Modification Of Treatment Regimen Research Articles

In silico drug repurposing approach to predict most effective HAART for HIV drug resistance variants prevalent in the Indian HIV-positive population.

HIV epidemics still exist as a major global public health burden, especially in middle- and low-income countries. Given the lack of approved vaccines, antiretroviral therapy (ART) remains the primary approach to reduce the mortality and morbidity linked to this disease. Effective treatment for HIV-1 requires the simultaneous administration of multiple drugs. However, the virus can show resistance to antiretroviral drugs, resulting in treatment failure. Therefore, this study focused on assessing the prevalence of mutations within the Indian HIV-positive population. After assessing the data, we intended to identify the most effective highly active ART (HAART) regimens for individuals with drug-resistant variants. Furthermore, our analysis revealed a spectrum of HIV mutations, with varying effects on protein stability. The significance of this analysis lies in its potential to optimize HAART selection for HIV-positive individuals by accounting for both prevalence and stability-altering mutations. By considering mutation effects on protein stability, we can modify treatment regimens, increasing the likelihood of therapy success and diminishing the risk of resistance. Moreover, this study contributes to the broader field of drug repurposing, offering insights into the rational design of antiretroviral therapies.

Low-density lipoprotein cholesterol response to statins according to comorbidities and co-medications: A population-based study

The response of low-density lipoprotein cholesterol (LDL-C) to statin therapy is variable, and may be affected by the presence of co-morbid conditions or the use of concomitant medications. Systematic variation in the response to statins based on these factors could affect the selection of the statin treatment regimen in population subgroups. We investigated whether common comorbidities and co-medications had clinically important effects on statin responses in individual patients. This register-based cohort study included 89,006 simvastatin or atorvastatin initiators with measurements of pre-statin and on-statin LDL-C levels, in Denmark, 2008-2018. We defined statin response as the percentage reduction in LDL-C, and used linear regression to estimate percentage reduction differences (PRD) according to 175 chronic comorbidities and 99 co-medications. We evaluated both the statistical significance (P-values corrected for multiple testing) and the clinical importance (PRD of 5 percentage points or more) of the observed associations. Concomitant use of oral blood-glucose lowering drugs, which included metformin in 96% of treated individuals, was associated with a greater response to statin therapy that was both statistically significant and clinically important, with a PRD of 5.18 (95% confidence interval: 4.79 to 5.57). No other comorbidity or co-medication reached the prespecified thresholds for a significant, clinically important effect on statin response. Overall, comorbidities and co-medications had little effect on statin response, and altogether explained only 1.7% of the total observed population variance. Most of the studied comorbidities and co-medications did not have a clinically important effect on statin response, suggesting no need to modify treatment regimens. However, use of metformin was associated with a significantly enhanced LDL-C response to statins, suggesting that lower statin doses may be effective in patients taking metformin.

Successful treatment of recurrent visceral leishmaniasis relapse in an immunocompetent adult female with functional hypopituitarism in Bangladesh.

Currently available treatment options are mostly effective in achieving long-term cure in visceral leishmaniasis (VL) patients. However, there have been reports of recurrence of this illness in both immunosuppressed and immunocompetent patients. We report the first case of recurrent VL relapse in a 19-year-old immunocompetent female with functional hypopituitarism (hypogonadotropic hypogonadism with central hypothyroidism) from Bangladesh, who has been treated three times previously with optimal dosage and duration- liposomal amphotericin B (LAmB) alone and in combination with miltefosine. We treated the patient successfully with a modified treatment regimen of 10 mg/kg body weight LAmB for two consecutive days along with oral miltefosine for seven days as loading dose. For secondary prophylaxis, the patient received 3 mg/kg body weight LAmB along with oral miltefosine for seven days monthly for five doses followed by hormonal replacement. The patient remained relapse free after 12 months of her treatment completion. In the absence of protective vaccines against Leishmania species and standard treatment regimen, this modified treatment regimen could help the management of recurrent relapse cases.

