Drug Of Choice Research Articles

Advances in Therapeutics to Alleviate Cognitive Decline and Neuropsychiatric Symptoms of Alzheimer’s Disease

Dementia exists as a ‘progressive clinical syndrome of deteriorating mental function significant enough to interfere with activities of daily living’, with the most prevalent type of dementia being Alzheimer’s disease (AD), accounting for about 80% of diagnosed cases. AD is associated with an increased risk of comorbidity with other clinical conditions such as hypertension, diabetes, and neuropsychiatric symptoms (NPS) including, agitation, anxiety, and depression as well as increased mortality in late life. For example, up to 70% of patients diagnosed with AD are affected by anxiety. As aging is the major risk factor for AD, this represents a huge global burden in ageing populations. Over the last 10 years, significant efforts have been made to recognize the complexity of AD and understand the aetiology and pathophysiology of the disease as well as biomarkers for early detection. Yet, earlier treatment options, including acetylcholinesterase inhibitors and glutamate receptor regulators, have been limited as they work by targeting the symptoms, with only the more recent FDA-approved drugs being designed to target amyloid-β protein with the aim of slowing down the progression of the disease. However, these drugs may only help temporarily, cannot stop or reverse the disease, and do not act by reducing NPS associated with AD. The first-line treatment options for the management of NPS are selective serotonin reuptake inhibitors/selective noradrenaline reuptake inhibitors (SSRIs/SNRIs) targeting the monoaminergic system; however, they are not rational drug choices for the management of anxiety disorders since the GABAergic system has a prominent role in their development. Considering the overall treatment failures and side effects of currently available medication, there is an unmet clinical need for rationally designed therapies for anxiety disorders associated with AD. In this review, we summarize the current status of the therapy of AD and aim to highlight novel angles for future drug therapy in our ongoing efforts to alleviate the cognitive deficits and NPS associated with this devastating disease.

Association between plasma imatinib levels and response to treatment of chronic myeloid leukemia in patients from Manaus, Brazil.

Imatinib mesylate (IM) is the drug of choice for the treatment of chronic myeloid leukemia (CML). However, despite most of the results obtained with this therapy being positive, some patients still present a suboptimal therapeutic response or still develop some type of resistance. Therefore, the aim of this study was to evaluate IM plasma levels in CML patients treated at a referral unit in Manaus and correlate them with variables that might interfere with these levels. Data from 52 patients were obtained through a standardized questionnaire containing clinical, sociodemographic, lifestyle, and use of other medication information, as well as an estimate of therapeutic adherence. Additionally, blood collection was performed to measure the plasma concentration of the drug using the HPLC-UV technique. Molecular studies were done to identify the presence of polymorphism in the ABCG2 C421A membrane transporter. Most patients were male with a mean age of 52 ± 12.3 years (95% CI 49.0-55.9). There was a high variation in drug concentrations in the range from 0 to 4694 ng/mL, with a mean of 1558.59 ± 989.79 ng/mL (95% CI 1283.0-1834.1). Approximately two-thirds of patients were classified in the drug-level range considered therapeutic, and there was a correlation between plasma concentration and higher molecular response. Additionally, most individuals had the normal genotype for the ABCG2 C421A polymorphism but further studies should be performed to reveal the role of this variable in the outcome of the disease in this population.

Aseptic necrosis of the femoral head

The article discusses the historical aspects of the study of aseptic necrosis, as well as the issues of therapy and early diagnosis of aseptic necrosis of the femoral head. The authors raise the issues of pathogenesis and discuss the factors influencing its development. So it is believed that the leading factors are excessive alcohol consumption, deep-sea diving and some autoimmune diseases. Attention is also paid to the long-term consequences of COVID-19 infection, in which significant complications from the musculoskeletal system are observed, including aseptic necrosis of the femoral head. The consequences of infection can be triggered both by the inflammatory process itself and as a high risk of complications during glucocorticosteroid therapy. The article focuses on the clinic of aseptic necrosis of the femoral head and its difference from the clinic of osteoarthritis. As well as the importance of early diagnosis of aseptic necrosis of the femoral head. The article discusses the issues of drug therapy, indications for it and the choice of drugs. The article provides a clinical example that demonstrates the importance of careful collection of complaints and anamnesis in a young patient with atypical hip pain, as well as the effectiveness of prescribed therapy according to clinical recommendations. A specific example demonstrates not only the importance of using magnetic resonance imaging in the diagnosis of aseptic necrosis of the femoral head, but also the effectiveness and safety of therapy. The possible synergism and pleiotropic effects of the prescribed therapy are also discussed. The emphasis is on the importance of further research to develop indications and criteria for the effectiveness of therapy for aseptic necrosis of the femoral head.

