Rapid evaluation of the Special Measures for Quality and challenged provider regimes: a mixed-methods study.

Background: Health-care organisations in England that are rated as inadequate for leadership and one other domain enter the Special Measures for Quality regime to receive support and oversight. A 'watch list' of challenged providers that are at risk of entering Special Measures for Quality also receive support. Knowledge is limited about whether or not the support interventions drive improvements in quality, the costs of the support interventions and whether or not the support interventions strike the right balance between support and scrutiny. Objective: To analyse the responses of trusts to the implementation of (1) interventions for Special Measures for Quality trusts and (2) interventions for challenged provider trusts to determine their impact on these organisations' capacity to achieve and sustain quality improvements. Design: This was rapid research comprising five interrelated workstreams: (1) a literature review using systematic methods; (2) an analysis of policy documents and interviews at the national level; (3) eight multisite, mixed-methods trust case studies; (4) an analysis of national performance and workforce indicators; and (5) an economic analysis. Results: The Special Measures for Quality/challenged provider regimes were intended to be 'support' programmes. Special Measures for Quality/challenged provider regimes had an emotional impact on staff. Perceptions of NHS Improvement interventions were mixed overall. Senior leadership teams were a key driver of change, with strong clinical input being vital. Local systems have a role in improvement. Trusts focus efforts to improve across multiple domains. Internal and external factors contribute to positive performance trajectories. Nationally, only 15.8% of Special Measures for Quality trusts exited the regime in 24 months. Entry into Special Measures for Quality/challenged provider regimes resulted in changes in quality indicators (such the number of patients waiting in emergency departments for more than 4 hours, mortality and the number of delayed transfers of care) that were more positive than national trends. The trends in staff sickness and absence improved after trusts left Special Measures for Quality/challenged provider regimes. There was some evidence that staff survey results improved. No association was found between Special Measures for Quality/challenged provider regimes and referral to treatment times or cancer treatment waiting times. NHS Improvement spending in case study trusts was mostly directed at interventions addressing 'training on cultural change' (33.6%), 'workforce quality and safety' (21.7%) and 'governance and assurance' (18.4%). The impact of Special Measures for Quality on financial stability was equivocal; most trusts exiting Special Measures for Quality experienced the same financial stability before and after exiting. Limitations: The rapid research design and 1-year time frame precludes longitudinal observations of trusts and local systems. The small number of indicators limited the quantitative analysis of impact. Measurement of workforce effects was limited by data availability. Conclusions: Empirical evidence of positive impacts of Special Measures for Quality/challenged provider regimes were identified; however, perceptions were mixed. Key lessons were that (1) time is needed to implement and embed changes; (2) ways to mitigate emotional costs and stigma are needed; (3) support strategies should be more trust specific; (4) poor organisational performance needs to be addressed within local systems; (5) senior leadership teams with stability, strong clinical input and previous Special Measures for Quality experience helped to enact change; (6) organisation-wide quality improvement strategies and capabilities are needed; (7) staff engagement and an open-listening culture promote continuous learning and a quality improvement 'mindset', which is critical for sustainable improvement; and (8) consideration of the level of sustainable funds required to improve patients' outcomes is needed. Future work: Future work could include evaluating recent changes to the regimes, the role of local systems and longitudinal approaches. Study registration: The review protocol is registered with PROSPERO (CRD42019131024). Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 11, No. 19. See the NIHR Journals Library website for further project information.

When health-care trusts in England have serious failings in the quality of care that they provide, they can be placed in 'Special Measures for Quality' and receive additional support from the NHS. There is also a list of 'challenged providers' at risk of entering Special Measures for Quality that receive support. In January 2019, of the 234 trusts in England, one-quarter had at some point been a challenged provider and/or entered Special Measures for Quality. We studied how trusts responded to entering the Special Measures for Quality or challenged provider regimes. We wanted to understand if the support that the trusts receive can help the trust to improve the quality of care provided to patients. We did this by reviewing the relevant literature; speaking to a range of staff in eight trusts and nearby health organisations; analysing costs; and observing meetings in four of these trusts. We also compared national performance information between Special Measures for Quality/challenged provider trusts and non-Special Measures for Quality/challenged provider trusts. We found that when a trust enters the Special Measures for Quality regime there is often an emotional impact on staff, who may experience low morale. Some staff thought that their trust received the right type of support, but others saw Special Measures for Quality as heavy-handed scrutiny or punishment. With hindsight, Special Measures for Quality was sometimes viewed more positively, as a pathway to make changes that were needed. Looking at all trusts in England, we found that when trusts entered Special Measures for Quality or became challenged providers they started to get better at seeing emergency department patients within 4 hours and reduced avoidable deaths. We also found that some parts of the staff survey results improved. We found that staff need time and space to make changes. Looking after staff and having a leadership and culture that supports continuous learning are important for making improvements. Regional health-care systems and local organisations have an important role to play in supporting trusts to make improvements.

