ABSTRACT
Background: Phenytoin (PHT) has been approved for the treatment of epilepsy. It belongs to the category of medications with a limited therapeutic window and requires therapeutic drug monitoring (TDM). PTH has been observed to induce a variety of Adverse drug reactions (ADRs) including ataxia, dystonia, nystagmus, dyskinesia, etc. Phenytoin-induced ataxia is an uncommonly observed ADR of Phenytoin whose reports are extremely limited. Case: Herein, we present a case report of a 16-year-old Asian patient with a past history of epilepsy that was admitted to a tertiary care hospital due to the development of ataxia, giddiness, and vomiting when taking Phenytoin in addition to Oxcarbazepine, Clobazam, and Levetiracetam to treat seizures. On admission, Magnetic resonance imaging (MRI) findings revealed bilateral variable cerebrospinal fluid (CSF) lesions in the parieto-occipital region of the periventricular area (periventricular leukomalacia). Additionally, serum Phenytoin levels were observed to be in the toxic range (40 µg/mL) due to which physicians confirmed the ADR to be due to Phenytoin toxicity. Thus, the Phenytoin drug was discontinued in the patient gradually and he was continued on clobazam, oxcarbazepine, and brivaracetam which led to reversal of the ADR in the patient. Conclusion: In this case, ataxia resulted from Phenytoin overdose, as confirmed by MRI and serum tests suggesting that TDM of Phenytoin is essential to prevent ADRs. Given the scarcity of ataxia cases caused by Phenytoin, awareness is lacking within the scientific community. Our aim is to provide insights to promote better monitoring and patient-centered treatment outcomes for epileptic patients.
ABSTRACT
Antibody-drug conjugates (ADCs), combining the cytotoxicity of the drug payload with the specificity of monoclonal antibodies, are one of the rapidly evolving classes of anti-cancer agents. These agents have been successfully incorporated into the treatment paradigm of many malignancies, including non-small cell lung cancer (NSCLC). The NSCLC is the most prevalent subtype of lung cancer, having a considerable burden on the cancer-related mortality and morbidity rates globally. Several ADC molecules are currently approved by the Food and Drug Administration (FDA) to be used in patients with NSCLC. However, the successful management of NSCLC patients using these agents was met with several challenges, including the development of resistance and toxicities. These shortcomings resulted in the exploration of novel therapeutic targets that can be targeted by the ADCs. This review aims to explore the recently identified ADC targets along with their oncologic mechanisms. The ADC molecules targeting these biomarkers are further discussed along with the evidence from clinical trials.
ABSTRACT
BACKGROUND AND OBJECTIVES: Arthralgia, myalgia, and neuropathic pain are the most common side effects observed due to paclitaxel chemotherapy. The aim of this study was to investigate the prophylactic role, maintenance, remission, and re-occurrence of arthralgia, myalgia, and neuropathic pain post-gabapentin therapy. METHODOLOGY: This study was conducted in the Department of Oncology, Dhiraj Hospital, Vadodara with a sample of 51 patients. Newly detected cancer patients who observed arthralgia, myalgia, and neuropathic pain due to paclitaxel were taken and a baseline pain assessment was done using the Common Terminology Criteria for Adverse Events (CTCAE) and painDETECT questionnaire. Gabapentin was given in the first cycle after symptoms appeared and prophylactic treatment was given in the subsequent three cycles and evaluation of pain was done post-gabapentin therapy to assess the symptomatic as well as prophylactic effect. RESULTS: At baseline, neuropathic pain score was 22.7 ± 3.6 which reduced to 0.01 ± 0.14 on subsequent follow-ups. Grade 2 arthralgia, myalgia, and neuropathic pain were more observed at baseline which reduces to Grade 0 in the third cycle. The difference in baseline and post-gabapentin therapy was statistically analyzed by conducting t-test which showed p-value <0.00001 and t-value was less than -2 which indicated a statistically significant result. CONCLUSION: This study shows that gabapentin reduces neuropathic pain. Prophylactic usage of gabapentin was highly effective at bringing about quick pain relief when compared to symptomatic treatment. In further follow-ups, it was noted that gabapentin maintained the impact throughout the cycles.
