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International Journal of Molecular... Mar 2023(), the causative agent of TB, is a recalcitrant pathogen that is rife around the world, latently infecting approximately a quarter of the worldwide population. The... (Review)
Review
(), the causative agent of TB, is a recalcitrant pathogen that is rife around the world, latently infecting approximately a quarter of the worldwide population. The asymptomatic status of the dormant bacteria escalates to the transmissible, active form when the host's immune system becomes debilitated. The current front-line treatment regimen for drug-sensitive (DS) strains is a 6-month protocol involving four different drugs that requires stringent adherence to avoid relapse and resistance. Poverty, difficulty to access proper treatment, and lack of patient compliance contributed to the emergence of more sinister drug-resistant (DR) strains, which demand a longer duration of treatment with more toxic and more expensive drugs compared to the first-line regimen. Only three new drugs, bedaquiline (BDQ) and the two nitroimidazole derivatives delamanid (DLM) and pretomanid (PMD) were approved in the last decade for treatment of TB-the first anti-TB drugs with novel mode of actions to be introduced to the market in more than 50 years-reflecting the attrition rates in the development and approval of new anti-TB drugs. Herein, we will discuss the pathogenesis, current treatment protocols and challenges to the TB control efforts. This review also aims to highlight several small molecules that have recently been identified as promising preclinical and clinical anti-TB drug candidates that inhibit new protein targets in .
Topics: Humans; Antitubercular Agents; Tuberculosis; Mycobacterium tuberculosis; Drug Delivery Systems; Clinical Protocols; Tuberculosis, Multidrug-Resistant
PubMed: 36982277
DOI: 10.3390/ijms24065202 -
Indian Journal of Pediatrics Mar 2023Shock in children is associated with significant mortality and morbidity, particularly in resource-limited settings. The principles of management include early... (Review)
Review
Shock in children is associated with significant mortality and morbidity, particularly in resource-limited settings. The principles of management include early recognition, fluid resuscitation, appropriate inotropes, antibiotic therapy in sepsis, supportive therapy for organ dysfunction, and regular hemodynamic monitoring. During the past decade, each step has undergone several changes and evolved as evidence that has been translated into recommendations and practice. There is a paradigm shift from protocolized-based care to personalized management, from liberal strategies to restrictive strategies in terms of fluids, blood transfusion, ventilation, and antibiotics, and from clinical monitoring to multimodal monitoring using bedside technologies. However, uncertainties are still prevailing in terms of the volume of fluids, use of steroids, and use of extracorporeal and newer therapies while managing shock. These changes have been summarized along with evidence in this article with the aim of adopting an evidence-based approach while managing children with shock.
Topics: Child; Humans; Shock, Septic; Sepsis; Shock; Fluid Therapy; Blood Transfusion; Anti-Bacterial Agents; Resuscitation
PubMed: 36715864
DOI: 10.1007/s12098-022-04434-3 -
Systematic Reviews Jan 2018Neoadjuvant (chemo-)radiation has proven to improve local control compared to surgery alone, but this improvement did not translate into better overall or... (Meta-Analysis)
Meta-Analysis Review
Addition of platinum derivatives to neoadjuvant single-agent fluoropyrimidine chemoradiotherapy in patients with stage II/III rectal cancer: protocol for a systematic review and meta-analysis (PROSPERO CRD42017073064).
BACKGROUND
Neoadjuvant (chemo-)radiation has proven to improve local control compared to surgery alone, but this improvement did not translate into better overall or disease-specific survival. The addition of oxaliplatin to fluoropyrimidine-based neoadjuvant chemoradiotherapy holds the potential of positively affecting survival in this context since it has been proven effective in the palliative and adjuvant setting of colorectal cancer. Thus, the objective of this systematic review is to assess the efficacy, safety, and quality of life resulting from adding a platinum derivative to neoadjuvant single-agent fluoropyrimidine-based chemoradiotherapy in patients with Union for International Cancer Control stage II and III rectal cancer.
METHODS
MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials will be systematically searched to identify all randomized controlled trials comparing single-agent fluoropyrimidine-based chemoradiotherapy to combined neoadjuvant therapy including a platinum derivative. Predefined data on trial design, quality, patient characteristics, and endpoints will be extracted. Quality of included trials will be assessed according to the Cochrane Risk of Bias Tool, and the GRADE recommendations will be applied to judge the quality of the resulting evidence. The main outcome parameter will be survival, but also treatment toxicity, perioperative morbidity, and quality of life will be assessed.
DISCUSSION
The findings of this systematic review and meta-analysis will provide novel insights into the efficacy and safety of combined neoadjuvant chemoradiotherapy including a platinum derivative and may form a basis for future clinical decision-making, guideline evaluation, and research prioritization.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42017073064.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Humans; Neoadjuvant Therapy; Oxaliplatin; Quality of Life; Rectal Neoplasms; Survival
PubMed: 29357929
DOI: 10.1186/s13643-018-0678-9 -
Bulletin of the Hospital For Joint... 2013Eight major "strategy trials" in rheumatoid arthritis (RA) are reviewed, with protocol-driven escalation of combinations of methotrexate and other small molecule... (Review)
Review
Evidence that the strategy is more important than the agent to treat rheumatoid arthritis. Data from clinical trials of combinations of non-biologic DMARDs, with protocol-driven intensification of therapy for tight control or treat-to-target.
