INFLUENCE OF EARLY TERMINATION OF TREATMENT OF PATIENTS WITH TUBERCULOSIS ON ITS EFFECTIVENESS

The effectiveness of a course of chemotherapy largely depends on the continuity and duration. An ineffective outcome of a course of chemotherapy, in addition to objective reasons, also has an additional factor that strengthens it – a break in treatment or its early termination. The aim of the work is to study the effectiveness of treatment of patients with pulmonary tuberculosis with preserved drug sensitivity of the pathogen with early termination of the course of chemotherapy. Materials and methods: A retrospective analysis of the outcomes of a course of chemotherapy of tuberculosis patients who prematurely interrupted treatment, registered for 1-2-3 chemotherapy regimens in the Perm Region, was carried out. Results: Interruptions in treatment or its early termination were present in 7.8% of patients registered for treatment with 1-2-3 chemotherapy regimens. At the stage of inpatient treatment, there is a separation from treatment in 3.5% of patients receiving treatment in the intensive phase of 1-2-3 chemotherapy regimens. Separation from treatment at the outpatient stage is noted in 7.9% of patients receiving treatment in the continuation phase of 1-2-3 chemotherapy regimens, these terms are insufficient for a full course of chemotherapy.. An additional unfavorable factor of intermittent treatment is the formation of secondary drug resistance of Mycobacterium tuberculosis. The ineffectiveness of the course of chemotherapy leads to an increase in the number of patients with tuberculosis and the tension of the epidemic situation. Conclusions: In the treatment of patients with drug-sensitive tuberculosis in the Perm Region, treatment is interrupted more often at the outpatient stage than at the inpatient stage (p=0.03), which requires further study of the reasons for preventing early termination of treatment. It was found that the termination of treatment prematurely in all patients led to the ineffectiveness of CT. Social factors (lack of income, unfavorable living conditions and distance from drug dispensaries, staffing of qualified medical personnel) can affect the adherence and effectiveness of treatment.

Effectiveness of biologic treatment of psoriasis vulgaris (certolizumab pegol in practice of dermatologist)

The work represents the prospective cohort analysis of patients with psoriasis treated with certolizumab pegol (CZP) at the Tula Regional Clinical Dermatovenerologic Dispensary in years 2017–2019, who achieved remission and discontinued CZP and real-time observation of the patients. The patients remained in sustained remission after discontinuation of certolizumab pegol (mean drug-free remission was 42 weeks). Patients who had not responded to systemic therapy prior to CZP treatment demonstrated good response to methotrexate and cyclosporin A, which suggests the modulation of immune response by certolizumab pegol. The obtained results demonstrate that intermittent treatment with certolizumab pegol effiiently controls psoriasis, reduces drug burden.

Successful Treatment of Myeloid Sarcoma in an Elderly Patient with Myelodysplastic Syndrome with Reduced-Dose Azacitidine

Myeloid sarcoma (MS), which involves extramedullary lesions, is classified as a unique subtype of acute myeloid leukemia (AML). At present, no standard treatments for MS have been established. The patient was an 89-year-old man with myelodysplastic syndrome-excess blast-2 (MDS-EB-2) with a 2-year history of intermittent treatment with azacitidine (AZA) during a 4-year history of MDS. He developed painful cutaneous tumors 8 months after the second discontinuation of AZA. They were refractory for antibiotics and topical tacrolimus hydrate. A tumor biopsy was performed, and the histological findings of the tumor lesion showed a proliferation of tumor cells that were positive for myeloperoxidase and CD68 and negative for CD4 and CD123. The patient was diagnosed with MDS-associated MS. MDS-EB-2 quickly progressed to AML with the appearance of peripheral blood blasts and 25% bone marrow blasts. Monotherapy with reduced-dose AZA (37.5 mg/m2 for 7 days, every 4–6 weeks) was restarted, and the MS quickly disappeared. The patient’s MS was successfully treated with 16 cycles of AZA treatment over a 22-month period. There have been 10 reported cases in which MS was successfully treated with AZA. Among the 10 cases, the patient in the present case was the oldest. Treatment with reduced-dose AZA should be considered as a therapeutic option for MS in elderly patients with MDS, especially patients who are ineligible for intensive chemotherapy.

Rapamycin and Rapalogs

Inhibition of mTORC1 (mechanistic Target Of Rapamycin Complex 1) signaling promotes health and longevity in diverse model organisms. Over the past decade, excitement has built over the possibility that treatment with the mTORC1 inhibitor rapamycin can be utilized to treat or prevent age-related disease in humans. However, concerns over the side effects of rapamycin on immunity and metabolism have precluded the routine use of rapamycin as a geroprotective therapy. Here, we discuss the evidence that these negative side effects of rapamycin are largely mediated by off-target inhibition of a second mTOR Complex (mTORC2). Further, we discuss how intermittent treatment with rapamycin, specific dietary regimens, and new molecules may provide routes to the safer and more selective inhibition of mTORC1. We conclude that the time is ripe for the development of therapies based on the safe and selective inhibition of mTORC1 for the treatment or prevention of diseases of aging.

Intermittent Treatment with the Psychodynamic Psychiatrist: A Patient-Centered Approach

This study examines the experiences of patients in treatment with psychodynamic psychiatrists on an intermittent basis following an initial brief period of intensive psychotherapy and stabilization. Patients with non-psychotic disorders who received intermittent treatment answered a web-based questionnaire describing the usefulness of various supportive, cognitive-behavioral, and psychodynamic interventions. Forty-eight out of 58 patients invited to participate completed the survey (83% response rate). The majority (75%) of respondents welcomed the intermittent treatment frame. Therapeutic factors deemed to be most helpful included supportive interventions such as ability to relate to the clinician, ability of clinician to listen empathically, and feeling supported by a non-judgemental therapist when talking about private matters. The majority of respondents also endorsed as highly beneficial various cognitive-behavioral interventions such as understanding how thinking patterns impact behavior and feelings and discussing alternative coping skills. Also highly rated were psychodynamic interventions, including understanding how the present is modeled from past experiences and expression and regulation of affect. In the open-ended qualitative feedback, therapeutic factors including collaboration, forming an alliance, and empathic attunement emerged as important. Our preliminary findings suggest that the intermittent psychodynamic treatment frame is well received by patients. Patients welcome integration of different psychotherapeutic approaches to individualize treatment. The common factors in psychotherapy are important patient-reported therapeutic factors in the intermittent treatment approach.

Relevance of Higher-Order Epistasis in Drug Resistance

We studied five chemically distinct but related 1,3,5-triazine antifolates with regard to their effects on growth of a set of mutants in dihydrofolate reductase. The mutants comprise a combinatorially complete data set of all 16 possible combinations of four amino acid replacements associated with resistance to pyrimethamine in the malaria parasite Plasmodium falciparum. Pyrimethamine was a mainstay medication for malaria for many years, and it is still in use in intermittent treatment during pregnancy or as a partner drug in artemisinin combination therapy. Our goal was to investigate the extent to which the alleles yield similar adaptive topographies and patterns of epistasis across chemically related drugs. We find that the adaptive topographies are indeed similar with the same or closely related alleles being fixed in computer simulations of stepwise evolution. For all but one of the drugs the topography features at least one suboptimal fitness peak. Our data are consistent with earlier results indicating that third order and higher epistatic interactions appear to contribute only modestly to the overall adaptive topography, and they are largely conserved. In regard to drug development, our data suggest that higher-order interactions are likely to be of little value as an advisory tool in the choice of lead compounds.