ABSTRACT
BACKGROUND: The present epidemic of dermatophytosis in India is marked by an increase in chronic, recurrent and disseminated cases. A combination of oral itraconazole and topical luliconazole is being increasingly utilised by dermatologists in India. The superiority of this combination is not supported by robust clinical trial data. OBJECTIVE: We conducted this randomised, open-label, two arms, parallel assignment intervention trial between November 2022 and May 2023 to determine the superiority of topical 1% Luliconazole over bland emollient as adjuvant to systemic Itraconazole therapy in the management of dermatophytosis. METHOD: In this study, 135 patients of either sex were randomised to two study cohorts. Major exclusions being concomitant medical illness, use of concomitant medication and substance abuse. Participants were randomly assigned to receive topical bland emollient, (Cohort I, n = 67) or topical luliconazole, (Cohort II, n = 68). Both cohorts received oral itraconazole 200 mg/day (100 mg BID) and levocetirizine 5 mg twice a day as a systemic regime. Clinical and mycological cure at the end of 6 weeks and clinical relapse among cure patients during 10-week follow-up were observed. RESULTS: The cure rates for Cohorts I and II at 6 weeks were 50 (74.62%) and 56 (82.35%), (p = .46), respectively. During the 4-week follow-up period, clinical relapses were observed in 16 (32%) of the 50 patients in Cohort I and 12 (21.43%) of the 56 patients in Cohort II (p = .18). Luliconazole cohort shows a significantly higher medical cost (p < .05). CONCLUSION: Our study shows a similar cure rate and relapse rate for patients receiving topical Luliconazole versus topical bland emollient as an adjuvant to the systemic itraconazole regime.
Subject(s)
Imidazoles , Itraconazole , Tinea , Humans , Itraconazole/therapeutic use , Antifungal Agents/therapeutic use , Emollients/therapeutic use , Tinea/drug therapy , RecurrenceABSTRACT
BACKGROUND: Dyskinesia is a movement disorder categorized by involuntary movement of muscle. Although dyskinesia can be brought on by taking medications, it can also be a symptom of a variety of diseases. Antiepileptic drug-induced involuntary movements have been well researched. Rare reports have been made for dyskinesia, a type of dystonia caused by phenytoin. The mechanism of its occurrence must be succinctly studied. CASE PRESENTATION: A 53-year-old Asian patient taking phenytoin (100 mg twice daily) experienced symptoms of perioral muscle involuntary movement, impaired speech, and generalized tremors and was admitted to the hospital. Brain magnetic resonance imaging showed significant development of encephalomalacia and porencephaly. The serum phenytoin levels were in the toxic range (33 g/ml). These were suggestive of phenytoin-induced dyskinesia. Levetiracetam and clonazepam were initiated, and the patient showed significant improvement in the symptoms. CONCLUSION: This case presented a substantial reference value for the differential diagnosis and treatment prognosis of phenytoin-induced dyskinesia. The phenytoin-induced dyskinesia in this patient was successfully reversed with prompt identification and treatment. According to the case study's findings, such people may benefit from periodic therapeutic drug monitoring.
