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Background: Seriously ill patients rate several health outcomes as states worse than death. It is unclear what factors underlie such valuations, and whether consideration of such states is useful when making medical decisions. Aim: We sought to (1) use qualitative approaches to identify states worse than death, (2) identify attributes common to such undesirable health states, and (3) determine how participants might use information on these states in making medical decisions. Design: Qualitative study of semi-structured interviews utilizing content analysis with constant comparison techniques. Setting, Participants: We interviewed adults age 65 or older with serious illnesses after discharge home from one of two urban, academic hospitals. Eligible patients were purposively sampled to achieve balance in gender and race. Results: Of 29 participants, 15 (52%) were female, and 15 were white (52%), with a median age of 72 (interquartile range 69, 75). Various physical, cognitive, and social impairments were identified as states worse than death. The most commonly reported attributes underlying states worse than death were perceived burden on loved ones and inability to maintain human connection. Patients believed information on states worse than death must be individualized, and were concerned their opinions could change with time and fluctuations in health status. Conclusions: Common factors underlying undesirable states suggest that for care to be patient-centered it must also be family-centered. Patients’ views on using states worse than death in decision making highlight barriers to using avoidance of such states as a quality measure, but also suggest opportunities for eliciting patients’ values.

During public health crises including the COVID-19 pandemic, resource scarcity and contagion risks may require health systems to shift-to some degree-from a usual clinical ethic, focused on the well-being of individual patients, to a public health ethic, focused on population health. Many triage policies exist that fall under the legal protections afforded by "crisis standards of care," but they have key differences. We critically appraise one of the most fundamental differences among policies, namely the use of criteria to categorically exclude certain patients from eligibility for otherwise standard medical services. We examine these categorical exclusion criteria from ethical, legal, disability, and implementation perspectives. Focusing our analysis on the most common type of exclusion criteria, which are disease-specific, we conclude that optimal policies for critical care resource allocation and the use of cardiopulmonary resuscitation (CPR) should not use categorical exclusions. We argue that the avoidance of categorical exclusions is often practically feasible, consistent with public health norms, and mitigates discrimination against persons with disabilities.

Rationale: Surrogate decision-makers of patients with chronic critical illness (CCI) are at high risk for symptoms of post-traumatic stress disorder (PTSD). Whether patient health status after hospital discharge is a risk factor for surrogate PTSD symptoms is not known. Objectives: To determine the association between patient health status 90 days after the onset of CCI and surrogate symptoms of PTSD. Methods: We performed a secondary analysis of the data from a multicenter randomized trial of a communication intervention for adult patients with CCI and their surrogate decision-makers. Results: Surrogate PTSD symptoms were measured at 90 days using the Impact of Events Scale–Revised. For patients who were alive at 90 days, location was used as a marker of health status and included the following categories: 1) home (relatively good health and low acuity), 2) acute rehabilitation (moderate care needs and impairments, generally expected to improve), 3) skilled nursing facility (moderate care needs and impairments, generally not expected to improve significantly or quickly), 4) long-term acute care facility (persistently high acute care needs and functional impairment), and 5) readmission to an acute care hospital (suggesting the highest acuity of illness and care needs of the cohort). Patients who died before 90 days were categorized as deceased. In the analyses, 365 surrogates and 256 patients were included. Among patients, 49% were female, and the mean age was 59 years. Among surrogates, 71% were female, and the mean age was 51 years. A directed acyclic graph was constructed to identify covariates to be included in the model. Compared with symptoms seen among surrogates of patients living at home, heightened PTSD symptoms were seen among surrogates of patients who were readmitted to an acute care hospital (β coefficient, 15.9; 95% confidence interval [CI], 4.5 to 27.3) or had died (β coefficient, 14.8; 95% CI, 8.8 to 20.9) at 90 days. Conclusions: Surrogates of patients with CCI who have died or have been readmitted to an acute care hospital at 90 days experience increased PTSD symptoms as compared with surrogates of patients who are living at home. These patients and surrogates represent a readily identifiable group who may benefit from enhanced emotional support.

