Key performance indicators for pharmaceutical services: A systematic review.

Background: Key performance indicators (KPIs) are a set of indicators that improve the quality of services provided by pharmacists. They enable the monitoring and evaluation of result progress and optimize decision-making for stakeholders. Currently, there is no systematic review regarding KPIs for pharmaceutical services. Objectives: To identify and assess the quality of KPIs developed for pharmaceutical services. Methods: A systematic review was conducted in PubMed, Scopus, EMBASE, and LILACS from the inception of the database until February 5th, 2024. Studies that developed a set of KPIs for pharmaceutical services were included. The indicators were evaluated using the Appraisal of Indicators through Research and Evaluation (AIRE) instrument. Two independent reviewers performed the study selection, data extraction, and quality assessment. Results: Fifteen studies were included. The studies were conducted in different regions, most of which were developed for clinical services in hospitals or ambulatory settings, and used similar domains for the development of KPIs such as medication review, patient safety, and patient counseling. Literature review combined with the Delphi technique was the method most used by the studies, with content validity by inter-rater agreement. Regarding methodological quality, most studies described information on the purpose, definition, and stakeholders' involvement in the set of KPIs. However, little information was observed on the strategy for risk adjustment, instructions for presenting and interpreting the indicator results, the detailed description of the numerator and denominator, evidence scientific, and the feasibility of the set of KPIs. Only one study achieved a high methodological quality in all domains of the AIRE tool. Conclusion: Our findings showed the potential of KPIs to monitor and assess pharmacy practice quality. Future studies should expand KPIs for other settings, explore validity evidence of the existing KPIs, provide detailed descriptions of evidence, formulation, and usage, and test their feasibility in daily practice.

Towards inclusive healthcare: Pharmacists' perceptions on academic preparedness and healthcare provision for the LGBTQIA+ community.

BACKGROUND: The community of lesbian, gay, bisexual, transgender, queer, intersex, asexual and other identities (LGBTQIA+), comprising sexual and gender minorities, frequently encounters violence, discrimination, and numerous obstacles in accessing healthcare services. Pharmacists have the potential to significantly contribute to the healthcare provision for this community. OBJECTIVE: To assess pharmacists' perceptions regarding academic preparedness and healthcare provision for the LGBTQIA+ community in Brazil. METHODS: An online cross-sectional survey was conducted from August 2022 to February 2023, focusing on the academic training of pharmacists and the provision of healthcare to the LGBTQIA+ community in Brazil. Data collection was achieved through a 28-question online questionnaire, comprising both closed-ended questions and Likert-type items. The study variables were subjected to an exploratory descriptive analysis. RESULTS: We received 261 complete and valid responses. A majority of pharmacists indicated that they provided healthcare to the LGBTQIA+ community (n = 161, 61.7%); however, they lacked formal education on LGBTQIA+ healthcare during their pharmacy program (n = 256, 98.1%). Most participants strongly agreed that pharmacists play a crucial role in promoting healthcare for this community (n = 213, 81.6%). However, only a small percentage felt confident in addressing issues related to the effectiveness and safety of hormone use for transgender patients (n = 38, 14.6%). Furthermore, less than a third believed that the healthcare provided by pharmacists should be differentiated for patients within and outside of the LGBTQIA+ community (n = 76, 29.1%). CONCLUSION: The results of this study underscore the necessity and significance of incorporating this topic both in pharmacy training and continuing education. This approach is crucial to enhance and bolster the clinical practice of pharmacists.

Role of pharmacist in the management of Hansen's Disease: A scoping review.

