Burden Of Morbidity Research Articles

Modification effects of immigration status and comorbidities on associations of heat and heatwave with stroke morbidity.

Heat and heatwave have been associated with stroke morbidity, but it is still unclear whether immigrants from different geographic regions and patients with comorbidity are more vulnerable to heat and heatwave. Time-stratified case-crossover design combined with generalized additive quasi-Poisson models were used to quantify the relative risks (RRs) of heat and heatwave on first-ever stroke morbidity during 0-7 lag days. Attributable fractions (AFs) were estimated to assess the first-ever stroke morbidity burden due to heat and heatwave. Stratified analyses for sex, age, disease subtypes, resident characteristics, and comorbidity type were performed to identify potential modification effects. Heat and heatwave were associated with first-ever stroke morbidity, with the AF of 2.535% (95% empirical confidence interval (eCI) = 0.748, 4.205) and 2.409% (95% confidence interval (CI) = 1.228, 3.400), respectively. Among northern and southern immigrants, the AF for heat was 2.806% (0.031, 5.069) and 2.798% (0.757, 4.428), respectively, and the AF for heatwave was 2.918% (0.561, 4.618) and 2.387% (1.174, 3.398), respectively, but the effects of both on natives were statistically insignificant. Among patients with hypertension, dyslipidemia, or diabetes, the AF for heat was 3.318% (1.225, 5.007), 4.237% (1.037, 6.770), and 4.860% (1.171, 7.827), respectively, and the AF for heatwave was 2.960% (1.701, 3.993), 2.771% (0.704, 4.308), and 2.652% (0.653, 4.185), respectively. However, the effects of both on patients without comorbidity were statistically insignificant. Heat and heatwave are associated with an increased risk of first-ever stroke morbidity among immigrants and those with comorbid hypertension, dyslipidemia, or diabetes, with the effects primarily due to non-native individuals. The author(s) are not authorized to share the data.

Metformin’s dual impact on Gut microbiota and cardiovascular health: A comprehensive analysis

Cardiovascular diseases (CVD) cause significant global morbidity, mortality and public health burden annually. CVD alters richness, diversity, and composition of Gut microbiota along with RAS and histopathological differences. Present study explores Metformin role in mitigating doxorubicin induced cardiovascular toxicity/remodeling. Animals were divided into 4 groups with n=6: Group I (N. Control) free access to diet and water; Group II (MET. Control) on oral Metformin (250 mg/kg) daily; Group III (DOX. Control) alternate day intraperitoneal Doxorubicin (3 mg/kg) totaling 18 mg/kg; Group IV (DOX. MET. Control) received both daily oral Metformin (250 mg/kg) and alternate day Doxorubicin (3 mg/kg). Gut microbial analysis was made from stool before animals were sacrificed for biochemical and histopathological analysis. Significant alterations were observed in ɑ and β-diversity with new genus from Firmicutes, specifically Clostridia_UCG-014, Eubacterium ruminantium, and Tunicibacter, were prevalent in both the DOX. Control and DOX.MET groups. Proteobacteria, represented by Succinivibrio, were absent in all groups. Additionally, Parabacteroides from the Bacteroidia phylum was absent in all groups except the N. control. In the DOX.MET Control group, levels of Angiotensin II ( 7.75± 0.49 nmol/min, p<0.01) and Renin (2.60±0.26 ng/ml/hr) were significantly reduced. Conversely, levels of CK-MB, Fibrinogen, Troponin, CRP ( p < 0.0001), and TNFɑ (p < 0.05) were elevated. Histopathological examination revealed substantial cardiac changes, including Fibrinogen and fat deposition and eosinophilic infiltration, as well as liver damage characterized by binucleated cells and damaged hepatocytes, along with altered renal tissues in the DOX.MET.Control group. The findings suggest that MET. significantly modifies gut microbiota, particularly impacting the Firmicutes and Proteobacteria phyla. The reduction in Angiotensin II levels, alongside increased inflammatory markers and myocardial damage, highlights the complex interactions and potential adverse effects associated with MET therapy on cardiovascular health.

Pattern of occupational lung disease among industrial workers attending a medical college of Eastern India.