Primary Treatment Modification and Treatment Tolerability Among Older Chemotherapy Recipients With Advanced Cancer

Older adults with advanced cancer are less likely to tolerate treatment with cytotoxic chemotherapy compared with younger patients due to their aging-related conditions. Hence, oncologists sometimes opt to employ primary treatment modifications (deviation from standard of care) during the first cycle of chemotherapy. To examine the association between primary treatment modification and treatment tolerability in older adults with advanced cancer who were starting new palliative chemotherapy regimens. This cohort study was a secondary analysis of the GAP70+ (Geriatric Assessment Intervention for Reducing Toxicity in Older Patients with Advanced Cancer) trial, which was conducted between July 2014 and March 2019. The GAP70+ trial included patients aged 70 years or older who had advanced (ie, incurable) cancer, had 1 or more geriatric assessment domain impairments, and planned to start a new palliative chemotherapy regimen. Data analysis was conducted in November 2022. Receipt of standard-of-care chemotherapy regimens vs primary treatment modification defined as any change from National Comprehensive Cancer Network guidelines or published clinical trials (eg, primary dose reduction, schedule change). Tolerability outcomes were assessed within 3 months of treatment. These outcomes included the following: (1) any grade 3 to 5 toxic effect, according to the National Cancer Institute Common Terminology Criteria for Adverse Events; (2) patient-reported functional decline, defined as the development of worse dependency in activities of daily living using scale scores; and (3) a composite adverse outcome (an end point that combined toxic effects, functional decline, and 6-month overall survival). Multivariable cluster-weighted generalized estimating equation models examined the association between primary treatment modification and outcomes adjusting for covariates. This study included 609 patients with a mean (SD) age of 77.2 (5.2) years; more than half (333 [54.7%]) were men. Race and ethnicity was available for 607 patients: 39 (6.4%) were Black, 539 (88.5%) were non-Hispanic White, and 29 (4.8%) were of other race or ethnicity. Nearly half (281 [46.1%]) received a primary modified treatment regimen. The most common cancer types were gastrointestinal cancer (228 [37.4%]) and lung cancer (174 [28.6%]). In multivariable analysis, primary treatment modification was associated with a reduced risk of grade 3 to 5 toxic effects (relative risk [RR], 0.85 [95% CI, 0.77-0.94]) and functional decline (RR, 0.80 [95% CI, 0.67-0.95]). Patients who received primary treatment modification had 32.0% lower odds of having a worse composite adverse outcome (odds ratio, 0.68 [95% CI, 0.48-0.97]). In this cohort study, primary treatment modification was associated with improved tolerability of chemotherapeutic regimens among older adults with advanced cancer and aging-related conditions. These findings may help optimize cancer treatment dosing in older adults with advanced cancer and aging-related conditions.

Improved Treatment Outcomes With Modified Induction Therapy in Acute Myeloid Leukemia (AML): A Retrospective Observational Study From a Regional Cancer Center.

The aggressive, genetically diverse group of malignant illnesses known as acute myeloid leukemia (AML) is characterized by clonally related myeloblast invasion of the bone marrow, blood, and other organs. The treatment regimen plays a crucial role in the management of AML, and it is associated with poor overall survival and enhanced risk of relapse. Induction therapy with a 7+3 DA regimen (daunorubicin + ara-C) has been the treatment of choice for young and fit patients. To evaluate the effect of dose modification in young and fit patients for a modified treatment regimen. This was a retrospective, observational study of AML patients to analyze the outcomes of modified induction therapy in AML patients enrolled at Dr. B. Borooah Cancer Institute, Guwahati, Assam, India, from October 2021 to March 2022. The outcomes of modified induction therapy with intensive chemotherapy (modified 7+3 DA) and low-intensity chemotherapy decitabine (10 days) and venetoclax + azacytidine (seven days) were considered after the first two cycles or 60 days, whichever was earlier. Data from 31 patients with de-novo AML was analyzed; the median age of the patients was 41 years (range: 2-71 years), and the male-to-female ratio was 1.8. There were seven patients in the pediatric age group (2-13 years), and 19%, 65%, and 13% of patients belonged to favorable, intermediate, and high-risk groups, respectively. With regards to modified induction therapy (n=31), 20 (65%) patients received modified "7+3 DA", nine (29%) received hypomethylating agents (HMA, decitabine only), and two patients received HMA (azacitidnie) + venetoclax. Additionally, 23/31 patients completed at least two cycles of induction therapy. Overall, 60 day-induction mortality was 13%, and the complete remission (CR) and partial remission (PR) rates were 48% and 26%, respectively. In patients who received modified "7+3 DA", the CR rate was 55%. The notable reduction in deaths due to infections observed in our study suggests that centers with limited resources for preventing neutropenic complications during induction therapies in AML patients could consider adopting this modified regimen.

The impact of elexacaftor/tezacaftor/ivacaftor on cystic fibrosis health-related quality of life and decision-making about daily treatment regimens: a mixed methods exploratory study.

