Multidimensional Treatment Research Articles

Changes in WHO classification of adrenal tumors and new ideas for multi-dimensional diagnosis and treatment

In 2022, WHO updated the classification and concept of adrenal cortical and medullary tumors. In terms of adrenal cortical tumors, the WHO classification further standardizes the nomenclature of nodular adrenal cortical disease and refines the pathological classification of primary aldosteronism. In terms of adrenal medullary tumors, the WHO classification unifies the concepts of pheochromocytoma and paraganglioma, and reclassifies various concepts, including paraganglioma-like neuroendocrine tumors. The new standards not only cover the clinical manifestations of the disease, but also include other multiple aspects such as the histological origin of the disease, immunohistochemical manifestations, physiological mechanisms of the disease, hereditary susceptibility and prognostic factors. This article intends to explore how to improve the diagnostic and therapeutic level of adrenal tumors.

Collaboration, coordination and communication as facilitators of transitions for patients with advanced cancer: a scoping review linked to the Pal-Cycles project

BackgroundPerson-centred care is becoming increasingly recognised as an important element of palliative care. The current review syntheses evidence in relation to transitions in advanced cancer patients with palliative care needs. The review focuses on specific elements which will inform the Pal-Cycles programme, for patients with advanced cancer transitioning from hospital care to community care. Elements of transitional models for cancer patients may include, identification of palliative care needs, compassionate communication with the patient and family members, collaborative effort to establish a multi-dimensional treatment plan, review and evaluation of the treatment plan and identification of the end of life phase.MethodsA scoping review of four databases (MEDLINE, EMBASE, CINAHL, PsycINFO) was conducted to identify peer-reviewed studies published from January 2013 to October, 2022. A further hand-search of references to locate additional relevant studies was also undertaken. Inclusion criteria involved cancer patients transitions of care with a minimum of two of components from those listed above. Studies were excluded if they were literature reviews, if transition of care was related to cancer survivors, involved non-cancer patients, had paediatric population, if the transition implied a change of therapy and or a lack of physical transit to a non-hospital place of care. This review was guided by Arksey and O’Malley’s framework and narrative synthesis was used.ResultsOut of 5695 records found, 14 records were selected. Transition models identified: increases in palliative care consultations, hospice referrals, reduction in readmission rates and the ability to provide end of life care at home. Transition models highlight emotional and spiritual support for patients and families. No uniform model of transition was apparent, this depends on the healthcare system where it is implemented.ConclusionsThe findings highlight the importance of collaboration, coordination and communication as central mechanisms for transitional model for patients with advanced cancer. This may require careful planning and will need to be tailored to the contexts of each healthcare system.

The Egyptian journey from having the highest prevalence of hepatitis C virus to being the first to achieve “gold tier” in conquering the disease

Hepatitis C virus (HCV) is a major global health concern, particularly in Egypt, due to historic schistosomiasis control efforts that inadvertently led to widespread HCV transmission. This study aimed to evaluate the efficacy of Egypt’s national strategies in controlling and reducing the prevalence of HCV, including introducing sofosbuvir and implementing the “100 Million Healthy Lives” campaign. The approach includes a review of epidemiological data, an analysis of the national HCV control strategies implemented, and an assessment of their outcomes, focusing on the period from 2006 to 2022. Significant milestones were achieved, including a drastic reduction in new HCV infections from 300 per 100,000 in 2014 to 9 per 100,000 in 2022 and successful treatment of over 4 million people. Egypt has become the first country in the world to achieve the “gold tier” status based on World Health Organization criteria on the path to eradication of HCV. Egypt’s comprehensive approach can serve as a model for similar endemic regions. Other nations with high HCV prevalence might benefit from adopting similar multidimensional strategies, emphasizing prevention and treatment.

Bayesian hierarchical profile regression for binary covariates.

