Suboptimal Drug Treatment Research Articles

Drug-related problems among pediatric intensive care units: prevalence, risk factors, and clinical pharmacists’ interventions

BackgroundDrug-related problems (DRPs) are frequently observed in intensive care units, resulting in a higher occurrence of drug side effects and increased treatment expenses. This study aimed to assess the prevalence of DRPs in pediatric patients admitted to the most prominent surgical and medical pediatric intensive care units (PICUs) in southern Iran, given the susceptibility of children to the effects of DRPs.MethodThis cross-sectional study was conducted at Namazi Hospital, which is affiliated with Shiraz University of Medical Sciences in Shiraz, Iran, from June 2022 to March 2023. The research focused on identifying and detecting drug-related problems (DRPs) among pediatric patients during their hospital stays across three medical wards, two pediatric intensive care units, and a surgical intensive care unit. The identification process occurred concurrently with patient treatment and utilized the Pharmaceutical Care Network of Europe’s data collection form for DRPs version 8.01. Before any documentation, all cases were thoroughly reviewed and validated by a professional focus group. The data gathered were then statistically analyzed using SPSS to evaluate the study’s outcomes.ResultDuring the study, 323 pediatric patients were involved, of whom 57% experienced at least one DRP. The primary issues identified during the study were suboptimal drug treatment, accounting for 41.13% of cases, followed by concerns related to treatment safety, which constituted 38.53% of cases. Drug-drug interactions were found to be the leading cause of DRPs, accounting for 36.26% of cases. Two significant factors associated with DRP occurrence were the number of prescribed drugs and the number of prescribed anticonvulsants. Out of all clinical pharmacist interventions, 97% were accepted.ConclusionPatients admitted to the PICUs experience a high occurrence of DRPs. It is essential to consider optimal dosage adjustment, particularly for pediatric patients with impaired kidney function.

Drug-Related Problems Prior to Hospitalization on Internal Medicine Wards

Drug-related hospitalisations pose a significant burden to the health-care system. The aim was to investigate the prevalence of drug-related problems (DRPs) and their association with hospital admissions in five internal medicine wards. The study included patients admitted to the nephrology, cardiology, gastroenterology, endocrinology and geriatric ward. Pharmaceutical Care Network Europe classification V9.1 was used for identifying DRPs. In total 535 patients participated in the study. We identified 954 DRPs (range 1-7) in 80.7% of patients. Most DRPs were identified on the endocrinology, cardiology and geriatric ward, and they were associated with the efficacy of treatment (71.4%), adverse drug events (10.2%) and unnecessary drug treatment (18.4%). DRPs were associated with the cause of hospitalisation in 74.4% of patients on the nephrology ward, 60.1% and 60.6% of patients in the cardiology and endocrinology ward, respectively, whereas this number was lower in the geriatric and gastroenterology wards (26.9% and 8.9%, respectively). Suboptimal drug treatment due to medication omissions, was often associated with the potential cause of hospital admission. Focusing on patients with specific diseases and DRPs, rather than reducing the number of medications in primary care, may be potentially rational in the attempt to reduce drug-related hospitalisations.

Application value of metagenomics next-generation sequencing in the diagnosis of respiratory virus infection after congenital heart surgery.

Timely and accurate pathogen diagnosis can be challenging in children who contract a respiratory virus following congenital heart surgery (CHS). This often results in suboptimal drug use and treatment delays. Metagenomics next-generation sequencing (mNGS) is a swift, efficient, and unbiased method for obtaining microbial nucleic acid sequences. This technology holds promise as a comprehensive diagnostic tool, especially for pathogens undetectable by traditional methods. However, the efficacy of mNGS in the context of congenital heart disease infections remains uncertain. This study aimed to explore the diagnostic value of mNGS for respiratory virus infections post-CHS. We conducted a retrospective analysis of patients who developed respiratory tract infections post-CHS and were admitted to our cardiac center between July 2021 and December 2022. The patients were categorized into the following two groups based on the diagnostic method used: (I) the mNGS group (comprising 62 patients); and (II) the conventional microbiological test (CMT) group (comprising 70 patients). Bronchoalveolar lavage fluid (BALF) samples from these patients were tested to identify pathogens. The mNGS group had significantly higher detection rates for both viral infections and mixed viral infections than the CMT group (56.45% vs. 17.14%, P<0.001, and 80.00% vs. 16.67%, P<0.001, respectively). In the mNGS group, 19.35% of the patients received antiviral therapy, and 61.29% received an anti-infective regimen adjustment. Conversely, in the CMT group, only 4.29% received antiviral therapy, and 28.57% received an anti-infective regimen adjustment. A higher percentage of patients showed improved respiratory symptoms in the mNGS group than the CMT group (74.19% vs. 44.29%, P=0.001). Additionally, the mNGS group had a shorter duration of mechanical ventilation and a reduced length of stay in the cardiac intensive care unit than the CMT group (P=0.012). Using mNGS for BALF enhances the detection of respiratory viral infections and coexisting viral infections post-CHS. This facilitates more precise treatment strategies and could potentially lead to improved patient outcomes.