Purpose Previous studies assessing impact of acute respiratory distress syndrome (ARDS) on mortality have shown conflicting results. We sought to assess the independent association of ARDS with in-hospital mortality among intensive care unit (ICU) patients with sepsis. Methods We studied two prospective sepsis cohorts drawn from the Early Assessment of Renal and Lung Injury (EARLI; n = 474) and Validating Acute Lung Injury markers for Diagnosis (VALID; n = 337) cohorts. ARDS was defined by Berlin criteria. We used logistic regression to compare in-hospital mortality in patients with and without ARDS, controlling for baseline severity of illness. We also estimated attributable mortality, adjusted for illness severity by stratification. Results ARDS occurred in 195 EARLI patients (41%) and 99 VALID patients (29%). ARDS was independently associated with risk of hospital death in multivariate analysis, even after controlling for severity of illness, as measured by APACHE II (odds ratio [OR] 1.65 (95% confidence interval [CI] 1.02, 2.67), p = 0.04 in EARLI; OR 2.12 (CI 1.16, 3.92), p = 0.02 in VALID). Patients with severe ARDS (P/F

Background and importance The introduction of the unit dose (DU) as a drug dispensing system produces a multiplicity of advantages, ranging from prescribing to administering therapies. Aim and objectives The purpose of this study was to evaluate, through the computerised prescription, the prescriptive appropriateness of antibiotic therapy and the economic impact of a targeted therapy after an antibiogram compared with empirical therapy. Material and methods The analysis was carried out by extrapolating, from the prescription software and administration in use, the antibiotic prescriptions subjected to a single request motivated (SRM) from 1 January 2019 to 31 December 2019. With the Modulab software, a clinical information management system, prescriptions with antibiograms were verified and divided into appropriate and inappropriate. Prescriptions initiated as empirical therapies were defined as appropriate if the results of the antibiogram confirmed the therapy already started or if the prescriptions changed following the antibiogram. Therapies were considered inappropriate if the antibiogram results were different from the antibiotics used as empirical therapy (resistant/intermediate) or were not tested. Prescriptions were grouped for empirically prescribed antibiotics and for sensitive antibiotics (as a result of the antibiogram), considering a median duration of therapy. The maximum daily dosage from the technical data sheet was considered for the calculation of the cost of the therapy. Only inappropriate prescriptions were considered in the pharmacoeconomic evaluation. Results During the study period, total prescriptions of antibiotics with SRM were 2067 of which 1322 (64%) had no antibiogram and 745 (36%) had an antibiogram. The latter were divided into appropriate (63%) and inappropriate (37%). The pharmacoeconomic analysis showed a cost of non-appropriate therapy of 53 950€, with a possible saving of around 49 274€ if the same had been transferred to the sensitive antibiotic resulting from the antibiogram. Conclusion and relevance We hope, in the future, to directly consult the antibiogram from the computerised prescription to highlight extemporaneously the limitations of long term empirical therapies both for prescriptive appropriateness and for cost savings. References and/or acknowledgements Conflict of interest No conflict of interest

Background and importance In clinical practice, the unit dose (UD) system allows minimisation of potential errors during prescription, preparation and therapy administration phases. In this context, the intervention of a pharmacist in clinical choices may optimise this process by assessing the appropriateness of prescriptions. At the time of UD therapy validation, the pharmacist takes part in the evaluation of the most appropriate therapeutic options through the inclusion of annotations on each individual prescription for each patient. Aim and objectives The aim of this work was to demonstrate how the intervention of pharmacists in this process is essential for patient safety and improving clinical risk management. Material and methods Therapies of all patients receiving the UD system in the period 1 March 2019 to 28 February 2020 were analysed, and all of the annotations included by the pharmacist were reviewed. The annotations were classified into seven subgroups, based on the type of potential errors identified regards: (1) duration of therapy; (2) dosage/frequency of administration; (3) interactions; (4) therapeutic indications; (5) method of reconstitution/dilution; (6) type of formulation; and (7) double prescriptions. These subgroups were further divided based on the potential risk of event/error, latent/active, and high and low risk (HR, LR) where high risk refers to potentially dangerous effects for patients. Results In the observed period, 11 881 patients were admitted to the UD regimen, of whom 5414 carried one or more annotations by the pharmacist, requesting specific changes to the prescriptions. In particular, based on the indicated subgroups, 10 537 notes were inserted and divided as follows: Notes 1235; (HR) 531 (43%); (LR) 704 (57%) Notes 4558; (HR) 1595 (35%); (LR) 2963 (65%) Notes 2329; (HR) 2073 (89%); (LR) 256 (11%) Notes 192; (HR) 192 (100%); (LR) 0 (0%) Notes 1396; (HR) 1368 (98%); (LR) 28 (2%) Notes 603; (HR) 30 (5%); (LR) 573 (95%) Notes 224; (HR) 137 (61%); (LR) 87 (39%) From this analysis, 38% of prescriptions were modified as specifically indicated by the Pharmacist. Conclusion and relevance This analysis demonstrated how the role of the pharmacist is critical in identifying potential errors that may occur at the time of prescription. This is necessary for minimising adverse effects for patients during specific therapeutic treatments. References and/or acknowledgements Conflict of interest No conflict of interest

