Trajectories of Disability and Long-Term Care Utilization After Acute Health Events.

Hip fractures, strokes, and heart attacks are common acute health events that can lead to long-term disability, care utilization, and unmet needs. However, such impacts, especially in the long term, are not fully understood. Using data from the Health and Retirement Study, 1992-2018, this study examines the long-term trajectories of individuals suffering such health shocks, comparing with individuals not experiencing health shocks. Hip fracture, stroke, and heart attack are confirmed to have severe implications for disability. In most cases of stroke and heart attack, informal caregivers provide the daily support needed by survivors, whereas following hip fracture, nursing home care is more relevant. These health shocks put individuals on worse trajectories of disability, care utilization, and unmet needs. There is no long-term recovery or convergence with individuals who do not suffer shocks. Unmet need is prevalent, even pre-shock and among individuals who do not experience health shocks, emphasizing the importance of preventative care measures. These findings support policy action to ensure hospitalized individuals, especially those aged 50 and above, receive rehabilitative services and other post-acute care. Furthermore, hospitalization is an event that requires the detection and addressing of unmet care needs beyond the short run.

'Thank goodness you're here'. Exploring the impact on patients, family carers and staff of enhanced 7-day specialist palliative care services: A mixed methods study.

BACKGROUND: Healthcare usage patterns change for people with life limiting illness as death approaches, with increasing use of out-of-hours services. How best to provide care out of hours is unclear. AIM: To evaluate the effectiveness and effect of enhancements to 7-day specialist palliative care services, and to explore a range of perspectives on these enhanced services. DESIGN: An exploratory longitudinal mixed-methods convergent design. This incorporated a quasi-experimental uncontrolled pre-post study using routine data, followed by semi-structured interviews with patients, family carers and health care professionals. SETTING/PARTICIPANTS: Data were collected within specialist palliative care services across two UK localities between 2018 and 2020. Routine data from 5601 unique individuals were analysed, with post-intervention interview data from patients (n = 19), family carers (n = 23) and health care professionals (n = 33; n = 33 time 1, n = 20 time 2). RESULTS: The mean age of people receiving care was 73 years, predominantly white (90%) and with cancer (42%). There were trends for those in the intervention (enhanced care) period to stay in hospital 0.16 days fewer, but be hospitalised 2.67 more times. Females stayed almost 3.5 more days in the hospital, but were admitted 2.48 fewer times. People with cancer had shorter hospitalisations (4 days fewer), and had two fewer admission episodes. Themes from the qualitative data included responsiveness (of the service); reassurance; relationships; reciprocity (between patients, family carers and staff) and retention (of service staff). CONCLUSIONS: Enhanced seven-day services provide high quality integrated palliative care, with positive experiences for patients, carers and staff.

In Vitro Antimicrobial Studies of Mesoporous Silica Nanoparticles Comprising Anionic Ciprofloxacin Ionic Liquids and Organic Salts.

The combination of active pharmaceutical ingredients in the form of ionic liquids or organic salts (API-OSILs) with mesoporous silica nanoparticles (MSNs) as drug carriers can provide a useful tool in enhancing the capabilities of current antibiotics, especially against resistant strains of bacteria. In this publication, the preparation of a set of three nanomaterials based on the modification of a MSN surface with cholinium ([MSN-Chol][Cip]), 1-methylimidazolium ([MSN-1-MiM][Cip]) and 3-picolinium ([MSN-3-Pic][Cip]) ionic liquids coupled with anionic ciprofloxacin have been reported. All ionic liquids and functionalized nanomaterials were prepared through sustainable protocols, using microwave-assisted heating as an alternative to conventional methods. All materials were characterized through FTIR, solution 1H NMR, elemental analysis, XRD and N2 adsorption at 77 K. The prepared materials showed no in vitro cytotoxicity in fibroblasts viability assays. The minimum inhibitory concentration (MIC) for all materials was tested against Gram-negative K. pneumoniae and Gram-positive Enterococcus spp., both with resistant and sensitive strains. All sets of nanomaterials containing the anionic antibiotic outperformed free ciprofloxacin against resistant and sensitive forms of K. pneumoniae, with the prominent case of [MSN-Chol][Cip] suggesting a tenfold decrease in the MIC against sensitive strains. Against resistant K. pneumoniae, a five-fold decrease in the MIC was observed for all sets of nanomaterials compared with neutral ciprofloxacin. Against Enterococcus spp., only [MSN-1-MiM][Cip] was able to demonstrate a slight improvement over the free antibiotic.

Outcome measures for economic evaluations and cost-effectiveness analyses of interventions for people with intellectual disabilities: A methodological systematic review.