Dysphagia, a common result of other medical conditions, is caused by malfunctions in swallowing physiology resulting in difficulty eating and drinking. The Modified Barium Swallow Study (MBSS), the most commonly used diagnostic tool for evaluating dysphagia, can be assessed using the Modified Barium Swallow Impairment Profile (MBSImP™). The MBSImP assessment tool consists of a hierarchical grouped data structure with multiple domains, a set of components within each domain which characterize specific swallowing physiologies, and a set of tasks scored on a discrete scale within each component. We lack sophisticated approaches to extract patterns of physiologic swallowing impairment from the MBSImP task scores within a component while still recognizing the nested structure of components within a domain. We propose a Bayesian hierarchical profile regression model, which uses a Bayesian profile regression model in conjunction with a hierarchical Dirichlet process mixture model to (1) cluster subjects into impairment profile patterns while respecting the hierarchical grouped data structure of the MBSImP, and (2) simultaneously determine associations between latent profile cluster membership for all components and the outcome of dysphagia severity. We apply our approach to a cohort of patients referred for an MBSS and assessed using the MBSImP. Our research results can be used to inform appropriate intervention strategies, and provide tools for clinicians to make better multidimensional management and treatment decisions for patients with dysphagia.

Effective multidimensional treatment identification of different chemical fertilizers: Response of insect dynamics and rice production

Effective management of fertilizers is essential in influencing the prevalence of insects in rice (Oryza sativa L.) fields. Over two years (2019-20 and 2020-21), an experiment conducted at Bangladesh Rice Research Institute (BRRI), Habiganj, during the boro season aimed to identify the most effective multidimensional treatment (EMT) by testing various combinations of chemical fertilizers and its effect on rice insects. The goal was to optimize rice grain yield while minimizing harmful insect infestation and supporting natural enemies. Eight different chemical fertilizer applications were used as follows: T1 contained a full mix of nitrogen (N), phosphorus (P), potassium (K), and sulfur (S); T2 had PKS but lacked N; T3 had NKS but lacked P; T4 had NPS but lacked K; T5 had NPK but lacked S; T6 had KS but lacked N and P; T7 had PS but lacked N and K; and T8 lacked all four elements - N, P, K, and S.The relationship between the dynamics of harmful insects and natural enemies was highly positively correlated (r = 0.72 to 0.97). In two consecutive growing years, the 2020-21 season exhibited notably higher counts of harmful insects, with Rice Leafroller (RLR) dominating in the booting stage and White Backed Planthopper (WBPH) in mid-tillering, while Green Mirid Bug (GMB) prevailed among natural enemies across both stages, surpassing insect pest counts, notably GMB, Lady bird beetle (LBB), Carabid beetle (CDB), and Staphylinid (STD). However, the yield was notably higher in the 2019-20 growing season despite these pest pressures. Throughout the mid-tillering and booting stages, T1 consistently exhibited the highest average populations of harmful insects and natural enemies, while T7 demonstrated the lowest count of harmful insects, followed by T2 at both growth stages. Additionally, the highest grain yield (GY) was consistently recorded in T1, followed by T5, T6, and T3, with yields of 7.98 t/ha, 7.63 t/ha, 7.38 t/ha, and 7.33 t/ha, respectively. In both stages, beneficial insects prevailed over harmful ones in all fertilizer applications, with significant declines noted in T2 and T7. Factor analysis showed successful selection for EMT in the MGIDI index for all variables except INT and GY during the 2019-20 season, with selection differentials (SD) ranging from −0.10 to 8.29. However, in 2020-21, selection was achieved for all variables with SD ranging from 0.37 to 6.08. According to the MGIDI index, the top-ranked EMTs were identified as T4 and T3 for the 2019-20 period, and T3 and T5 for the 2020-21 period. The EMT shared in both years, T3, proved effective because of its positive impact on enhancing natural enemies throughout both periods (with SD ranging from 4.76 to 8.29 for 2019-20 and 3.03 to 6.08 for 2020-21), and its notable contribution to rice grain yield (SD = 0.37) in 2020-21. This study uniquely integrates EMT to optimize rice grain yield while simultaneously managing harmful insect infestations and supporting natural enemies, addressing a critical need in sustainable rice cultivation. The suggestion is to give preference to fertilizer application T3, which omits P but contains N and K, to improve rice grain yield and boost natural enemies, thereby reducing harmful insect infestation. Moreover, future investigations should concentrate on refining fertilizer blends to strike a harmony between maximizing yield and fostering ecological robustness in rice cultivation.