Elexacaftor/tezacaftor/ivacaftor (ETI) has reduced many symptoms of cystic fibrosis (CF). We sought to identify the impact of ETI on both symptoms and treatment decisions among adults with CF. Participants were enrolled in a cross-sectional study. Surveys were sent via a RedCap link. Semistructured interviews were administered remotely via Microsoft Teams. Interviews were audio recorded and professionally transcribed. We assessed Cystic Fibrosis Questionnaire-Revised (CFQ-R) subscales for physical, respiratory, emotion, and treatment, and analyzed semistructured interviews covering CF treatment regimens and daily living. Quantitative and qualitative results were analyzed separately and via a mixed-methods convergence coding matrix. Twenty-four adults with CF taking ETI were included. CFQ-R subscale scores (mean scores/standard deviation) were physical (82.1/22.8), respiratory (83.7/11.2), emotion (65.3/14.2), and treatment (57.5/20.1). Three themes about decision-making for non-ETI-treatments emerged: (1) How I'm feeling, (2) Not noticing a difference, and (3) Uncertainty about long-term impact of modifying treatment regimens, and we found participants weighed each of these factors in their treatment decisions. Key findings from mixed-methods analysis show that among individuals experiencing higher CFQ-R scores for physical and respiratory compared to emotion and treatment, there were statements indicating that while those participants were experiencing better physical health, many continued their burdensome treatment regimens. With little long-term data on the impact of reducing non-ETI treatments, participants weighed how they were feeling, treatment efficacy beliefs, and risk tolerance when making treatment decisions.

Chemo-Toxicity Calculator use in shared decision-making for chemotherapy treatment planning.

403 Background: Chemotherapy related symptoms and toxicities are frequent among cancer patients, especially those ≥ 65 years old. These symptoms and toxicities can contribute to patients having a decreased quality of life and unmet treatment outcomes. The modified CARG, Chemo-Toxicity Calculator, is an assessment of function, comorbidity, cognition, psychological state, social activity/support and nutrition. The goal of using the calculator, was to improve shared decision-making between the physician, patient and caregiver. Discussions focused on treatment, modifying treatment regimens and other alternatives such as palliative or hospice. Methods: Rocky Mountain Cancer Centers introduced the modified CARG, Chemo-Toxicity Calculator, in 2022 as part of cancer patient workflow for 10 physicians. In 2022, 156 patients completed the Chemo-Toxicity Calculator to identify and predict the risk of initiation or continuation of chemotherapy treatment in patients ≥ 65 years old. Using the CARG assessment allowed the physician and patient to have open discussions about the pros and cons of initiation or continuation of chemotherapy treatment or if they should pursue alternative treatment. 27 of these patients (17.3%) elected to receive hospice care in lieu of traditional treatment. The Chemo-Toxicity Calculator link was added in the electronic health record (EHR) for access at the point of care. Process: 1. Review patients at the time of initial treatment and subsequent lines of therapy. 2. CARG assessment completed for patients ≥ 65 years old. 3. Shared decision-making discussion including the voice of the patient. 4. Psychosocial interventions and care coordination. Results: As of May 2023,10 providers administered the modified CARG assessment on 244 patients. The tool identified patients that would not benefit from treatment and instances where cycle one dose reduction would be appropriate to reduce toxicity risk. Of the 244 patients who completed the assessment, 47 (19.2%) elected alternative treatment. Conclusions: The Chemo-Toxicity Calculator is a functional, practical first step toward the inclusion of a geriatric assessment for all patients ≥ 65 years old. Patients understand it, and it sets the stage for shared decision-making discussions. This valued intervention aids subsequent discussions about dose reduction and ongoing risks of treatment. Actions taken based on the results of the Chemo-Toxicity Calculator, reduced toxicity by dose reductions and helped patients choose an alternative to chemotherapy.

Scenarios warranting modified treatment regimens in leprosy: A 5-year retrospective study from a tertiary care center