BACKGROUND: Mainstream economic evaluations methods may not be appropriate to capture the range of effects triggered by interventions for people with intellectual disabilities. In this systematic review, we aimed to identify, assess and synthesise the arguments in the literature on how the effects of interventions for people with intellectual disabilities could be measured in economic evaluations. METHOD: We searched for studies providing relevant arguments by running multi-database, backward, forward citation and grey literature searches. Following title/abstract and full-text screening, the arguments extracted from the included studies were summarised and qualitatively assessed in a narrative synthesis. RESULTS: Our final analysis included three studies, with their arguments summarised in different methodological areas. CONCLUSIONS: Based on the evidence, we suggest the use of techniques more attuned to the population with intellectual disabilities, such sensitive preference-based instruments to collect health states data, and mapping algorithms to obtain utility values.

Analytical Frameworks and Outcome Measures in Economic Evaluations of Digital Health Interventions: A Methodological Systematic Review.

BACKGROUND: Digital health interventions (DHIs) can improve the provision of health care services. To fully account for their effects in economic evaluations, traditional methods based on measuring health-related quality of life may not be appropriate, as nonhealth and process outcomes are likely to be relevant too. PURPOSE: This systematic review identifies, assesses, and synthesizes the arguments on the analytical frameworks and outcome measures used in the economic evaluations of DHIs. The results informed recommendations for future economic evaluations. DATA SOURCES: We ran searches on multiple databases, complemented by gray literature and backward and forward citation searches. STUDY SELECTION: We included records containing theoretical and empirical arguments associated with the use of analytical frameworks and outcome measures for economic evaluations of DHIs. Following title/abstract and full-text screening, our final analysis included 15 studies. DATA EXTRACTION: The arguments we extracted related to analytical frameworks (14 studies), generic outcome measures (5 studies), techniques used to elicit utility values (3 studies), and disease-specific outcome measures and instruments to collect health states data (both from 2 studies). DATA SYNTHESIS: Rather than assessing the quality of the studies, we critically assessed and synthesized the extracted arguments. Building on this synthesis, we developed a 3-stage set of recommendations in which we encourage the use of impact matrices and analyses of equity impacts to integrate traditional economic evaluation methods. LIMITATIONS: Our review and recommendations explored but not fully covered other potentially important aspects of economic evaluations that were outside our scope. CONCLUSIONS: This is the first systematic review that summarizes the arguments on how the effects of DHIs could be measured in economic evaluations. Our recommendations will help design future economic evaluations. HIGHLIGHTS: Using traditional outcome measures based on health-related quality of life (such as the quality-adjusted life-year) may not be appropriate in economic evaluations of digital health interventions, which are likely to trigger nonhealth and process outcomes.This is the first systematic review to investigate how the effects of digital health interventions could be measured in economic evaluations.We extracted and synthesized different arguments from the literature, outlining advantages and disadvantages associated with different methods used to measure the effects of digital health interventions.We propose a methodological set of recommendations in which 1) we suggest that researchers consider the use of impact matrices and cost-consequence analysis, 2) we discuss the suitability of analytical frameworks and outcome measures available in economic evaluations, and 3) we highlight the need for analyses of equity impacts.

Trade-offs during the COVID-19 pandemic: A discrete choice experiment about policy preferences in Portugal.

The need to control the sanitary situation during the COVID-19 pandemic has led governments to implement several restrictions with substantial social and economic impacts. We explored people's trade-offs in terms of their income, life restrictions, education, and poverty in the society, compared to their willingness to avoid deaths. We applied a web-based discrete choice experiment to elicit preferences of the Portuguese citizens for these attributes and computed the marginal rate of substitution in terms of avoided deaths. We recorded 2,191 responses that faced the possibility of having 250 COVID-19 related deaths per day as the worst possible outcome from the choice levels presented. Estimates suggested that individuals would be willing to sacrifice 30% instead of 10% of their income to avoid approximately 47 deaths per day during the first six months of 2021. For the same period, they would also accept 30% of the students' population to become educationally impaired, instead of 10%, to avoid approximately 25 deaths; a strict lockdown, instead of mild life restrictions, to avoid approximately 24 deaths; and 45% of the population to be in risk of poverty, instead of 25%, to avoid approximately 101 deaths. Our paper shows that avoiding deaths was strongly preferred to the remaining societal impacts; and that being a female, as well as working on site, led individuals to be more averse to such health hazards. Furthermore, we show how a DCE can be used to assess the societal support to decision-making during times of crisis.

