Repurposing approved therapeutics for new indication: Addressing unmet needs in psoriasis treatment.
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ABSTRACT:
SUBMITTER: Jain H
PROVIDER: S-EPMC8663928 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The negative symptoms of schizophrenia represent an impairment of normal emotional responses, thought processes and behaviors, and include blunting or flattening of affect, alogia/aprosody, avolition/apathy, anhedonia, and asociality. Negative symptoms contribute to a reduced quality of life, increased functional disability, increased burden of illness, and poorer long-term outcomes, to a greater degree than positive symptoms. Primary negative symptoms are prominent and persistent in up to 26% of patients with schizophrenia, and they are estimated to occur in up to 58% of outpatients at any given time. Negative symptoms respond less well to medications than positive symptoms, and to date treatment options for negative symptoms have been limited, with no accepted standard treatment. Modest benefits have been reported with a variety of different agents, including second-generation antipsychotics and add-on therapy with antidepressants and other pharmacological classes. Recent clinical research focusing on negative symptoms target novel biological systems, such as glutamatergic neurotransmission. Different approaches include: enhancing N-methyl-D-aspartate receptor function with agents that bind directly to the glycine ligand site or with glycine reuptake inhibitors; influencing the metabotropic glutamate receptor (mGluR2/3) with positive allosteric modulators; and stimulating nicotinic acetylcholine receptors. In conclusion, the lack of clearly efficacious pharmacological treatments for the management of negative symptoms represents a significant unmet need, especially considering the importance of these symptoms on patient outcomes. Hence, further research to identify and characterize novel pharmacological treatments for negative symptoms is greatly needed.
| S-EPMC4020880 | biostudies-literature
Project description:For the initial phase of pandemic of coronavirus disease 2019 (COVID-19), repurposing drugs that in vitro inhibit severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been attempted with overlooked or overestimated efficacy owing to limited clinical evidence. Most early clinical trials have the defects of study design, small sample size, non-randomized design, or different timings of treatment initiation. However, well-designed studies on asymptomatic or mild, or pediatric cases of COVID-19 are scarce and desperately needed to meet the clinical need. However, a trend could be observed based on current clinical evidence. Remdesivir and favipiravir may shorten the recovery time; lopinavir/ritonavir does not demonstrate treatment efficacy in severe patients. Triple therapy of ribavirin, lopinavir, and interferon β-1b showed early viral negative conversion, and the major effect may be related to interferon. Some small sample-size studies showed that interleukin-6 inhibitors may demonstrate clinical improvement; non-critical patients may benefit from convalescent plasma infusion in small sample-size studies; and the role of hydroxychloroquine or chloroquine in the treatment and prophylaxis of COVID-19 remains unclear. Combination therapy of traditional Chinese medicine with antiviral agents (ex. interferon, lopinavir, or arbidol) may alleviate inflammation in severe COVID-19 patients based on small sample-sized observational studies and experts' opinion. Most of the published studies included severe or critical patients with COVID-19. Combination therapy of antiviral agents and immune-modulating drugs is reasonable especially for those critical COVID-19 patients with cytokine release syndrome. Drugs to blunt cytokine release might not benefit for patients in the early stage with mild disease or the late stage with critical illness. Traditional Chinese medicine with antiviral effects on SARS-CoV-2 and immune-modulation is widely used for COVID-19 patients in China, and is worthy of further studies. In this review, we aim to highlight the available therapeutic options for COVID-19 based on current clinical evidence and encourage clinical trials specific for children and for patients with mild disease or at the early stage of COVID-19.