Objectives: To study the scenarios warranting modified treatment regimens in leprosy. Materials and Methods: A 5-year retrospective study was carried out in a tertiary care center by analyzing the data collected from national leprosy eradication program (NLEP) records. Results: During the 5-year study period, 171 patients received treatment for leprosy from our center. Thirtyone patients (31/171, 18.1%) required substitution of standard multidrug therapy (MDT) with alternate drugs or required alternate treatment regimens. The patients who required modified treatment included 18 men (18/31, 58.1%) and 13 women (41.9%). Male/female ratio was 1.4:1. Indications for treatment modification were adverse drug reactions to standard MDT (ADR) (21/31, 67.7%) and lack of response to standard MDT (10/31, 32.3%). The most common scenario that warranted a modification of standard MDT was dapsone-induced hemolysis (12/31, 38.7%). Seven (7/31, 22.6%) and two (2/31, 6.5%) patients needed a change in treatment due to drug-induced hepatitis and drug-induced maculopapular rash, respectively. Limitations: Retrospective study design, study conducted in single tertiary referral center and small sample size were the limitations. Conclusion: Nearly one-fifth of patients with leprosy required modifications in standard MDT. The most common indication (in two-third of patients who needed a modified treatment) for modification of treatment regimen was adverse drug reactions.

Trends and Characteristics of Blood Pressure Prescription Fills Before and During the COVID-19 Pandemic in the United States.

The COVID-19 pandemic disrupted healthcare in the United States and raised concerns about certain antihypertensives, and may have impacted both prescribing practices and access to blood pressure (BP) medications. We assessed trends in BP prescription fills before and during the first year of the COVID-19 pandemic, using cross-sectional data for BP fills and tablets in the IQVIA (IMS Health) National Prescription Audit® database. Drugs filled via retail (92% coverage), mail-order (78% coverage), and long-term care (72% coverage) channels from January 2018 through December 2020 were included. Data were projected nationally and by state. Between 2.9 and 3.4 billion BP tablets were dispensed monthly until February 2020, increasing sharply to 3.8 billion in March 2020 and declining to 3.5 billion in April, then increasing at 3-month intervals until December 2020. The number of tablets per fill increased slightly over time, with the largest increase (from 66.7 to 68.6) during February-March, 2020. Tablets were dispensed through retail channels (99.7 billion), mail-order (14.7 billion), and long-term care (5.3 billion). Rates of patients initiating new medications decreased during 2020 compared to prior years. Fills did not vary significantly by drug class. A sharp increase in BP fills occurred with COVID-19 emergence, suggesting patients may have secured medications in preparation for potential access limitations. A decrease in new fills, indicating decreased initiation and/or modification of treatment regimens, suggests need for efforts to re-engage patients in the healthcare system and provide alternative ways to obtain medication refills and adjustments.

18F]FDG-PET/CT in patients with bacteremia: Clinical impact on patient management and outcome.

Bacteremia is the presence of viable bacteria in the bloodstream, a complicated and potentially dangerous systemic medical condition that may range from asymptomatic and clinically relatively indolent cases to more severe bloodstream infection (BSI) and ultimately life-threatening septic shock with fatal outcome. BSI is classified as simple (bacteremia only) or complex (BSI with metastatic spread), and the morbidity is higher in the latter, probably due to insufficient eradication. Treatment of simple BSI is usually short-term antibiotic courses, whereas complex BSI with metastatic foci requires more advanced treatment including long-term antibiotics or invasive drainage to gain infection control. Thus, identifying metastatic infection has an important clinical impact but remains a challenge; only half of the patients progress to complex BSI, and many patients present without relevant signs or symptoms, so imaging is pivotal. This review summarizes the potential role and recommendations of [18F]FDG-PET/CT in BSI, based on the relatively sparse and heterogeneous literature. [18F]FDG-PET/CT should be considered in suspected complex BSI, in patients at high risk of metastatic spread, and in BSI in ICU patients. [18F]FDG-PET/CT has an impact on patient management, treatment strategy, and patient outcome, mainly by directing the diagnostic process toward more specific diagnostics or by modifying treatment regimens resulting in reduced relapse rates and reduced mortality. Finally, a negative scan may obviate the need for further workup.

Programmatic management of rifampicin-resistant tuberculosis with standard regimen in Cameroon: a retrospective cohort study

ObjectivesTo describe treatment outcomes for rifampicin-resistant tuberculosis (Rr-TB) started on standard regimen and the frequency of acquired drug resistance in patients treated using the standard treatment regimen (STR) in Cameroon between 2015-2019. MethodsThis is a retrospective cohort study. Rr-TB patients were initiated on the STR, including a fluoroquinolone (FQ), a second-line injectable drug (SLI), and companion drugs. In case of resistance to fluoroquinolones (FQr) at baseline, FQ, SLI and ethionamide were replaced by bedaquiline, delamanid, and linezolid in a modified treatment regimen (mTR), FQr-mTR. In case of resistance to SLI (SLIr) at baseline, SLI was replaced by linezolid (LZD), SLIr-mTR. Logistic regression and competing risk regression were used to estimate predictors of early (first eight weeks) mortality and overall mortality, respectively. ResultsOf 709 patients started on a standard regimen, treatment success occurred in 84.7% (587/693), 72.7% (8/11) and 100% (10/10) of patients treated with STR, FQr-mTR and SLIr-mTR as final regimens, respectively. Three (0.6%) patients acquired FQr during treatment. Early mortality occurred in 4.1% (29/709) and was associated with being HIV positive, male sex and being underweight. Overall mortality was associated with missing drug-susceptibility testing results at baseline, being HIV positive, age>40 and male sex. ConclusionProgrammatic management of Rr-TB, with additional second-line drug resistance treated with mTR, resulted in excellent treatment outcomes.