The role of Fintech firms' sustainability during the COVID-19 period.

This study investigates the moderating role of environmental disclosures on the market performance of 48 Fintech and 140 non-Fintech firms during the pandemic using data from 2011 to 2022. Ordinary least squares and correlations were used for data analysis. The study's first finding revealed that Fintech firms had a better environmental performance (78.4%) than non-Fintech firms during the pandemic. The study's second finding indicated that environmental disclosures are crucial for shareholders and contributed almost 10.2% to the Fintech firms' market performance during the pandemic. This study's contribution is significant in enhancing the understanding of the shareholders' sensitivity towards sustainability disclosures during financial crisis. The findings of this study are essential for policymakers, start-up entrepreneurs, and shareholders.

Parametric Study and Electrocatalyst of Polymer Electrolyte Membrane (PEM) Electrolysis Performance.

An investigation was conducted to determine the effects of operating parameters for various electrode types on hydrogen gas production through electrolysis, as well as to evaluate the efficiency of the polymer electrolyte membrane (PEM) electrolyzer. Deionized (DI) water was fed to a single-cell PEM electrolyzer with an active area of 36 cm2. Parameters such as power supply (50-500 mA/cm2), feed water flow rate (0.5-5 mL/min), water temperature (25-80 °C), and type of anode electrocatalyst (0.5 mg/cm2 PtC [60%], 1.5 mg/cm2 IrRuOx with 1.5 mg/cm2 PtB, 3.0 mg/cm2 IrRuOx, and 3.0 mg/cm2 PtB) were varied. The effects of these parameter changes were then analyzed in terms of the polarization curve, hydrogen flowrate, power consumption, voltaic efficiency, and energy efficiency. The best electrolysis performance was observed at a DI water feed flowrate of 2 mL/min and a cell temperature of 70 °C, using a membrane electrode assembly that has a 3.0 mg/cm2 IrRuOx catalyst at the anode side. This improved performance of the PEM electrolyzer is due to the reduction in activation as well as ohmic losses. Furthermore, the energy consumption was optimal when the current density was about 200 mA/cm2, with voltaic and energy efficiencies of 85% and 67.5%, respectively. This result indicates low electrical energy consumption, which can lower the operating cost and increase the performance of PEM electrolyzers. Therefore, the optimal operating parameters are crucial to ensure the ideal performance and durability of the PEM electrolyzer as well as lower its operating costs.

Examining disparities relating to service reach and patient engagement with COVID-19 remote home monitoring services in England: a mixed methods rapid evaluation