Qualitative Classification of Late Systemic Symptoms in Head and Neck Cancer Survivors.

Improved rates of cancer control have increased the head and neck cancer survivor population. Cancer survivorship clinics are not widely available in the USA, and longitudinal supportive care for patients undergoing multimodal therapy has not advanced at a pace commensurate with improvements in cancer control. Consequently, a large head and neck cancer survivor population whose quality of life may be chronically and/or permanently diminished presently exists. This lack of awareness perpetuates under-recognition and under-investigation, leaving survivors' (mostly detrimental) experiences largely uncharted. We conducted a qualitative exploration of survivors' experiences, aiming to unpack the profound impact of late systemic symptoms on daily life, encompassing work, relationships, and self-identity in the head and neck cancer survivor community. The study included 15 remitted head and neck survivors, ≥12 months from their final treatment, who participated in semi-structured interviews conducted by a medical oncologist. Data analysis comprised qualitative thematic analysis, specifically inductive hierarchical linear modeling, enriched by a deductive approach of anecdotal clinical reporting. Results highlighted that 43.36% of all quotation material discussed in the interviews pertained to chronic emotion disturbance with significant implications for other domains of life. A central symptom cluster comprised impairments in mood/emotions, daily activity, and significant fatigue. Dysfunction in sleep, other medical conditions, and cognitive deficits comprised a secondary cluster. Physical dysfunctionality, encompassing pain, appetite, and eating, and alterations in experienced body temperature, constituted a tertiary cluster, and perhaps were surprisingly the least discussed symptom burden among head and neck cancer survivors. Symptoms causing heightened long-term survivor burden may be considered epiphenomenal to central physical dysfunctionality, albeit being presently the least represented in cancer survivor care programs. Moving forward, the development of targeted and multi-dimensional treatment programs that encompass physical, psychosocial, and spiritual domains are needed to increase clinical specificity and effective holistic long-term solutions that will foster a more compassionate and informed future of care for the cancer survivorship community.

Hepatocellular Carcinoma: Beyond the Border of Advanced Stage Therapy.

Hepatocellular carcinoma (HCC) is the deadliest emergent health issue around the globe. The stronger oncogenic effect, proteins, and weakened immune response are precisely linked with a significant prospect of developing HCC. Several conventional systemic therapies, antiangiogenic therapy, and immunotherapy techniques have significantly improved the outcomes for early-, intermediate-, and advanced-stage HCC patients, giving new hope for effective HCC management and prolonged survival rates. Innovative therapeutic approaches beyond conventional treatments have altered the landscape of managing HCC, particularly focusing on targeted therapies and immunotherapies. The advancement in HCC treatment suggested by the Food and Drug Administration is multidimensional treatment options, including multikinase inhibitors (sorafenib, lenvatinib, regorafenib, ramucirumab, and cabozantinib) and immune checkpoint inhibitors (atezolizumab, pembrolizumab, durvalumab, tremelimumab, ipilimumab, and nivolumab), in monotherapy and in combination therapy to increase life expectancy of HCC patients. This review highlights the efficacy of multikinase inhibitors and immune checkpoint inhibitors in monotherapy and combination therapy through the analysis of phase II, and III clinical trials, targeting the key molecular pathways involved in cellular signaling and immune response for the prospective treatment of advanced and unresectable HCC and discusses the upcoming combinations of immune checkpoint inhibitors-tyrosine kinase inhibitors and immune checkpoint inhibitors-vascular endothelial growth factor inhibitors. Finally, the hidden challenges with pharmacological therapy for HCC, feasible solutions for the future, and implications of possible presumptions to develop drugs for HCC treatment are reported.