Background: Stakeholders and healthcare professionals have an essential role in the elimination of Hansen's Disease. Of these, pharmacists provide core services that assist the management of these patients with the supply of medicines and clinical actions. Objectives: To summarize evidence on the role of pharmacist in the management of Hansen's Disease. Methods: A literature search was performed in MEDLINE, Embase, Scopus, Web of Sciences, LILACS, and Google Scholar for studies published until September 29th, 2022 without language restriction. Studies that reported actions provided by pharmacists in the management of patients with Hansen's Disease were included. The pharmacist interventions identified in the studies were described based on key domains in DEPICT v.2. Two independent reviewers performed study selection and data extraction and any disagreements were resolved by third and fourth authors. Results: A total of 751 records were identified, of which 8 studies fully met the eligibility criteria. Most of them were conducted in Brazil (n = 5), in an ambulatory setting (n = 8) and the most common study design was descriptive cross-sectional (n = 6). Different roles of pharmacists were identified, such as medication review, therapeutic drug monitoring, patient education, drug information, and dispensing. All studies described pharmacist interventions for patients through one-on-one contact and face-to-face. Pharmacists were responsible for patient counseling (n = 8), suggestions for change in therapy (n = 2), and monitoring results report (n = 2). The studies reported benefits associated with pharmacist interventions, despite the limited descriptions regarding these actions. Conclusions: Few studies that described the activities of pharmacists in the management of Hansen's Disease were found. As the studies did not offer a satisfactory level of description and quality, further research should be conducted to strengthen this field.

Prevalence and incidence of depressive symptoms in pharmacy students: A systematic review.

BACKGROUND: Pharmacy students are at high risk of developing depressive symptoms that can adversely influence their professional future. However, there are no summarized data on the subject. OBJECTIVE: To summarize the prevalence and incidence of depressive symptoms in pharmacy students. METHODS: A literature search was performed using PubMed, PsycINFO, CINAHL, LILACS, and SCOPUS databases until January 2022. We included observational studies that assessed the prevalence or incidence of depressive symptoms among pharmacy students using a validated screening instrument. Two independent investigators performed the study selection, data extraction, and quality assessment using the Joanna Briggs Institute (JBI) checklist for prevalence studies. The estimate of depressive symptoms was summarized as a narrative synthesis using structured tables. RESULTS: Of the 695 records retrieved in the search, 19 studies met the eligibility criteria. All were cross-sectional studies, published between 2009 and 2022. The number of pharmacy students ranged from 30 to 610. Most studies were conducted in Asia (n = 9) and the Americas (n = 7), and included only public university students (n = 12). The studies used several instruments to screen students for depressive symptoms, mainly Patient Health Questionnaire-9 (n = 7), Beck Depression Inventory (n = 5), and Depression, Anxiety, and Stress Scale 21 (n = 4). Most studies (n = 15) evaluated only the prevalence of depressive symptoms. The estimate of overall, mild, moderate, and severe depressive symptoms ranged from 4.8% to 78.8%, 9.1% to 42.1%, 5.8% to 30.0%, and 0% to 50.0%, respectively. Regarding methodological quality, the score ranged from 4 to 7 out of 9 points according to the JBI checklist. CONCLUSION: A high proportion of depressive symptoms were observed in pharmacy students. This finding points to the urgent need to develop strategies for screening, early identification of symptoms, and intervention to improve the mental health of students.

Influence of Genetic Polymorphisms on the Pharmacokinetics of Trazodone Hydrochloride: A Scoping Review and Future Perspective.

BACKGROUND: Trazodone hydrochloride is an antidepressant used in clinical practice. As a substrate of cytochrome P450 enzymes that is vulnerable to P-glycoprotein transport, several factors can alter its plasma concentration, and hence, dose adjustment may be required. The aim of this scoping review was to identify genetic polymorphisms that influence the pharmacokinetics of trazodone hydrochloride. METHODS: A literature search was performed using PubMed, PubMed Central, BVS/BIREME, EBSCOhost, Web of Science, Embase, Cochrane Library, and Medline databases for studies published until August 2021. The search strategy was based on the following keywords: Trazodone OR "m-chlorophenyl piperazine" AND "Pharmacogenetics" OR "Genetics" OR "Cytochrome P-450 Enzyme System" OR "Polymorphism, Single Nucleotide" OR "Polymorphism, Genetic." RESULTS: The search retrieved 684 candidate articles; 307 duplicates were eliminated. In total, 377 articles were eligible for the first screen. However, only 4 met the eligibility criteria, and 12 polymorphisms in 5 different genes (CYP2D6, CYP1A2, CYP3A4, CYP3A5, and ABCB1). Notably, only C3435T ABCB1 influenced the pharmacokinetics of trazodone hydrochloride. Individuals with the T/T genotype had lower area under the curve, half-life, and maximum concentration values with a higher clearance rate. CONCLUSIONS: Polymorphisms in CYP450 do not seem to directly influence the pharmacokinetics of trazodone hydrochloride or its metabolites. By contrast, genetic polymorphisms in ABCB1 seem to have an important effect on the pharmacokinetics of trazodone hydrochloride by enhancing drug metabolism and elimination.