| S-EPMC7751753 | biostudies-literature
Project description:ImportanceIt is unclear if helping patients meet resource needs, such as difficulty affording food, housing, or medications, improves clinical outcomes.ObjectiveTo determine the effectiveness of the Health Leads program on improvement in systolic and diastolic blood pressure (SBP and DBP, respectively), low-density lipoprotein cholesterol (LDL-C) level, and hemoglobin A1c (HbA1c) level.Design, setting, and participantsA difference-in-difference evaluation of the Health Leads program was conducted from October 1, 2012, through September 30, 2015, at 3 academic primary care practices. Health Leads consists of screening for unmet needs at clinic visits, and offering those who screen positive to meet with an advocate to help obtain resources, or receive brief information provision.Main outcomes and measuresChanges in SBP, DBP, LDL-C level, and HbA1c level. We compared those who screened positive for unmet basic needs (Health Leads group) with those who screened negative, using intention-to-treat, and, secondarily, between those who did and did not enroll in Health Leads, using linear mixed modeling, examining the period before and after screening.ResultsA total of 5125 people were screened, using a standardized form, for unmet basic resource needs; 3351 screened negative and 1774 screened positive. For those who screened positive, the mean age was 57.6 years and 1811 (56%) were women. For those who screened negative, the mean age was 56.7 years and 909 (57%) were women. Of 5125 people screened, 1774 (35%) reported at least 1 unmet need, and 1021 (58%) of those enrolled in Health Leads. Median follow-up for those who screened positive and negative was 34 and 32 months, respectively. In unadjusted intention-to-treat analyses of 1998 participants with hypertension, the Health Leads group experienced greater reduction in SBP (differential change, -1.2; 95% CI, -2.1 to -0.4) and DBP (differential change, -1.0; 95% CI, -1.5 to -0.5). For 2281 individuals with an indication for LDL-C level lowering, results also favored the Health Leads group (differential change, -3.7; 95% CI -6.7 to -0.6). For 774 individuals with diabetes, the Health Leads group did not show HbA1c level improvement (differential change, -0.04%; 95% CI, -0.17% to 0.10%). Results adjusted for baseline demographic and clinical differences were not qualitatively different. Among those who enrolled in Health Leads program, there were greater BP and LDL-C level improvements than for those who declined (SBP differential change -2.6; 95% CI,-3.5 to -1.7; SBP differential change, -1.4; 95% CI, -1.9 to -0.9; LDL-C level differential change, -6.3; 95% CI, -9.7 to -2.8).Conclusions and relevanceScreening for and attempting to address unmet basic resource needs in primary care was associated with modest improvements in blood pressure and lipid, but not blood glucose, levels.
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Project description:We present several novel drugs in development for enhancing cognition, treating negative symptoms, and providing improved options for treatment-resistant patients. Drug makers aim to enhance safety profiles and increase patient compliance to therapy.
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Project description:With the establishment of the immune surveillance mechanism since the 1950s, attempts have been made to activate the immune system for cancer treatment through the discovery of various cytokines or the development of antibodies up to now. The fruits of these efforts have contributed to the recognition of the 3rd generation of anticancer immunotherapy as the mainstream of cancer treatment. However, the limitations of cancer immunotherapy are also being recognized through the conceptual establishment of cold tumors recently, and colorectal cancer (CRC) has become a major issue from this therapeutic point of view. Here, it is emphasized that non-clinical strategies to overcome the immunosuppressive environment and clinical trials based on these basic investigations are being made on the journey to achieve better treatment outcomes for the treatment of cold CRC.
