Unnecessary Drug Research Articles

The Impact of Pharmacogenomics on Tacrolimus Dosing and Levels among Lung Transplant Recipients

Purpose Immunosuppression after organ transplantation is typically protocol-driven and does not account for individual patient differences. Tacrolimus, the most common calcineurin inhibitor and the backbone of immunosuppression, is dosed based on trough levels but there is significant heterogeneity in dosing. Lung transplant recipients with pharmacogenomic variants impacting tacrolimus metabolism may require different dosing of the drug to achieve the same target level. Methods Blood samples collected from lung transplant recipients were analyzed using a comprehensive pharmacogenomic profile, MediMap™, developed by the Inova Genomics Laboratory. Baseline characteristics as well as data on tacrolimus levels and dosing were collected. Comparisons between those with and without identifiable genotypes that impact tacrolimus metabolism were performed. Results There were 59 lung transplant recipients with blood samples analyzed using MediMap™ testing. 16.9% patients were identified to have a genotype that predicted an altered response to tacrolimus, 25.4% to voriconazole, and 6.8% to both. Age, gender, and underlying lung disease were not different between the groups, however, there were more Caucasians among standard metabolizers compared to altered metabolizers (91.7% vs. 36.4%, p=0.0002). Those with altered tacrolimus metabolism required a higher daily dose at three months to achieve a therapeutic drug level compared to those without (5.5mg vs. 2.8mg, p=0.038) despite equal azole use between the groups. Time to initial therapeutic level after transplant surgery was 3.7 days vs. 2.8 days (p=0.11). All patients experienced a supratherapeutic tacrolimus level (>20ng/mL) in the first few months post-transplant, however the altered metabolizers had slightly more acute kidney injury than standard metabolizers (18% vs. 8.6%, p=0.24). Conclusion Knowledge of pharmacogenomic profile prior to transplant could inform initial dosing and potentially result in less subtherapeutic and supratherapeutic levels of tacrolimus. Indeed, better understanding of individual pharmacogenomic differences in tacrolimus and other commonly used medications post-transplant may prove invaluable in our quest to avoid unnecessary drug toxicity while optimizing long-term allograft and patient survival.

BAT in the Diagnosis of Drug Allergy: a Novel Tool in Clinical Daily Practice?

The aim of this study is to critically review the relevant literature published on basophil activation test, presenting the current knowledge and future perspectives. Basophil activation test (BAT) results varied accordingly to the class of the drug studied, and have promising results in immediate hypersensitivity reactions to pyrazolone (selective reactors), neuromuscular blockers, beta-lactams, and platinum compounds, all examples of classical IgE-mediated hypersensitivity drug reactions. Currently, BAT is applied in research settings, but based in the results of our review, the test can be considered as a diagnostic tool for daily practice for selected patients and selected drugs, when the test is available, particularly for patients who experienced severe reactions and when diagnosis cannot be stablished by serum-specific IgE and skin testing, in order to avoid unnecessary drug provocations tests.

Antibiotic stewardship targets in the outpatient setting

Outpatient prescriptions comprise 60% of antibiotic use. This study prospectively identified inappropriate antibiotic use enabling a focused approach to outpatient antimicrobial stewardship. Outpatients at the Veterans Affairs Western New York Healthcare System were identified via an electronic antibiotic alert from June 2017 to September 2017. Descriptive statistics and multivariable logistic regression identified stewardship targets. Of the 1,063 patients, 40% of antibiotic prescriptions were not indicated. Urinary tract infections (21%), bronchitis (20%), skin structure infections (17%), and sinusitis (10%) were common causes of inappropriate antibiotic use. Azithromycin (37%) was prescribed unnecessarily most often, followed by ciprofloxacin (16%), amoxicillin/clavulanate (13%), and cephalexin (12%). The correct drug was chosen in 52%, dose in 81%, and duration in 75% of patients. When the antibiotic was indicated, the correct drug was 2.9 times more likely to be prescribed and 2 times more likely to have the correct duration and receive care in the emergency room. Focusing on 4 drugs; amoxicillin/clavulanate, azithromycin, ciprofloxacin, and cephalexin accounted for 80% of unnecessary drug use. This study provides a guide to concentrate efforts during implementation of an outpatient stewardship program. Poor antibiotic prescribing was found in the outpatient setting. This study identifies areas for improvement via stewardship.