BackgroundThe adoption of remote methods of care has been accelerated by the COVID-19 pandemic, but concerns exist relating to the potential impact on health disparities. This evaluation explores the implementation of COVID-19 remote home monitoring services across England, focussing on patients experiences and engagement with the service. MethodsThe study was a rapid, multi-site, mixed methods evaluation. Data were collected between January and June 2021. We conducted qualitative interviews with staff service leads, and patients and carers receiving the service. We conducted quantitative surveys with staff delivering the service, and patients and carers receiving the service across 28 sites in England, UK. Qualitative data were analysed using thematic analysis and quantitative data were analysed using univariate and multivariate methods. FindingsMany sites designed their service to be inclusive to the needs of their local population. Strategies included widening eligibility criteria, prioritising vulnerable groups, and creating referral pathways. Many sites also adapted their services according to patient needs, including providing information in different languages or more accessible formats, offering translation services, offering non-digital options, or providing face-to-face assessments. Despite these adaptions, disparities were reported across patient groups (e.g. age, health status, ethnicity, level of education) in their experience of and engagement with the service. InterpretationServices must determine how best to design and implement remote monitoring services to be of value to all populations. National guidance should play a role in supporting services to best serve the needs of their populations, and patients and staff must play an active role in service design. FundingThis is independent research funded by the National Institute for Health Research, Health Services & Delivery Research programme (RSET Project no. 16/138/17; BRACE Project no. 16/138/31) and NHSEI. NJF is an NIHR Senior Investigator. The views expressed in this publication are those of the authors and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSEvidence shows COVID-19 has a disproportionate impact on certain population groups, such as ethnic minority groups, older adults and those with comorbidities. The rapid adoption and spread of remote home monitoring services in England must be accompanied by evaluations at a local level to monitor the impact on health disparities in local populations. Added value of this studyThis rapid mixed methods evaluation of COVID-19 home monitoring services adopted across 28 sites in England aimed to increase understanding of how services have been designed and delivered to address local population needs to increase accessibility to the service and facilitate engagement with the service. We add to the literature by identifying a range of local service adaptations which aim to increase reach and facilitate patient engagement, and consider their potential impact on health disparities. We found strategies included prioritising vulnerable groups, creating referral pathways, offering translation services, offering non-digital options, or providing face-to-face assessments. Despite efforts to adapt services to meet local needs, disparities across patient groups in their experience of, and engagement with, the service (related to age, health status, ethnicity, and level of education) were reported. Implications of the available evidenceAt both a national and local level, and particularly given the increasing use of remote home monitoring schemes, lessening health disparities must be a primary focus in the design and delivery of remote monitoring models for COVID-19 and other conditions. Future research should focus on how best to design and evaluate remote monitoring services, for a range of conditions, especially for patients residing in areas where significant health disparities persist, as well as addressing the effectiveness of any strategies on specific population groups.

Patients' and carers' experiences of, and engagement with remote home monitoring services for COVID-19 patients: a rapid mixed-methods study

IntroductionRemote home monitoring models were implemented during the COVID-19 pandemic to shorten hospital length of stay, reduce unnecessary hospital admission, readmission and infection, and appropriately escalate care. Within these models, patients are asked to take and record readings and escalate care if advised. There is limited evidence on how patients and carers experience these services. This study aimed to evaluate patient experiences of, and engagement with, remote home monitoring models for COVID-19. MethodsA rapid mixed-methods study in England. We conducted a cross-sectional survey and interviews with patients and carers. Interview findings were summarised using rapid assessment procedures sheets and grouping data into themes (using thematic analysis). Survey data were analysed using descriptive statistics. ResultsWe received 1069 surveys (18% response rate) and conducted interviews with patients (n=59) and carers (n=3). Care relied on support from staff members, and family/friends. Patients and carers reported positive experiences and felt that the service and human contact reassured them and was easy to engage with. Yet, some patients and carers identified problems with engagement. Engagement was influenced by: patient factors such as health and knowledge, support from family/friends and staff, availability and ease-of-use of informational and material resources (e.g. equipment), and service factors. ConclusionRemote home monitoring models place responsibility on patients to self-manage symptoms in partnership with staff; yet many patients required support and preferred human contact (especially for identifying problems). Caring burden and experiences of those living alone, and barriers to engagement should be considered when designing and implementing remote home monitoring services. Patient or public contributionFor this evaluation, members of the study team met with service user and public members of the BRACE PPI group and Health and Care Panel and patient representatives from RSET in a series of workshops. These workshops informed study design, data collection tools, data interpretation and to discuss study dissemination for Phase 2. For example, patient facing documents, such as the consent form, topic guides, patient survey and patient information sheet were reviewed by this group. Additionally, PPI members helped to pilot patient surveys and interview guides with the research team. We also asked some members of the public to pilot the patient survey. Members of the PPI group were given the opportunity to comment on the manuscript. One PPI member commented on the manuscript and the manuscript was amended accordingly.

Addressing COVID-19 health disparities through a regional community health response.