Hanseníase virchowiana e eritema nodoso hanseníco em gestante de 34 semanas sem diagnóstico prévio / Virchowian leprosy and erythema nodosum leprosum in a 34-week pregnant woman without any previous diagnosis

Relatamos um caso de uma paciente feminina, gestante de terceiro trimestre, em acompanhamento pré-natal regular na unidade básica de saúde, com boa evolução gestacional, porém apresentando lesões de pele há cerca de um ano, acompanhadas de alteração de sensibilidade, além de fáscies infiltrada e madarose. Sendo o Brasil um país endêmico em Hanseníase, ocupando o 2º lugar no mundo em número de novos casos, chama a atenção o diagnóstico tardio da paciente em questão. Aproveitamos este emblemático relato de caso para discutir aspectos importantes em relação à terapêutica no período gestacional (poliquimioterapia conforme manual do ministério, sem nenhuma alteração por conta da gestação), desfecho obstétrico, orientações quanto à lactação (não contra-indicada com a mãe em tratamento; pelo contrário, devendo ser estimulada) e cuidado ao recém nato. [au]

We report a case of a pregnant female patient in the third trimester undergoing regular prenatal care at a Basic Health Unit, with good gestational evolution, but presenting skin lesions for approximately a year accompanied by changes in sensitivity, in addition to facial infiltration and madarosis. Considering Brazil as an endemic country for leprosy, ranking 2nd in the world concerning the number of new cases, late diagnosis of the patient in question stands out. We use this emblematic case report to discuss important aspects concerning the treatment of leprosy during the gestational period (multidrug therapy according to the Ministry of Health manual, without any changes due to pregnancy), obstetric outcome, guidelines regarding breastfeeding (not contraindicated with the mother in treatment; on the contrary, it should be stimulated) and care for the newborn. [au]

Formal home care use and spousal health outcomes.

This study explores the relationship between formal home care provided by paid professionals and spousal health outcomes. We use data from the Survey of Health, Ageing, and Retirement in Europe, a panel of older adults living in several European countries. We match new formal home care users to non-users to eliminate baseline (t-1) differences between couples who decide to seek formal home care in t and those who do not. After considering several potentially confounding changes between baseline and t, and looking closer at specific subgroups, we conclude that in the short run, use of formal home care is unlikely to affect spousal physical or mental health.

Boosting Antimicrobial Activity of Ciprofloxacin by Functionalization of Mesoporous Silica Nanoparticles.

Mesoporous silica nanoparticles (MSNs) are very promising nanomaterials for treating bacterial infections when combined with pharmaceutical drugs. Herein, we report the preparation of two nanomaterials based on the immobilization of ciprofloxacin in mesoporous silica nanoparticles, either as the counter-ion of the choline derivative cation (MSN-[Ch][Cip]) or via anchoring on the surface of amino-group modified MSNs via an amide bond (MSN-Cip). Both nanomaterials were characterized by TEM, FTIR and solution 1H NMR spectroscopies, elemental analysis, XRD and N2 adsorption at 77 K in order to provide the desired structures. No cytotoxicity from the prepared mesoporous nanoparticles on 3T3 murine fibroblasts was observed. The antimicrobial activity of the nanomaterials was determined against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Klebsiella pneumoniae) bacteria and the results were promising against S. aureus. In the case of B. subtilis, both nanomaterials exhibited higher antimicrobial activity than the precursor [Ch][Cip], and in the case of K. pneumoniae they exhibited higher activity than neutral ciprofloxacin.

Doctors' response to queues: Evidence from a Portuguese emergency department.

We evaluate how doctors in an emergency department react to the number of patients waiting for treatment. Our outcomes reflect the time spent with the patient, the intensity of treatment, and discharge destination. Using visit-level data in a Lisbon-area hospital, we use a fixed effects model to exploit variation in the queue size while addressing endogeneity using the number of arrivals to the hospital in the previous 60 min as an instrumental variable. Furthermore, we estimate doctors' reactions separately for patients with different degrees of urgency, as measured by the Manchester triage system. Results show that doctors discharge patients more rapidly as queues become longer, and this effect is stronger for patients that do not have life-threatening conditions. We also find that the intensity of diagnosis/treatment procedures decreases when patients face longer queues, driven by the extensive margin. Finally, doctors are less likely to admit patients to inpatient care. We interpret the results in the light of the doctors' incentives literature, explaining how these agents behave in the context of a National Health Service, with no financial incentives.

Exploring the Structural Properties of Positively Charged Peptide Dendrimers.

We report a combined experimental and computational approach to study the structural behavior of positively charged peptide dendrimers. Third-generation dendrimers containing combinations of positive/neutral amino acid residues in the different dendrimer generations were synthesized and their overall size evaluated using diffusion NMR. Molecular dynamics simulations were performed to obtain a comprehensive description of the molecular-level phenomena substantiating the structural differences observed. Comparison of the results presented with previous findings reveals a striking charge-dependent tendency in these systems, where the simple number and placement of charged amino acids in the sequence allows an extensive control over the exhibited structural features. Indeed, we observe that peptide dendrimers bearing progressively higher amounts of charged residues are characterized by an increasing structural plasticity, with a myriad of conformational states equally accessible to them. On the other hand, dendrimers containing only small amounts of charged residues evidence, to some extent, a characteristic structural rigidity.