Functional movement disorders: positive diagnostic criteria

Functional movement disorders (FMDs) are a complex medical problem requiring a set of different diagnostic and treatment approaches: neurological, psychiatric, psychotherapeutic, and neurophysiological. With the advent of positive criteria for the diagnosis of FMDs, the latter are no longer just a diagnosis of exclusion, which is difficult for clinical interpretation. The review considers positive clinical and instrumental diagnostic criteria and presents the neurophysiological characteristics of functional tremor and functional myoclonus, which allow one to suspect this diagnosis. Their timely recognition is extremely important, as this permits patients to reduce the cost of unnecessary examinations and ineffective drugs and increases the chances for successful treatment, since the best prognosis is noted with the shortest duration of the disease.

Assessment of Completeness of Prescription and Rational Drug Use Practice at Felege Hiwot Referral Hospital, North West Ethiopia

Background : Rational drug use is a tool through which safe, effective and economic medication is provided. Rational prescribing and dispensing ensure adherence to treatment and protects drug consumers from unnecessary adverse drug reactions. Objective: The assessment of the rational drug use practice and completeness of prescription is important to identify the most common drug use problem and propose appropriate interventions. Methodology : A combination of retrospective and prospective quantitative cross sectional study was conducted in outpatient pharmacy .Drug containing prescriptions (n=669 ) prescribed from July 1, 2014 to September 30, 2015 were selected by systematic sampling technique for prescriber indicators analysis and patients interviewed (n=90 ) for patient care indicator analysis. Results : The mean number of drugs per prescription was 1.46; percentage of prescriptions containing less than two drugs per prescription was 85.05%. Antibiotics and injection were prescribed in prescription were 42.04 %, 0.73% respectively. The weight of the patient was omitted 100% and the diagnoses of 87% were not written. The strength and duration of the drug were clearly stated in 81.89%, 74.61% of the prescriptions respectively. 32.74% and 20.93% of the prescriptions contain the name of the prescribers and dispensers respectively. 80 (88.89%) of patients interviewed had adequate knowledge of how to take the medication prescribed. From all drugs received by the patients only 68.03% were adequately labeled. The average counseling and dispensing time was 1 min 20sec and 11min 54 sec respectively. Conclusion : From the results of the study, we can be concluded that not all prescriptions were complete as few of them lack the necessary information. So there is a need for managerial and educational intervention to improve rational drug use and to enhance good prescribing and dispensing practices. Keywords : rational drug use, patient care indicators, prescribing indicators, EDL, tracer drug DOI : 10.7176/JHMN/60-02 Publication date :March 31 st 2019

The separation of trypanosomes from blood by anion exchange chromatography: From Sheila Lanham's discovery 50 years ago to a gold standard for sleeping sickness diagnosis.

