is an ongoing problem that needs to be addressed now.