Subject(s)
Dyskinesia, Drug-Induced , Dystonia , Humans , Middle Aged , Phenytoin/adverse effects , Dyskinesia, Drug-Induced/etiology , Dyskinesia, Drug-Induced/drug therapy , Anticonvulsants/adverse effects , Levetiracetam/therapeutic useABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. The incidence of HCC is affected by genetic and non-genetic factors. Genetically, mutations in the genes, tumor protein P53 (TP53), catenin beta 1 (CTNNB1), AT-rich interaction domain 1A (ARIC1A), cyclin dependent kinase inhibitor 2A (CDKN2A), mannose 6-phosphate (M6P), smooth muscle action against decapentaplegic (SMAD2), retinoblastoma gene (RB1), cyclin D, antigen presenting cells (APC), AXIN1, and E-cadherin, have been shown to contribute to the occurrence of HCC. Non-genetic factors, including alcohol consumption, exposure to aflatoxin, age, gender, presence of hepatitis B (HBV), hepatitis C (HCV), and non-alcoholic fatty liver disease (NAFLD), increase the risk of HCC. RECENT FINDINGS: The severity of the disease and its occurrence vary based on geographical location. Furthermore, men and minorities have been shown to be disproportionately affected by HCC, compared with women and non-minorities. Ethnicity has been reported to significantly affect tumorigenesis and clinical outcomes in patients diagnosed with HCC. Generally, differences in gene expression and/or the presence of comorbid medical diseases affect or influence the progression of HCC. Non-Caucasian HCC patients are significantly more likely to have poorer survival outcomes, compared to their Caucasian counterparts. Finally, there are a number of factors that contribute to the success rate of treatments for HCC. CONCLUSION: Assessment and treatment of HCC must be consistent using evidence-based guidelines and standardized outcomes, as well as international clinical practice guidelines for global consensus. Standardizing the assessment approach and method will enable comparison and improvement of liver cancer research through collaboration between researchers, healthcare providers, and advocacy groups. In this review, we will focus on discussing epidemiological factors that result in deviations and changes in treatment approaches for HCC.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis B , Hepatitis C , Liver Neoplasms , Male , Humans , Female , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/epidemiology , Liver Neoplasms/therapy , Prevalence , Hepatitis B/complications , Hepatitis B/genetics , Hepatitis C/complications , Hepatitis C/epidemiology , Treatment OutcomeABSTRACT
Cancer diagnosis and management have been a slow-evolving area in medical science. Conventional therapies have by far proved to have various limitations. Also, the concept of immunotherapy which was thought to revolutionize the management of cancer has presented its range of drawbacks. To overcome these limitations nanoparticulate-derived diagnostic and therapeutic strategies are emerging. These nanomaterials are to be explored as they serve as a prospect for cancer theranostics. Nanoparticles have a significant yet unclear role in screening as well as therapy of cancer. However, nanogels and Photodynamic therapy is one such approach to be developed in cancer theranostics. Photoactive cancer theranostics is a vivid area that might prove to help manage cancer. Also, the utilization of the quantum dots as a diagnostic tool and to selectively kill cancer cells, especially in CNS tumors. Additionally, the redox-sensitive micelles targeting the tumor microenvironment of the cancer are also an important theranostic tool. This review focuses on exploring various agents that are currently being studied or can further be studied as cancer theranostics.
Subject(s)
Nanoparticles , Nanostructures , Neoplasms , Photochemotherapy , Humans , Theranostic Nanomedicine/methods , Neoplasms/drug therapy , Nanoparticles/therapeutic use , Photochemotherapy/methods , Nanostructures/therapeutic use , Tumor MicroenvironmentABSTRACT
Medulloblastoma (MB) is one of the most common pediatric malignant tumors arising from the central nervous system with an unknown etiology and variable prognosis. Relapsed or refractory MB in pediatric patients after intensive anticancer therapy (chemo-, radiotherapy) is associated with treatment resistance and poor survival prognosis. Metronomic chemotherapy in combination with mTOR inhibitors may have advantages due to an alternate mechanism of cytotoxicity and a favourable adverse effects profile. Furthermore, it is considered to be a prospective anticancer regimen regardless of the presence/absence of molecular targets. The present study reported a successful result of this treatment option with optimal tolerability in relapsed MB in a pediatric male patient and highlighted the advantages for a selected group of patients.
ABSTRACT
Lung cancer is amongst the most pervasive malignancies having high mortality rates. It is broadly grouped into non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). The concept of personalized medicine has overshadowed the conventional chemotherapy given to all patients with lung cancer. The targeted therapy is given to a particular population having specific mutations to help in the better management of lung cancer. The targeting pathways for NSCLC include the epidermal growth factor receptor, vascular endothelial growth factor receptor, MET (Mesenchymal epithelial transition factor) oncogene, Kirsten rat sarcoma viral oncogene (KRAS), and anaplastic lymphoma kinase (ALK). SCLC targeting pathway includes Poly (ADP-ribose) polymerases (PARP) inhibitors, checkpoint kinase 1 (CHK 1) pathway, WEE1 pathway, Ataxia Telangiectasia and Rad3-related (ATR)/Ataxia telangiectasia mutated (ATM), and Delta-like canonical Notch ligand 3 (DLL-Immune checkpoint inhibitors like programmed cell death protein 1 (PD-1)/ programmed death-ligand 1 (PD-L1) inhibitors and Cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) blockade are also utilized in the management of lung cancer. Many of the targeted therapies are still under development and require clinical trials to establish their safety and efficacy. This review summarizes the mechanism of molecular targets and immune-mediated targets, recently approved drugs, and their clinical trials for lung cancer.