To combat racial/ethnic and socioeconomic health disparities associated with COVID-19 in our surrounding communities, the Cleveland Clinic Community Health & Partnership team developed a comprehensive program focused on connecting and communicating with local officials, faith-based organizations, and individual community members. Since March of 2020, our team has donated resources (e.g., personal protective equipment) to local organizations, referred thousands of community members to community or clinical resources, and partnered with federally-qualified health centers to support community COVID-19 testing. Future work will include the use of these networks to deploy the COVID-19 vaccine.

Convalescent plasma: A potential therapeutic option for COVID-19 patients

The new coronavirus disease (COVID-19) outbreak has challenged us to take unprecedented steps to bring this pandemic under control. In view of the urgency of this situation, convalescent plasma which was used in previous coronavirus outbreaks has emerged as one of the treatment options in this current pandemic. This is mainly due to the fact that convalescent plasma has been studied in a few case series with promising outcomes. In addition, on-going large clinical trials aimed to further evaluate the effectiveness, safety, and optimal dosage, duration and timing of administration of convalescent plasma are indeed revealing a certain level of promising results. Therefore, this article aims to provide an overview of possible mechanisms of actions of convalescent plasma, its benefits and its level of usage safeness by summarizing the existing evidence on the use of convalescent plasma in COVID-19 patients.

Convalescent plasma: A potential therapeutic option for COVID-19 patients

The new coronavirus disease (COVID-19) outbreak has challenged us to take unprecedented steps to bring this pandemic under control. In view of the urgency of this situation, convalescent plasma which was used in previous coronavirus outbreaks has emerged as one of the treatment options in this current pandemic. This is mainly due to the fact that convalescent plasma has been studied in a few case series with promising outcomes. In addition, on-going large clinical trials aimed to further evaluate the effectiveness, safety, and optimal dosage, duration and timing of administration of convalescent plasma are indeed revealing a certain level of promising results. Therefore, this article aims to provide an overview of possible mechanisms of actions of convalescent plasma, its benefits and its level of usage safeness by summarizing the existing evidence on the use of convalescent plasma in COVID-19 patients.

Microencapsulation of Lactobacillus plantarum 299v incorporated with oligofructose in chitosan coated-alginate beads and its storage stability in ambarella juice

Aims@#Microencapsulation has been used to protect the viability of probiotics in harsh environments such as gastrointestinal conditions and food composition. The present study aimed to optimize the microencapsulation of Lactobacillus plantarum 299v (Lp299v) using co-extrusion by varying two parameters (calcium chloride (CaCl2) and oligofructose (FOS) concentrations) and storage stability of the beads produced in ambarella juice at refrigerated and room temperature. @*Methodology and results@#Chitosan coated-alginate microcapsule prepared with 4.0% (w/v) FOS and 2.5% (w/v) CaCl2 showed highest microencapsulation efficiency (93%). The microcapsules were subjected to gastrointestinal treatment and storage test in ambarella juice. Both encapsulated Lp299v with and without FOS showed higher viabilities compared with free cells after incubated in simulated gastric juice (SGJ) and simulated intestinal juice (SIJ). After 5 h of incubation in SIJ, the viabilities of both encapsulated probiotic with and without FOS were more than 107 CFU/mL. The Lp299v were stored in ambarella juice under refrigerated (4 °C) and room temperature (25 °C) for 4 weeks. At 25 °C, all forms of Lp299v lost their viabilities after one week. On the other hand, at 4 °C, viable cells count of both encapsulated Lp299v with and without FOS were reported to be more than 107 CFU/mL after 4 weeks of storage. @*Conclusion, significance and impact of study@#Microencapsulation with FOS was able to improve Lp299v’s viability during storage in low pH fruit juices compared to those without FOS. The microencapsulated probiotics could be applied in ambarella juice for the development of functional food.

Maternal diabetes impairs the initiation of meiosis in murine female germ cells.