P589: AGE AND AGE-ADAPTED RISK FACTORS HIGHLY INFLUENCE SURVIVAL PROBABILITY IN AML PATIENTS – A RETROSPECTIVE ANALYSIS

Background: Advanced age is strongly associated with inferior overall survival in patients with acute myeloid leukemia (AML). Despite advances in modified treatment regimen and genetic analyses of underlying mutations the prognosis for patients above the age of 65 remains poor. Aims: The aim was to determine patient-related risk factors and disease-associated variables. Methods: 915 AML patients (498 < 65 years, 417 ≥ 65 years) treated at the University Hospital of Düsseldorf were analyzed. Patients were diagnosed between 2008 and 2020 comprising 484 males and 431 females. Median age was 63 years. Patients’ survival was calculated using Kaplan-Meier-plots and multivariate regression analyses were performed to identify prognostic factors for survival. Results: Age itself proved to be an independent risk factor for survival: 6.9 months within the group of patients ≥ 65 years, 166 months in patients < 65 years (p < 0.001). In patients ≥ 65 years aberrant cytogenetic findings and an inferior ECOG status were more frequent at the time of diagnosis. Comparison of survival within the same cytogenetic risk group yielded significant differences between the two age-stratified cohorts: Bearing cytogenetic aberrations associated with a favorable prognosis in the group with patients aged over 65 was associated with a median survival of 18 months whereas patients younger than 65 did not reach estimated median survival time (p < 0.001). When comparing patients with the same ECOG-status, advanced age was the most decisive prognostic factor for survival. This was highly significant in patients with ECOG status 0. In the group with higher ECOG status an influence of age was notable but of lower significance. In patients with pathologic lung function tests age turned out to be significant for survival: 26 months (≥ 65 years) vs. not reached (< 65 years) (p = 0.008). In patients with pathologic cardiac ultrasound findings results were similar with 26 months (≥ 65 years) vs. not reached (< 65 years) (p = 0.001). Whether AML was de novo or secondary affected survival probability only in the group aged below 65 (166 months de novo AML, 69 months secondary AML). Summary/Conclusion: Age has significant influence on patient- and leukemia-related factors, thus modulating the impact of other parameters on the prognosis. We were able to confirm the following independent negative predictive parameters on survival in AML patients: increasing age ≥ 65 years, high-risk genetic aberrations, comorbidities (lung, heart) and higher ECOG-status.

Intermittent PI3Kδ inhibition sustains anti-tumour immunity and curbs irAEs

Phosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1–3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in human patients with head and neck cancer in a neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses of AMG319, immune-related adverse events (irAEs) required treatment to be discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells, which probably contributed to toxicity; this points towards a specific mode of action for the emergence of irAEs. A modified treatment regimen with intermittent dosing of PI3Kδi in mouse models led to a significant decrease in tumour growth without inducing pathogenic T cells in colonic tissue, indicating that alternative dosing regimens might limit toxicity.

Elevated Kir2.1/nuclear N2ICD defines a highly malignant subtype of non-WNT/SHH medulloblastomas

Medulloblastoma (MB) is one of the most common childhood malignant brain tumors (WHO grade IV), traditionally divided into WNT, SHH, Group 3, and Group 4 subgroups based on the transcription profiles, somatic DNA alterations, and clinical outcomes. Unlike WNT and SHH subgroup MBs, Group 3 and Group 4 MBs have similar transcriptomes and lack clearly specific drivers and targeted therapeutic options. The recently revised WHO Classification of CNS Tumors has assigned Group 3 and 4 to a provisional non-WNT/SHH entity. In the present study, we demonstrate that Kir2.1, an inwardly-rectifying potassium channel, is highly expressed in non-WNT/SHH MBs, which promotes tumor cell invasion and metastasis by recruiting Adam10 to enhance S2 cleavage of Notch2 thereby activating the Notch2 signaling pathway. Disruption of the Notch2 pathway markedly inhibited the growth and metastasis of Kir2.1-overexpressing MB cell-derived xenograft tumors in mice. Moreover, Kir2.1high/nuclear N2ICDhigh MBs are associated with the significantly shorter lifespan of the patients. Thus, Kir2.1high/nuclear N2ICDhigh can be used as a biomarker to define a novel subtype of non-WNT/SHH MBs. Our findings are important for the modification of treatment regimens and the development of novel-targeted therapies for non-WNT/SHH MBs.