Drug-related problems and associated factors among patients with kidney dysfunction at a tertiary hospital in southwestern Uganda: a prospective observational study

BackgroundKidney dysfunction is a common, progressive condition that is increasingly becoming a global public health issue. Because the kidneys are the major route for drug excretion, impaired renal function can change the pharmacokinetics and pharmacodynamics of drugs that are renally excreted. Additionally, patients with kidney dysfunction often have co-morbidities and the associated use of multiple medications which increases the risk of drug-related problem (DRP) occurrence. This study aimed to determine the prevalence, types, and factors associated with DRPs in patients with kidney dysfunction.MethodWe conducted a prospective observational study over 3 months among hospitalized patients diagnosed with acute kidney injury or chronic kidney disease who were hospitalized in the medical ward, and patients attending the renal outpatient clinic at Mbarara Regional Referral Hospital. A total of 183 participants were enrolled through the use of a consecutive sampling technique. DRPs were classified according to the PCNE classification version 9.1. Data analysis was carried out using SPSS version 25.ResultsA total of 174 patients with kidney dysfunction were included in the study with a mean ± SD age of 50.34 ± 18.13 years. A total of 219 DRPs were incurred by 138 (79.3%) study participants. The most common DRPs were ‘Untreated symptoms or indication’ (35.6%) followed by ‘adverse event (possibly) occurring’ (28.3%), and ‘effect of drug treatment not optimal’ (23.3%). Antimicrobials were the most involved drugs in suboptimal drug treatment (31.3%) and unnecessary drug treatment (32.1%). The study showed that length of hospital stay ≥ 5 days (AOR = 6.39, 95% CI: 1.75–23.27; p-value = 0.005) significantly increased the risk of DRP occurrence.ConclusionThe current results, in agreement with previous literature, showed a high burden of DRPs among patients with kidney dysfunction. Antimicrobials were the most involved drugs in suboptimal as well as in unnecessary drug treatment. Longer hospital stay significantly increased the risk of DRPs. The high prevalence of DRPs in patients with kidney dysfunction and the potential impact on antimicrobial resistance underscores the importance of regular medication reviews and close monitoring of patients with renal dysfunction.

Potential and Challenges in Application of Physiologically Based Pharmacokinetic Modeling in Predicting Diarrheal Disease Impact on Oral Drug Pharmacokinetics.

Physiologically based pharmacokinetic (PBPK) modeling is a physiologically relevant approach that integrates drug-specific and system parameters to generate pharmacokinetic predictions for target populations. It has gained immense popularity for drug-drug interaction, organ impairment, and special population studies over the past two decades. However, an application of PBPK modeling with great potential remains rather overlooked - prediction of diarrheal disease impact on oral drug pharmacokinetics. Oral drug absorption is a complex process involving the interplay between physicochemical characteristics of the drug and physiological conditions in the gastrointestinal tract. Diarrhea, a condition common to numerous diseases impacting many worldwide, is associated with physiological changes in many processes critical to oral drug absorption. In this review, we outline key processes governing oral drug absorption, provide a high-level overview of key parameters for modeling oral drug absorption in PBPK models, examine how diarrheal diseases may impact these processes based on literature findings, illustrate the clinical relevance of diarrheal disease impact on oral drug absorption, and discuss the potential and challenges of applying PBPK modeling in predicting disease impacts. Significance Statement Statement Pathophysiological changes resulting from diarrheal diseases can alter important factors governing oral drug absorption, contributing to suboptimal drug exposure and treatment failure. Physiologically based pharmacokinetic (PBPK) modeling is an in silico approach that has been increasingly adopted for drug-drug interaction potential, organ impairment, and special population assessment. This minireview highlights the potential and challenges of using PBPK modeling as a tool to improve our understanding of how diarrheal diseases impact oral drug pharmacokinetics.