Background and importance In the context of the single dose, the pharmacist is involved in the validation of patients‘ personalised therapies, attempting to minimise errors in therapy. Aim and objectives The aim of this study was to evaluate, through the computerised prescription, the increase in prescribing appropriateness of antibiotic therapy, following notification by the pharmacist, with relative money saving costs. Material and methods The analysis was carried out by extrapolating, from the unit dose (UD) software, prescriptions of antibiotics subjected to a single request motivated (SRM) in the period from 1 January 2019 to 31 December 2019. We analysed inappropriate prescriptions where the hospital pharmacist affixed the ‘note’, sent immediately to the prescriber. These prescriptions were divided into inappropriate for: posology, duration of therapy and interaction/incompatibility. Subsequently, the variation in prescriptions due to the pharmacist’s intervention was evaluated (ie, the number of inappropriate prescriptions which were changed by the physician was extrapolated). In the pharmacoeconomic field, we evaluated the expenditure of inappropriate prescriptions without notification of the hospital pharmacist and the savings obtained following the change in therapy. Results During the study period, total prescriptions of antibiotics with SRM were 2067; 216 (10.45%) were not appropriate. The number of prescriptions modified following the pharmacist’s intervention was 104 (48%). Pharmacoeconomic analysis showed that the expenditure incurred for the dispensation of antibiotics related to inappropriate prescriptions changed by notification from the pharmacist was 77 537€ for 12 months. If the physician had not modified the therapies, the expenses would have been 162 762€ and therefore the amount of money saved was 85 225€ in 12 months. Conclusion and relevance The control and validation of medical prescriptions by the pharmacist produced an important added value to the risk management process, in that in almost 50% of cases the pharmacist’s notes led to an actual change in the medical prescription. The use of computerised prescriptions and single dose management contributed strongly to the objectives of verifying prescriptive appropriateness as a tool to govern effectiveness, efficiency and costs in healthcare. References and/or acknowledgements Conflict of interest No conflict of interest

Background Despite increased emphasis on providing higher-quality patient- and family-centered care in the intensive care unit (ICU), there are no widely accepted definitions of such care in the ICU. Objectives To determine (1) aspects of care that patients and families valued during their ICU encounter, (2) outcomes that patients and families prioritized after hospital discharge, and (3) outcomes perceived as equivalent to or worse than death. Methods Semistructured interviews (n = 49) of former patients of an urban, academic medical ICU and their family members. Two investigators reviewed all transcripts line by line to identify key concepts. Codes were created and defined in a codebook with decision rules for their application and were analyzed using qualitative content analysis. Results Salient themes were identified and grouped into 2 major categories: (1) processes of care within the ICU— communication, patient comfort, and a sense that the medical team was “doing everything” (ie, providing exhaustive medical care) and (2) patient and surrogate outcomes after the ICU—survival, quality of life, physical function, and cognitive function. Several outcomes were deemed worse than death: severe cognitive/physical disability, dependence on medical machinery/equipment, and severe/constant pain. Conclusion Although survival was important, most participants qualified this preference. Simple measures of mortality rates may not represent patient- or family-centered outcomes in evaluations of ICU-based interventions, and new measures that incorporate functional outcomes and patients’ and family members’ views of life quality are necessary to promote patient-centered, evidence-based care.