Human African trypanosomiasis (HAT), or sleeping sickness, is a neglected tropical disease that is fatal if untreated, caused by Trypanosoma brucei gambiense and T. brucei rhodesiense. In its 2012 roadmap, WHO targeted HAT for elimination as a public health problem in 2020 and for zero transmission in 2030. Diagnosis of HAT is a multistep procedure comprising of clinical suspicion, confirmation, and stage determination. Suspects are identified on clinical signs and/or on screening for specific antibodies. Parasitological confirmation of suspects remains mandatory to avoid unnecessary toxic drug administration. The positive predictive value of the antibody detection tests is low. Simple parasite detection techniques, microscopic examination of lymph node aspirate, or stained thick blood films lack sensitivity, whereas in T. brucei gambiense patients, the number of blood trypanosomes may be very low. Parasite concentration techniques are therefore indispensable. Half a century ago, Sheila Lanham discovered a technique to separate trypanosomes from the blood of infected rodents, based on anion exchange chromatography with diethyl amino ethyl (DEAE) cellulose, a weak anion exchanger. Between pH 6−9, trypanosome surface is less negatively charged than that of blood cells. When blood is poured on top of a DEAE cellulose column, blood cells are retained, whereas parasites pass the column together with the elution buffer. The result is a pure suspension of trypanosomes that retain their morphology and infectivity. Because cell surface charges vary among trypanosome and mammal species, the optimal buffer pH and ionic strength conditions for different combinations of host and trypanosome species were established. Lanham's technique revolutionized the diagnosis of HAT. It is indispensable in the production of the Card Agglutination Test for Trypanosomiasis (CATT), the most used field test for screening in T. brucei gambiense HAT foci and essential to confirm the diagnosis in suspected people. Lumsden and colleagues developed the mini anion exchange centrifugation technique (mAECT). After adaptation for field conditions, its superior diagnostic and analytical sensitivity compared to another concentration technique was demonstrated. It was recommended as the most sensitive test for demonstrating trypanosomes in human blood. At the beginning of the 21st century, the mAECT was redesigned, allowing examination of a larger volume of blood, up to 0.35 ml with whole blood and up to 10 ml with buffy coat. The plastic collector tube in the new kit is also used for detection of trypanosomes in the cerebrospinal fluid. Unfortunately, mAECT also has some disadvantages, including its price, the need to centrifuge the collector tube, and the fact that it is manufactured on a noncommercial basis at only two research institutes. In conclusion, 50 years after Sheila Lanham's discovery, CATT and mAECT have become essential elements in the elimination of HAT.

Diagnosis and treatment choices of suspected benign paroxysmal positional vertigo: current approach of general practitioners, neurologists, and ENT physicians.

Benign paroxysmal positional vertigo (BPPV) is a frequently underdiagnosed cause of vertigo, potentially due to the underuse of diagnostic and therapeutic canalith repositioning procedures (CRPs). We aimed to investigate self-reported use of the diagnostic and therapeutic approach to BPPV patients by Lithuanian neurologists, ear, nose, and throat (ENT) physicians, and general practitioners (GPs), and to explore potential reasons for the underuse of the maneuvers. Neurologists, ENT physicians, and GPs were invited to complete a written questionnaire focused on diagnostic and therapeutic practices related to BPPV. Between-group differences and associations between responses were analyzed statistically. In total, 97 neurologists, 85 ENT physicians and 142 GPs (21.1%, 26.8%, and 5.7%, respectively, of all corresponding licensed Lithuanian physicians) completed the questionnaire. 24% of neurologists, 33% ENT physicians and 50% GPs do not perform diagnostic maneuvers for patients with suspected BPPV, and 28%, 61%, and 84%, respectively, do not perform CRPs. Years of clinical experience was a negative predictor of CRP performance [OR 0.97 (95% CI 0.95-0.99), p = 0.001]. Frequent reasons for not performing CRPs were time taken for the procedure, fear of provoking symptoms, and lack of knowledge. All physicians frequently ordered additional imaging or consultations for suspected BPPV and reported prescribing a range of medications. A significant proportion of Lithuanian neurologists, ENT physicians, and GPs do not employ diagnostic maneuvers and CRPs for BPPV patients, contrary to established guidelines. Lack of expertise and time available is a common culprit that leads to unnecessary drug prescribing and investigation.

Increased health information technology investment decreases uncompensated care cost: A study of Texas hospitals.