Use of cannabis in the treatment of animals: a systematic review of randomized clinical trials.

Cannabis is used in the treatment of several human conditions; however, its use is still less explored in veterinary medicine. This systematic review aims to summarize the evidence of efficacy and safety of the use of cannabis for the treatment of animal disease. A literature search was performed for studies published until 16 March 2021 in five databases. Randomized clinical trials (RCTs) that reported the efficacy or safety of cannabis in the treatment of animal disease were included. The RoB 2 Tool was used to assess the risk of bias. A total of 2427 records were identified, of which six studies fully met the eligibility criteria. RCTs were conducted in dogs with osteoarthritis (n = 4), with epilepsy (n = 1), and with behavioral disorders (n = 1). All studies used cannabidiol (CBD) oil in monotherapy or in combination with other drugs. Studies used CBD at 2 or 2.5 mg kg-1 twice daily (n = 4), orally (n = 5), during 4 or 6 weeks (n = 3), and compared CBD with placebo (n = 5). CBD significantly reduced pain and increased activity in dogs with osteoarthritis (n = 3). Moreover, CBD significantly reduced the frequency of seizures in dogs with epilepsy (n = 1) and the aggressive behavior of dogs (n = 1). Although promising results were identified, studies were heterogeneous and presented risks of bias that required caution in the interpretation of findings. Therefore, there was some evidence to support the use of CBD in dogs with osteoarthritis to reduce pain and increased activity, but limited evidence against epilepsy and behavioral problems. In addition, CBD was well tolerated with mild adverse effects. More RCTs with high quality of evidence are needed, including greater numbers of animal subjects, additional species, and clear readout measures to confirm these findings.

Contribution of MicroRNAs in Chemoresistance to Cisplatin in the Top Five Deadliest Cancer: An Updated Review.

Cisplatin (DDP) is a well-known anticancer drug used for the treatment of numerous human cancers in solid organs, including bladder, breast, cervical, head and neck squamous cell, ovarian, among others. Its most important mode of action is the DNA-platinum adducts formation, inducing DNA damage response, silencing or activating several genes to induce apoptosis; these mechanisms result in genetics and epigenetics modifications. The ability of DDP to induce tumor cell death is often challenged by the presence of anti-apoptotic regulators, leading to chemoresistance, wherein many patients who have or will develop DDP-resistance. Cancer cells resist the apoptotic effect of chemotherapy, being a problem that severely restricts the successful results of treatment for many human cancers. In the last 30 years, researchers have discovered there are several types of RNAs, and among the most important are non-coding RNAs (ncRNAs), a class of RNAs that are not involved in protein production, but they are implicated in gene expression regulation, and representing the 98% of the human genome non-translated. Some ncRNAs of great interest are long ncRNAs, circular RNAs, and microRNAs (miRs). Accumulating studies reveal that aberrant miRs expression can affect the development of chemotherapy drug resistance, by modulating the expression of relevant target proteins. Thus, identifying molecular mechanisms underlying chemoresistance development is fundamental for setting strategies to improve the prognosis of patients with different types of cancer. Therefore, this review aimed to identify and summarize miRs that modulate chemoresistance in DDP-resistant in the top five deadliest cancer, both in vitro and in vivo human models.