Subject(s)
Ataxia Telangiectasia , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Vascular Endothelial Growth Factor A , Immunotherapy , B7-H1 Antigen/metabolismABSTRACT
As the world's most prevalent cancer, breast cancer imposes a significant societal health burden and is among the leading causes of cancer death in women worldwide. Despite the notable improvements in survival in countries with early detection programs, combined with different modes of treatment to eradicate invasive disease, the current chemotherapy regimen faces significant challenges associated with chemotherapy-induced side effects and the development of drug resistance. Therefore, serious concerns regarding current chemotherapeutics are pressuring researchers to develop alternative therapeutics with better efficacy and safety. Due to their extremely biocompatible nature and efficient destruction of cancer cells via numerous mechanisms, phytochemicals have emerged as one of the attractive alternative therapies for chemotherapeutics to treat breast cancer. Additionally, phytofabricated nanocarriers, whether used alone or in conjunction with other loaded phytotherapeutics or chemotherapeutics, showed promising results in treating breast cancer. In the current review, we emphasize the anticancer activity of phytochemical-instigated nanocarriers and phytochemical-loaded nanocarriers against breast cancer both in vitro and in vivo. Since diverse mechanisms are implicated in the anticancer activity of phytochemicals, a strong emphasis is placed on the anticancer pathways underlying their action. Furthermore, we discuss the selective targeted delivery of phytofabricated nanocarriers to cancer cells and consider research gaps, recent developments, and the druggability of phytoceuticals. Combining phytochemical and chemotherapeutic agents with nanotechnology might have far-reaching impacts in the future.
ABSTRACT
Immune checkpoints are unique components of the body's defense mechanism that safeguard the body from immune responses that are potent enough to harm healthy body cells. When proteins present on the surface of T cells recognize and bind to the proteins present on other tumor cells, immune checkpoints are triggered. These proteins are called immunological checkpoints. The T cells receive an on/off signal when the checkpoints interact with companion proteins. This might avert the host's immune system from eliminating cancer cells. The standard care plan for the treatment of non-small cell lung cancer (NSCLC) has been revolutionized with the use of drugs targeting immune checkpoints, in particular programmed cell death protein 1. These drugs are now extended for their potential to manage SCLC. However, it is acknowledged that these drugs have specific immune related adverse effects. Herein, we discuss the use of immune checkpoint inhibitors in patients with NSCLC and SCLC, their outcomes, and future perspectives.