Structuring Peptide Dendrimers through pH Modulation and Substrate Binding.

Dendrimers are a family of ramified synthetic molecules. pH effects and electrostatic interactions are known to be crucial players to explain the conformational and functional behaviors observed in these systems. Nonetheless, to date, no computational study involving these systems has explicitly addressed the protonation equilibrium taking place at different pH values for dendrimers containing multiple ionizable sites. Herein, we present the results of constant-pH molecular dynamics simulations performed at several pH values for four peptide dendrimers of different generations (from one to four) composed of the same type of amino acids: histidines, serines, and diaminopropionic acid. These dendrimers are known to catalyze the hydrolysis of pyrene sulfonate esters. Constant-pH MD simulations in the presence of substrate molecules at the optimum pH for catalysis are also reported. The results show that first and second generation dendrimers are almost structurally unresponsive to pH variations. For third and fourth generation dendrimers, pH plays a structuring role, with markedly different behaviors being observed when passing from acidic to neutral pH. Protonation-conformation coupling effects influence several intramolecular interactions, which, in turn, modulate the shape and structure at the different pH values. The atypical and highly pH-dependent protonation profiles of some histidine residues are also investigated. The interactions between dendrimers and substrates restrict the conformational space available to the dendrimers and enforce conformational homogeneity. This structuring effect is a consequence of the dendrimer-substrate interactions which occur through stabilizing hydrogen bonds and ion pairs between the substrate sulfonate groups and the dendrimer residues. Our results provide original fundamental data contributing to the development of novel pH-modulated dendritic systems and the improvement of the existing ones.

Predicting the Thermodynamics and Kinetics of Helix Formation in a Cyclic Peptide Model.

The peptide Ac-(cyclo-2,6)-R[KAAAD]-NH2 (cyc-RKAAAD) is a short cyclic peptide known to adopt a remarkably stable single turn α-helix in water. Due to its simplicity and the availability of thermodynamic and kinetic experimental data, cyc-RKAAAD poses as an ideal model for evaluating the aptness of current molecular dynamics (MD) simulation methodologies to accurately sample conformations that reproduce experimentally observed properties. In this work, we extensively sample the conformational space of cyc-RKAAAD using microsecond-timescale MD simulations. We characterize the peptide conformational preferences in terms of secondary structure propensities and, using Cartesian-coordinate principal component analysis (cPCA), construct its free energy landscape, thus obtaining a detailed weighted discrimination between the helical and nonhelical subensembles. The cPCA state discrimination, together with a Markov model built from it, allowed us to estimate the free energy of unfolding (-0.57 kJ/mol) and the relaxation time (∼0.435 µs) at 298.15 K, which are in excellent agreement with the experimentally reported values (-0.22 kJ/mol and 0.42 µs, Serrano, A. L.; Tucker, M. J.; Gai, F. J. Phys. Chem. B, 2011, 115, 7472-7478.). Additionally, we present simulations conducted using two enhanced sampling methods: replica-exchange molecular dynamics (REMD) and bias-exchange metadynamics (BE-MetaD). We compare the free energy landscape obtained by these two methods with the results from MD simulations and discuss the sampling and computational gains achieved. Overall, the results obtained attest to the suitability of modern simulation methods to explore the conformational behavior of peptide systems with a high level of realism.

Unfolding the conformational behavior of peptide dendrimers: insights from molecular dynamics simulations.

We present here the first comprehensive structural characterization of peptide dendrimers using molecular simulation methods. Multiple long molecular dynamics simulations are used to extensively sample the conformational preferences of five third-generation peptide dendrimers, including some known to bind aquacobalamine. We start by analyzing the compactness of the conformations thus sampled using their radius of gyration profiles. A more detailed analysis is then performed using dissimilarity measures, principal coordinate analysis, and free energy landscapes, with the aim of identifying groups of similar conformations. The results point to a high conformational flexibility of these molecules, with no clear "folded state", although two markedly distinct behaviors were found: one of the dendrimers displayed mostly compact conformations clustered into distinct basins (rough landscape), while the remaining dendrimers displayed mainly noncompact conformations with no significant clustering (downhill landscape). This study brings new insight into the conformational behavior of peptide dendrimers and may provide better routes for their functional design. In particular, we propose a yet unsynthesized peptide dendrimer that might exhibit enhanced ability to coordinate aquocobalamin.