Hysteroscopic and morphological evaluation of endometrium in reproductive age women with comorbid polycystic ovarian syndrome and chronic endometritis in the protocols of in vitro fertilization

Summary. Today, infertility, which is associated with polycystic ovary syndrome, is a pressing problem in obstetrics, gynecology and reproductive medicine. Polycystic ovary syndrome (PCOS) is a common endocrine disease that affects about 6 to 20 % of women of childbearing potential. Its main signs are ovulatory and menstrual dysfunction (including anovulation), increased levels of gonadotropin-releasing hormone, hypersecretion of luteinizing hormone, hyperandrogenemia, metabolic disorders and morphological changes in the endometrium and ovaries. The aim of the study – to evaluate hysteroscopic and morphological changes in the endometrium of women with infertility against the background of PCOS and chronic endometritis and to analyze the effect of a modified treatment regimen in the protocols of in vitro fertilization on the manifestations of chronic endometritis. Materials and Methods. We examined 140 women with endocrine infertility against the background of PCOS and chronic endometritis, which were divided into 2 study groups, depending on the cause and treatment approach for infertility, as well as 35 women with male-caused infertility who comprised the control group. All examined patients underwent hysteroscopy, targeted biopsy and immunohistochemical study of the endometrium. Histological study of the endometrium was performed by staining the tissue with hematoxylin and eosin according to a standard protocol in order to understand the structural changes of the endometrium in women of the study groups. Immunohistochemical testing involved the detection of CD138 using standard Daco antibody kits (Denmark). Results. Patients with PCOS and chronic endometritis used standard anti-inflammatory treatment which followed our modified protocol. This resulted in significantly reduced manifestations of chronic endometritis. The modified protocol includes inositol and alpha-lipoic acid in pre-pregnancy preparation; PRP therapy of the uterine cavity; and lipofundin infusions on day 2–3 of the menstrual cycle and on the day of embryo transfer. Conclusions. Histological examination of the endometrium with manifestations of stromal-adenomatous polyps revealed reduced signs of cytogenic stroma proliferation, decreased perivascular edema and the number of erythrocyte diapedesis. The number of glandular elements and the size of the glands also decreased

IMPROVEMENT OF ERADICATION THERAPY IN CHILDREN WITH DUODENAL ULCER ASSOCIATED WITH HELICOBACTER PYLORI

The aim: To evaluate the efficacy of the drug VitD children with H.pylori-associated duodenal ulcer. Materials and methods: Two treatment groups of children with DU were formed: I - 60 children with H. pylori-associated DU, who received the optimal scheme of anti- Helicobacter therapy (AHBT) for Chernivtsi region; II - 62 children with H. pylori-associated DU who received a modified treatment regimen: AGBT + VitD at a dose of 2000 IU / day for 1 month. The effectiveness of the treatment was evaluated taking into account the Relative Risk Reduction (RRR) of the adverse event and Number Needed to Treat (NNT). Results: All children with DU and a positive H. pylori infection test showed changes in serum VitD levels: 81.9% deficiency and 18.1% insufficiency. Successful eradication was achieved in 77.1% of children, in particular in the first group 73.3%, in the second - 82.2%. Predictors of successful eradication are the duration of infection, H. pylori CagA (+), VitD level. When using the VitD treatment regimen in children with DU associated with CagA (+) strain H.pylori, RRR was observed 2.29 times (χ2 = 6.34, pφ&lt;0.05) with NNT 1.59. Conclusions: Due to the reduced level of serum VitD in children with H. pylori-associated DU, it is advisable to include in the treatment regimen the adjuvant component of AHBT in the form of VitD. Predictors of effective eradication of H. pylori are CagA (+) strain of H. pylori, duration of infection and VitD level.