Occupational lung diseases (OLDs) contribute a significant proportion to the global burden of pulmonary morbidities but are grossly misdiagnosed due to the relative lack of attribution given to occupational exposures. Obstructive lung diseases are known to be associated with long-lasting disability and loss of earning capacity (LOEC) among workers in industrial setups, thus reducing nationwide productivity. In this context, the study aimed to find out the pattern of OLD and factors associated with the severity of it among patients in a tertiary care hospital. The study was a record-based secondary data analysis conducted in the Medical Records Department of a Medical College in Kolkata. A computerized database of patients attending Special Medical Board (SMB) examinations from the Department of Medical Records was utilized for data collection. A data abstraction format was constructed to collect information on pulmonary morbidity, occupational exposure, and sociodemographic and behavioral variables. Extracted data were analyzed in Microsoft Excel and Statistical Package for Social Sciences (SPSS) software. After a review of records, it was shown that 62.3% (66 out of 106 people) of the study subjects had an obstructive type of OLD, the most common being Jute Byssinosis. A negative correlation (Spearman's ρ = -0.136) was found between pulmonary function (FEV1/FVC) and LOEC (%) in the study subjects. In the multivariable logistic regression, exposure to organic dust was found to be significantly associated with worsened lung function {adjusted-Odd's Ratio (95% Confidence Interval) =3.11 (1.1-8.8), P value = 0.03}. OLD is an understated health issue, especially in an industrial diaspora of developing countries, like India. Healthcare facilities should utilize their resources properly for the advancement of medical surveillance in industries where organic dust is produced. Health education of the stakeholders regarding the consequences of OLDs and the benefits of preventive primary approaches will go a long way in alleviating the burden of disease.

Subspecialty physicians’ perspectives on barriers and facilitators of hepatitis C treatment: a qualitative study

IntroductionThe hepatitis C virus (HCV) causes chronic and curable disease with a substantial burden of morbidity and mortality across the globe. In the United States (US) and other developed countries, incidence of HCV is increasing and people who inject drugs are disproportionately affected. However, HCV treatment rates amongst patients with substance use disorders (SUD) are suboptimal. In this study, we aimed to understand the perspectives of subspecialist physicians who care for substantial numbers of patients with HCV, including addiction medicine, infectious diseases, and hepatology physicians, to better understand barriers and facilitators of HCV treatment.MethodsWe recruited subspecialty physicians via purposive and snowball sampling and conducted semi-structured interviews with 20 physicians at 12 institutions across the US. We used a mixed deductive and inductive approach to perform qualitative content analysis with a rapid matrix technique.ResultsThree major themes emerged: (1) Perceptions of patient complexity; (2) Systemic barriers to care, and (3) Importance of multidisciplinary teams. Within these themes, we elicited subthemes on the effects of patient-level factors, provider-level factors, and insurance-based requirements.ConclusionOur results suggest that additional strategies are needed to reach the “last mile” untreated patients for HCV care, including decentralization and leverage of telehealth-based interventions to integrate treatment within primary care clinics, SUD treatment facilities, and community harm reduction sites. Such programs are likely to be more successful when multidisciplinary teams including pharmacists and/or peer navigators are involved. However, burdensome regulatory requirements continue to hinder this expansion in care and should be eliminated.

Chagas Disease in the Non-Endemic Area of Rome, Italy: Ten Years of Experience and a Brief Overview.

Chagas disease (CD) is a parasitic infection endemic in Latin America and also affects patients in Western countries due to migration flows. This has a significant impact on health services worldwide due to its high morbidity and mortality burden. This paper aims to share our experience at the National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, in Rome, Italy, where to date, a total of 47 patients-mainly Bolivian women-diagnosed with CD have received treatment with benznidazole, with all but one presenting with chronic disease. Most of the patients were recruited through the first extensive screening program held in 2014 at our Institute. About a quarter of our patients showed adverse effects to benznidazole, including a case of severe drug-induced liver injury, but 83% completed a full course of treatment. In addition to the description of our cohort, the paper reports a brief overview of the disease compiled through a review of the existing literature on CD in non-endemic countries. The growing prevalence of CD in Western countries highlights the importance of screening at-risk populations and urges public concern and medical awareness about this neglected tropical disease. There are still many unanswered questions that need to be addressed to develop a personalized approach in treating patients.

Inflammation unites diverse acute and chronic diseases.