An effective complex approach to the management of patients with chronic musculoskeletal low back pain and pains in other body sites

Low back pain (LBP) is a major public health problem globally. As life expectancy increases, the number of people with LBP will further increase in the coming decades. LBP is the leading cause of work productivity and activity impairment worldwide, therefore training of neurologists, primary care physicians, and general practitioners for timely and accurate diagnosis of LBP, as well as effective treatment of patients with LBP is an economically and socially significant challenge for medical practice. The clinical case describes the successful management of a female patient with LBP. It provides a modern, clear and effective approach to the diagnosis and treatment of musculoskeletal LBP. The typical comorbid disorders and factors that contribute to the pain syndrome chronicity are presented. The female patient was treated using a complex approach that included disease awareness conversations, kinesiotherapy, and pharmacotherapy in the form of a 10-day nonsteroidal anti-inflammatory drug (NSAID) course. Nimesil (nimesulide) with proven efficacy and safety in the treatment of musculoskeletal pain has become a drug of choice. It should be noted that nimesulide was prescribed to the patient from the first days of treatment concurrently with the beginning of a training course in kinesiology. The patient experienced a rapid pain relief while taking pharmacotherapy, which played an important role in supporting adherence to recommendations for increasing physical activity and taking training courses in kinesiology. The patient reported a significant decrease in pain on Day 10. After 1.5-month treatment, the pain regressed and she returned to her normal daily activities. The presented approach to therapy allows to provide LBP patients with a relatively fast pain relief, and the 6-month follow up period demonstrated sustainability of the therapeutic effect achieved.

Determination of drug-related problems in the hematology service: a prospective interventional study

BackgroundPatients with hematological malignancies often require multidrug therapy using a variety of antineoplastic agents and supportive care medications. This increases the risk of drug-related problems (DRPs). Determining DRPs in patients hospitalized in hematology services is important for patients to achieve their drug treatment goals and prevent adverse effects. This study aims to identify DRPs by the clinical pharmacist in the multidisciplinary team in patients hospitalized in the hematology service of a university hospital in Turkey.MethodsThis study was conducted prospectively between December 2022 and May 2023 in the hematology service of Suleyman Demirel University Research and Application Hospital in Isparta, Turkey. DRPs were determined using the Pharmaceutical Care Network Europe (PCNE) 9.1 Turkish version.ResultsThis study included 140 patients. Older age, longer hospital stay, presence of acute lymphoblastic leukemia, presence of comorbidities, higher number of medications used, and polypharmacy rate were statistically significantly higher in the DRP group than in the non-DRP group (p < 0.05). According to multivariate logistic regression analysis, the probability of DRP in patients with polypharmacy was statistically significant 7.921 times (95% CI: 3.033–20.689) higher than in patients without polypharmacy (p < 0.001).Every 5-day increase in the length of hospital stay increased the likelihood of DRP at a statistically significant level (OR = 1.476, 95% CI: 1.125–1.938 p = 0.005). In this study, at least one DRP was detected in 69 (49.3%) patients and the total number of DRPs was 152. Possible or actual adverse drug events (96.7%) were the most common DRPs. The most important cause of DRPs was drug choice (94.7%), and the highest frequency within its subcategories was the combination of inappropriate drugs (93.4%).ConclusionsThis study shows the importance of including a clinical pharmacist in a multidisciplinary team in identifying and preventing DRPs in the hematology service.

Comparative evaluation of intensified short course regimen and standard regimen for adults TB meningitis: a protocol for an open label, multi-center, parallel arms, randomized controlled superiority trial (INSHORT trial)