Whole-Body Photobiomodulation Therapy Propels the Fibromyalgia Patient into the Recomposition Phase: A Reflexive Thematic Analysis.

Recent evidence has identified great promise for the novel whole-body photobiomodulation therapy (PBMT) for individuals with fibromyalgia (FM). However, currently no evidence has documented the experiences of participants. The objective of this study was to qualitatively assess treatment experience and response in a group of participants with FM undergoing a course of whole-body PBMT. An interpretive hermeneutic phenomenological study situated within the worldview of pragmatism was undertaken. A convenience sample of individuals with FM were included if they had undertaken a novel 6-week trial of PBMT. Individuals undertook semi-structured interviews exploring treatment experience and multidimensional treatment responses during Week 3 and Week 6. Sixteen trial participants (47.3 ± 10.9 years) took part in this study. The analysis produced three overarching themes that were previously identified from a baseline study (namely, 'Body Structure & Function', 'Activities & Participation', and 'Environment') with an additional five sub-themes that highlighted the intervention experience. Subsequently, four important processes were observed and identified: increased motivation; feeling proud; improved confidence; feeling like 'old self'. This ultimately culminated in the identification of a positive spiral, which we have termed 'recomposition'. We believe our study is the first in the field of chronic pain management to utilise qualitative methodology to directly assess the acceptability and efficacy of a specific medical intervention in a clinical trial, and the first study to qualitatively assess whole-body PBMT experience. The findings are compelling and warrant further work to support the introduction of this device into the National Health Service (NHS).

Modulation of long noncoding RNAs by polyphenols as a novel potential therapeutic approach in lung cancer: A comprehensive review.

Lung cancer stands as a formidable global health challenge, necessitating innovative therapeutic strategies. Polyphenols, bioactive compounds synthesized by plants, have garnered attention for their diverse health benefits, particularly in combating various cancers, including lung cancer. The advent of whole-genome and transcriptome sequencing technologies has illuminated the pivotal roles of long noncoding RNAs (lncRNAs), operating at epigenetic, transcriptional, and posttranscriptional levels, in cancer progression. This review comprehensively explores the impact of polyphenols on both oncogenic and tumor-suppressive lncRNAs in lung cancer, elucidating on their intricate regulatory mechanisms. The comprehensive examination extends to the potential synergies when combining polyphenols with conventional treatments like chemotherapy, radiation, and immunotherapy. Recognizing the heterogeneity of lung cancer subtypes, the review emphasizes the need for the integration of nanotechnology for optimized polyphenol delivery and personalized therapeutic approaches. In conclusion, we collect the latest research, offering a holistic overview of the evolving landscape of polyphenol-mediated modulation of lncRNAs in lung cancer therapy. The integration of polyphenols and lncRNAs into multidimensional treatment strategies holds promise for enhancing therapeutic efficacy and navigating the challenges associated with lung cancer treatment.

Symptom burden and its associations with clinical characteristics in patients with COPD: a clustering approach.

Symptom burden in patients with COPD is often under-recognised. In this cross-sectional analysis, we aimed to study the severity of a variety of (non-)respiratory symptoms in patients with and without COPD and to explore the associations between clusters based on symptom severity and other clinical characteristics. Characteristics were assessed in 538 patients with COPD from primary, secondary and tertiary care and 116 non-COPD participants. The severity of 20 symptoms was measured using a visual analogue scale (VAS), ranging from 0 mm (no symptom) to 100 mm (maximum severity). K-means cluster analysis was applied to symptom severity in the patient sample only. People with COPD were comparable with non-COPD participants in terms of gender (58% versus 55% male, p=0.132) and age (64±9 years versus 63±6 years, p=0.552) and had a reduced forced expiratory volume in 1 s (57±23% predicted versus 111±17% predicted, p<0.001). The COPD group had higher VAS scores for most symptoms (p<0.05). The most severe symptoms in patients with COPD were dyspnoea, fatigue and muscle weakness while non-COPD participants mainly experienced insomnia and micturition. Three clusters were identified in the patient sample. Health status and care dependency differed between all clusters, while functional mobility, exacerbation history and lung function differed between cluster 1 and the other two clusters (p<0.05). People with COPD report a high burden of respiratory as well as non-respiratory symptoms. Cluster analysis demonstrated a co-occurrence of different levels of symptom severity, highlighting the heterogeneity of symptoms experience. Identifying clusters of patients with shared symptom experiences will help us to understand the impact of the disease and define integrated, multidimensional treatment strategies.