Inflammation and immunity contribute pivotally to diverse acute and chronic diseases. Inflammatory pathways have become increasingly targets for therapy. Yet, despite substantial similarity in mechanisms and pathways, the scientific, medical, pharma and biotechnology sectors have generally focused programs finely on a single disease entity or organ system. This insularity may impede progress in innovation and the harnessing of powerful new insights into inflammation biology ripe for clinical translation. A multidisciplinary thinktank reviewed highlights how inflammation contributes to diverse diseases, disturbed homeostasis, ageing and impaired healthspan. We explored how common inflammatory and immune mechanisms that operate in key conditions in their respective domains. This consensus review highlights the high degree of commonality of inflammatory mechanisms in a diverse array of conditions that together contribute a major part of the global burden of morbidity and mortality and present an enormous challenge to public health and drain on resources. We demonstrate how that shared inflammatory mechanisms unite many seemingly disparate diseases, both acute and chronic. The examples of infection, cardiovascular conditions, pulmonary diseases, rheumatological disorders, dementia, cancer and ageing illustrate the overlapping pathogenesis. We outline opportunities to synergize, reduce duplication and consolidate efforts of the clinical, research and pharmaceutical communities. Enhanced recognition of these commonalties should promote cross-fertilization and hasten progress in this rapidly moving domain. Greater appreciation of the shared mechanisms should simplify understanding seemingly disparate diseases for clinicians and help them to recognize inflammation as a therapeutic target which the development of novel therapies is rendering actionable.

INTRAOPERATIVE USE OF DEFENSIVE ANTIBACTERIAL COATING (DAC) FOR COMPLEX SURGERIES IN COMPLEX HOSTS

Periprosthetic joint infections (PJIs) and osteosynthesis-associated infections (OSIs) present significant challenges in trauma and orthopaedic surgery, substantially impacting patient morbidity, mortality, and economic burden. This concern is heightened in patients with pre-existing comorbidities, such as diabetes mellitus, which are not always modifiable at presentation. A novel intraoperative strategy to prevent these infections is the use of Defensive Antibacterial Coating (DAC), a bio-absorbable antibiotic-containing hydrogel applied to implant surfaces at implantation, acting as a physical barrier to prevent infection.The purpose of this study is to assess the use of a commercially available hydrogel (DAC), highlighting its characteristics that make it suitable for managing PJIs and OSIs in orthopaedics and traumatology. Twenty-five patients who underwent complex orthopaedic procedures with intraoperative application of DAC between March 2022 and April 2023 at a single hospital site were included. Post-operative assessment encompassed clinical, laboratory, and radiographic examinations.In this study, 25 patients were included, with a mean age of 70 ± 14.77 years and an average ASA grade of 2.46 ± 0.78. The cohort presented an average Charleston Comorbidity score of 5.45 ± 2.24. The procedures included 8 periprosthetic fractures, 8 foot and ankle surgeries, 5 upper limb surgeries, and 4 elective hip and knee surgeries. Follow-up assessments at 6 weeks and 6 months revealed no evidence of PJI or OSI in any patients, nor were any treatments for PJI or OSI required during the interim period.DAC demonstrated efficacy in preventing infections in high-risk patients undergoing complex orthopaedic procedures. Our findings warrant further investigation into the use of DAC in complex hosts with randomized control trials.

The Problem with Delaying Measles Elimination.

Measles is a highly infectious disease leading to high morbidity and mortality impacting people's lives and economies across the globe. The measles vaccine saves more lives than any other vaccine in the Essential Programme of Immunization and is also the most cost-effective vaccine, with an extremely high return on investment. This makes achieving measles elimination through vaccination a key child health intervention, particularly in low-income countries, where the overwhelming majority of measles deaths continue to occur. All countries and regions of the world have committed to achieving measles elimination, yet many have faced challenges securing political commitment at national and global levels and predictable, timely, and flexible support from global donors, and experienced setbacks during the COVID-19 pandemic. This has happened against a backdrop of stagnant measles vaccination coverage and declining enthusiasm for vertical programmes, culminating in a World Health Organization Strategic Advisory Group of Experts (WHO SAGE) review of the feasibility of measles eradication in 2019. Sustaining the elimination of measles long term is extremely difficult, and some countries have lost or nearly lost their measles elimination status in the face of ongoing importation of cases from neighbouring or closely connected countries in which elimination had been delayed. Thus, a widening equity gap in measles immunisation coverage creates challenges for all countries, not just those facing the greatest burden of measles morbidity and mortality. Delaying elimination of measles in some countries makes it cumulatively harder for all countries to succeed for three principal reasons: increased inequity in measles immunisation coverage makes outbreaks more likely to happen and to be larger; political will is very difficult to sustain; and immunity may wane to a point that transmission is re-established. New strategies are needed to support countries and regions in their vision for a world without measles, including ways to galvanise domestic, regional and global resources and ignite the political will that is essential to make the vision a reality.