Many previous research studies have demonstrated that investing in health information technology (IT) in a hospital setting has potential benefits, including eliminating duplicate or unnecessary tests and adverse drug events, conserving healthcare provider time and effort by making information more readily available, and reducing cost by increasing efficiency or productivity metrics. However, the effect of health IT on uncompensated care has not been reported yet. The objective of this study was to examine the effect of health IT investment on uncompensated care provided by hospitals. The general linear model (GLM) with log link and normal distribution was used to estimate the association between health IT spending and the provision of uncompensated care using Texas American Hospital Association (AHA) data from 2004 to 2010. The total health IT investment was significantly and negatively associated with the provision of uncompensated care. When health IT investment was increased by 10%, the provision of uncompensated care was reduced by 2.7%. Health IT investment was also significantly and negatively associated with bad debt. When health IT investment was increased by 10%, bad debt was decreased by 3.2%. Health IT investment was negatively associated with the provision of uncompensated care. This means that health IT could reduce administrative burden and improve efficiency of tracking patient insurance status and billings.

Medication Error Patients Admitted to Medical Ward in Primary Hospital, Ethiopia: Prospective Observational Study

Medication error (ME) is broadly defined as any error in the prescribing, dispensing, or administration of a drug. ME is the single most preventable cause of patient harm. An infinite number of medication error exist because of the rapidly expanding array of drug products available, the growing number of diseases being recognized & diagnosed, and the growing number of patients entering the health care system. To evaluate the most frequently encountered drug class undergo medication errors, to identify sources of medication error and evaluate predictors of medication errors among patients admitted to medical ward in primary hospital, northwest Ethiopia. Prospective observational study was conducted from April 1/2018-October/2019G.C. All adult patients who met inclusion criteria were included in the study. Patient medication adherence was evaluated using morisky adherence scale. Independent predictors of outcome identified and strength of association between dependent and independent variables determined by using binary logistic regression analysis and statistical significance was considered at p<0.05. Two hundred sixty patients were included in the analysis. Among these, majority of them were encountered medication errors. Anti-infective drugs were mostly prescribed as well as medication error encountered. Unnecessary drug therapy is the most common error. Proportion of patients with medication error is lower among patients who are on 1-3 drugs as compared to those patient who are on more than five drugs (p=0.025). Patients who stayed less than one week less likely encountered medication errors as compared to those stay more than a week (p=0.024). Since medication availability is significant determinant for medication error, hospital should try to avail medication and prevent medication errors. Clinical pharmacists should involve in multidisciplinary team and continuous patient medication reconciliation should be integral part of patient medical management.

The status of proton pump inhibitor use: a prescription survey of 45 hospitals in China.

proton pump inhibitors (PPI) have been widely used in the clinic but inappropriate prescribing has also increased dramatically. to describe the prescribing patterns and assess the appropriateness of the prescribed PPI use in 45 hospitals in China. PPI prescriptions for non-hospitalized patients were collected from hospitals in Beijing, Chengdu, Guangzhou and Hangzhou of China over a 40-day period in 2016. These data were analyzed using the prescription number, proportion and economic indicators (defined daily dose system [DDD], defined daily cost [DDC] and drug utilization index [DUI]). The evaluation criteria of PPI use was based on Martindale: The Complete Drug Reference, New Materia Medica and drug instructions. in total, 357,687 prescriptions using oral PPI and 38,216 prescriptions using injectable PPI were assessed. The average age of PPI users was 53 years. The most commonly used oral PPI was rabeprazole, while the most common injectable PPI was pantoprazole. The DDD of oral rabeprazole and DDC of injectable rabeprazole were the highest. Meanwhile, only the DUI values of oral rabeprazole, lansoprazole and ilaprazole were less than 1.0. The clinical diagnosis of some users included well identified risky comorbidities such as kidney disease (2.9%). Furthermore, between 32.6% and 56.8% of the PPI prescriptions were used for inappropriate indications. this survey demonstrated that PPI use was accompanied by unapproved indications and excessive dosages. Comprehensive measures are urgently needed to improve PPI use and reduce unnecessary drug costs.

Drug therapy problems among patients with cardiovascular disease admitted to the medical ward and had a follow-up at the ambulatory clinic of Hiwot Fana Specialized University Hospital: The case of a tertiary hospital in eastern Ethiopia.