Effects of Complex Therapy with Lifestyle Modification in Patients with Hypertension and Obesity

Obesity is a global problem of the modern working population and a negative factor in the development of hypertension. In obese patients, adipose tissue dysfunction leads to increased leptin secretion. Failure to treat in time leads to complications and deterioration of quality of life. Therefore, it is important to prevent and treat both conditions, primarily in terms of lifestyle adjustments. The objective: to investigate anthropometric, morphometric, biochemical parameters and quality of life of patients with obesity and hypertension on the background of standard and modified therapy with lifestyle adjustments. Materials and methods. Analysis of the results of treatment of 128 patients with hypertension I–II stage and 1–2 degrees and obesity (mean age 48.4±0.9 years) and as a control examined 21 relatively healthy people. After the first examination, patients with hypertension and obesity were divided into two groups – main (group 1) and experimental (group 2). Patients in both groups received standard antihypertensive therapy (ACE inhibitors, calcium channel blockers, thiazide diuretics) and received dietary and exercise recommendations, smoking cessation, salt restriction to 5 mg / day, and alcohol reduction. In contrast to the experimental group (group 2), patients of the main group (group 1) received individual dietary recommendations in the form of DASH-diet, the energy value of which was daily energy needs reduced by 300–400 kcal and omega-3 PUFA at a dose of 1007 mg (Including: eicosapentaenoic acid – 33% docosahexaenoic acid – 22%), coenzyme Q10 – 10 mg, vitamin E – 3 mg 1 g/d for 60 days. When assigning patients to the main (group 1) and experimental group (group 2), in addition to age, sex, physical activity, also took into account the compliance of patients to lifestyle changes, which was assessed on a 5-point system. Patients who were more willing and more motivated to follow the full recommendations of nutrition, increased physical activity, and those who had a higher rate of compliance were assigned to the main group. Approaches to exercise recommendations were the same in both groups – at least 90 minutes / week or 30 minutes / 3 times a week, or at least 10,000 steps daily. Before and after treatment, a laboratory biochemical study of blood and urine parameters and determination of leptin levels. Quality of life was assessed by the SF-36 questionnaire. Results. In obese patients % FM and BMI on average 1.4–1.5 times higher than the control group (38.6±0.7; р&lt;0.001; 32.3±0.3 kg/m2; р&lt;0.001). According to the results of repeated examination, normalization of blood pressure was achieved in all patients, regardless of treatment tactics. In 28 people from the experimental group (group 2), the average weight increased by 1–5 kg, decreased in 9 people, in the other 27 did not change (Me 0.0; Min –16.0; Max 10.0; р=0.01). In the main group (group 1), weight loss was found in 20 men and 28 women, ie in 75% of patients (–3.0±0.3 kg; р&lt;0.01, Me –3.0; Min –0.7; Max –11.0) and although these results were lower than expected, we can conclude that there was a greater effect on weight loss in patients who followed a modified treatment regimen with lifestyle adjustments. BMI in the dynamics of treatment in both groups did not change significantly, although in the main group there was a significant statistical decrease in % FM (–2.3±0.6; р&lt;0.01), additionally found a statistically significant difference between the groups (р&lt;0.01). Anthropometric parameters decreased significantly in the main group of patients, mainly due to waist circumference (in 26 patients; р&lt;0.01). The components of quality of life PF, RP, BP, reflecting the physical activity of patients, and components VT, SF, RE, which are the result of the psycho-emotional state of patients, were significantly lower than those of the control group. At the end of the course of treatment, the indicators of PF components in the experimental group and additionally RP, BP, SF and RE in the main group significantly improved. Analysis of leptin levels in obese patients showed herder dependence: in men with grade 2 and 3 obesity, hormone levels increased significantly compared with women and men with a BMI &lt;35 kg/m. Conclusions. Obesity is pathogenetically associated with adipose tissue dysfunction: 56.2% of people have increased serum leptin levels and its level does not decrease significantly with weight loss, which is probably associated with a symptom complex of psycho-physiological changes that negatively affect quality of life patients and their commitment to treatment. Treatment of obesity by adjusting lifestyle, exercise, low-calorie DASH-diet was reflected in improved quality of life and reduced the weight of 75% of patients in the main group (group 1).