BackgroundDespite several incremental improvements in the management of tuberculous meningitis (TBM), the mortality rates remain high. In spite of national and international guidelines, variation in the choice, dose, and duration of drugs exist between countries and clinicians. We propose to evaluate a shorter and more effective regimen containing agents with augmented intracerebral drug exposure and anti-inflammatory approaches to improve disability-free survival among patients with TBM. Our strategy incorporates the various developments in the field of TBM over the last two decades and only few trials have evaluated a composite of these strategies in the overall outcomes of TBM.MethodsAn open label, parallel arms, randomized controlled superiority trial will be conducted among 372 participants across 6 sites in India. Eligible participants will be randomly allocated in 1:1:1 ratio into one of the three arms. The intervention arm consists of 2 months of high-dose rifampicin (25 mg/kg), moxifloxacin (400 mg), pyrazinamide, isoniazid, aspirin (150 mg), and steroids followed by rifampicin, isoniazid, and pyrazinamide for 4 months. The second intervention arm includes all the drugs as per the first arm except aspirin and the patients in the control arm will receive treatment according to the National TB Elimination Program guidelines. All participants will be followed up for 1 year after the treatment. DiscussionCurrent WHO regimens have agents with poor central nervous system drug exposure and is too long. It does not reflect the accumulating evidence in the field. We propose a comprehensive clinical trial incorporating the emerging evidence accrued over the last two decades to shorten the duration and improve the treatment outcomes. This multi-centric trial may generate crucial evidence with policy and practice implications in the treatment of TBM.Trial registrationClinical Trial Registry India CTRI/2023/05/053314. Registered on 31 May 2023 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=ODYzMzg=&Enc=&userName=CTRI/2023/05/053314). ClinicalTrials.gov NCT05917340. Registered on 6 August 2023 (https://classic.clinicaltrials.gov/ct2/show/NCT05917340).Protocol versionVersion 1.3 dated 12 July 2023.

Consistent and informed choice of drug and route of administration is key to increasing adherence to osteoarthritis treatment

The need to follow an integrated approach when prescribing treatment for patients suffering from osteoarthritis (OA) is beyond doubt. It is clear that success depends on the implementation of recommendations for both lifestyle modification and the introduction of pharmacological agents with different compositions and mechanisms of action aimed at reducing pain, stiffness, inflammation, normalizing joint function, and preventing cartilage destruction. The arsenal of such drugs is increasing, and the evidence base of effectiveness and safety is being enriched. Considering the heterogeneity of OA patients seeking help in terms of gender, age, body mass index, financial wealth, comorbidity, clinical manifestations of the disease, radiological stage of the disease and its duration, experience of previous treatment, a reasonable and agreed upon choice with the patient not only of the drug is relevant, but also the method of administration. The article provides a clinical example of a justified and coordinated choice of treatment for a patient with a generalized form of OA, synovitis of the knee joint, suffering from obesity, depression, low adherence to treatment using the example of prescribing a chondroprotector, the active component of which is a bioactive extract from small sea fish. The treatment effect was confirmed by clinical and instrumental assessment methods over time.

Abstract PO2-06-06: Effectiveness and prognostic predictors of primary systemic therapy for de-novo Stage IV breast cancer - Supplementary analysis of JCOG1017 PRIM-BC