Differentially expressed plasmatic microRNAs in Brazilian patients with Coronavirus disease 2019 (COVID-19): preliminary results.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is known that host microRNAs (miRNAs) can be modulated to favor viral infection or to protect the host. Herein, we report preliminary results of a study aiming at identifying differentially expressed plasmatic miRNAs in Brazilian patients with COVID-19. METHODS AND RESULTS: miRNAs were extracted from the plasma of eight patients with COVID-19 (four patients with mild COVID-19 and four patients with severe/critical COVID-19) and four healthy controls. Patients and controls were matched for sex and age. miRNA expression levels were detected using high-throughput sequencing. Differential miRNA expression and enrichment analyses were further evaluated. A total of 18 miRNAs were differentially expressed between patients with COVID-19 and controls. miR-4433b-5p, miR-6780b-3p, miR-6883-3p, miR-320b, miR-7111-3p, miR-4755-3p, miR-320c, and miR-6511a-3p were the most important miRNAs significantly involved in the PI3K/AKT, Wnt/ß-catenin, and STAT3 signaling pathways. Moreover, 42 miRNAs were differentially expressed between severe/critical and mild patients with COVID-19. miR-451a, miR-101-3p, miR-185-5p, miR-30d-5p, miR-25-3p, miR-342-3p, miR-30e-5p, miR-150-5p, miR-15b-5p, and miR-29c-3p were the most important miRNAs significantly involved in the Wnt/ß-catenin, NF-κß, and STAT3 signaling pathways. CONCLUSIONS: If validated by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in a larger number of participants, the miRNAs identified in this study might be used as possible biomarkers for the diagnosis and severity of COVID-19.

Assessment of Renal Function in Head and Neck Cancer Patients Treated with Cisplatin: Different Biomarkers and Acute Kidney Injury Classifications.

Cisplatin is associated with dose-limiting nephrotoxicity, and the timely detection of acute kidney injury (AKI) can affect morbimortality. Therefore, this study aimed to investigate the tools for monitoring renal function in AKI. This was a retrospective, cohort study. Cisplatin-treated patients with head and neck cancer were included. Nephrotoxicity was assessed using serum creatinine, estimated creatinine clearance, serum electrolytic alterations, and plasma kidney injury molecule-1 (KIM-1). The toxicity severity was classified according to Common Terminology Criteria for Adverse Events (CTCAE), and AKI was classified by Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN). A total of 81 participants were included, of whom only 32 did not have AKI. Almost 90% of participants had a decreased estimated glomerular filtration rate five (D5) days after chemotherapy. The AKI estimate differs between AKIN and RIFLE; more participants were diagnosed by the RIFLE at D5, 19.5% versus 2.4% by AKIN, and fifteen had a discordance between these classifications. All laboratory markers showed significant changes on D5. KIM-1 appeared a possible biomarker when considering CTCAE or AKIN classifications (p < 0.05 on D5), but not when RIFLE classification was used (p = 0.0780). Further studies may seek to understand the profiles of different biomarkers together.

Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses.

PURPOSE: To summarize the evidence of efficacy and safety of the use of ketamine and esketamine for depression. METHODS: A literature search was performed in Medline, the Cochrane Library, LILACS, and CRD until November 2020. We included systematic reviews with meta-analyses of randomized controlled trials on the use of ketamine and esketamine in adult patients with depression. Two authors independently performed the study selection and data extraction. The AMSTAR-2 tool was used to appraise the quality of included reviews. RESULTS: A total of 118 records were identified, and 11 studies fully met the eligibility criteria. Compared to control, ketamine improved the clinical response at 40 min to 1 week and clinical remission at 80 min to 72 h, and esketamine improved both outcomes at 2 h to 4 weeks. Ketamine and esketamine also had a beneficial effect on the depression scales score and suicidality. For adverse events, oral ketamine did not show significant change compared to control, while intranasal esketamine showed difference for any events, such as dissociation, dizziness, hypoesthesia, and vertigo. Most reviews were classified as "critically low quality," and none of them declared the source of funding of the primary studies and assessed the potential impact of risk of bias in primary studies. CONCLUSION: Ketamine and esketamine showed a significant antidepressant action within a few hours or days after administration; however, the long-term efficacy and safety are lacking. In addition, the methodological quality of the reviews was usually critically low, which may indicate the need for higher quality evidence in relation to the theme.

Dysregulated MicroRNAs as Biomarkers or Therapeutic Targets in Cisplatin-Induced Nephrotoxicity: A Systematic Review.