Self-Assembled Matrine-PROTAC Encapsulating Zinc(II) Phthalocyanine with GSH-Depletion-Enhanced ROS Generation for Cancer Therapy.

The integration of a multidimensional treatment dominated by active ingredients of traditional Chinese medicine (TCM), including enhanced chemotherapy and synergistically amplification of oxidative damage, into a nanoplatform would be of great significance for furthering accurate and effective cancer treatment with the active ingredients of TCM. Herein, in this study, we designed and synthesized four matrine-proteolysis-targeting chimeras (PROTACs) (depending on different lengths of the chains named LST-1, LST-2, LST-3, and LST-4) based on PROTAC technology to overcome the limitations of matrine. LST-4, with better anti-tumor activity than matrine, still degrades p-Erk and p-Akt proteins. Moreover, LST-4 NPs formed via LST-4 self-assembly with stronger anti-tumor activity and glutathione (GSH) depletion ability could be enriched in lysosomes through their outstanding enhanced permeability and retention (EPR) effect. Then, we synthesized LST-4@ZnPc NPs with a low-pH-triggered drug release property that could release zinc(II) phthalocyanine (ZnPc) in tumor sites. LST-4@ZnPc NPs combine the application of chemotherapy and phototherapy, including both enhanced chemotherapy from LST-4 NPs and the synergistic amplification of oxidative damage, through increasing the reactive oxygen species (ROS) by photodynamic therapy (PDT), causing an GSH decrease via LST-4 mediation to effectively kill tumor cells. Therefore, multifunctional LST-4@ZnPc NPs are a promising method for killing cancer cells, which also provides a new paradigm for using natural products to kill tumors.

Beyond vulvodynia: from a correct diagnosis to a multidisciplinary care program. A referral center experience.

Vulvodynia is a chronic pain condition without an identifiable cause. As such, it is a diagnosis of exclusion, and all other causes of vulvar pain should be excluded. Although a standard treatment for vulvodynia has not been established yet, multidisciplinary care programs appear to be effective. The aim of this retrospective monocentric study was to analyze the prevalence of vulvodynia among women referred to our institution for a suspected diagnosis and to evaluate the efficacy of a multidimensional treatment plan. The primary outcome was the prevalence of vulvodynia following differential diagnosis. Secondary outcomes included: prevalence of the differential diagnoses, symptom resolution rate following treatment, and the relation between persistence of symptoms and (a) patients' age; (b) coexisting chronic overlapping pain conditions (COPCs). After having ruled out all other causes of vulvar pain, only 40.1% of women were considered as affected by vulvodynia. The most frequent differential diagnoses included lower genital tract infections (25.3%), vulvar lichen sclerosus (17.6%) and vulvovaginal atrophy (8.2%). Following a multidisciplinary care program, resolution of symptoms was observed in 13.6% cases, improvement in 64.3% and persistence in 21.9%. We did not find a statistically significant association between persistence of symptoms and age > 38years (OR 2.10; p = 0.30). Women with one or more COPCs other than vulvodynia had a 75% increased risk of not obtaining a resolution of symptoms (OR 1.75; p = 0.44). A thorough differential diagnosis and a multidisciplinary care program may represent a first way out of the muddle in the management of these patients.