Fewer than one-third of US residents have completed an advance directive (AD) to guide care when seriously ill.1 Clinician-focused efforts to increase AD completion, such as Medicare payments for advance care planning (ACP), have been ineffective.2 In contrast, patient-facing interventions that enable independent completion of ADs show early promise.3 Self-service platforms also reveal changes in demand for ADs and preferences for future care. We sought to quantify changes in patient completion of ADs and expressed preferences during the coronavirus disease 2019 (COVID-19) pandemic by monitoring users of a web-based AD platform from January 2019 to April 2020.

ispartof: INTENSIVE CARE MEDICINE vol:45 issue:12 pages:1806-1809 ispartof: location:United States status: published

Background: The Centers for Medicare & Medicaid Services (CMS) recently instituted physician reimbursements for advance care planning (ACP) discussions with patients. Aim: To measure public support for similar programs. Design: Cross-sectional online and in-person surveys. Setting/Participants: English-speaking adults recruited at public parks in Philadelphia, Pennsylvania, from July to August 2013 and online through survey sampling international Web-based recruitment platform in July 2015. Participants indicated support for 6 programs designed to increase advance directive (AD) completion or ACP discussion using 5-point Likert scales. Participants also indicated how much money (US$0-US$1000) was appropriate to incentivize such behaviors, compared to smoking cessation or colonoscopy screening. Results: We recruited 883 participants: 503 online and 380 in-person. The status quo of no systematic approach to motivate AD completion was supported by 67.0% of participants (63.9%-70.1%). The most popular programs were paying patients to complete ADs (58.0%; 54.5%-61.2%) and requiring patients to complete ADs or declination forms for health insurance (54.1%; 50.8%-57.4%). Participants more commonly supported paying patients to complete ADs than paying physicians whose patients complete ADs (22.6%; 19.8%-25.4%) or paying physicians who document ACP discussions (19.1%; 16.5%-21.7%; both P < .001). Participants supported smaller payments for AD completion and ACP than for obtaining screening colonoscopies or stopping smoking. Conclusions: Americans view payments for AD completion or ACP more skeptically than for other health behaviors and prefer that such payments go to patients rather than physicians. The current CMS policy of reimbursing physicians for ACP conversations with patients was the least preferred of the programs evaluated.

Background No validated conceptual framework exists for understanding the outcomes of patient- and family-centered care in critical care. Objective To explore the meaning of intensive care unit among patients and their families by using freelisting. Methods The phrase intensive care unit was used to prompt freelisting among intensive care unit patients and patients' family members. Freelisting is an anthropological technique in which individuals define a domain by listing all words that come to mind in response to a topic. Salience scores, derived from the frequency with which a word was mentioned, the order in which it was mentioned, and the length of each list, were calculated and analyzed. Results Among the 45 participants, many words were salient to both patients and patients' family members. Words salient solely for patients included consciousness, getting better, noisy, and personal care. Words salient solely for family members included sadness, busy, professional, and hope. The words suffering, busy, and team were salient solely for family members of patients who lived, whereas sadness, professionals, and hope were salient solely for family members of patients who died. The words caring and death were salient for both groups. Conclusions Intensive care unit patients and their families define intensive care unit by using words to describe sickness, caring, medical staff, emotional states, and physical qualities of the unit. The results validate the importance of these topics among patients and their families in the intensive care unit and illustrate the usefulness of freelisting in critical care research.