Neonatal sepsis-a peek into our findings in Northwest Nigeria: a prospective study

BackgroundNeonatal sepsis is still a global health concern as it contributes to a high burden of neonatal morbidity and mortality especially in developing countries. The aim of the study is to give an insight into neonatal sepsis: risk factors, sepsis types, clinical features, pathogen burden with their antibiotic sensitivities, and outcome of admission in our facility. The study was a prospective hospital-based study conducted over 10 months, October 2018–July 2019.ResultOf the 248 term neonates with features of sepsis enrolled in the study 94 (37.9%) were confirmed to have sepsis. Late-onset sepsis LOS (68%) was found to be the most common, and most of the neonates were delivered elsewhere. Clinical features were non-specific for both early-onset (EOS) and LOS and include fever, jaundice, poor suck, and depressed primitive reflexes. Infections were mostly caused by gram-negative bacteria, and while Staphylococcus aureus was the single most common isolate for both EOS and LOS. Antibiotic sensitivity was highest with ciprofloxacin for both EOS and LOS. Mortality was high at 14.9% and was mostly contributed to by Staphylococcus aureus infection.ConclusionNeonatal sepsis is still a burden with mostly non-specific clinical features. The local prevalent organisms were Staphylococcus aureus, Enterobacter agglomerans and Klebsiella pneumonia with good antibiotic susceptibility to ciprofloxacin. Most presented with late-onset sepsis and therefore infection is likely to be community-acquired which to a great extent can be prevented with robust public health interventions.

Neurocysticercosis- An overlooked tropical disease

Introduction. Background: Neurocysticercosis (NCC), a parasitic disease caused by the pork tapeworm Taenia solium (T. solium), is a significant public health concern in endemic countries. It is estimated to contribute to roughly 30% of all epilepsy cases and leads to chronic morbidity in nearly 70% of affected patients. This study aimed to determine the prevalence of anti-cysticercus antibodies to T. solium in individuals with recent-onset seizures. We employed two serological techniques: Enzyme-Linked Immuno Sorbent Assay (ELISA) and Enzyme-Linked Immuno Transfer Blot (EITB). Materials and Methods: A total of 100 serum samples were collected: 50 from patients experiencing recent-onset seizures (cases) and 50 from age-matched healthy controls. All samples were analyzed for the presence of anti-cysticercus antibodies to T. solium. Results: Among the 50 cases, EITB detected anti-cysticercus antibodies in six patients (12%), while ELISA identified antibodies in three patients (6%). Notably, only two cases tested positive using both EITB and ELISA. In the control group, one individual was seropositive by EITB, and none were positive by ELISA. Conclusion: This study underscores the critical role of implementing high-quality screening methods, employing a vigilant diagnostic approach, and taking prompt preventive measures to mitigate the burden of morbidity associated with NCC.

Healthcare Seeking Behavior of People Below Poverty Line: Pattern and Determinants

ABSTRACT The severity and type of morbidity largely define the health-seeking behavior of an individual, although the socioeconomic determinants also play an important role. In this paper, the health-seeking behavior of individuals from the “Below Poverty Line” is analyzed by using the individual-level data of the Indian Human Development Survey (IHDS)-II (2011–12). The trend and pattern of both major and short-term morbidity among the individuals from the “Below Poverty Line” are analyzed along with the comparison with individuals from the “Above Poverty Line.” Further, The logit regression model is used to determine the prominent socioeconomic factors of health-seeking behavior among individuals from “Below Poverty Line” and the decomposition analysis is conducted to determine the factor contributing to widening or narrowing the gap in getting treatment by individuals from both income groups. The result shows that individuals from the “Below Poverty Line” have a comparatively lower burden of major morbidity but also get lower treatments. The condition of women is more concerning. Socioeconomic factors such as “place of residence,” “education,” marital status, “age,” and “caste” are significant to the health-seeking behaviors of individuals from the “Below Poverty Line.” Further, “education” and “primary activity” are two major factors for both major and short-term morbidity that widen the gap in the health-seeking behavior of individuals from both income groups. However, factors such as “place of residence” and caste increase the gap in case of only short-term morbidity.