Surgical treatment of orbital tumors in a single center: Analysis and results.

Orbital tumors, arising within the bony orbit and its contents, present diverse challenges due to their varied origins and complex anatomical context. These tumors, classified as primary, secondary, or metastatic, are further subdivided into intraconal and extraconal based on their relationship with the muscle cone. This classification significantly influences surgical approach and management. This study highlights surgical experiences with orbital tumors, underscoring the importance of tailored surgical approaches based on the lesion's site and its proximity to the optic nerve. This retrospective study at the National Institute of Cancer's Head and Neck Department (2005-2014) analyzed 29 patients with orbital tumors treated with surgery, radiotherapy, chemotherapy, or combinations of them. Patient demographics, tumor characteristics, and treatment responses were evaluated using computed tomography (CT), magnetic resonance imaging, and positron emission tomography-CT imaging. Malignant tumors often required orbital exenteration and reconstruction, highlighting the study's commitment to advancing orbital tumor treatment. 29 patients (18 females and 11 males, age 18-88 years, mean 53.5 years) with orbital tumors exhibited symptoms such as decreased vision and exophthalmos. Tumors included primary lesions like choroidal melanoma and secondary types like epidermoid carcinoma. Treatments varied, involving a multidisciplinary team for surgical approaches like exenteration, with follow-up from 1 to 9 years. Radiotherapy and chemotherapy were used for specific cases. Our study underscores the need for a multidisciplinary approach in treating orbital tumors, involving various surgical specialists and advanced technologies like neuronavigation for tailored treatment. The integration of surgery with radiotherapy and chemotherapy highlights the effectiveness of multidimensional treatment strategies.

The Effects of Different Exercise Types on Cognitive and Physical Functions in Dementia Patients: A Randomized Comparative Study

Purpose: The physical and cognitive effects of aerobic exercise on dementia have been extensively studied. Further investigation of other types of exercise with different physiological effects is still needed. This study aimed to determine cognitive and physical effects of 6-week aerobic, balance, and combined (aerobic-balance) exercise programs on dementia. Materials and Methods: A total of 31 mild to moderate dementia patients aged 65-90 years were divided into three exercise groups. Before and after the 6-week exercise program, mental rotation, spatial orientation, visual memory, and mental status were assessed for cognitive functions, while fall risk, reaction time, lower limb strength, and frailty were assessed for physical functions. Comprehensive cognitive and physical assessments were performed to provide a holistic approach to dementia. Results: When post-exercise values were compared with pre-exercise values, only frailty decreased significantly in the aerobic exercise group (p=0.017). After exercise program in balance and combined exercise groups, mental rotation (p=0.005, p=0.032), spatial orientation (p=0.020, p=0.035), mental status (p=0.007, p=0.014), and lower extremity strength (p=0. 010, p=0.005) increased significantly, while fall risk (p=0.005, p=0.005), reaction time (p=0.028, p=0.016), and frailty (p=0.020, p=0.009) decreased significantly. Moreover, in contrast to combined and aerobic exercise, improvement in visual memory was also observed in the balance exercise group (p=0.016). Conclusions: These findings suggest that balance and combined exercises may have broader effects on dementia than aerobic exercise. It emphasizes the importance of designing exercise programs for dementia patients, considering the cognitive and physical deficits of the patients, and creating a multidimensional treatment approach.

Transtheoretical and transdiagnostic models in the treatment of anxiety

This text explores a comprehensive and contemporary approach to addressing anxiety, focusing on the concepts of transtheoretical diagnoses and transdiagnostic treatments. The complexity of anxiety and the need to consider multiple dimensions, such as biological, behavioral, cognitive, systemic and spiritual factors, are recognized. The importance of making a complete diagnosis that includes the patient's personal history is highlighted and the relevance of a multidimensional treatment that combines psychoeducation, relaxation techniques and verbal therapy is underlined.