Objectives Physicians adopt evidence-based guidelines with variable consistency. Narratives, or stories, offer a novel dissemination strategy for clinical recommendations. The study objective was to compare whether evidence-based narrative versus traditional summary improved recall of opioid prescribing guidelines from the American College of Emergency Physicians (ACEP). Methods This was a prospective, randomized controlled experiment to compare whether narrative versus summary promoted short-term recall of six themes contained in the ACEP opioid guideline. The experiment was modeled after the free-recall test, an established technique in studies of memory. At a regional conference, emergency physicians (EPs) were randomized to read either a summary of the guideline (control) or a narrative (intervention). The fictional narrative was constructed to match the summary in content and length. One hour after reading the text, participants listed all content that they could recall. Two reviewers independently scored the responses to assess recall of the six themes. The primary outcome was the total number of themes recalled per participant. Secondary outcomes included the proportion of responses in each study arm that recalled individual themes and the proportion of responses in each arm that contained falsely recalled or extraneous information. Results Ninety-five physicians were randomized. Eighty-two physicians completed the experiment, for a response rate of 86%. The mean of the total number of themes recalled per participant was 3.1 in the narrative arm versus 2.0 in the summary arm (difference = 1.1, 95% confidence interval [CI] = 0.6 to 1.7). For three themes, the proportion of responses that recalled the theme was significantly greater in the narrative arm compared to the summary arm, with the differences ranging from 20% to 51%. For one theme, recall was significantly greater in the summary arm. For two themes, there was no statistically significant difference in recall between the arms. In the summary arm, 54% of responses were found to contain falsely recalled or extraneous information versus 21% of responses in the narrative arm (difference = 33%, 95% CI = 14% to 53%). Conclusions Physicians exposed to a narrative about opioid guidelines were more likely to recall guideline content at 1 hour than those exposed to a summary of the guidelines. Future studies should examine whether the incorporation of narratives in dissemination campaigns improves guideline adoption and changes clinical practice. Resumen Objetivos Los medicos adoptan las guias clinicas basadas en la evidencia de forma variable. Las historias, o narraciones, ofrecen una estrategia novedosa de difusion de las recomendaciones clinicas. El objetivo fue comparar si una narracion basada en la evidencia frente al resumen tradicional mejoro el recuerdo de las guias clinicas para la prescripcion de opiaceos del American College of Emergency Physicians (ACEP). Metodologia Estudio prospectivo controlado y aleatorizado para comparar si la narracion frente al resumen promociono el recuerdo a corto plazo de seis temas contenidos en la guias clinica de opiaceos del ACEP. El estudio se inspiro en el test del recuerdo libre, una tecnica establecida en los estudios de memoria. En una conferencia regional, los urgenciologos se aleatorizaron a leer un resumen de la guia (control) o una narracion (intervencion). La narracion ficticia se construyo para equiparar al resumen en contenido y longitud. Una hora tras la lectura, los participantes enumeraron todo el contenido que pudieron recordar. Dos revisores de forma independiente puntuaron las respuestas para evaluar el recuerdo de los seis temas. El resultado principal fue el numero total de temas recordados por cada participante. Los resultados secundarios incluyeron la proporcion de respuestas en cada brazo del estudio de temas individualmente recordados y la proporcion de respuestas en cada brazo del estudio que contuvieron recuerdo falso o informacion superflua. Resultados Se aleatorizaron 95 medicos. Ochenta y dos medicos completaron el estudio, con un porcentaje de respuesta de un 86%. La media de temas recordados por participante fue de 3,1 en el brazo de la narracion frente a 2,0 en el brazo del resumen (diferencia 1,1, IC 95% = 0,6 a 1,7). Para tres temas, la proporcion de respuestas que recordaron el tema fue significativamente mayor en el brazo de la narracion en comparacion con el brazo del resumen, con un rango de diferencias de un 20% a un 51%. Para un tema, el recuerdo fue significativamente mayor en el brazo del resumen. Para dos temas, no hubo diferencias estadisticamente significativas en el recuerdo entre los brazos. En el brazo del resumen, se encontro un 54% de las respuestas falsamente recordadas o con informacion superflua frente a un 21% en el brazo de la narracion (diferencia 33%, IC 95% = 14% a 53%). Conclusiones Los medicos expuestos a una narracion sobre las guias de opiaceos tuvieron una probabilidad mayor de recordar al cabo de una hora el contenido de la guia clinica que aquellos expuestos a un resumen de la guia clinica. Estudios futuros deberian examinar si la incorporacion de narraciones en las campanas de difusion mejora la adopcion de la guia clinica y cambia la practica clinica.

OBJECTIVES: The ICU is a place of frequent, high-stakes decision making. However, the number and types of decisions made by intensivists have not been well characterized. We sought to describe intensivist decision making and determine how the number and types of decisions are affected by patient, provider, and systems factors. DESIGN: Direct observation of intensivist decision making during patient rounds. SETTING: Twenty-four-bed academic medical ICU. SUBJECTS: Medical intensivists leading patient care rounds. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: During 920 observed patient rounds on 374 unique patients, intensivists made 8,174 critical care decisions (mean, 8.9 decisions per patient daily, 102.2 total decisions daily) over a mean of 3.7 hours. Patient factors associated with increased numbers of decisions included a shorter time since ICU admission and an earlier slot in rounding order (both p < 0.05). Intensivist identity explained the greatest proportion of variance in number of decisions per patient even when controlling for all other factors significant in bivariable regression. A given intensivist made more decisions per patient during days later in the 14-day rotation (p < 0.05). Female intensivists made significantly more decisions than male intensivists (p < 0.05). CONCLUSIONS: Intensivists made over 100 daily critical care decisions during rounds. The number of decisions was influenced by a variety of patient- and system-related factors and was highly variable among intensivists. Future work is needed to explore effects of the decision-making burden on providers’ choices and on patient outcomes.