| S-EPMC9994045 | biostudies-literature
Project description:Studies on the psychosocial and emotional burden of psoriasis have been extensive; however, there is limited knowledge and awareness of patients' attitude and behavior towards psoriasis treatment. To understand psoriasis patients' attitude and behavior towards treatment of psoriasis, especially those treated with biologics, a multi-stage study qualitative and quantitative methodology was conducted among psoriasis patients. An online survey was conducted with 45 moderate-to-severe psoriasis patients each in Australia, Japan, South Korea, and Taiwan for 20 min. This was followed by qualitative in-depth interviews conducted among psoriasis patients in Australia (n = 3) and Japan (n = 2) for 60 min. All of the findings were workshopped with key opinion leaders and patient advisory groups to identify potential solutions addressing patients' unmet needs. Five common insights were identified across the region, highlighting patients' attitude and behavior towards psoriasis treatment, especially for those treated with biologics. These insights comprised the following: (i) one of the key factors driving patients' treatment choice included their ability to enjoy clear skin for longer period (68%); (ii) bio-maintenance patients had a higher expectation (4.9 months) of how long their skin could stay clear, compared to their pre-biologics initiation days (2.9 months); (iii) once a good response is achieved, bio-maintenance patients were more concerned about symptoms returning (44%) than development of side-effects (19%); (iv) bio-maintenance patients felt psychologically and physically affected during flare-ups despite being on more efficacious treatment; and (v) bio-maintenance patients still felt they were at risk of flare-ups (4.5/7), almost similar risk perception as non-biologics patients (4.9/7). Findings from this study showed that psoriasis patients look for treatment with the least risk of flare-ups so that they were able to enjoy clear skin for a long time.
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Project description:The incidence of type 1 diabetes (T1D) is increasing worldwide and there is a very large need for effective therapies. Essentially no therapies other than insulin are currently approved for the treatment of T1D. Drugs already in use for type 2 diabetes and many new drugs are under clinical development for T1D, including compounds with both established and new mechanisms of action. Content of the Review: Most of the new compounds in clinical development are currently in Phase 1 and 2. Drug classes discussed in this review include new insulins, SGLT inhibitors, GLP-1 agonists, immunomodulatory drugs including autoantigens and anti-cytokines, agents that regenerate ?-cells and others. Regulatory Considerations: In addition, considerations are provided with regard to the regulatory environment for the clinical development of drugs for T1D, with a focus on the United States Food and Drug Administration and the European Medicines Agency. Future opportunities, such as combination treatments of immunomodulatory and beta-cell regenerating therapies, are also discussed.
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Project description:There are currently no FDA-approved therapeutics available to treat Rift Valley fever virus (RVFV) infection. In an effort to repurpose drugs for RVFV treatment, a library of FDA-approved drugs was screened to determine their ability to inhibit RVFV. Several drugs from varying compound classes, including inhibitors of growth factor receptors, microtubule assembly/disassembly, and DNA synthesis, were found to reduce RVFV replication. The hepatocellular and renal cell carcinoma drug, sorafenib, was the most effective inhibitor, being non-toxic and demonstrating inhibition of RVFV in a cell-type and virus strain independent manner. Mechanism of action studies indicated that sorafenib targets at least two stages in the virus infectious cycle, RNA synthesis and viral egress. Computational modeling studies also support this conclusion. siRNA knockdown of Raf proteins indicated that non-classical targets of sorafenib are likely important for the replication of RVFV.
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Project description:Melanoma represents an increasing public health burden with extensive unmet needs in Latin America (LA). A mutation in the BRAF gene is present in approximately 50% of all melanomas in White populations and is a target of precision medicine, with the potential to dramatically improve patient outcomes. Thus, increased access to BRAF testing and therapy is LA must be explored. At a multi-day conference, a panel of Latin American experts in oncology and dermatology were provided with questions to address the barriers limiting access to testing for BRAF mutation in patients with melanoma in LA, who may be eligible for targeted therapy to improve their prognosis. During the conference, responses were discussed and edited until a consensus on addressing the barriers was achieved. Identified challenges included ignorance of BRAF-status implications, limited human and infrastructural resources, affordability and reimbursement, fragmented care delivery, pitfalls in the sample journey, and lack of local data. Despite the clear benefits of targeted therapies for BRAF-mutated melanoma in other regions, there is no clear path to prepare LA for a sustainable personalized medicine approach to this disease. Due to melanoma's time-sensitive nature, LA must aim to provide early access to BRAF testing and consider mutational status within treatment decision making. To this end, recommendations are provided and include establishing multidisciplinary teams and melanoma referral centers and improving access to diagnosis and treatment.
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