Eight major "strategy trials" in rheumatoid arthritis (RA) are reviewed, with protocol-driven escalation of combinations of methotrexate and other small molecule non-biological disease modifying antirheumatic drugs (DMARDs). All documented the value of intensive treatment adjusted according to quantitative data, generally a disease activity score (DAS) or its 28 joint count version (DAS28). Three of the 8 trials, TICORA, Dutch DAS-driven care, and CAMERA, may be termed "pure strategy trials," to com- pare a protocol-driven "intensive" strategy to usual care. Five other trials, BeSt, CIMESTRA, TICORA 2, Step-down versus step-up, and TEAR, may be termed "hybrid trials," in which an initial parallel design was supplemented with incremental protocol-driven intensification of treatment. A strategy of aiming for low disease activity or remission appears more important than the specific agent used. In group data, the proportion of good responses seen in these trials with combinations of non-biologic, small molecule DMARDs are comparable to data from clinical trials of biological agents although responses appear more rapid with biological agents, and certain individual patients may require a biologic agent for adequate control. These trials also illustrate the value of a quantitative index, monitored frequently for rational intensification of therapy. The data make a compelling case for both routine monitoring with a quantitative index and consideration of routine adjustment of therapy at each visit. Combinations of methotrexate with other non-biologic DMARDs and glucocorticoids, toward a target of low disease activity or remission, may improve outcomes for patients with RA at levels similar to biologic agents in many patients.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Clinical Protocols; Clinical Trials as Topic; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Remission Induction; Research Design; Treatment Outcome
PubMed: 24219039
DOI: No ID Found -
The Journal of Allergy and Clinical... Sep 2008Hypersensitivity reactions (HSRs) to chemotherapeutic drugs, including mAbs, often require that the provoking medication be discontinued, thus raising a dilemma for the...
BACKGROUND
Hypersensitivity reactions (HSRs) to chemotherapeutic drugs, including mAbs, often require that the provoking medication be discontinued, thus raising a dilemma for the caregiver: further use could precipitate a severe, even fatal, allergic reaction on re-exposure, but alternative drugs might be poorly tolerated or much less effective compared with the preferred agent.
OBJECTIVE
We have developed a standardized rapid desensitization protocol for achieving temporary tolerization to drug allergens. In this study we evaluate the safety and efficacy of this protocol.
METHODS
Ninety-eight patients who had HSRs in response to treatment with carboplatin, cisplatin, oxaliplatin, paclitaxel, liposomal doxorubicin, doxorubicin, or rituximab received rapid desensitization to these agents. A standardized 12-step protocol was used, with treatment given intravenously or intraperitoneally. Initial desensitizations occurred in the medical intensive care unit, whereas most subsequent infusions took place in an outpatient setting. Safety and efficacy of the protocol were assessed by review of treatment records.
RESULTS
Of the 413 desensitizations performed, 94% induced mild or no reactions. No life-threatening HSRs or deaths occurred during the procedure, and all patients received their full target dose. Most reactions occurred during the first desensitization. Reactions were most commonly reported at the last step of the protocol. Desensitizations through the intravenous and intraperitoneal routes were equally effective.
CONCLUSIONS
Our standardized 12-step protocol for rapid drug desensitization is safe and effective and has been adopted as the standard of care at our institutions in treating patients with HSRs to chemotherapeutic drugs, including mAbs.
Topics: Adult; Aged; Antineoplastic Agents; Clinical Protocols; Desensitization, Immunologic; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Skin Tests; Treatment Outcome
PubMed: 18502492
DOI: 10.1016/j.jaci.2008.02.044 -
Current Opinion in Pediatrics Jun 2016Sepsis is the leading cause of pediatric death worldwide. In the United States alone, there are 72 000 children hospitalized for sepsis annually with a reported... (Review)
Review
PURPOSE OF REVIEW
Sepsis is the leading cause of pediatric death worldwide. In the United States alone, there are 72 000 children hospitalized for sepsis annually with a reported mortality rate of 25% and an economic cost estimated to be $4.8 billion. However, it is only recently that the definition and management of pediatric sepsis has been recognized as being distinct from adult sepsis.
RECENT FINDINGS
The definition of pediatric sepsis is currently in a state of evolution, and there is a large disconnect between the clinical and research definitions of sepsis which impacts the application of research findings into clinical practice. Despite this, it is the speed of diagnosis and the timely implementation of current treatment guidelines that has been shown to improve outcomes. However, adherence to treatment guidelines is currently low and it is only through the implementation of protocols that improved care and outcomes have been demonstrated.
SUMMARY
The current management of pediatric sepsis is largely based on adaptations from adult sepsis treatment; however, distinct physiology demands more prospective pediatric trials to tailor management to the pediatric population. Adherence to current and emerging practice guidelines will require that protocolized care pathways become a commonplace.
Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Child; Clinical Protocols; Early Diagnosis; Fluid Therapy; Guideline Adherence; Humans; Practice Guidelines as Topic; Sepsis; Time Factors; United States
PubMed: 26983000
DOI: 10.1097/MOP.0000000000000337 -
Neural Networks : the Official Journal... Mar 2024This paper addresses a distributed time-varying optimization problem with inequality constraints based on multi-agent systems over switching communication graphs. To...
This paper addresses a distributed time-varying optimization problem with inequality constraints based on multi-agent systems over switching communication graphs. To reduce the influence of time-varying inequality constraints, an exact penalty method and smoothing technique are employed. Then, a Hessian-based distributed control protocol is presented to seek the time-varying optimal solution of the distributed time-varying optimization problem by virtue of only local information and interaction. It is shown that all agents not only achieve finite-time consensus but also track the time-varying global optimal target eventually. Compared with the existing distributed optimization protocols, the proposed control protocol is suitable for more general distributed time-varying optimization problems and enjoys high-efficiency convergence. Finally, numerical examples and experiment on moving target tracking of Unmanned Aircraft Vehicle (UAV) are performed to illustrate the effectiveness of the proposed control protocol.
Topics: Consensus; Aircraft; Communication; Time Pressure
PubMed: 38091766
DOI: 10.1016/j.neunet.2023.11.067 -
Hematology/oncology Clinics of North... Apr 2017Angioimmunoblastic T-cell lymphoma is a follicular T-helper-derived neoplasm displaying a peculiar morphologic appearance and biological complexity. New mutations have... (Review)
Review
Angioimmunoblastic T-cell lymphoma is a follicular T-helper-derived neoplasm displaying a peculiar morphologic appearance and biological complexity. New mutations have been described that contribute to elucidating the underlying pathogenetic events. The disease behaves aggressively and typically affects elderly patients. The outcomes reported with anthracycline-containing regimens are poor; therefore autologous transplantation in first remission should be offered whenever possible. Newer approaches are urgently needed for relapsed and refractory patients. Newly approved agents show activity in pretreated patients but response durations are short. Innovative induction strategies (CHOP + biologic agent) should be designed to enhance response quality, facilitate transplantation, and prolong survival.
Topics: Antineoplastic Combined Chemotherapy Protocols; Autografts; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Lymphoma, Follicular; Lymphoma, T-Cell; Prednisone; Stem Cell Transplantation; Survival Rate; Vincristine
PubMed: 28340875
DOI: 10.1016/j.hoc.2016.12.001 -
ISA Transactions Mar 2019This paper investigates the consensus problem of multiple discrete-time integrator agents with communication constraints and additive process noise. It proposes a...
This paper investigates the consensus problem of multiple discrete-time integrator agents with communication constraints and additive process noise. It proposes a protocol to achieve the approximate consensus of agents over inter-agent communication networks with finite bit rates. Under that protocol, dynamic encoding and decoding algorithms are implemented for each pair of neighboring agents to transmit quantized states at a finite bit rate. With received quantized states of neighboring agents, the control input of each agent is locally computed. Particularly input saturation is introduced into the local controllers of agents and places both lower and upper bounds on the local control inputs of agents. These control input bounds can be known in advance and greatly enhance the robustness of the consensus protocol. Under the proposed protocol, the approximate consensus can be guaranteed at any finite bit rate to encode the states of agents. It is shown that even a single bit per time step is enough for the desired approximate consensus. The additive process noise does not increase the bit rate required for that approximate consensus. Moreover, the proposed consensus protocol can be designed with only an upper bound on the number of agents and is more robust than some previous consensus protocols which may require the global information of the inter-agent network topology, such as the second largest eigenvalue of the Laplacian matrix. Even when some communication links are broken due to communication failure or some nodes leave, the same set of consensus parameters can still robustly guarantee the expected approximate consensus. Simulations are conducted to illustrate the effectiveness of the proposed quantized consensus protocol.
PubMed: 30473149
DOI: 10.1016/j.isatra.2018.11.006 -
Veterinary and Comparative Oncology Sep 2013The aim of the study was to report the outcome of treatment of 97 dogs with lymphoma that received a multi-agent chemotherapy protocol containing epirubicin as the...
The aim of the study was to report the outcome of treatment of 97 dogs with lymphoma that received a multi-agent chemotherapy protocol containing epirubicin as the primary anthracycline. Seventy-five dogs received a 25-week protocol with no maintenance phase whilst 22 dogs received a maintenance phase. Complete response rate was 96% and time to first relapse (TTR) and overall survival (OS) time for all dogs were 216 and 342 days, respectively. Dogs with T-cell lymphoma and those classified as WHO substage b had significantly poorer OS times and TTR. The protocol was well tolerated with toxicity similar to doxorubicin-containing protocols. Epirubicin as part of a multi-agent protocol is safe and effective in the treatment of canine multicentric lymphoma. There is a high initial response rate and an overall median survival time that is similar to other published doxorubicin-containing protocols.
Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Dog Diseases; Dogs; Epirubicin; Female; Lymphoma; Male; Retrospective Studies
PubMed: 22372620
DOI: 10.1111/j.1476-5829.2011.00311.x