Abstract Background The optimal choice of drug is important in treating metastatic breast cancer, and the efficacy of the drug should be determined early, especially in cases of progression. On the other hand, untreated de novo Stage IV (dnST-IV) patients are expected to be more sensitive to drugs, but no detailed data are available. In JCOG1017 (Randomized trial of primary tumor resection in dnST-IV), dnST-IV patients were treated with primary systemic therapy for 3 months according to breast cancer subtypes before randomization. We already presented the results of primary endpoint. Primary tumor resection (PTR) could not significantly prolong the overall survival of de-novo stage IV breast cancer patients with sensitivity to primary systemic therapy. We conducted the supplementary analysis of JCOG1017 to clarify the efficacy of primary systemic therapy for dnST-IV and develop optimal treatment strategies for dnST-IV breast cancer. Methods In JCOG1017, systemic therapy was performed for each subtype/metastatic status as follows; 1) hormone therapy: ER+ HER2- and no life-threatening metastases, 2) weekly PTX therapy: life-threatening metastases, or ER-HER2-, 3) trastuzumab + pertuzumab + docetaxel (HPD) therapy OR trastuzumab + paclitaxel (HPTX) therapy: ER-HER2+. 4) hormone therapy: ER+HER2+ and no life-threatening metastases. The non-PD rate (no increase of more than 10% of the sum of the diameters of the target lesions compared before systemic therapy), the responses rate (cCR or cPR), and overall survival (OS) of responder (cCR or cPR)/non-responder (cSD or cPD) and PD/non-PD were examined. Results Among 569 patients who received primary systemic therapy in JCOG 1017, the non-PD rate was 77.2% and the response rate was 29.0% after 3 months of systemic therapy. By subtype, the non-PD rate was 78.2% for ER-HER2-, 75.4% for ER+HER2-, 92.9% for ER-HER2+, and 66.7% for ER+HER2+. The response rate was 36.4% for ER-HER2-, 13.4% for ER+HER2-, 81.0% for ER-HER2+, and 40.3% for ER+HER2+. In multivariable analysis, the non-PD rate was higher in postmenopausal (odds ratio [OR] 1.673, p=0.0240) and PgR-positive (OR 2.391, p= 0.0019) patients besides subtypes. Analysis results by drug were as follows; 1) hormone therapy (non-PD rate: 72.9%) was more effective for PgR-positive (OR 3.258, p&amp;lt; 0.0001), less effective for patients with visceral metastasis (OR 0.605, p=0.0334) and HER2-positive (OR 0.365, p=0.0016), 2) wPTX (non-PD rate: 76.1%) was no significant predictors of efficacy, 3) HPD/HPTX (non-PD rate: 92.7%) was more effective in patients with visceral metastasis (OR 15.818, p=0.0030). PD patients had much worse OS (hazard ratio [HR] 0.501, p&amp;lt; 0.0001) compared to non-PD, whereas responders had a little worse OS (HR 0.788, p=0.0538) compared to non-responders. Similar tendency was observed in any drug. Discussion Predictors of response to primary systemic therapy differed by subtype, with the need for treatment strategies tailored to PgR, HER2 expression, and the status of visceral metastasis. In the ER+HER2+ group, the efficacy of hormonal therapy alone was low, and combination therapy with molecular-targeted agents was considered necessary. The non-PD rate reflected prognosis in determining the efficacy of primary systemic therapy for dnST-IV. Citation Format: Tadahiko Shien, Akihiko Shimomura, Makoto Ishitobi, Kiyo Tanaka, Takahiro Tsukioki, Takashi Yamanaka, Fumitaka Hara, Kenjiro Aogi, Yasuhiro Yanagita, Michiko Tsuneizumi, Naohito Yamamoto, Hiroshi Matsumoto, Akihiko Suto, Ken-ichi Watanabe, Michiko Harao, Chizuko Kanbayashi, Mitsuya Ito, Keisei Anan, Shigeto Maeda, Keita Sasaki, Gakuto Ogawa, Haruhiko Fukuda, Hiroji Iwata. Effectiveness and prognostic predictors of primary systemic therapy for de-novo Stage IV breast cancer - Supplementary analysis of JCOG1017 PRIM-BC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-06-06.

Abstract PO5-16-08: Breast cancer in men: 15 years of experience in an oncology reference center in northern Mexico

Abstract Background Breast cancer in men accounts for about 1% of all breast cancers. Classic risk factors include increasing age, a family history of cancer, and mutations in predisposing genes. The alteration of the estrogen-androgen ratio has been as involved in the genesis of this cancer due to its increased risk in conditions such as liver dysfunction, obesity, marijuana use, thyroid disease, Klinefelter’s syndrome, hormonal therapies, orchitis, cryptorchidism, and testicular damage. Purpose Hereby we aim to update the analysis of the published demographic, clinical and treatment-related characteristics of this disease in our center including the last 15 years, as well as newly identified relevant variables that will serve as the basis for awareness and screening programmes for our population. Methods We performed a retrospective observational analysis of the medical records of men diagnosed with breast cancer that were treated in “Centro Universitario Contra el Cáncer” between January 2007 and December 2022. A total of seventeen cases of male breast cancer were included in the analysis. The variables included are age at diagnosis, body mass index, comorbidities, cigarette and alcohol use, method of diagnosis, histological type/grade, clinical stage, estrogen, progesterone, and human epidermal growth factor receptor-2 (HER2) receptor status, and treatment received. We also looked at the dates of symptom onset, diagnosis, and treatment to determine the intervals between these events. SPSS v25 software was used for data analysis. The Shapiro-Wilk test was employed to determine the normality of the variables. Variables with a normal distribution were described with median and interquartile range for the 25th and 75th percentiles. Categorical variables were expressed as absolute numbers and percentages. Results Although we found some similarities between the characteristics of our population and those reported in the American and European series, there were many significant differences. Mean age at diagnosis was 62.9 (±11.7) years, 5.5 years earlier than the reported age of 68.4 years. In terms of risk factors, our population was twice as likely to report a family history of cancer as the American series (41% vs. 15-20%). Overweight and obesity together accounted for 76.5% followed by alcohol consumption in 70.6% and cigarette smoking in 47.1% of patients. Diabetes mellitus and systemic arterial hypertension were present in 70% of our population. These entities are known to alter the estrogen-androgen ratio. The initial symptom in 88.2% of patients was a retroareolar tumor. The mean time from symptom onset to cancer diagnosis was 14.4 months. Estrogen and/or progesterone receptor status was positive in 82.3%. HER2 overexpression was not found. 17.6% of the cancers were classified as triple negative in contrast to the 0.3% reported in other series. Regarding treatment, 88.3% underwent upfront surgery, of which 76% were modified radical mastectomies. Axillary node dissection was performed in 86.6% of the cases and sentinel node biopsy in the rest. Seventy-six percent of patients received chemotherapy and radiotherapy in the adjuvant setting. Tamoxifen was the most common drug of choice (87.5%) in the patients considered as candidates for hormonal therapy Conclusions This study updates the results previously reported from our center with additional information that enabled new important conclusions to be drawn about our population. These findings provide the basis for a better understanding of this disease, which is necessary to establish public policies and recommendations to reduce the negative impact of this type of cancer. Table. Demographic and Clinical Characteristics of the Patients Citation Format: Fernando Peña, Javier A. Martínez-Moyano, Francisco Alvarado-Villarreal, Carlos Salazar-Mejía, David Hernández-Barajas, Oscar Vidal-Gutiérrez. Breast cancer in men: 15 years of experience in an oncology reference center in northern Mexico [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-16-08.