Background:Pharmacotherapy is important in reducing morbidity and mortality related to cardiovascular diseases. However, these advantages are limited by drug therapy problems that can impact on a patient’s quality of life, prolong hospital stays, and increase the overall burden of healthcare expenditures. Therefore, this study was aimed to assess drug therapy problems among patients with cardiovascular diseases who were hospitalized and received follow-up at the ambulatory clinic of Hiwot Fana Specialized University Hospital.Methods:An institution-based cross-sectional study design was used to collect data from patients with cardiovascular diseases who were admitted to the medical ward and those who had received follow-up at the ambulatory clinic of Hiwot Fana Specialized University Hospital. The collected data were coded, entered, and analyzed using SPSS version 16. The associations of selected categorical variables were done using binary logistic and multivariate logistic regression analyses.Results:Out of 216 study participants, females accounted for 123 (57%), whereas 93 (43%) of them were males. Among cardiovascular diseases identified in the medical ward and ambulatory clinics of Hiwot Fana Specialized University Hospital, congestive heart failure 96 (44.4%) and hypertension 93 (43.1%) were the two most commonly diagnosed disorders. Of the total participants involved in the study, 131 (60.65%) had drug therapy problems. Among the seven classes of drug therapy problems assessed, the most commonly observed was the need for additional drug therapy 76 (58%); followed by cases related to unnecessary drug therapy and noncompliance both of which were estimated to be 16 (12.2%). In addition, of independent variables, only the use of more than three drugs was significantly associated in both binary logistic (crude odds ratio = 0.41, 95% confidence interval = 0.234–0.719, p = 0.002) and multivariate logistic regressions (adjusted odds ratio = 4.86, 95% confidence interval = 1.625–14.536, p = 0.005) as compared with those patients who were using less than three drugs.Conclusion:The findings of the study indicated that more than half of the study participants experienced drug therapy problems, for which 58% required additional drug therapy. The risk of drug therapy problem is found to increase with the use of more than three drugs. Since these problems are adversely affecting the treatment outcome of patients, this is an area which requires special attention and the cooperation of healthcare professionals to tackle it.

Adverse Event Management in Patients with BRAF V600E-Mutant Non-Small Cell Lung Cancer Treated with Dabrafenib plus Trametinib.

Therapies for advanced non-small cell lung cancer (NSCLC) continue to become more sophisticated. Chemotherapeutics are giving way to newer approaches such as immune checkpoint inhibitors and targeted therapies for greater efficacy and improved outcomes. Dabrafenib plus trametinib combination therapy was first approved for the treatment of metastatic melanoma harboring the BRAF V600-mutation in 2014. In 2017, the U.S. Food and Drug Administration approved the combination for patients with NSCLC with the same mutation based on an ≈ 65% response rate and median progression-free survival of 10-11 months. BRAF mutations are a high-frequency event in melanoma (≈ 50%), whereas the overall incidence in lung cancer is ≈ 2%, but similar in number, because of the high incidence of the disease. As a new approach in NSCLC treatment, dabrafenib plus trametinib has a unique toxicity profile that is likely unfamiliar to care providers in thoracic and general oncology who have not used the combination to treat patients with melanoma. Common adverse events such as pyrexia, fatigue, and nausea, as well as a range of less frequent cutaneous, ocular, and hemorrhagic events, can be observed during treatment with dabrafenib plus trametinib. Previous experience in metastatic melanoma revealed that these events can be effectively managed to improve patient quality of life and reduce unnecessary drug discontinuation. The aim of this review is to summarize treatment guidelines, along with key insights obtained from previous clinical-trial and real-world experience in patients with metastatic melanoma, to properly manage toxicities associated with dabrafenib plus trametinib for NSCLC. IMPLICATIONS FOR PRACTICE: The combination of dabrafenib plus trametinib has demonstrated substantial clinical activity in patients with BRAF V600E-mutant non-small cell lung cancer, leading to U.S. Food and Drug Administration approval. Although the combination has a manageable safety profile, many toxicities associated with the regimen may not be familiar to thoracic specialists or general oncologists. Extensive clinical experience with the combination in patients with metastatic melanoma has provided a wealth of strategies to identify and manage adverse events associated with dabrafenib plus trametinib. These can be used by medical oncologists to enhance early recognition of toxicities and facilitate effective management, thereby improving quality of treatment for patients.