Gestational diabetes mellitus (GDM) is characterized by an initial diagnosis of glucose intolerance during pregnancy. There is increasing evidence supporting the association between GDM and the inhibited development of several organs in offspring. In the present study, a murine GDM model was established in mice by intraperitoneal injection of streptozotocin to evaluate the effect of maternal diabetes on the initiation of meiosis in female germ cells of offspring. The effect of GDM on the initiation of meiosis in the offspring was evaluated by reverse transcription-quantitative polymerase chain reaction, flow cytometry and hematoxylin and eosin staining. The results showed that, compared with the control group, fetal ovary growth was inhibited, the expression levels of meiosis­specific genes, stimulated by retinoic acid gene 8, synaptonemal complex protein, and DNA meiotic recombinase were inhibited, and the number of primordial/primary follicles was reduced in the GDM group. These may have been induced by an increase of apoptosis and inhibition of growth, as the mRNA levels of p21, a vital G1 cell cycle inhibitor, and apoptotic genes were upregulated, whereas the expression levels of genes important in folliculogenesis were decreased in the GDM group. In conclusion, the data obtained in the present study suggested that maternal diabetes may impair the initiation of meiosis and ovarian growth via growth inhibition, cell cycle arrest and the induction of apoptosis.

Iodine deficiency: Clinical implications.

Iodine is crucial for thyroid hormone synthesis and fetal neurodevelopment. Major dietary sources of iodine in the United States are dairy products and iodized salt. Potential consequences of iodine deficiency are goiter, hypothyroidism, cretinism, and impaired cognitive development. Although iodine status in the United States is considered sufficient at the population level, intake varies widely across the population, and the percentage of women of childbearing age with iodine deficiency is increasing. Physicians should be aware of the risks of iodine deficiency and the indications for iodine supplementation, especially in women who are pregnant or lactating.

Persistence of Th1/Tc1 responses one year after tetravalent dengue vaccination in adults and adolescents in Singapore.

To characterize the cell mediated immunity (CMI) induced by the investigational CYD tetravalent dengue vaccine (TDV), we developed a whole-blood, intracellular cytokine staining (ICS) assay and a multiplex assay, each requiring 3 mL of blood. We assessed CMI before and 28 d after a first and third injection of CYD-TDV and one year after the third injection in a subset of 80 adolescents and adults enrolled in a phase II trial in Singapore (ClinicalTrial.gov NCT NCT00880893). CD4/IFNγ/TNFα responses specific to dengue NS3 were detected before vaccination. Vaccination induced YF-17D-NS3-specific CD8/IFNγ responses, without significant TNFα, and a CYD-specific Th1/Tc1 cellular response in all participants, which was characterized by predominant IFNγ secretion compared with TNFα, associated with low level IL-13 secretion in multiplex analysis of peripheral blood mononuclear cells (PBMC) supernatants after restimulation with each the CYD vaccine viruses. Responses were directed mainly against CYD-4 after the first vaccination, and were more balanced against all four serotypes after the third vaccination. The same qualitative profile was observed one year after the third vaccination, with approximately 2-fold lower NS3-specific responses, and 3-fold lower serotype-specific cellular responses. These findings confirm previous observations regarding both the nature and specificity of cellular responses induced by CYD-TDV, and for the first time demonstrate the persistence of cellular responses after one year. We also established the feasibility of analyzing CMI with small blood samples, allowing such analysis to be considered for pediatric trials.

Heart failure in hypophosphatemic rickets: complications from high-dose phosphate therapy.

OBJECTIVE: To report a rare case of hypophosphatemic rickets (HR) leading to extensive cardiac complications. METHODS: We present the clinical course and autopsy findings of a patient with HR, treated with chronic phosphate-only therapy as a child, who subsequently developed tertiary hyperparathyroidism leading to extensive cardiac calcifications and complications. We also review the literature on the pathophysiology of calcifications from HR. RESULTS: A 34-year-old man was diagnosed with HR at 4 years of age after presenting with growth delay and leg bowing. Family history was negative for the disease. He was initiated on high-dose phosphate therapy (2-6 g of elemental phosphorus/day) with sporadic calcitriol use between 4-18 years of age. For 6 years he received phosphate-only therapy. Subsequently, he developed nephrocalcinosis, heart valve calcifications, severe calcific coronary artery disease, heart block, and congestive heart failure. At a young age, he required an aortic valve replacement and a biventricular pacemaker that was subsequently upgraded to an implantable cardioverter defibrillator. Autopsy showed extensive endocardial, myocardial, and coronary artery calcifications. CONCLUSION: Cardiac calcification is a known sequela of tertiary hyperparathyroidism when it occurs in patients with renal failure, but it is rarely seen in HR due to high phosphate therapy. Phosphate alone should never be used to treat HR; high doses, even with calcitriol, should be avoided. It is important to be cognizant of high-dose phosphate effects and to consider parathyroidectomy for autonomous function, if needed. This case emphasizes the importance of appropriate therapy, monitoring, and management of patients with HR.