Colorectal carcinoma peritoneal metastases-derived organoids: results and perspective of a model for tailoring hyperthermic intraperitoneal chemotherapy from bench-to-bedside

BackgroundPeritoneal metastases from colorectal cancer (CRCPM) are related to poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been reported to improve survival, but peritoneal recurrence rates are still high and there is no consensus on the drug of choice for HIPEC. The aim of this study was to use patient derived organoids (PDO) to build a relevant CRCPM model to improve HIPEC efficacy in a comprehensive bench-to-bedside strategy.MethodsOxaliplatin (L-OHP), cisplatin (CDDP), mitomycin-c (MMC) and doxorubicin (DOX) were used to mimic HIPEC on twelve PDO lines derived from twelve CRCPM patients, using clinically relevant concentrations. After chemotherapeutic interventions, cell viability was assessed with a luminescent assay, and the obtained dose–response curves were used to determine the half-maximal inhibitory concentrations. Also, induction of apoptosis by different HIPEC interventions on PDOs was studied by evaluating CASPASE3 cleavage.ResultsResponse to drug treatments varied considerably among PDOs. The two schemes with better response at clinically relevant concentrations included MMC alone or combined with CDDP. L-OHP showed relative efficacy only when administered at low concentrations over a long perfusion period. PDOs showed that the short course/high dose L-OHP scheme did not appear to be an effective choice for HIPEC in CRCPM. HIPEC administered under hyperthermia conditions enhanced the effect of chemotherapy drugs against cancer cells, affecting PDO viability and apoptosis. Finally, PDO co-cultured with cancer-associated fibroblast impacted HIPEC treatments by increasing PDO viability and reducing CASPASES activity.ConclusionsOur study suggests that PDOs could be a reliable in vitro model to evaluate HIPEC schemes at individual-patient level and to develop more effective treatment strategies for CRCPM.

Rationale for the Inclusion of β-Blockers Among Major Antihypertensive Drugs in the 2023 European Society of Hypertension Guidelines.

We address the reasons why, unlike other guidelines, in the 2023 guidelines of the European Society of Hypertension β-blockers (BBs) have been regarded as major drugs for the treatment of hypertension, at the same level as diuretics, calcium channel blockers, and blockers of the renin-angiotensin system. We argue that BBs, (1) reduce blood pressure (the main factor responsible for treatment-related protection) not less than other drugs, (2) reduce pooled cardiovascular outcomes and mortality in placebo-controlled trials, in which there has also been a sizeable reduction of all major cause-specific cardiovascular outcomes, (3) have been associated with a lower global cardiovascular protection in 2 but not in several other comparison trials, in which the protective effect of BBs versus the other major drugs has been similar or even greater, with a slightly smaller or no difference of global benefit in large trial meta-analyses and a similar protective effect when comparisons extend to BBs in combination versus other drug combinations. We mention the large number of cardiac and other comorbidities for which BBs are elective drugs, and we express criticism against the exclusion of BBs because of their lower protective effect against stroke in comparison trials, because, for still uncertain reasons, differences in protection against cause-specific events (stroke, heart failure, and coronary disease) have been reported for other major drugs. These partial data cannot replace global benefits as the main deciding factor for drug choice, also because in the general hypertensive population whether and which type of event might occur is unknown.