Topic Modelling for Medical Prescription Fraud and Abuse Detection

SummaryMedical prescription fraud and abuse have been a pressing issue in the USA, resulting in large financial losses and adverse effects on human health. The size and complexity of the healthcare systems as well as the cost of medical audits make use of statistical methods necessary to generate investigative leads in prescription audits. We analyse prescriber–drug associations by utilizing the real world Medicare part D prescription data from New Hampshire. In particular, we propose the use of topic models to group drugs with respect to the billing patterns and exhibit the potential aberrant behaviours while using medical specialities as a covariate. The prescription patterns of the providers are retrieved with an emphasis on opioids and aggregated into distance-based measures which are visualized by concentration functions. This output can enable healthcare auditors to identify leads for audits of providers prescribing medically unnecessary drugs.

Reducing Palivizumab Dose Requirements Through Rational Dose Regimen Design.

Palivizumab for respiratory syncytial virus (RSV) immunoprophylaxis in premature infants poses a significant economic challenge. Although standard dosing of palivizumab results in unnecessary drug accumulation without additional clinical benefit, some clinicians have moved outside of evidence‐based practice by implementing untested dose modifications, potentially jeopardizing efficacy. Using an industry‐developed population pharmacokinetic model, this study evaluated the previously published alternate dosing regimens and developed a revised regimen that minimizes palivizumab dose requirements while maintaining established therapeutic concentrations. All published dose modifications resulted in unacceptably high proportions of infants not attaining minimum protective concentrations, compromising efficacy. Through intelligent dose regimen design, a clinically practical palivizumab regimen was devised that reduces drug use by 25%, while enabling a greater proportion of infants attaining early season target concentrations, particularly those at greatest risk of the consequences of RSV infection. This novel regimen has the potential to substantially change clinical practice and increase drug availability.

Protease activity sensors noninvasively classify bacterial infections and antibiotic responses.

BackgroundRespiratory tract infections represent a significant public health risk, and timely and accurate detection of bacterial infections facilitates rapid therapeutic intervention. Furthermore, monitoring the progression of infections after intervention enables ‘course correction’ in cases where initial treatments are ineffective, avoiding unnecessary drug dosing that can contribute to antibiotic resistance. However, current diagnostic and monitoring techniques rely on non-specific or slow readouts, such as radiographic imaging and sputum cultures, which fail to specifically identify bacterial infections and take several days to identify optimal antibiotic treatments.MethodsHere we describe a nanoparticle system that detects P. aeruginosa lung infections by sensing host and bacterial protease activity in vivo, and that delivers a urinary detection readout. One protease sensor is comprised of a peptide substrate for the P. aeruginosa protease LasA. A second sensor designed to detect elastases is responsive to recombinant neutrophil elastase and secreted proteases from bacterial strains.FindingsIn mice infected with P. aeruginosa, nanoparticle formulations of these protease sensors—termed activity-based nanosensors (ABNs)—detect infections and monitor bacterial clearance from the lungs over time. Additionally, ABNs differentiate between appropriate and ineffective antibiotic treatments acutely, within hours after the initiation of therapy.InterpretationThese findings demonstrate how activity measurements of disease-associated proteases can provide a noninvasive window into the dynamic process of bacterial infection and resolution, offering an opportunity for detecting, monitoring, and characterizing lung infections.FundNational Cancer Institute, National Institute of Environmental Health Sciences, National Institutes of Health, National Science Foundation Graduate Research Fellowship Program, and Howard Hughes Medical Institute.