Adrenal insufficiency.

Adrenocortical insufficiency may arise through primary failure of the adrenal glands or due to lack of ACTH stimulation as a result of pituitary or hypothalamic dysfunction. Prolonged administration of exogenous steroids will suppress the hypothalamic-pituitary-adrenal axis, and hence cortisol secretion. We review briefly the causes, investigation, and treatment of adrenal insufficiency, and highlight aspects of particular relevance to patients with adrenal tumors.

Discovery of selective small molecular TACE inhibitors for the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, inflammatory disease that afflicts 1-2% of the world population, characterized by an immune mediated inflammatory synovitis that leads to joint destruction, functional impairment, and reduced quality of life. The treatment goals of RA should be longterm substantial relief of pain, arrested joint inflammation and damage, and improved function. Current treatment can be divided into four classes, namely general analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease modifying anti-rheumatic drugs (DMARDs) and biological agents (tumor-necrosis factor modifiers). However, gastrointestinal (GI) side effects of NSAIDs cannot be neglected, direct joint injections of glucocorticoids cannot be injected more than once every 3 months, synthetic DMARDs is far from optimal and only minority of patients achieved longterm remission, the biologics are very expensive to manufacture, need to be injected, and can cause allergic reactions. An alternative and good approach to the treatment of this disease is to lower the levels of tumour necrosis factor-α (TNF-α) in RA, which can be achieved by selectively inhibiting the tumour necrosis factor-α converting enzyme (TACE) that generate these cytokines using cheaper small molecules. This review focuses on the current status of selective small molecule inhibitors of TACE, with respect to lead compound search, inhibitors design approach, structure-activity relationship (SAR) and pharmacological studies in animals and humans. Through these methods, new hope is emerging for the treatment of RA through selective inhibition of TACE.

New hope for the treatment of osteoarthritis through selective inhibition of MMP-13.

Osteoarthritis (OA) is the leading cause of joint pain and disability in middle-aged and elderly patients, and is characterized by progressive loss of articular cartilage that eventually leads to a complex process involving degradation of various components of the cartilage matrix, chief among them are the cartilage-specific type II collagen (CII) and aggrecan. While the loss of aggrecan is thought to be an early and reversible process, degradation of CII is considered to be irreversible and a key step in the loss of structural and functional integrity of cartilage. Among the various matrix metalloproteinases (MMPs), MMP-13 is specifically expressed in the cartilage of human OA patients and is not present in normal adult cartilage. It is the major collagenase in OA cartilage and has the highest activity against CII. However, the clinical utility of broad-spectrum MMP inhibitors developed for treatment of OA has been restricted by dose- and duration-dependent musculoskeletal side effects in humans. Consequently, selectively inhibiting the MMP-13 would seem to be an attractive therapeutic objective. This review mainly focuses on selective MMP-13 inhibitors development in terms of OA since the late 90s, in terms of synthetic compounds of low molecular mass incorporating specific zinc-binding groups, non-zinc-binding groups. In addition, dual inhibitors of MMP-13 and aggrecanase are also reviewed. Special emphasis is placed on logistic concerns for lead compound search as well as the structure-activity relationship (SAR) in this field. Through these methods, new hope is emerging for the treatment of OA through selective inhibition of MMP-13.

Effect of low-dose decitabine in combination with imatinib mesylate in K562 cells / 白血病·淋巴瘤

