Global availability of parenteral nutrition: Pre- and post-COVID-19 pandemic surveys.

OBJECTIVE: Parenteral nutrition represents a therapeutic option for patients with type 3 intestinal failure. If used exclusively, parenteral nutrition has to be complete to provide all essential nutrients. The aim was to assess the availability of parenteral nutrition in all parts of the world, to better comprehend the global situation, and to prepare an action plan to increase access to parenteral nutrition. METHODS: An international survey using an electronic questionnaire was conducted in August 2019 and repeated in May 2022. An electronic questionnaire was sent to 52 members or affiliates of the International Clinical Nutrition Section of the American Society for Parenteral and Enteral Nutrition. Questions addressed the availability of parenteral nutrition admixtures and their components, reimbursement, and prescribing pre- and post-COVID-19 pandemic. All participating countries were categorized by their economic status. RESULTS: Thirty-six country representatives responded, answering all questions. Parenteral nutrition was available in all countries (100%), but in four countries (11.1%) three-chamber bags were the only option, and in six countries a multibottle system was still used. Liver-sparing amino acids were available in 18 (50%), kidney-sparing in eight (22.2%), and electrolyte-free in 11 (30.5%) countries (30.5%). In most countries (n = 28; 79.4%), fat-soluble and water-soluble vitamins were available. Trace elements solutions were unavailable in four (11.1%) countries. Parenteral nutrition was reimbursed in most countries (n = 33; 91.6%). No significant problems due to the coronavirus pandemic were reported. CONCLUSIONS: Despite the apparent high availability of parenteral nutrition worldwide, there are some factors that may have a substantial effect on the quality of parenteral nutrition admixtures. These shortages create an environment of inequality.

In search of effective therapies: the current landscape of phase II trials in patients with advanced soft tissue sarcoma.

PURPOSE: Soft tissue sarcomas (STS) are diagnosed in 4-6 cases per 100 000 people a year and are associated with an unfavorable prognosis. Around one-third of patients will develop metastatic disease that requires palliative systemic therapy. Current therapeutic options have limited activity, and new treatments are tested, mainly in phase II trials. There is high variability and no standardization of phase II designs. We aimed to analyze the current landscape of phase II studies in STS and evaluate how its statistical design can affect the results. METHODS: Full-text phase II studies published in STS patients between 2005 and 2020 were identified and analyzed. RESULTS: We have identified 102 trials, of which 77.4% were single-arm trials, 16.7% were randomized comparative trials (RCT), and 5.9% were randomized noncomparative trials. Including multiple cohorts, 22 randomized and 128 single-arm cohorts were analyzed. Nearly 80% of trials reported full statistical bases of the design. Over 20 different primary endpoints were used, with PFS as the most common in RCT trials (81.8%) and ORR (36.7%) and 3-months progression-free survival (PFS) rate (21.9%) in single-arm trials. Overall, 27.3% of RCT and 37.5% of single-arm trials were positive. Among single-arm trials, studies using 3- or 6-month rates were more often positive than those based on ORR. CONCLUSIONS: There is high heterogeneity in sarcoma trial designs, mainly in primary-endpoint and hypotheses used for size calculation. There is an unmet need for standardization that will incorporate factors associated with the rarity of the disease, outcomes detected in previous trials and real-life studies, and specific characteristics of new therapeutic agents.

Malignant complications of masturbation - a case study. / Zlosliwe nastepstwa masturbacji - opis przypadku.

We present a case of a 32-years-old female patient diagnosed with paranoid schizophrenia for many years who has developed neuroleptic malignant syndrome (NMS) as a result of long-acting antipsychotic's injection. Since the initial ineffectiveness of benzodiazepines, the course of electroconvulsive therapy (ECT) has been carried out. In spite of the initial promising response to ECT 3 weeks after the admission her somatic and mental state deteriorated greatly, that was hardly explicable solely by the potential loss of effectiveness of ECT or laboratory tests. Diagnostics extended with imaging tests and gynecological examination revealed the connective tissue-covered cap of a popular multivitamin supplement in patient's vagina. During the following deepened interview, she admitted that in fact 6 months ago a piece had gotten stuck while masturbating. However due to the sense of shame and subjective lack of disturbing symptoms she had left it unsaid. One month after the evacuation of the foreign body she has been discharged from the hospital remaining the full remission. The presented case shows that inflammation in the body can complicate catatonia and NMS, causing a non-specific course and difficulties in diagnosis and treatment. In some patients, the inflammatory process may be caused by a foreign body located in various natural orifices in the body. It appears significant in the group of psychiatric patients. Once again it highlights the tremendous role of meticulously conducted interview including the patient's autoerotic life.

Burden of hospitalizations in newly diagnosed heart failure patients in Poland: real world population based study in years 2013-2019.