1849. Identification of Antimicrobial Stewardship Targets in the Outpatient Setting

BackgroundOutpatient prescriptions consist of 60% of all antibiotic use. Prior studies have shown antibiotic overuse in the outpatient setting which contributes to rising rates of resistance and unnecessary adverse drug events. This study aimed to prospectively identify antibiotic stewardship targets in outpatient settings including drug selection, dose, duration, and if guideline criteria was met to necessitate an antibiotic.MethodsThe patient population consisted of outpatients seen at the Veterans Affairs Western New York Healthcare System and its affiliated community-based outreach clinics. Patients were prospectively identified via on a real-time alert received by the infectious disease pharmacist at the time when an oral antibiotic was prescribed from June to September 2017. Data were then collected via chart review and all infections were evaluated based on guidelines. Descriptive statistics and a multivariable logistic regression was used to identify stewardship targets.ResultsOf the 1,063 patients included, the most common infections treated included skin and skin structure infection (26.3%), urinary tract infection (18.1%), and sinusitis (11.9%). Azithromycin was the most commonly used antibiotic (27%), followed by cephalexin (13%) and ciprofloxacin (12%). Overall, 40% of antibiotics prescribed were not indicated for use. The incorrect drug was chosen for indication in 40%, the improper dose was ordered in 22%, and the incorrect duration was used in 30%. ICD-10 codes were unreliable in capturing oral antibiotic use, as only 41% antibiotic use was associated with an ICD-10 code relating to an infection. Per the multivariable logistic regression, when the antibiotic was indicated, patients were 2.9 times more likely to receive the correct drug (95% CI, 2.2–3.8) and two times more likely to receive the correct duration for the antibiotic (95% CI, 1.5–2.7). Emergency room patients were twice as likely to receive an antibiotic when indicated based on guidelines (95% CI, 1.5–2.7) compared with those seen in clinics.ConclusionPoor antibiotic prescribing practices was found throughout the outpatient setting. This study provides a guide to focus efforts during implementation an outpatient stewardship program.Disclosures All authors: No reported disclosures.

PH/NIR-responsive semiconducting polymer nanoparticles for highly effective photoacoustic image guided chemo-photothermal synergistic therapy

Multifunctional drug delivery nanoplatform (PDPP3T@PSNiAA NPs) based on NIR absorbing semiconducting polymer nanoparticles for pH/NIR light-controllably regulated drug release has been successfully prepared. In this strategy, pH/thermal-sensitive multifunctional polymer polystyrene-b-poly(N-isopropylacrylamide-co-acrylic acid) (PSNiAA) was meticulously designed and synthesized using the reversible addition fragmentation chain transfer (RAFT) polymerization method. Furthermore, PSNiAA was used to functionalize diketopyrrolopyrrole-based semiconducting polymer (PDPP3T) to combine photothermal capacity and pH/thermo-responsive drug release in one entity. The prepared PDPP3T@PSNiAA NPs exhibited high photothermal conversion efficiency (η = 34.1%) and excellent photoacoustic (PA) brightness. Meanwhile, benefiting from the photothermal effect of PDPP3T and the pH/thermal-responsive properties of PSNiAA, Dox-loaded PDPP3T@PSNiAA NPs (PDPP3T@PSNiAA-Dox NPs) were able to controllably regulate the release of Dox by pH/NIR light, in which the enhanced drug release at acidic condition upon NIR irradiation phenomenon would minimize unnecessary drug release in normal tissues and was highly beneficial for precise synergistic chemo- and photothermal therapy.