Вплив антропометричних факторів та даних акушерсько-гінекологічного анамнезу на ризик невдалої імплантації після запліднення in vitro

Infertility is a significant demographic and socio-economic problem, which is solved with assisted reproductive technologies. Relevance of the infertility problem continues to grow, which leads to the search for new methods to improve the success of assisted reproductive technologies. Purpose — to analyze the effect of anthropometric factors, obstetrical and gynaecological history on the risk of implantation failure in women with infertility who have fertilization in vitro. Materials and methods. An analysis of 106 infertile women who were treated with assisted reproductive technologies in September 2019 — February 2021. The control group consisted of women who received infertility treatment according to the standard treatment regimens: controlled ovarian stimulation, gamete sampling, intracytoplasmic sperm injection and embryo transfer. The study group included patients who received antiplatelet agents, anticoagulants and intravenous immunoglobulins G in addition to the standard therapy. Results. In this study, no differences were found in the two study groups regarding age, height, weight, body mass index, menarche, menstrual duration, coitus (p&gt;0.05). During the analysis, it was found that with increasing age of a woman, the risk of unsuccessful implantation increases, OR=1.11 (95% CI 1.01–1.21) for each year, with increasing patient height, the risk decreases (p=0.006), OR=0.85 (95% CI 0.76–0.96) for each centimetre, with an increase in the number of sexual intercourses per week (p=0.012), OR=1.71 (95% CI 1.12–2.60) the risk increases by each unit. Implantation success with using modified treatment regimens with additional aspirin, low molecular weight heparins, intravenous immunoglobulins G, was higher (p=0.049), OR=0.37 (95% CI 0.14–0.99) compared to the standard infertility treatment scheme. Conclusions. This study found unfavourable effects of age, woman's height, and sexual intercourses on embryo implantation. Additional use of aspirin, low molecular weight heparin, intravenous immunoglobulin G as a supplemental therapy to standard treatment regimens of infertility with IVF had a successful impact on the effectiveness of embryo implantation. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: implantation failure, infertility, assisted reproductive technologies, in vitro fertilization (IVF).

Modelling the antimicrobial pharmacodynamics for bacterial strains with versus without acquired resistance to fluoroquinolones or cephalosporins

Antimicrobial resistance threatens therapeutic options for human and animal bacterial diseases worldwide. Current antimicrobial treatment regimens were designed against bacterial strains that were fully susceptible to them. To expand the useable lifetime of existing antimicrobial drug classes by modifying treatment regimens, data are needed on the antimicrobial pharmacodynamics (PD) against strains with reduced susceptibility. In this study, we generated and mathematically modelled the PD of the fluoroquinolone ciprofloxacin and the cephalosporin ceftriaxone against non-typhoidal Salmonella enterica subsp. enterica strains with varying levels of acquired resistance. We included Salmonella strains across categories of reduced susceptibility to fluoroquinolones or cephalosporins reported to date, including isolates from human infections, food-animal products sold in retail, and food-animal production. We generated PD data for each drug and strain via time-kill assay. Mathematical models were compared in their fit to represent the PD. The best-fit model's parameter values across the strain susceptibility categories were compared. The inhibitory baseline sigmoid Imax (or Emax) model was best fit for the PD of each antimicrobial against a majority of the strains. There were statistically significant differences in the PD parameter values across the strain susceptibility categories for each antimicrobial. The results demonstrate predictable multiparameter changes in the PD of these first-line antimicrobials depending on the Salmonella strain's susceptibility phenotype and specific genes conferring reduced susceptibility. The generated PD parameter estimates could be used to optimise treatment regimens against infections by strains with reduced susceptibility.

Neutropenia and management of cancer patients during the COVID-19 pandemic

The COVID-19 pandemic has significantly affected the management of patients with cancer. Due to the quarantine restrictions imposed to some extent around the world, it was necessary to modify treatment regimens by reducing the number of sessions of chemotherapy and radiation therapy, as well as by postponing surgery. The volume of cancer screening has also been reduced. All this, from our point of view, in the long run may not have a very positive effect on the course of treatment and prognosis of cancer. Therefore, doctors today are constantly faced with the task of maintaining the effectiveness of treatment of malignant neoplasms, on the one hand, and reducing the risk of coronavirus — on the other, because, according to many sources, cancer patients are at risk of adverse COVID-19 course. This is especially true for patients with chemotherapy-induced neutropenia. In this article we wanted to demonstrate the latest approaches to the management of cancer patients in this difficult period. We also considered the options for wider use of granulocyte colony-stimulating factors to prevent neutropenia in the COVID-19 era. It is still controversy about this in the medical scientific community. Unfortunately, the data available today are not enough to make unambiguous statements about a particular patient management, but by analyzing the large number of publications made during the pandemic year, as well as updated National Comprehensive Cancer Network guidelines, we were able to answer most of the questions that interest us.