Lung Transplant for Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) carries a high burden of morbidity and mortality to patient and a high cost to health care systems. Lung transplantation is a last resort available for end-stage COPD patients interested in pursuing it and meeting the strict transplant requirements. It requires commitment from patients and their loved ones to support them through this tough process. This review will cover history of transplant, indications, candidate selection, evaluation testing, transplant listing, type of transplant (single versus bilateral), posttransplant complications, immunosuppression, and rejection. It is tailored to the COPD patient when applicable; however, many aspects of lung transplantation are shared amongst all lung diseases eligible for transplant.

COVID-19 antibody responses in individuals with natural immunity and with vaccination-induced immunity: a systematic review and meta-analysis

BackgroundThe COVID-19 pandemic has caused a large mortality and morbidity burden globally. For individuals, a strong immune response is the most effective means to block SARS-CoV-2 infection. To inform clinical case management of COVID-19, development of improved vaccines, and public health policy, a better understanding of antibody response dynamics and duration following SARS-CoV-2 infection and after vaccination is imperatively needed.MethodsWe systematically analyzed antibody response rates in naturally infected COVID-19 patients and vaccinated individuals. Specifically, we searched all published and pre-published literature between 1 December 2019 and 31 July 2023 using MeSH terms and “all field” terms comprising “COVID-19” or “SARS-CoV-2,” and “antibody response” or “immunity response” or “humoral immune.” We included experimental and observational studies that provided antibody positivity rates following natural COVID-19 infection or vaccination. A total of 44 studies reporting antibody positivity rate changes over time were included.ResultsThe meta-analysis showed that within the first week after COVID-19 symptom onset/diagnosis or vaccination, antibody response rates in vaccinated individuals were lower than those in infected patients (p < 0.01), but no significant difference was observed from the second week to the sixth month. IgG, IgA, and IgM positivity rates increased during the first 3 weeks; thereafter, IgG positivity rates were maintained at a relatively high level, while the IgM seroconversion rate dropped.ConclusionsAntibody production following vaccination might not occur as quickly or strongly as after natural infection, and the IgM antibody response was less persistent than the IgG response.

Multiple chronic diseases and psychological distress among adults in the United States: the intersectionality of chronic diseases, race/ethnicity, immigration, sex, and insurance coverage.

Psychological distress significantly contributes to the burdens of morbidity and mortality in the United States (U.S.), but our understanding is limited with regards to the risk factors associated with psychological distress. We used nationally representative data to examine (1) the comorbidities of chronic diseases and their risks for psychological distress and (2) the ways in which chronic diseases combine with demographic factors such as sex, race/ethnicity, immigration status, and health insurance coverage to affect the patterning of psychological distress. We analyzed the 2005-2018 National Health Survey Interview cross-sectional data on U.S. adults aged ≥ 18 years (n = 351,457). We fitted sequential multivariable logistic regression models. There was a dose-response relationship between the number of chronic diseases and psychological distress, with increased number of chronic diseases associated with increased psychological distress risk. Females (vs. males) and those without health insurance (vs. insured) were more likely to experience psychological distress. Immigrants (vs. non-immigrants) and racial/ethnic minorities (vs. White individuals) were less likely to experience psychological distress. There were significant interactions between chronic diseases and insurance coverage, immigration status, and race/ethnicity, but the three-way interactions were not statistically significant with psychological distress: chronic disease status vs. immigration status vs. health insurance coverage, and chronic disease vs. race/ethnicity vs. immigration status. The findings suggest a critical need to consider the complex ways in which chronic diseases and psychosocial factors combine to affect psychological distress and their implications for tailoring mental health screening, initiatives to reduce distress, and prevention strategies for effectively addressing health-related disparities in the general population.