AIMS: We aim to report trends in unplanned hospitalizations among newly diagnosed heart failure patients with regard to hospitalizations types and their impact on outcomes. METHODS AND RESULTS: A nation-wide study of all citizens in Poland with newly diagnosed heart failure based on ICD-10 coding who were beneficiaries of either public primary, secondary, or hospital care between 2013 and 2018 in Poland. Between 1 January 2013 and 31 December 2019, there were 1 124 118 newly diagnosed heart failure patients in Poland in both out- and inpatient settings. The median observation time was 946 days. As many as 49% experienced at least one acute heart failure hospitalization. Once hospitalized, 44.6% patients experienced at least one all-cause rehospitalization and 26% another heart failure rehospitalization. The latter had the highest Charlson co-morbidity index (1.36). The 30 day heart failure readmission rate was 2.96%. Kaplan-Meier analysis revealed very early readmissions (up to 1-7 days) were associated with better survival compared with rehospitalization between 8 and 30 days. All-cause mortality was related to the number of hospitalization with adjusted estimated hazard ratios: 1.550 (95% CI: 1.52-158) for the second HF hospitalization, 2.158 (95% CI: 2.098-2.219) for third, and 2.788 (95% CI: 2.67-2.91) for the fourth HF hospitalization and subsequent ones, as compared with the first hospitalization. CONCLUSIONS: Among newly diagnosed heart failure patients in Poland between 2013 and 2019, nearly half required at least one unplanned heart failure hospitalization. The risk of death was growing with every other hospital reoccurrence due to heart failure.

Indirect Costs of Rheumatoid Arthritis Depending on Type of Treatment-A Systematic Literature Review.

The economic burden of rheumatoid arthritis (RA) on society is high. Disease-modifying antirheumatic drugs (DMARDs) are the cornerstone of therapy. Biological DMARDs are reported to prevent disability and improve quality of life, thus reducing indirect RA costs. We systematically reviewed studies on the relationship between RA and indirect costs comparing biological treatment with standard care. Studies, economic analyses, and systematic reviews published until October 2018 through a MEDLINE search were included. A total of 153 non-duplicate citations were identified, 92 (60%) were excluded as they did not meet pre-defined inclusion criteria. Sixty-one articles were included, 17 of them (28%) were reviews. After full-text review, 28 articles were included, 11 of them were reviews. Costs associated with productivity loss are substantial; in several cases, they may represent over 50% of the total. The most common method of estimation is the Human Capital method. However, certain heterogeneity is observed in the method of estimating, as well as in the resultant figures. Data from included trials indicate that biological therapy is associated with improved labor force participation despite an illness, in which the natural course of disease is defined by progressive work impairment. Use of biological DMARDs may lead to significant indirect cost benefits to society.

Manual work in cold environments and its impact on selection of materials for protective gloves based on workplace observations.

This article presents a workplace observations on manual work in cold environments and its impact on the selection of materials for protective gloves. The workplace observations was conducted on 107 workers in 7 companies and involved measurements of the temperature of air and objects in the workplaces; in addition the type of surface and shape of the objects was determined. Laboratory tests were also carried out on 11 materials for protective gloves to be used in cold environments. Protective characteristics, including mechanical properties (wear, cut, tear, and puncture resistance), insulation properties (thermal resistance), functional parameters, and hygienic properties (resistance to surface wetting, material stiffness) were evaluated. Appropriate levels of performance and quality, corresponding to the protective and functional properties of the materials, were determined. Based on the results of manual work and laboratory tests, directions for the selection of materials for the construction of protective gloves were formulated with a view to improving work ergonomics.

Peptide-based inhibitors of protein-protein interactions.

Protein-protein interactions (PPIs) are key elements of several important biological processes and have emerged as valuable targets in medicinal chemistry. Importantly, numerous specific protein-protein interactions (e.g., p53-HDM2 and Bcl-2-BH3 domains) were found to be involved in the development of several diseases, including various types of cancer. In general, the discovery of new synthetic PPI inhibitors is a challenging task because protein surfaces have not evolved in a manner that allows for specific binding of low molecular weight compounds. Here, we review the discovery strategies for peptide-based PPI inhibitors. Although peptide-based drug candidates exhibit significant drawbacks (in particular, low proteolytic stability), modifications of either the side chains or backbone could provide molecules of interest. Moreover, due to the large molecular size of peptide-based compounds, the discovery of molecules that specifically interact with extended protein surfaces is possible. Two major strategies for constructing peptide-based PPI inhibitors are as follows: (a) cyclization (e.g., stapled peptides) and (b) modification of the backbone structure (e.g., ß-peptides and peptoids). These approaches for constructing PPI inhibitors enhance both the inhibitory activity and pharmacokinetic properties compared with non-modified α-peptides.