Urotensin II (U-II) is a disulfide bridged peptide hormone identified as the ligand of a G-protein-coupled receptor. Human U-II (H-Glu-Thr-Pro-Asp-c[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH) has been described as the most potent vasoconstrictor compound identified to date. We have recently identified both a superagonist of human U-II termed P5U (H-Asp-c[Pen-Phe-Trp-Lys-Tyr-Cys]-Val-OH) and the compound termed urantide (H-Asp-c[Pen-Phe-D-Trp-Orn-Tyr-Cys]-Val-OH), which is the most potent UT receptor peptide antagonist described to date. In the present study, we have synthesized four analogues of P5U and urantide in which the Trp(7) residue was replaced by the highly constrained L-Tpi and D-Tpi residues. The replacement of the Trp(7) by Tpi led to active analogues. Solution NMR analysis allowed improving the knowledge on conformation-activity relationships previously reported on UT receptor ligands.

The new allelic variant HLA-B*38:55Q differs from the closest related B*38:01:01 by one nucleotide substitution at position 373 in exon 3 (TGC>CGC). This results in a difference of one amino acid at residue 101 of the HLA-B heavy chain, from a neutral-polar Cys to a basic-polar Arg, thus impairing disulphide bridge formation in the alpha-2 domain. This alteration of the secondary structure probably affects the maturation of the heavy chain and the level of surface expression, making the HLA-B*38:55Q undetectable by standard serological typing.

Urotensin II (U-II) is a disulfide bridged peptide hormone identified as the ligand of a G protein-coupled receptor. Human U-II (H-Glu-Thr-Pro-Asp-c[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH) has been described as the most potent vasoconstrictor compound identified to date. We have recently identified both a superagonist of hU-II termed P5U (H-Asp-c[Pen-Phe-Trp-Lys-Tyr-Cys]-Val-OH) and the compound termed urantide (H-Asp-c[Pen-Phe-DTrp-Orn-Tyr-Cys]-Val-OH), which is the most potent UT receptor peptide antagonist described to date. In the present study, we have synthesized several analogues of P5U and urantide in which the Asp(4) residue in N-terminus position was replaced with coded and noncoded amino acids. The replacement of the Asp(4) residue by Tic led to an analogue, compound 14, more potent as antagonist (pK(B) = 8.94) compared to urantide. Furthermore, a different SAR was observed for the P5U compared to the urantide analogues. NMR and docking studies revealed a different binding mode for the agonist and antagonist ligands which could explain the observed SAR.

SUMMARY An Andisol from the Vesuvian volcanic area, low in organic matter, was treated with wheat straw (20/1 w/w) and urea (500/1 w/w) in pots, and maintained at 60–90% of field capacity in an open greenhouse in order to study the yields and properties of humic acids after 30, 122 and 224 d, and 1, 2 and 3 years of incubation. During the first year the yields increased, but subsequently they showed a decrease. However, the chemical and spectroscopic properties of humic acids remained substantially constant. The chemical characteristics of modified lignin from added wheat straw were recognized in the properties of humic acids by UV-visible, FT-IR and 13C CP-MAS NMR spectroscopic analysis. Evidence was obtained that these modifications included the microbial removal of carbohydrates, the oxidative destruction or transformation of the side chains of lignin units, the demethylation of mainly guaiacyl, and subsequent oxidation of catechol-like structures to o-quinone. The latter can be postulated to promote the nucleophilic addition of amino compounds with formation of aromatic amines in humic acids.