Quality of prescribing in older people from a broad family physician perspective: a descriptive pilot study

ObjectivesTo investigate the quality of drug treatment in older people from a broad family physician perspective, and to provide evidence for power calculations in full-scale studies on prescribing quality.DesignDescriptive, retrospective...

Optimization and Evaluation of Piperacillin-Tobramycin Combination Dosage Regimens against Pseudomonas aeruginosa for Patients with Altered Pharmacokinetics via the Hollow-Fiber Infection Model and Mechanism-Based Modeling.

Augmented renal clearance (ARC) in critically ill patients can result in suboptimal drug exposures and treatment failure. Combination dosage regimens accounting for ARC have never been optimized and evaluated against Pseudomonas aeruginosa by use of the hollow-fiber infection model (HFIM). Using a P. aeruginosa isolate from a critically ill patient and static-concentration time-kill experiments (SCTKs), we studied clinically relevant piperacillin and tobramycin concentrations, alone and in combinations, against two inocula (105.8 and 107.6 CFU/ml) over 72 h. We subsequently evaluated the effects of optimized piperacillin (4 g every 4 h [q4h], given as 0.5-h infusions) plus tobramycin (5 mg/kg of body weight q24h, 7 mg/kg q24h, or 10 mg/kg q48h, given as 0.5-h infusions) regimens on killing and regrowth in the HFIM, simulating a creatinine clearance of 250 ml/min. Mechanism-based modeling was performed in S-ADAPT. In SCTKs, piperacillin plus tobramycin (except combinations with 8 mg/liter tobramycin and against the low inoculum) achieved synergistic killing (≥2 log10 versus the most active monotherapy at 48 h and 72 h) and prevented regrowth. Piperacillin monotherapy (4 g q4h) in the HFIM provided 2.4-log10 initial killing followed by regrowth at 24 h and resistance emergence. Tobramycin monotherapies displayed rapid initial killing (≥5 log10 at 13 h) followed by extensive regrowth. As predicted by mechanism-based modeling, the piperacillin plus tobramycin dosage regimens were synergistic and provided ≥5-log10 killing with resistance suppression over 8 days in the HFIM. Optimized piperacillin-tobramycin regimens provided significant bacterial killing and suppressed resistance emergence. These regimens appear to be highly promising for effective and early treatment, even in the near-worst-case scenario of ARC.

Number of drugs in the medication list as an indicator of prescribing quality: a validation study of polypharmacy indicators in older hip fracture patients.

PurposeIndicators based on the number of drugs in the medication list are sometimes used to reflect quality of drug treatment. This study aimed to evaluate the concurrent validity of such polypharmacy indicators, i.e., their ability to differentiate between appropriate and suboptimal drug treatment.MethodsIn 200 hip fracture patients (≥65 years of age), consecutively recruited to a randomized controlled study in Sahlgrenska University Hospital in 2009, quality of drug treatment at study entry was assessed according to a gold standard as well as to indicators based on the number of drugs in the medication list. As gold standard, two specialist physicians independently assessed and then agreed on the quality for each patient, after initial screening with Screening Tool of Older Persons’ potentially inappropriate Prescriptions (STOPP) and Screening Tool to Alert to Right Treatment (START). Suboptimal drug treatment was defined as ≥1 STOPP/START outcomes assessed as clinically relevant at the individual level.ResultsA total of 141 (71 %) patients had suboptimal drug treatment according to the gold standard. The corresponding figures according to the indicators ≥5 and ≥10 drugs were 149 (75) and 49 (25 %), respectively. The sensitivity for the indicators ≥5 and ≥10 drugs to detect suboptimal drug treatment was 0.86 (95 % confidence interval: 0.80; 0.92) and 0.32 (0.25; 0.40), respectively. The specificity was 0.53 (0.41; 0.65) and 0.93 (0.82; 0.97).ConclusionsThe findings suggest that no polypharmacy indicator could serve as a general indicator of prescribing quality; cut-offs for such indicators need to be chosen according to purpose.