Real-life use of letermovir prophylaxis for cytomegalovirus in heart transplant recipients.

Cytomegalovirus (CMV) remains the predominant opportunistic infection following solid organ transplantation (SOT). While valganciclovir is the drug of choice for CMV prophylaxis, its utility can be compromised due to the risk of cytopenia. Letermovir, a novel agent approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant recipients and high-risk kidney transplant recipients, exhibits reduced toxicity. This study aims to present the practical application of letermovir as both primary and secondary prophylaxis against CMV in heart transplant recipients (HTR). In this observational, retrospective, single-center study, we included all consecutive adult HTRs from June 2020 to January 2022 who were administered letermovir for CMV prophylaxis. We documented instances of CMV breakthrough infections, side effects related to letermovir, changes in neutropenia following the switch from valganciclovir to letermovir, and any drug interactions with the immunosuppressive regimen. The study comprised 10 patients: two received primary prophylaxis with letermovir due to a high risk of CMV infection (donor-positive, recipient-negative serostatus), and eight received it as secondary prophylaxis following a CMV infection. The median duration of letermovir administration was 8 months (range 3-12 months). No CMV breakthrough infections were reported while on prophylaxis. However, three patients experienced CMV breakthrough infections after discontinuing letermovir prophylaxis (30%). No significant side effects were observed, although one patient reported digestive intolerance. Among the nine patients on tacrolimus, six needed reduced doses after switching to letermovir. This real-life study appears to support the effectiveness of letermovir prophylaxis in HTR. Nonetheless, the risk of CMV infection post-treatment cessation is notable. Further drug monitoring and research on the efficacy of letermovir for CMV prophylaxis in SOT patients is warranted.

Frequency of Hematological Response in Patients with Chronic Myeloid Leukemia (Chronic Phase) with Imatinib After Three Months Presenting to CMH Rawalpindi

Objective: To find the frequency of haematological response in patients of chronic myeloid leukaemia (Chronic Phase) after three months of Imatinib Mesylate therapy, presenting to CMH Rawalpindi Study Design: Cross-sectional study. Place and Duration of Study: Department of Oncology Combined Military Hospital, Rawalpindi Pakistan, from Jan to Jun 2020. Methodology: Forty-six patients aged 18 and above within the chronic phase of CML were included. Patients underwent detailed clinical history, examination, baseline investigations, and bone marrow studies at presentation. Enrolled patients were given 400mg of Imatinib, and a complete haematological response was noted at the end of 3 months of therapy. Results: In our study, the age of patients ranged from 18 to 67 years, with a mean age of 47.2+10.6 years. 33(71.7%)were male, and 13(28.3%) were female. 42(91.3%) patients achieved complete haematological response to Imatinib at three months of therapy. Adverse drug reactions exhibited were oedema 18(39.1%), gastrointestinal disturbance 12(26.1%), anaemia 05(10.9%), and skin reactions 03(6.5%). Conclusion: This study has concluded that Imatinib Mesylate is highly effective in treating chronic phase CML at the haematological level and can be considered the drug of first choice in CML-CP.

Interleukin 17 as a central component of the pathogenesis of pain associated with immunoinflammatory process: А new “target” of pharmacotherapy