ABSTRACT
BACKGROUND: The prevalence of head and neck cancer (HNC) is increasing rapidly, and the prognosis is poor in the advance stage. For the patient suffering from advance stage HNC, the improvement in quality of life and decrease mortality remain as the mainstay of treatment. The aim was to assess the change in quality-adjusted life-years (QALYs) in recurrent or metastatic HNC patients receiving cetuximab plus cisplatin and cetuximab plus cisplatin-paclitaxel. METHODS: It was a single-centric prospective-observational study. Patients were divided into two cohorts based on the chemotherapy regimens they were prescribed. Patients in cohort 1 were prescribed with cetuximab and cisplatin and in cohort 2 were prescribed with cetuximab, cisplatin, and paclitaxel. The QALYs were the primary outcome of the study, and it was calculated using EQ-5D-5L instrument. Patients were followed until the completion of the therapy, i.e., six chemotherapy cycles. The statistical analysis was carried out using SPSS for descriptive and inferential analysis. RESULTS: Amongst 175 patients screened, 100 patients were enrolled which further distributed in cohorts 1 and 2 equally. The mean QALYs were 0.016 and 0.017 at the time of diagnosis, i.e., before initiation of chemotherapy for patients in cohorts 1 and 2, respectively. At every chemotherapy cycle, the QALYs were calculated. After the completion of six chemotherapy cycles, the mean QALYs were 0.029 and 0.032 for patients in cohorts 1 and 2, respectively. CONCLUSION: The three-drug therapy consisting of cetuximab, cisplatin, and paclitaxel has shown significant improvement in patients' QALYs compared to two-drug regimens of cetuximab and cisplatin. Thus, if the therapy consisted of three-drug regimen is used instead of two-drug regimen, it will have a positive impact on humanistic outcome in recurrent or metastatic HNC patients.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Humans , Cetuximab/therapeutic use , Cisplatin , Carcinoma, Squamous Cell/pathology , Quality of Life , Prospective Studies , Head and Neck Neoplasms/drug therapy , Paclitaxel , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathologyABSTRACT
The immune system plays a significant role in the development, invasion, progression, and metastasis of head and neck cancer. Over the last decade, the emergence of immunotherapy has irreversibly altered the paradigm of cancer treatment. The current treatment modalities for head and neck squamous cell carcinoma (HNSCC) include surgery, radiotherapy, and adjuvant or neoadjuvant chemotherapy which has failed to provide satisfactory clinical outcomes. To encounter this, there is a need for a novel or targeted therapy such as immunological targets along with conventional treatment strategy for optimal therapeutic outcomes. The immune system can contribute to promoting metastasis, angiogenesis, and growth by exploiting the tumor's influence on the microenvironment. Immunological targets have been found effective in recent clinical studies and have shown promising results. This review outlines the important immunological targets and the medications acting on them that have already been explored, are currently under clinical trials and are further being targeted.
Subject(s)
Head and Neck Neoplasms , Immunomodulation , Humans , Squamous Cell Carcinoma of Head and Neck/therapy , Head and Neck Neoplasms/therapy , Immunotherapy/methods , Tumor MicroenvironmentABSTRACT
A combination of monoclonal antibodies prescribed along with the conventional standard of care has a potential to provide significant improvement in patients suffering from head and neck cancer. This combination has also shown a significant decrease in toxicities and improved overall quality of life. Cetuximab acts by inhibiting the human epidermal growth factors as its overexpression in head and neck tumours that are responsible for treatment failure, resistance, and metastasis. Whereas, bevacizumab acts by inhibiting the vascular endothelial growth factor since its overexpression leads to induction of tumour angiogenesis. Current research has not shown any remarkable beneficial effect in disease outcomes. Thus, the addition of these monoclonal antibodies to the standard regimen for head and neck cancer can be considered a prospect that might be beneficial. Cetuximab has already been included as an option under special recommendations in recurrent/metastatic head and neck cancer by NCCN in a platinum-based regimen as well as in combination with radiation therapy. This review outlines the applicability of cetuximab and bevacizumab in the treatment of head and neck cancer as well as the clinical trials performed that give an idea about the efficacy and safety of these monoclonal antibodies. Based upon the literature reviewed, it can be deduced that immunotherapy is to be adopted and different targets are to be explored in it in order to combat head and neck cancer. Currently, immunotherapeutic drugs of two major targets have been discussed. These agents are even effective in combination with other therapeutic modalities that are not being able to achieve desirable outcomes due to issues such as resistance and toxicities. Thus, newer targets as well as newer agents acting on established targets are to be explored in order to improve disease outcomes.