The purpose of this systematic review was to map out and summarize scientific evidence on dysregulated microRNAs (miRNAs) that can be possible biomarkers or therapeutic targets for cisplatin nephrotoxicity and have already been tested in humans, animals, or cells. In addition, an in silico analysis of the two miRNAs found to be dysregulated in the majority of studies was performed. A literature search was performed using eight databases for studies published up to 4 July 2021. Two independent reviewers selected the studies and extracted the data; disagreements were resolved by a third and fourth reviewers. A total of 1002 records were identified, of which 30 met the eligibility criteria. All studies were published in English and reported between 2010 and 2021. The main findings were as follows: (a) miR-34a and miR-21 were the main miRNAs identified by the studies as possible biomarkers and therapeutic targets of cisplatin nephrotoxicity; (b) the in silico analysis revealed 124 and 131 different strongly validated targets for miR-34a and miR-21, respectively; and (c) studies in humans remain scarce.

Adverse Drug Event-Related Admissions to a Pediatric Emergency Unit.

OBJECTIVES: The objectives of this study were to analyze adverse drug events (ADEs) related to admissions to a pediatric emergency unit and to identify the associated risk factors. METHODS: This was a prospective study. Demographic data and details of medications were collected for each patient admitted. Case studies were performed by clinical pharmacists and the clinical team to discuss whether the admission was due to an ADE and to characterize the ADE. Multivariate logistic regression was used for statistical analysis. RESULTS: In total, 1708 pediatric patients were included in this study. Adverse drug events were the cause of hospital admission in 12.3% of the studied population. The majority of patients presenting with an ADE were in the age group of 0 to 5 years (61.6%), had a mean ± SD age of 4.9 ± 3.9 years, were female (51.2%), were Caucasian (72.0%), and had infectious disorders (49.3%). High frequencies of medication errors (68.8%), use of drugs to treat respiratory disorders (27.7%), and ADEs of mild severity (75.3%) were reported. The risk of being admitted to the pediatric emergency unit for any ADE increased in cases of neurological (odds ratio [OR], 4.63; 95% confidence interval [CI], 2.38-8.99), dermatological (OR, 3.16; 95% CI, 1.93-5.18), and respiratory (OR, 3.02; 95% CI, 1.89-4.83) disorders. CONCLUSIONS: A high frequency of ADE-related admissions to the pediatric emergency unit was observed. The risk of being admitted to the pediatric emergency unit for any ADE increased in cases of neurological, dermatological, and respiratory disorders. Clinical pharmacists play an important role in the identification of ADEs and the education of child caregivers and health care providers concerning pediatric medication.

Role of pharmacist during the COVID-19 pandemic: A scoping review.

BACKGROUND: Since the start of the new Coronavirus (COVID-19) outbreak in December 2019, pharmacists worldwide are playing a key role adopting innovative strategies to minimize the adverse impact of the pandemic. OBJECTIVES: To identify and describe core services provided by the pharmacist during the COVID-19 pandemic. METHODS: A literature search was performed in MEDLINE, Embase, Scopus, and LILACS for studies published between December 1st, 2019 and May 20th, 2020 without language restriction. Studies that reported services provided by pharmacists during the COVID-19 pandemic were included. Two independent authors performed study selection and data extraction with a consensus process. The pharmacist's intervention identified in the included studies were described based on key domains in the DEPICT v.2. RESULTS: A total of 1189 records were identified, of which 11 studies fully met the eligibility criteria. Most of them were conducted in the United States of America (n = 4) and China (n = 4). The most common type of publication were letters (n = 4) describing the workplace of the pharmacist in hospitals (n = 8). These findings showed the different roles of pharmacists during the COVID-19 pandemic, such as disease prevention and infection control, adequate storage and drug supply, patient care and support for healthcare professionals. Pharmacists' interventions were mostly conducted for healthcare professionals and patients (n = 7), through one-to-one contact (n = 11), telephone (n = 6) or video conference (n = 5). The pharmacists' main responsibility was to provide drug information for healthcare professionals (n = 7) as well as patient counseling (n = 8). CONCLUSIONS: A reasonable number of studies that described the role of the pharmacists during the COVID-19 pandemic were found. All studies reported actions taken by pharmacists, although without providing a satisfactory description. Thus, future research with more detailed description as well as an evaluation of the impact of pharmacist intervention is needed in order to guide future actions in this and/or other pandemic.