Immunogenicity of a Rotavirus VP8* Multivalent Subunit Vaccine in Mice.

Rotavirus remains a significant public health threat, especially in low-income countries, where it is the leading cause of severe acute childhood gastroenteritis, contributing to over 128,500 deaths annually. Although the introduction of the Rotarix and RotaTeq vaccines in 2006 marked a milestone in reducing mortality rates, approximately 83,158 preventable deaths persisted, showing ongoing challenges in vaccine accessibility and effectiveness. To address these issues, a novel subcutaneous vaccine formulation targeting multiple rotavirus genotypes has been developed. This vaccine consists of nine VP8* proteins from nine distinct rotavirus genotypes and sub-genotypes (P[4], P[6], P[8]LI, P[8]LIII, P[8]LIV, P[9], P[11], P[14], and P[25]) expressed in E. coli. Two groups of mice were immunized either with a single immunogen, the VP8* from the rotavirus Wa strain (P[8]LI), or with the nonavalent formulation. Preliminary results from mouse immunization studies showed promising outcomes, eliciting antibody responses against six of the nine immunogens. Notably, significantly higher antibody titers against VP8* P[8]LI were observed in the group immunized with the nonavalent vaccine compared to mice specifically immunized against this genotype alone. Overall, the development of parenteral vaccines targeting multiple rotavirus genotypes represents a promising strategy in mitigating the global burden of rotavirus-related morbidity and mortality, offering new avenues for disease prevention and control.

Optimization of treatment strategies for elderly patients with advanced non-small cell lung cancer.

Lung cancer stands as a malignant neoplasm bearing the highest burden of morbidity and mortality within the elderly population on a global scale. Among the lung cancer subtypes, non-small cell lung cancer (NSCLC) prevails as the most prevalent. As age advances, elderly patients often present with an increased prevalence of comorbidities, diminished organ reserve function, and alterations in drug pharmacokinetics, including absorption, distribution, metabolism, and clearance. These factors collectively contribute to a reduction in their capacity to tolerate therapeutic interventions. Regrettably, there exists a paucity of research data and evidence regarding the management of elderly patients afflicted by advanced lung cancer. This article endeavors to compile and elucidate strategies for the enhancement of treatment approaches, with the aim of aiding clinical decision-making. Prior to the selection of clinical treatment modalities for elderly patients with advanced NSCLC, a comprehensive assessment should be conducted, taking into account various facets, including tumor characteristics, patient age, physiological status, and the presence of comorbidities. The treatment strategy should be implemented in a tiered fashion, thereby affording the opportunity for the tailoring of individualized therapeutic approaches for elderly patients afflicted by advanced NSCLC. The demographic of elderly patients confronting advanced NSCLC presents a complex landscape marked by intricate underlying conditions, necessitating the imperative optimization of treatment strategies.

Hyponatraemia-treatment standard 2024.

Hyponatraemia is the most common electrolyte disorder in hospital patients associated with increased morbidity, mortality, hospital stay and financial burden. The speed of a correction with 3% sodium chloride as a 100- to 150-ml intravenous bolus or continuous infusion depends on the severity and persistence of the symptoms and needs frequent biochemical monitoring. The rapid intermittent administration of hypertonic saline is preferred for treatment of symptomatic hyponatraemia. In asymptomatic mild hyponatraemia, an adequate solute intake with an initial fluid restriction (FR) of 500ml/day adjusted according to the serum sodium (sNa) levels is preferred. Almost half of the syndrome of inappropriate antidiuretic hormone (SIADH) patients do not respond to FR as first-line therapy. At present, urea and tolvaptan are considered the most effective second-line therapies in SIADH. However, the evidence for guidance on the choice of second-line therapy of hypotonic hyponatraemia is lacking. Oral urea is considered to be a very effective and safe treatment. Mild and asymptomatic hyponatraemia is treated with adequate solute intake (salt and protein) and initial FR with adjustments based on sNa levels. Specific treatment with vaptans may be considered in either euvolaemic or hypervolaemic patients with high ADH activity. In order to ensure optimal patient outcome, close monitoring and readiness for administration of either hypotonic fluids or desmopressin may be crucial in the decision-making process for specific treatment and eventual overcorrection consequences. According to the guidelines, gradual correction and clinical evaluation is preferable over rapid normalization of sNa towards the laboratory reference ranges.