Prospective study validating a multidimensional treatment decision score predicting the 24-month outcome in untreated patients with clinically isolated syndrome and early relapsing–remitting multiple sclerosis, the ProVal-MS study

IntroductionIn Multiple Sclerosis (MS), patients´ characteristics and (bio)markers that reliably predict the individual disease prognosis at disease onset are lacking. Cohort studies allow a close follow-up of MS histories and a thorough phenotyping of patients. Therefore, a multicenter cohort study was initiated to implement a wide spectrum of data and (bio)markers in newly diagnosed patients.MethodsProVal-MS (Prospective study to validate a multidimensional decision score that predicts treatment outcome at 24 months in untreated patients with clinically isolated syndrome or early Relapsing–Remitting-MS) is a prospective cohort study in patients with clinically isolated syndrome (CIS) or Relapsing–Remitting (RR)-MS (McDonald 2017 criteria), diagnosed within the last two years, conducted at five academic centers in Southern Germany. The collection of clinical, laboratory, imaging, and paraclinical data as well as biosamples is harmonized across centers. The primary goal is to validate (discrimination and calibration) the previously published DIFUTURE MS-Treatment Decision score (MS-TDS). The score supports clinical decision-making regarding the options of early (within 6 months after study baseline) platform medication (Interferon beta, glatiramer acetate, dimethyl/diroximel fumarate, teriflunomide), or no immediate treatment (> 6 months after baseline) of patients with early RR-MS and CIS by predicting the probability of new or enlarging lesions in cerebral magnetic resonance images (MRIs) between 6 and 24 months. Further objectives are refining the MS-TDS score and providing data to identify new markers reflecting disease course and severity. The project also provides a technical evaluation of the ProVal-MS cohort within the IT-infrastructure of the DIFUTURE consortium (Data Integration for Future Medicine) and assesses the efficacy of the data sharing techniques developed.PerspectiveClinical cohorts provide the infrastructure to discover and to validate relevant disease-specific findings. A successful validation of the MS-TDS will add a new clinical decision tool to the armamentarium of practicing MS neurologists from which newly diagnosed MS patients may take advantage.Trial registration ProVal-MS has been registered in the German Clinical Trials Register, `Deutsches Register Klinischer Studien` (DRKS)—ID: DRKS00014034, date of registration: 21 December 2018; https://drks.de/search/en/trial/DRKS00014034

Effective family‐based program options for justice‐involved youth

AbstractFamilies play a significant role both in youth's development of criminal behavior and in their desistance of criminal behavior. Nonetheless, programming for families of justice‐involved youth is limited. This article describes two family‐based programs found in the National Institute of Justice CrimeSolutions database. Among 19 programs for families, only the Functional Family Therapy and Multidimensional Treatment Foster Care for Adolescents are documented as effective in helping justice‐involved youths and their families. The discussion proposes how these programs could be used to harness services under special education law for students with emotional and behavioral disabilities who are overrepresented in juvenile correctional facilities.

Inotropic drugs in septic shock

Septic shock is a life-threatening condition characterized by a complex underlying mechanism that requires a multidimensional treatment approach. Sepsis-induced cardiomyopathy plays a significant role in the development of multiple organ failure. The focus of this review is to determine the evidence-based data of the commonly used inotropic drugs in the management of septic shock during clinical hypoperfusion and reduced myocardial performance. Current guidelines recommend adding dobutamine to norepinephrine or using epinephrine alone in septic-induced cardiomyopathy, while suggesting against the use of levosimendan. Although dobutamine increases cardiac contractility and heart rate, it also decreases systemic vascular resistance. Epinephrine has a greater potency than dobutamine but does not demonstrate a clinical difference in hemodynamic improvement. Milrinone is preferred for cases involving pulmonary hypertension and right ventricular failure but should be avoided in the presence of renal dysfunction. Levosimendan improves cardiac performance and promotes coronary blood flow, but later evidence mentioned significant arrhythmia compared to other inotropic agents. Due to the narrow therapeutic window of these agents, precise therapeutic targets are crucial.