FAS and FASL variations in outcomes of tobacco- and alcohol-related head and neck squamous cell carcinoma patients.

Radiotherapy and cisplatin lead to cell killing in head and neck squamous cell carcinoma patients, but adverse events and response to treatment are not the same in patients with similar clinicopathological aspects. The aim of this prospective study was to evaluate the roles of TP53 c.215G > C, FAS c.-671A > G, FAS c.-1378G > A, FASL c.-844 C > T, CASP3 c.-1191A > G, and CASP3 c.-182-247G > T single nucleotide variants in toxicity, response rate, and survival of cisplatin chemoradiation-treated head and neck squamous cell carcinoma patients. Genomic DNA was analyzed by polymerase chain reaction for genotyping. Differences between groups of patients were analyzed by chi-square test or Fisher's exact test, multiple logistic regression analysis, and Cox hazards model. One hundred nine patients with head and neck squamous cell carcinoma were enrolled in study. All patients were smokers and/or alcoholics. Patients with FAS c.-671GG genotype, FAS c.-671AG or GG genotype, and FASL c.-844CC genotype had 5.52 (95% confidence interval (CI): 1.42-21.43), 4.03 (95% CI: 1.51-10.79), and 5.77 (95% CI: 1.23-27.04) more chances of presenting chemoradiation-related anemia of grades 2-4, lymphopenia of grade 3 or 4, and ototoxicity of all grades, respectively, than those with the remaining genotypes. FAS c.-671GG genotype was also seen as an independent predictor of shorter event-free survival (hazard ratio (HR): 2.05; P = 0.007) and overall survival (HR: 1.83; P = 0.02) in our head and neck squamous cell carcinoma patients. These findings present, for the first time, preliminary evidence that inherited abnormalities in apoptosis pathway, related to FAS c.-671A > G and FASL c.-844 C > T single nucleotide variants, can alter toxicity and survival of tobacco- and alcohol-related head and neck squamous cell carcinoma patients homogeneously treated with cisplatin chemoradiation.

Role of epigenetic mechanisms in cisplatin-induced toxicity.

Cisplatin (CDDP) is a highly effective antineoplastic agent, widely used in the treatment of various malignant tumors. However, its major problems are side effects associated to toxicity. Considerable inter-individual differences have been reported for CDDP-induced toxicity due to genetic and epigenetic factors. Genetic causes are well described; however, epigenetic modifications are not fully addressed. In the last few years, many evidences were found linking microRNA to the development of CDDP-mediated toxicity, particularly nephrotoxicity. In this review, we described how genetic and epigenetic modifications can be important determinants for the development of toxicity in patients treated with CDDP, and how these alterations may be interesting biomarkers for monitoring toxicity induced by CDDP. Considering the validation in different studies, we suggest that miR-34a, -146b, -378a, -192, and -193 represent an attractive study group to evaluate potential biomarkers to detect CDDP-related nephrotoxicity.

Colistin and polymyxin B for treatment of nosocomial infections in intensive care unit patients: pharmacoeconomic analysis.

Background The emergence and rapid spread of multidrug-resistant gram-negative bacteria related to nosocomial infections is a growing worldwide problem, and polymyxins have become important due to the lack of new antibiotics. Objectives To evaluate the outcomes and pharmacoeconomic impact of using colistin and polymyxin B to treat nosocomial infections. Setting Neurosurgical, cardiovascular, or transplantation intensive care unit (ICU) at the Clinical Hospital of the University of Campinas (São Paulo, Brazil). Method A retrospective cohort study was conduct in patients in the ICU. The renal function was determined daily during treatment by measuring the serum creatinine. A cost minimization analysis was performed to compare the relative costs of treatment with colistin and polymyxin B. Main outcomes measure The outcomes were 30-day mortality and frequency and onset of nephrotoxicity after beginning treatment. Results Fifty-one patients treated with colistin and 51 with polymyxin B were included. 30-day mortality was observed in 25.49% and 33.33% of patients treated with colistin and polymyxin B, respectively; Nephrotoxicity was observed in 43.14% and 54.90% of patients in colistin and polymyxin B groups, respectively; and onset time of nephrotoxicity was 9.86 ± 13.22 days for colistin and 10.68 ± 9.93 days for polymyxin B group. Colistin treatment had a lower cost per patient compared to the cost for polymyxin B treatment (USD $13,389.37 vs. USD $13,639.16, respectively). Conclusion We found no difference between 30-day mortality and nephrotoxicity between groups; however, colistin proved to be the best option from a pharmacoeconomic point of view.