Patent characteristics for leishmaniasis treatment as a basis for freedom-to-operate analysis

Among the main zoonoses with the highest morbidity burden is leishmaniasis. The parasite of the genus Leishmania is its etiological agent. There are three forms of the disease: cutaneous, mucocutaneous and visceral. Pentavalent antimonial drugs are used for leishmaniasis treatment, however toxic side effects and parasite resistance have been detected. Intellectual Property Rights (IPRs) protect inventions that promote benefits to society, and patents are particularly notable for preserving advancements in biotechnology. To introduce innovative technologies, it is necessary to analyze the elements and processes involved in the development of products that may be protected by IPRs. This process consists of product deconstruction into its elements for an intellectual property analysis to contemplate commercial viability, and to determine strategies to avoid infringing third party rights (Freedom-to-Operate approach). In this project, a sample of patents protecting treatments directed against leishmaniasis were evaluated in order to know their characteristics, and to establish useful elements for Freedom-to-operate strategies. Open access patent databases were used (The Lens, Google patents, Patentscope, among others), and relevant characteristics such as claims, owners, technology protection region, or year of application for protection were determined. The sample obtained includes patents from 1967 to 2023. The majority of patents were found to be located in countries such as Brazil or the United States, and described developments focused on compounds derived from chemical synthesis, polypeptides, extracts, antigens, or structural components of the parasite. There are several patents that have already expired and whose information can be freely used. The Bolar exemption would allow the use of information from these patents for regulatory compliance purposes. This study provides an overview of what has been patented for leishmaniasis treatment, and information on Freedom-to-operate focus.

Chimeric antigen receptor adoptive immunotherapy in central nervous system tumors: state of the art on clinical trials, challenges, and emerging strategies to addressing them.

Central nervous system (CNS) tumors represent a significant unmet medical need due to their enduring burden of high mortality and morbidity. Chimeric antigen receptor (CAR) T-cell therapy emerges as a groundbreaking approach, offering hope for improved treatment outcomes. However, despite its successes in hematological malignancies, its efficacy in solid tumors, including CNS tumors, remains limited. Challenges such as the intricate tumor microenvironment (TME), antigenic heterogeneity, and CAR T-cell exhaustion hinder its effectiveness. This review aims to explore the current landscape of CAR T-cell therapy for CNS tumors, highlighting recent advancements and addressing challenges in achieving therapeutic efficacy. Innovative strategies aim to overcome the barriers posed by the TME and antigen diversity, prevent CAR T-cell exhaustion through engineering approaches and combination therapies with immune checkpoint inhibitors to improving treatment outcomes. Researchers have been actively working to address these challenges. Moreover, addressing the unique challenges associated with neurotoxicity in CNS tumors requires specialized management strategies. These may include the development of grading systems, monitoring devices, alternative cell platforms and incorporation of suicide genes. Continued research efforts and clinical advancements are paramount to overcoming the existing challenges and realizing the full potential of CAR T-cell therapy in treating CNS tumors.

Meeting complex multidimensional needs in older patients and their families during and beyond critical illness.

To highlight the emerging crisis of critically ill elderly patients and review the unique burden of multidimensional morbidity faced by these patients and caregivers and potential interventions. Physical, psychological, and cognitive sequelae after critical illness are frequent, durable, and robust across the international ICU outcome literature. Elderly patients are more vulnerable to the multisystem sequelae of critical illness and its treatment and the resultant multidimensional morbidity may be profound, chronic, and significantly affect functional independence, transition to the community, and quality of life for patients and families. Recent data reinforce the importance of baseline functional status, health trajectory, and chronic illness as key determinants of long-term functional disability after ICU. These risks are even more pronounced in older patients. The current article is an overview of the outcomes of older survivors of critical illness, putative interventions to mitigate the long-term morbidity of patients, and the consequences for families and caregivers. A multimodal longitudinal approach designed to follow patients for one or more years may foster a better understanding of multidimensional morbidity faced by vulnerable older patients and families and provides a detailed understanding of recovery trajectories in this unique population to optimize outcome, goals of care directives, and ongoing informed consent to ICU treatment.