Modern pathogenetic therapy of inflammatory rheumatic diseases (IRD) is aimed not only at reducing disease activity (although achieving remission and low disease activity remains the main goal of treatment), but also at eliminating as quickly and completely as possible the main symptoms that cause a decrease in the quality of life of patients. Particular importance is attached to effective control of chronic pain – the main and most distressing manifestation of IRD. To solve this problem, the pathogenesis of chronic pain in IRD continues to be actively studied, aimed at finding new ”targets” of pharmacotherapy. Thus, the role of central sensitization (CS) and comorbid fibromyalgia in the formation of clinical manifestations of IRD is now clearly proven. Signs of CS, depending on the instrument of its detection, are determined in 20–40% of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA).Interleukin (IL) 17 plays a fundamental role in the development of chronic pain in IIRD. This cytokine takes a leading position in the development of the ”cytokine cascade”, inducing the synthesis of various cytokines and chemokines, as well as chemotaxis and activation of neutrophils and T cells. Induction of synthesis of inflammatory mediators (including prostaglandin E2) determines the role of IL-17 in activation of nociceptors and their sensitization. IL-17 also takes an active part in neuroimmune interactions by activating glia cells and affecting receptors present on the membrane of neurons of the posterior horns of the spinal cord. This defines the role of IL-17 as one of the inductors of CS development. Pharmacologic blockade of IL-17 is a known pathway to suppress the activity of IIRPs such as PsA and AxSpA. However, this mechanism also allows for significant effects on chronic pain. In particular, the IL-17 inhibitor ixekizumab has shown high analgesic potential in a series of studies in PsA and AxSpA (SPIRIT-P1 and SPIRIT-P2, COAST V and COAST W). It is important to note that this drug demonstrated a very rapid analgesic effect: pain intensity was significantly reduced already 7 days after the first injection. These data suggest a specific effect of ixekizumab on the nociceptive system, independent of the anti-inflammatory effect. This fact allows us to consider ixekizumab as a drug of choice for the treatment of patients with PsA and AxSpA who experience severe pain and have signs of CS and fibromyalgia.

Relationship between the efficacy of sulfonylurea therapy and structural variants of the ABCC8 (rs757110) and KCNJ11 (rs5219) genes in patients with type 2 diabetes mellitus with different phenotypes

Recently, a large number of studies have been conducted to investigate the variability of response in the treatment of diabetes mellitus (T2DM), which make personalized medicine possible. However, the available data are insufficient to decide on the choice of sugar-lowering drugs in T2DM. The search for phenotypic and clinical factors of pharmacogenetic response to therapy continues. Aim of the study was to investigate the relationship between the effectiveness of sulfonylurea therapy and structural variants of the ABCC8 (rs757110) and KCNJ11 (rs5219) genes in T2DM patients with clinical phenotypes. Material and methods. A cross-sectional clinical and pharmacogenetic study of 1271 patients with T2DM receiving sulfonylurea monotherapy (SU) or in combination with metformin and divided into three clinical phenotypes: with insulin deficiency (insulinopenic phenotype), with obesity and moderate insulin resistance (classical phenotype) and with severe insulin resistance (insulin-resistant phenotype) was performed. A glycated hemoglobin content of less than 7% was considered as a good response to SU therapy. Results. Patients with a good response to SU therapy with a classic phenotype had a longer duration of diabetes compared to patients with absence of good response (5.68 ± 5.22 vs 9.12 ± 6.10 years, respectively, p &lt; 0.001) and a later age at diagnosis of T2DM (54.05 ± 7.18 vs 49.37 ± 7.65 years, respectively, p &lt; 0.001); patients with an insulin-resistant phenotype had T2DM established at an older age (54.35 ± 7.91 vs 50.10 ± 7.51 years, respectively, p = 0.001). Logistic regression analysis did not reveal a statistically significant association of the genotype of the structural variant of the ABCC8 gene (rs757110) with the effectiveness of SU in clinical phenotypes. The T/T genotype of the KCNJ11 gene (rs5219) was associated with a better response to SU therapy only in the group of T2DM patients with the classic phenotype (odds ratio 1.85, 95% confidence interval 1.05–3.25, p = 0.041). Conclusions. In patients with type 2 diabetes, predictors of a good response to SU with a classic phenotype were a later age of T2DM diagnosis, a shorter duration of diabetes, and the presence of the T/T genotype of the structural variant of the KCNJ11 gene (rs5219); with an insulin-resistant phenotype, a later age of T2DM diagnosis; with the insulinopenic phenotype no clinical and genetic predictors of the SU effectiveness were identified.

Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care.

De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients. Cumulative immunosuppression has been shown to contribute to post-transplant malignancy (PTM) risk. There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs, independent of the net effect of immunosuppression. Calcineurin inhibitors such as tacrolimus may promote tumourigenesis, whereas mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil, may limit tumour progression. Liver transplantation (LT) is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable, which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort. However, there is limited clinical data on this subject in both LT and other solid organ transplant recipients. To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation. A literature search was conducted using MEDLINE and Embase databases using the key terms "solid organ transplantation", "tacrolimus", "mycophenolic acid", and "carcinogenicity", in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022. Related terms, synonyms and explosion of MeSH terms, Boolean operators and truncations were also utilised in the search. Reference lists of retrieved articles were also reviewed to identify any additional articles. Excluding duplicates, abstracts from 1230 records were screened by a single reviewer, whereby 31 records were reviewed in detail. Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria. A total of 6 studies were included in this review. All studies were large population registries or cohort studies, which varied in transplant era, type of organ transplanted and immunosuppression protocol used. Overall, there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation. Furthermore, no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients. The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies, and its application in solid organ transplantation, is yet to be confirmed in clinical studies. Thus, the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.