Residual Effect of Renal Denervation in Patients With Truly Resistant Hypertension

See related article, p 526–532 The SYMPLICITY investigators reported a 25- to 30-mm Hg decrease in office systolic blood pressure 6 to 12 months after renal sympathetic denervation in patients with resistant hypertension.1,2 In the SYMPLICITY studies,1,2 resistant hypertension was a systolic blood pressure of ≥160 mm Hg (150 mm Hg in patients with diabetes mellitus) on treatment with ≥3 different classes of antihypertensive drugs.1,2 This definition of resistant hypertension complies with current guidelines3 but is weak and urgently needs revision.4 Indeed, patients categorized as being apparently resistant according to this generic definition often cumulate clinical conditions that do not justify renal denervation as the preferred treatment option. These conditions include white-coat hypertension,5 poor adherence,6 suboptimal drug treatment, undiagnosed secondary hypertension,3 and isolated systolic hypertension in the elderly, a highly prevalent and difficult to treat form of hypertension driven by arterial stiffening rather than enhanced sympathetic drive.7 Neither the SYMPLICITY studies nor most nonrandomized observational reports published subsequently8 implemented a systematic strategy for differentiating between truly resistant hypertension and conditions that might benefit from an alternative approach, such as addressing the …

Umsetzung der ESH/ESC-Hypertonie-Richtlinien mithilfe verschiedener Blutdruckmessmethoden

Better understanding of epidemiology and pathophysiology of arterial hypertension has resulted in new definitions of blood pressure levels and treatment targets. The main reason for worldwide modest outcomes in the treatment of hypertension is suboptimal drug treatment including incomplete dose titration and an inadequate antihypertensive drug combinations. New techniques such as teletransmission of home blood pressure measurement together with ambulant 24-hour-blood-pressure-monitoring could serve as a solution to provide the physician the opportunity for an adequate antihypertensive therapy, in order to improve drug compliance and to shorten the time until reaching optimal blood pressure.

Does the drug sensitivity of malaria parasites depend on their virulence?

BackgroundChemotherapy can prompt the evolution of classical drug resistance, but selection can also favour other parasite traits that confer a survival advantage in the presence of drugs. The experiments reported here test the hypothesis that sub-optimal drug treatment of malaria parasites might generate survival and transmission advantages for virulent parasites.MethodsTwo Plasmodium chabaudi lines, one derived from the other by serial passage, were used to establish avirulent and virulent infections in mice. After five days, infections were treated with various doses of pyrimethamine administered over 1 or 4 days. Virulence measures (weight and anaemia), parasite and gametocyte dynamics were followed until day 21.ResultsAll treatment regimes reduced parasite and gametocyte densities, but infections with the virulent line always produced more parasites and more gametocytes than infections with the avirulent line. Consistent with our hypothesis, drug treatment was disproportionately effective against the less virulent parasites. Treatment did not affect the relative transmission advantage of the virulent line. Neither of the lines contained known mutations conferring classical drug resistance.ConclusionDrug-sensitivity of malaria parasites can be virulence-dependent, with virulent parasites more likely to survive sub-optimal treatment. If this proves to be general for a variety of drugs and parasite species, selection imposed by sub-optimal drug treatment could result in the evolution of more aggressive malaria parasites.

Effectiveness of a nursing support program for patients with recurrent ovarian cancer receiving pegylated liposomal doxorubicin (Caelyx®/Doxil®)

Pegylated liposomal doxorubicin (PLD) has become the preferred alternative for ovarian cancer patients who have failed platinum-based therapy, but side effects, such as palmar-plantar erythrodysesthesia (PPE), may lead to sub-optimal drug exposure and treatment discontinuation. A prospective Canadian multicentre open-label study evaluated the effects of a nurse-administered education and support program on treatment adherence and tolerability in 112 women with recurrent ovarian cancer. Subjects received an average of four four-week PLD cycles, the recommended number of courses required to evaluate the efficacy from PLD. Side effects were common, but 75% of patients were able to complete > 3 cycles and 59% completed > 4 cycles of PLD chemotherapy. With proactive nursing intervention, the incidence of PLD-associated grade three-four toxicities such as PPE and mucositis was substantially decreased. Nursing intervention may allow more patients to receive chemotherapy on schedule, thus reproducing the conditions of the clinical study in which the efficacy of the drug has been established.