A prospective observational study of drug therapy problems in medical ward of a referral hospital in northeast Ethiopia

BackgroundDrug therapy problem is any undesirable event experienced by a patient during drug therapy that interferes with achieving the desired goals of therapy. Drug therapy problems are common causes of patient morbidity and mortality. There was no study that has been done on drug therapy problems in the study area, Dessie referral hospital, northeast Ethiopia.MethodA prospective observational study was conducted among hospitalized patients in the medical ward of Dessie referral hospital from March 01 to May 31, 2014. Ethical approval was obtained and informed consent was signed by each study participant before the commencement of the study. All patients admitted to the ward during the study period were included in the study. Data regarding each patient’s demographics, medical condition, drug therapy and patient compliance to the drug therapy were collected using pretested checklists, and drug therapy problems were determined based on the standard practice and textbooks. Descriptive statistical analysis was done using SPSS Version 20 Software.ResultA total of 147 patients were included, 75.51% of whom experienced at least one drug therapy problem. During the 3 month period a total of 159 drug therapy problems were identified of which needs additional drug therapy (35.85%) was the most common followed by unnecessary drug therapy (30.19%) and dosage too low (13.2%). Antibiotics, 75 (40.32%) was the most frequent drug class involved in drug therapy problems followed by cardiovascular drugs, 69 (37.1%) and nonsteroidal anti-inflammatory drugs, 9 (4.84%). Ceftriaxone (25.81%) was the most frequent specific drug prone to the drug therapy problems followed by spiranolactone (14.52%), enalapril (6.45%) and furosemide (6.45%).ConclusionsThree out of four patients experienced at least one drug therapy problem during their hospital stay in the medical ward, with the most commonly observed DTP being no drug therapy prescribed for a condition requiring drug treatment.

FACTOR-X DEFICIENCY: A RARE DISORDER TO BE LOOKED FOR IN CASES OF CONGENITAL BLEEDING TENDENCY

ABSTRACTFactor X deficiency is a rare, autosomal recessive disorder that involves the coagulation cascade. People with this disorder present with a myriad of early life bleeding complications. We report here a 23-year-old male, who presented with bleeding complications (prolonged bleeding from surgical wounds, unresolving hematomas, uncontrolled nasal bleeding, hematuria and hematochezia) at different stages of his life but was diagnosed very late for factor X deficiency after comprehensive evaluation for clotting factors. He was managed by repeated transfusions of fresh frozen plasma and detailed counselling. Factor X deficiency is a rare life-threatening disease and must be differentiated from other disorders of coagulation. The patients are advised to avoid activities with high levels of physical contact, unnecessary invasive interventions and drugs that remarkably affect liver functions and seek immediate medical care in case of bleeding from any site.KEYWORDSHemorrhage (MeSH); Bleeding disorder (Non-MeSH); Factor X Deficiency (MeSH); Inherited (Non-MeSH); Blood Coagulation Disorders, Inherited (MeSH); Blood Coagulation Disorders (MeSH).

Proven immunologically-mediated drug hypersensitivity in children with a history of multiple drug intolerances

BackgroundChildren may be referred to pediatric allergy clinics for reactions to multiple drugs. Multiple drug hypersensitivity (MDH) is defined as immunologically-mediated hypersensitivity to 2 or more chemically different drugs. ObjectiveThe aim of this study is to report the allergy workup results of children who had a history of potential hypersensitivity reactions to 2 or more unrelated drugs. MethodsThis study was conducted in the Pediatric Allergy and Immunology department of our hospital. Children who described hypersensitivity reactions to 2 or more drugs were included and were evaluated by allergy workup (skin and/or provocation tests) between January 2011 and July 2016. ResultsDuring the study period, 886 children were evaluated for a history of drug intolerance. Of these children, 73 (8.2%) had a history of drug reactions to 2 or more chemically different drugs. The median age of the children who had a history of reactions to 2 or more drugs was 7.8 (min-max: 2.5-16.4) years, and 59% (n = 43) were male. Among the suspected drugs, antibiotics (65.9%) ranked first, and nonsteroid anti-inflammatory drugs (34.1%) were the second. All 73 children were evaluated with skin or provocation tests with the suspected drugs, and MDH was confirmed in only 2 (2.7%) children. ConclusionMultiple drug hypersensitivity is uncommon in children. The incidence and prevalence of MDH may vary with the specific population studied. Evaluating children with a history of MDH, by performing drug hypersensitivity testing, will help avoid the morbidity associated with unnecessary drug avoidance.