Polymorphisms in DNA mismatch repair pathway genes predict toxicity and response to cisplatin chemoradiation in head and neck squamous cell carcinoma patients.

Head and neck squamous cell carcinoma (HNSCC) is treated with cisplatin (CDDP) and radiotherapy (RT), and distinct results are observed among patients with similar clinicopathological aspects. This prospective study aimed to investigate whether MLH1 c.-93G>A (rs1800734), MSH2 c.211+9C>G (rs2303426), MSH3 c.3133G>A (rs26279), EXO1 c.1765G>A (rs1047840), and EXO1 c.2270C>T (rs9350) single nucleotide polymorphisms (SNPs) of the mismatch repair (MMR) pathway change side effects and response rate of 90 HNSCC patients treated with CDDP and RT. DNA from peripheral blood was analyzed by PCR-based methods to obtain genotypes. It was observed 4.27-fold and 4.69-fold increased risks of presenting pronounced nephrotoxicity with treatment in patients with MSH3 GG and EXO1 rs9350 CC genotypes compared with patients with GA or AA and CT or TT genotypes, respectively. MSH3 GG or GA and GT haplotype of EXO1 rs1047840 and rs9350 SNPs conferred to patients 10.29 and 4.00 more chances of presenting pronounced ototoxicity after treatment than MSH3 AA genotype and other EXO1 haplotypes, respectively. Patients with EXO1 rs1047840 GA or AA genotype and AC haplotype of EXO1 rs1047840 and rs9350 SNPs had both 9.55-fold increased risks of achieving partial response or stable disease instead of complete remission after treatment than patients with EXO1 GG genotype and other EXO1 haplotypes, respectively. For the first time, our data show preliminary indication that inherited alterations of DNA MMR pathway, related to MSH3 rs26279, EXO1 rs1047840 and EXO1 rs9350 SNPs, modify toxicity and response to chemoradiation in HNSCC, and may contribute to future personalized treatment of patients.

Leukocytoclastic vasculitis complicating cisplatin + radiation treatment for laryngeal cancer: a case report.

BACKGROUND: Leukocytoclastic vasculitis is typically mediated by deposition of immune complexes and is related to many causes, including medication. To the best of our knowledge, leukocytoclastic vasculitis related to cisplatin has not yet been described in the scientific literature. CASE PRESENTATION: We report a rare case of leukocytoclastic vasculitis after the first cycle of high-dose cisplatin chemotherapy in a patient with larynx carcinoma. A 48-year-old Caucasian man with larynx carcinoma received a high-dose of cisplatin monochemotherapy (100 mg/m2 every 21 days), along with 70 Gy of radiotherapy divided into 35 sessions, as a therapeutic schedule. Twelve days after the first chemotherapy administration and after 8 sessions of radiotherapy (total of 16 Gy), the patient presented with acute onset of palpable purpura in the lower limbs. The patient was hospitalized for 10 days, and during this period, he underwent several examinations to rule out infectious, autoimmune, and neoplastic disorders. A skin biopsy showed leukocytoclastic vasculitis with a positive pattern for IgM and C3, as detected through direct immunofluorescence. Twenty-five days after cisplatin administration, the chemotherapy regimen was changed to carboplatin AUC 5, and the episodes of purpura ceased, reinforcing the hypothesis of an adverse reaction to cisplatin. CONCLUSIONS: Cisplatin can induce leukocytoclastic vasculitis and clinicians should be aware of this potential effect for better case management and diagnosis.