Subject(s)
Antineoplastic Agents , Head and Neck Neoplasms , Humans , Cetuximab/therapeutic use , Antibodies, Monoclonal/therapeutic use , Bevacizumab/therapeutic use , Vascular Endothelial Growth Factor A , Quality of Life , Antibodies, Monoclonal, Humanized/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Head and Neck Neoplasms/drug therapy , Antineoplastic Agents/therapeutic useABSTRACT
Triple-negative breast cancer (TNBC) showcases a labyrinthine network exhibiting deficient expression of Estrogen receptor (ER), Progesterone receptor (PR), and Human-epidermal growth factor receptor-2 (HER2). This restricts the conventional chemotherapeutic, hormonal, and few targeted regimens in showing efficient anti-tumor response. Antibody-drug conjugates (ADCs) are target-specific conjugates comprising a monoclonal antibody attached to the desired cytotoxic payload with the support of a stable linker. They are designated as one of the encouraging sets of targeted therapies that have unveiled affirmative outcomes owing to increased specificity in targeting the undetectable or deficiently expressed targets. Another virtue of ADCs lending superiority to this approach is the presence of inherent bystander effect which has a detrimental influence on the tumor microenvironment (TME) devoid of antigen expression. In the current scenario, FDA-approved Sacituzumab govitecan is widely being utilized to mitigate TNBC while many other ADCs are being studied in clinical trials. Additionally, a focus has been set on revelation of application of Trastuzumab deruxtecan in HER2-low metastatic breast cancer which widens the current therapeutic horizon dealing with such carcinomas. After making an effort towards sketching ADCs profile, we conclude that this novel approach deserves to be investigated through future campaigns owing to its remarkable bystander effect, ability to precisely recognize the antigen and spare the naïve cells from detrimental toxicity. Exploration of the remarkable potential of Sacituzumab govitecan in multiple indications including TNBC portrays the prominence of ADCs and prompts the bright future of this therapeutic approach. In this review, we present the basic foundation of ADCs alongside summarizing the building blocks of several ADCs used in TNBC. Furthermore, by shedding light on the therapeutic regimens and concomitant effects of various ADCs derived from the supportive backbone of clinical trials, we have attempted to convene several segments of ADCs and portray their potentialities time ahead.
Subject(s)
Carcinoma , Immunoconjugates , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Immunoconjugates/therapeutic use , Receptors, Estrogen , Bystander Effect , Tumor MicroenvironmentABSTRACT
An unheard mobilization of resources to find SARS-CoV-2 vaccines and therapies has been sparked by the COVID-19 pandemic. Two years ago, COVID-19's launch propelled mRNA-based technologies into the public eye. Knowledge gained from mRNA technology used to combat COVID-19 is assisting in the creation of treatments and vaccines to treat existing illnesses and may avert pandemics in the future. Exploiting the capacity of mRNA to create therapeutic proteins to impede or treat a variety of illnesses, including cancer, is the main goal of the quickly developing, highly multidisciplinary field of biomedicine. In this review, we explore the potential of mRNA as a vaccine and therapeutic using current research findings.
ABSTRACT
Triple negative breast cancer (TNBC) portraying deficient expression of estrogen receptor (ER), progesterone receptor (PR) and Human epidermal growth factor receptor 2 (HER2) is known to be the most aggressive subtype associated with poor prognosis and interventional strategies limited to chemotherapy and breast conserving surgery. Some TNBC incidences have also been reported with positive circ-HER2 expression thus rendering circ-HER2 a potential immunotherapy target to direct drug development. Resistance and recurrence reported with traditional approaches has led us towards the application of immunotherapeutic interventions owing to their anti-tumor efficacy. This review provides an elaborative insight on potential molecular biomarkers to be targeted by immunotherapy. Additionally, clinical trials proposing the application of immunotherapy in neoadjuvant, adjuvant and metastatic TNBC setting have also been included. The gathered evidence indicates a positive application of immunotherapy in TNBC with therapeutic limitation available only owing to the possibility of adverse events which can be dealt considering risk-to-benefit ratio. Furthermore, potential targets to aim for therapeutic vaccines along with evidence from clinical trials have also been mentioned.
Subject(s)
Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/metabolism , Immunotherapy , Receptors, Estrogen/metabolism , Neoadjuvant TherapyABSTRACT
Tuberculosis is a stern, difficult to treat chronic infection caused by acid-fast bacilli that tend to take a long time to be eradicated from the host's environment. It requires the action of both innate and adaptive immune systems by the host. There are various pattern recognition receptors present on immune cells, which recognize foreign pathogens or its product and trigger the immune response. The epigenetic modification plays a crucial role in triggering the susceptibility of the host towards the pathogen and activating the host's immune system against the invading pathogen. It alters the gene expression modifying the genetic material of the host's cell. Epigenetic modification such as histone acetylation, alteration in non-coding RNA, DNA methylation and alteration in miRNA has been studied for their influence on the pathophysiology of tuberculosis to control the spread of infection. Despite several studies being conducted, many gaps still exist. Herein, we discuss the immunopathophysiological mechanism of tuberculosis, the essentials of epigenetics and the recent encroachment of epigenetics in the field of tuberculosis and its influence on the outcome and pathophysiology of the infection.