Nursing support program to decrease or prevent side effects of pegylated liposomal doxorubicin (PLD) in patients with recurrent epithelial ovarian cancer (REOC)

8198 Background: A significant long-term survival with PLD compared to topotecan was recently reported in a phase III randomized study of women with REOC (Gyn. Oncol. 2004). PLD is known to be relatively less toxic than topotecan and conventional doxorubicin, however side effects such as palmar-plantar erythrodysesthesia (PPE) may lead to sub-optimal drug exposure and treatment discontinuation. Methods: A nursing support program was created to determine if patient education and proactive nursing care could improve treatment outcomes by decreasing the occurrence and/or severity of PLD-related side effects. Patients who agreed to participate in the program were: educated about potential toxicities associated with PLD, received written instructions on the prevention and management of side effects and were provided with a diary to record symptoms and interventions. Results: A total of 112 ovarian cancer patients who relapsed after one or more prior therapies were accrued in 8 different centers. PLD was administered as 2nd, 3rd and ≥ 4th line therapy in 51%, 34% and 15% of patients, respectively. The majority of patients (85%) received a Taxol/platinum combination as 1st line therapy. The median patient age was 62 years (32–87). The average dose of PLD was 40.4 mg/m2 (35–50) every 28 days for an average of 4.01 cycles (1–23). Efficacy was evaluated using clinical symptoms and/or radiological evaluation. A majority of patients (69%) benefited from therapy characterized as disease stabilization or better. Overall the frequency of adverse events, in these heavily pretreated patients, was similar to that observed in a previous phase III clinical trial (Gordon JCO 2001) where patients had received only one prior therapy. However, the incidence of some grade 3/4 toxicities was substantially decreased, thus grade 3/4 PPE and mucositis were reduced from 21% to 4% and 8% to 3%, respectively. Conclusions: The nursing support program helped to reduce the severity of PPE and mucositis in patients receiving PLD for recurrent epithelial ovarian cancer. No significant financial relationships to disclose.

Sub-optimal drug treatment of diabetes and cardiovascular risk in diabetic patients in Turkey. A countrywide survey

The present study is a snapshot of how diabetic patients are treated for diabetes and coexisting cardiovascular risk factors in Turkey. We also addressed the question of what percentage of these patients are treated appropriately according to the current guidelines. Next step will be to determine which pharmacological treatment strategies affect mortality and morbidity in these patients and whether there are regional differences in these outcomes. To get a representative picture, Turkey was splitted into four parts with different ethnic and socioeconomic features then centers were randomized within each of these parts. Number of the centers in a region were calculated according to the population of that region. 305 physicians in 11 cities participated in data collection during a period of 3 months. Consecutive 2226 diabetic patients patients who were above 55 years of age were included. Detailed information was obtained about the demographic features and the cardiovascular risk factor and diabetes status of the patients together with relevant drug treatment. Laboratory analyses were done locally and recorded if performed during the last 3 months. Most patients were treated with oral antidiabetic monotherapy regardless of diabetes duration, metabolic control and complication and cardiovascular risk factor status. There was a trend among physicians except for endocrinologists to underprescribe insulin. Monotherapy also was the main mode of treatment for hypertension. Angiotensin converting enzyme inhibitors were generally not used as first line treatment contrary to the recommendations and angiotensin converting enzyme inhibitors and angiotensin receptor blockers are not prescribed for renoprotection in microalbuminuric patients. Statins, fibrates, metformin and aspirin were largely underused. The present study indicates that diabetic patients are undertreated in Turkey. Therefore every effort should be spent to implement current guidelines in diabetic patients in order to prevent macro and microvascular complications of diabetes.