Pharmacological treatments for psychotic depression

Despite the overall efficacy of antidepressant and antipsychotic combination therapy for the treatment of psychotic depression, data on the most appropriate choice of individual drugs for the combination treatment are limited. Researchers recently conducted a network meta‐analysis to compare the efficacy and safety of various pharmacological treatment options for patients who had major depressive episodes with psychotic features (Oliva et al., 2024).

Emerging Perspectives on the Impact of Diabetes Mellitus and Anti-Diabetic Drugs on Premenstrual Syndrome. A Narrative Review.

Diabetes mellitus (DM) and premenstrual syndrome (PMS) are global health challenges. Both disorders are often linked to a range of physical and psychological symptoms that significantly impact the quality of life of many women. Yet, the exact relation between DM and PMS is not clear, and the management of both conditions poses a considerable challenge. In this review, we aimed to investigate the interplay between DM, anti-diabetic drugs, and the different theories and symptoms of PMS. Female sex hormones are implicated in the pathophysiology of PMS and can also impair blood glucose control. In addition, patients with diabetes face a higher susceptibility to anxiety and depression disorders, with a significant number of patients experiencing symptoms such as fatigue and difficulty concentrating, which are reported in patients with PMS as well. Complications related to diabetic medications, such as hypoglycemia (with sulfonylurea) and fluid retention (with thiazolidinediones) may also mediate PMS-like symptoms. DM can, in addition, disturb the normal gut microbiota (GM), with a consequent loss of beneficial GM metabolites that guard against PMS, particularly the short-chain fatty acids and serotonin. Among the several available anti-diabetic drugs, those (1) with an anti-inflammatory potential, (2) that can preserve the beneficial GM, and (3) possessing a lower risk for hypoglycemia, might have a favorable outcome in PMS women. Yet, well-designed clinical trials are needed to investigate the anti-diabetic drug(s) of choice for patients with diabetes and PMS.

Cancer-associated venous thrombosis in adults (second edition): A British Society for Haematology Guideline.

A shared decision on the most appropriate agent for the treatment of cancer-associated thrombosis should consider the following factors, which should be reassessed as patients continue along their cancer care pathway: risk of bleeding; tumour site; suitability of oral medications; potential for drug-drug interactions; and patient preference and values regarding choice of drug. Continuing anticoagulation beyond 6 months in patients with cancer-associated venous thromboembolism and active cancer is recommended.

Epidemiology of physical activity and sedentary behavior levels among patients entering treatment for substance use disorder in the United States: a descriptive study.

Little is known about physical activity behaviors among people with SUD. This study aimed to (a) describe self-reported moderate-to-vigorous physical activity (MVPA) and sedentary (SED) behaviors of adults with SUD initiating treatment (b), determine the potential contributions of drug of choice (DOC) on these behaviors, and (c) determine the potential contributions of level of care and demographic variables on these behaviors. Secondary data that was collected via surveys including demographic information, psychological health, drug of choice, MVPA (categorized as inactive, insufficiently active, meets guidelines, exceeds guidelines) and SED (<4 h/day, 4-<6 h/day, 6-8 h/day, >8 h/day) were analyzed from 1,293 patients in inpatient/outpatient treatment facilities across the United States. On average, over half (51%) of patients entering treatment reported not meeting guidelines, but sitting time was generally low (median= 360 min/day). MVPA levels differed based on level of care (p<0.001) with 48% of patients in detox facilities reporting inactivity compared to 37% in residential and 29% in outpatient programs. MVPA and SED levels differed by sex with women less likely to report sitting <4 h/day (27.9% vs. 38.2%, p<0.001) and more likely to report sitting for >8 h/day (31.5% vs. 21.8%, p<0.001) compared to men. SED differed by race (p=0.01), with 54% of Black patients reporting <4 h/day compared to 33% of White patients. Understanding activity behavior patterns among individuals entering SUD treatment provides opportunities for identifying the extent of lifestyle behavior needs and opportunities to develop personalized treatment strategies.