ABSTRACT
Drug-eluting contact lens can substitute the multiple eye drop therapy. However, loading hydrophobic drug like cyclosporine in the contact lens is very challenging, due to low drug uptake (via soaking method); and alteration in the swelling and optical properties which restricts its clinical application. To address the above issues, graphene oxide (GO, large surface area with oxygen containing functional groups) was incorporated in the contact lenses during fabrication. These GO-laden contact lenses (SM-GO-Cys) as well as blank contact lenses (SM-Cys) were soaked in the solution of cyclosporine. Alternatively, cyclosporine-laden contact lenses (DL-Cys-20) and cyclosporine-GO-laden contact lenses (DL-Cys-20-GO) were fabricated by adding drug and drug-GO (at various level of GO) during fabrication, respectively. Contact angle and swelling data showed increase in water holding capacity of GO laden contact lenses. Optical property was significantly improved due to molecular dispersion of drug on the surface of GO sheets. The drug uptake and in vitro release profile was improved with GO-laden contact lenses by soaking method (SM-GO-Cys-400n) due to hydrophobic interactions between GO and drug. Adding cyclosporine-GO (DL-Cys-20-GO-800n) during fabrication significantly improved drug release kinetics with higher drug leaching (during extraction and sterilization) due to increased swelling, improved dissolution and molecular dispersion of drug on GO sheets. Ocular irritation and histopathological studies demonstrated the safety of GO-contact lens. The in vivo drug release studies in the rabbit eye showed significant improvement in mean residence time (MRT) and area under the curve (AUC) using DL-Cys-20-GO-800n contact lens compared to eye drop solution with reduction in protein adherence value. The study demonstrated that the incorporation of GO into the contact lens can control the release of cyclosporine as well as improved the lens swelling and transmittance properties.
Subject(s)
Contact Lenses , Graphite , Animals , Cyclosporine , Hydrogels , RabbitsABSTRACT
OBJECTIVE: This study aims to investigate the change in quality adjusted life-years (QALYs) after providing oncology pharmacist services to assess its impact on humanistic outcome. METHODS: It was a prospective, single-centered study conducted for a period of two years at Bharat cancer Hospital and Nirali memorial radiation center, Surat. Patients were recruited into the control group (CG) and the intervention group (IG). The oncology pharmacist services (OPS) were provided only to the IG. The humanistic outcome was measured by incorporating the EQ-5D-5L instrument to calculate quality-adjusted life-years (QALYs) in both the groups. Patients have been provided with the EQ-5D-5L questionnaire at the pre-determined intervals i.e. before the commencement of chemotherapy and then after every chemotherapy cycle till the completion of treatment. The analysis was carried out using descriptive analysis (frequency distribution for categorical variables and measures of central tendency (median and average) and dispersion (std. deviation) for quantitative variables). RESULTS: A total of 230 patients were screened and from them 105 patients were recruited, out of which 54 patients were in CG and 51 patients in IG. AC regimen followed by weekly paclitaxel was prescribed in majority of the patients (CG: 59.3%; IG: 60.8%) followed by AC-TRA and AC regimen alone. The majority of patients in the CG were facing improper administration of pre-medication (83.3%), lack of knowledge regarding chemo-mixing, counselling in nursing staff (66.7%) and a sub-therapeutic dose of anti-emetics (37%). The baseline QALY at the inception of chemotherapy was 0.040 and 0.014 in CG and IG, respectively. After the completion of the 6 chemotherapy cycle, the QALY was found to be 0.042 and 0.043 in CG and IG, respectively. CONCLUSION: The study has demonstrated that the improvisation in QALY after provision of oncology pharmacist services reflect the positive impact of oncology pharmacist on humanistic outcomes. The study also provided the opportunity to identify the thrust area where more clinical pharmacy exposure is needed in order to improve patient care.