Self-driven solutions and resilience adapted by people with drug-resistant tuberculosis and their caregivers in Bengaluru and Hyderabad, India: a qualitative study

One-fifth of people with drug-resistance tuberculosis (DR-TB) who were initiated on newer shorter treatment regimen (with injection) had unfavourable treatment outcomes in India as on 2020. Evidence on self-driven solutions and resilience adapted by people with DR-TB (PwDR-TB) towards their multi-dimensional disease and treatment challenges are scarce globally, which we aimed to understand. In this qualitative study using positive deviance framework, we conducted semi-structured in-depth interviews among consenting adult PwDR-TB (7 women, 13 men) who completed shorter treatment regimen (including injections) with maximum treatment adherence. The study was conducted in the southern districts of Bengaluru and Hyderabad, India between June 2020 and December 2022. Caregivers (14 women, 6 men) and health providers (8 men, 2 women) of PwDR-TB were also interviewed. Interviews were conducted in local language (Kannada, Tamil, Telugu, Urdu and Hindi) and inquired about practices, behaviours, experiences, perceptions and attributes which enabled maximum adherence and resilience of PwDR-TB. Interviews were audio recorded, transcribed, and translated to English and coded for thematic analysis using inductive approach. Distinctive themes explanatory of the self-driven solutions and resilience exhibited by PwDR-TB and their caregivers were identified: (i) Self-adaptation towards the biological consequences of drugs, by personalised nutritional and adjuvant practices, which helped to improve drug ingestion and therapeutic effects. Also home remedies and self-plans for ameliorating injection pain. (ii) Perceptual adaptation towards drugs aversion and fatigue, by their mind diversion practices, routinisation and normalisation of drug intake process. and constant reinforcement and re-interpretation of bodily signs of disease recovery (iii) Family caregivers intense and participatory care for PwDR-TB, by aiding their essential life activities and ensuring survival, learning and fulfilling special nutritional needs and goal oriented actions to aid drug intake (iv) Health care providers care, marked by swift and timely risk mitigation of side-effects and crisis response (v) Acquired self-efficacy of PwDR-TB, by their decisive family concerns resulting in attitudinal change. Also being sensitised on the detrimental consequences of disease and being motivated through positive examples. Synthesised findings on self-driven solutions and resilience towards the multi-dimensional DR-TB challenges provides opportunity for developing and testing new interventions for its effectiveness in DR-TB care settings globally. Designing and testing personalised cognitive interventions for PwDR-TB: to inculcate attitudinal change and self-efficacy towards medication, developing cognitive reinforcements to address the perception burden of treatment, skill building and mainstreaming the role of family caregivers as therapeutic partners of PwDR-TB, curating self-adaptive behaviours and practices of PwDR-TB to normalise their drug consumptions experiences could be the way forward in building resilience towards DR-TB. United States Agency for International Development (USAID) through Karnataka Health Promotion Trust (KHPT), Bengaluru, India.

Adding New Dimensions to 3D Cancer Models.

Understanding patient-specific responses to anticancer therapies and how individual tumors interact with their tumor microenvironment (TME) is a challenging task. To measure the impact of the TME on diverse and clinically relevant treatments, Ramos Zapatero and colleagues coupled patient-derived organoid (PDO) and cancer-associated fibroblast (CAF) cocultures with high-throughput mass cytometry-based assessment of cell state. Using a newly developed "Trellis" algorithm enabled integration and analysis of highly complex, multidimensional treatment response data. This work showed that tumor cell response to chemotherapy was associated with both intrinsic and nonintrinsic signaling states, whereby proliferative rate, growth factor signaling, and CAFs interaction influenced chemoprotection. Furthermore, the work suggests a potential role for the TME in promoting lineage plasticity associated with drug resistance. In all, the pipeline described provides a blueprint for exploring the intricate interplay of factors influencing cancer treatment response.