The authors report a method for planning, constructing, and running grounding installations. This method has been fully tested by SIP for exchanges and networks in areas characterized by a particularly high specific resistivity; and by ENEL for links in line-carried waves on HV overhead lines. The approach developed aims at making it reliable over a considerable length of time and optimizing the cost/benefit ratio for each system. >

IMPORTANCE: Policies and practices that promote advance care planning and advance directive completion implicitly assume that patients’ choices for end-of-life (EOL) care are stable over time, even with changes in health status. OBJECTIVE: To systematically evaluate the evidence on the stability of EOL preferences over time and with changes in health status. EVIDENCE REVIEW: We searched for longitudinal studies of patients’ preferences for EOL care in PubMed, EMBASE, and using citation review. Studies restricted to preferences regarding the place of care at the EOL were excluded. FINDINGS: A total of 296 articles were assessed for eligibility, and 59 met inclusion criteria. Twenty-four articles had sufficient data to extract or calculate the percentage of individuals with stable preferences or the percentage of total preferences that were stable over time. In 17 studies (71%) more than 70% of patients’ preferences for EOL care were stable over time. Preference stability was generally greater among inpatients and seriously ill outpatients than among older adults without serious illnesses (P < .002). Patients with higher education and who had engaged in advance care planning had greater preference stability, and preferences to forgo therapies were generally more stable than preferences to receive therapies. Among 9 of the 24 studies (38%) assessing changes in health status, no consistent relationship with preference changes was identified. CONCLUSIONS AND RELEVANCE: Considerable variability among studies in the methods of preference assessment, the time between assessments, and the definitions of stability preclude meta-analytic estimates of the stability of patients’ preferences and the factors influencing these preferences. Although more seriously ill patients and those who engage in advance care planning most commonly have stable preferences for future treatments, further research in real-world settings is needed to confirm the utility of advance care plans for future decision making.

To study the effect of second-line treatment with tetracycline (T) combination therapy in patients with Helicobacter pylori (H. pylori) infection after failure of triple one-week therapy with a proton pump inhibitor, omeprazole (O) with amoxycillin (A) and claritromycin (C) or metronidazole (M).Three hundred twenty-five naive patients (146 males, 179 females, mean age 50, range 18-76), with H. pylori infection, were randomised to receive one-week triple therapy b.i.d. with O 20 mg; A 1 g; C 500 mg (OAC7 163 pts) or O 20 mg; A 1 g; M 500 mg (OAM7 162 pts). H. pylori status was determined before therapy by histology and 3 months after the end of treatment by C-13 urea breath test (UBT). When eradication did not occur, the patients were retreated with OTA7: O 20 mg b.i.d.; T 500 mg t.i.d. and A1 g b.i.d. for another week. H. pylori was assessed by C-13 UBT 3 months after the end of retreatment. Statistical analysis was done by c2 and Student t test.Three hundred and ten patients have completed the study with compliance95%: 15 patients complained of side effects (diarrhea, nausea, urticaria, abdominal pain): 9 group OAC7, 6 group OAM7. After the first treatment h. pylori eradication were obtained in 124/154 (80.5%) (PP) OAC7 group and 123/156 (78.8%) (PP) OAM7 group (ns). 49/63 patients (77.7%) were negative after second-line treatment with OTA7 regimen.In personal experience the drug compliance was excellent. The rate of eradication after one-week therapy-omeprazole combined with A+C or with A+M-was satisfactory. The retreatment with tetracycline combination regimen cured 77.7% of patients: that seems to be a promising options, in clinical practice, after an eradication failure.

Previous investigations indicate that alpha-melanocyte-stimulating hormone (alpha-MSH) and certain synthetic analogues of it exert antimicrobial effects against bacteria and yeasts. However, these molecules have weak activity in standard microbiology conditions and this hampers a realistic clinical use. The aim in the present study was to identify novel peptides with broad-spectrum antimicrobial activity in growth medium. To this purpose, the Gly10 residue in the [DNal(2')-7,Phe-12]-MSH(6-13) sequence was replaced with conventional and unconventional amino acids with different degrees of conformational rigidity. Two derivatives in which Gly10 was replaced by the residues Aic and Cha, respectively, had substantial activity against Candida strains, including C. albicans, C. glabrata, and C. krusei and against gram-positive and gram-negative bacteria. Conformational analysis indicated that the helical structure along residues 8-13 is a key factor in antimicrobial activity. Synthetic analogues of alpha-MSH can be valuable agents to treat infections in humans. The structural preferences associated with antimicrobial activity identified in this research can help further development of synthetic melanocortins with enhanced biological activity.