Objective Imatinib mesylate (IM) is the most active agent in treating chronic myeloid leukemia (CML). 5-Aza-2-deoxycytidine (DAC) is a cytosine analogue that inhibits DNA methylation and the activity in myeloid leukemia. Therefore,we investigated combining these two drugs in human leukemia cell line K562. Methods The effects of IM and DAC was examined in K562 cells including cell viability using MTT method,cell cycle phase and cell death using flow cytometric (FCM),and the expression of bcr-abl mRNA by RT-PCR. Results Both DAC and IM resulted in time and concentration-dependent induction of cell death. DAC and IM in combination produced a greater inhibition of growth against K562 cells (F =43.947,165.580,321.193,296.101,P<0.05). The main effect and interaction between two drugs was statistically significant (F = 202.759,168.457,417.538,P <0.001) after 24 h,48 h,72 h and a greater reduction in expression of bcr-abl mRNA than either agent alone. The difference was statistically significant (F =71.981,P <0.05). The number of G1 phase cells were increased significantly when induced by single agent. 48 h incubation with IM 0.2 μmol/L alone or combined with DAC 4 μmol/L showed 6.7 %,8.4 % pre-apoptosis cells,respectively. After incubation for 48 h with DAC 4 μmol/L,the expression of mRNA were decreased by 14 %,IM 0.2 μmol/L showed 40 % reduction,and combination group were significantly depressed for the mRNA expression by 60 %. Conclusion The combination of DAC and IM showed synergistic effects on cell death in K562 cells. These data suggested that DAC used in combination with IM has clinical potential in the treatment of chronic myeloid leukemia.

Vitamin d and serum cytokines in a randomized clinical trial.

Background. The role of vitamin D in the body's ability to fight influenza and URI's may be dependent on regulation of specific cytokines that participate in the host inflammatory response. The aim of this study was to test the hypothesis that vitamin D can influence intracellular signaling to regulate the production of cytokines. Subjects and Methods. This study was a 3-month prospective placebo-controlled trial of vitamin D3 supplementation in ambulatory adults [Li-Ng et al., 2009]. 162 volunteers were randomized to receive either 50 µg/d (2000 IU) of vitamin D3 or matching placebo. 25(OH)D and the levels of 10 different cytokines (IL-2, 4, 5, 6, 8, 10, 13, GM-CSF, IFN-γ, TNF-α) were measured in the serum of participants at baseline and the final visit. There were 6 drop-outs from the active vitamin D group and 8 from the placebo group. Results. In the active vitamin D group, we found a significant median percent decline in levels of GM-CSF (-62.9%, P < .0001), IFN-γ (-38.9%, P < .0001), IL-4 (-50.8%, P = .001), IL-8 (-48.4%, P < .0001), and IL-10 (-70.4%, P < .0001). In the placebo group, there were significant declines for GM-CSF (-53.2%, P = .0007) and IFN-γ (-34.4%, P = .0011). For each cytokine, there was no significant difference in the rate of decline between the two groups. 25(OH)D levels increased in the active vitamin D group from a mean of 64.3 ± 25.4 nmol/L to 88.5 ± 23.2 nmol/L. Conclusions. The present study did not show that vitamin D3 supplementation changed circulating cytokine levels among healthy adults.

Conivaptan: Evidence supporting its therapeutic use in hyponatremia.

INTRODUCTION: The available treatment options for euvolemic and hypervolemic hyponatremia are limited, and consist mainly of fluid restriction, diuresis, or hypertonic solutions. Most of these therapies are neither well tolerated nor totally effective, and many are associated with significant adverse effects. Vasopressin receptor antagonists, also known as vaptans, are a new class of agents that now offer an additional treatment option for hyponatremic patients. Conivaptan hydrochloride, a competitive antagonist of vasopressin V1a and V2 receptors, is the first agent in this class to be approved for treatment of euvolemic and hypervolemic hyponatremia in hospitalized patients. AIMS: This review critically assesses the evidence that support the use of conivaptan for the treatment of patients with euvolemic and hypervolemic hyponatremia. EVIDENCE REVIEW CONCLUSION: Conivaptan is effective in raising serum sodium levels in a predictable and safe fashion in euvolemic and hypervolemic hyponatremic patients. Conivaptan provides the first molecularly targeted approach for correcting hyponatremia in hospitalized patients.

Tree-in-bud pattern on thoracic CT due to pulmonary intravascular metastases from pancreatic adenocarcinoma.

We report a case of pulmonary intravascular metastases from pancreatic adenocarcinoma manifesting as tree-in-bud pattern on thoracic computed tomography. Although infectious bronchiolitis is the most common cause of tree-in-bud pattern, this case emphasizes that the differential diagnoses include pulmonary intravascular metastases, particularly in patients with extrapulmonary adenocarcinomas.