Palliative care for persons with late-stage Alzheimer's and related dementias and their caregivers: protocol for a randomized clinical trial.

BACKGROUND: Limited access to specialized palliative care exposes persons with late-stage Alzheimer's disease and related dementias (ADRD) to burdensome treatment and unnecessary hospitalization and their caregivers to avoidable strain and financial burden. Addressing this unmet need, the purpose of this study was to conduct a randomized clinical trial (RCT) of the ADRD-Palliative Care (ADRD-PC) program. METHODS: The study will use a multisite, RCT design and will be set in five geographically diverse US hospitals. Lead investigators and outcome assessors will be masked. The study will use 1:1 randomization of patient-caregiver dyads, and sites will enroll N = 424 dyads of hospitalized patients with late-stage ADRD with their family caregivers. Intervention dyads will receive the ADRD-PC program of (1) dementia-specific palliative care, (2) standardized caregiver education, and (3) transitional care. Control dyads will receive publicly available educational material on dementia caregiving. Outcomes will be measured at 30 days (interim) and 60 days post-discharge. The primary outcome will be 60-day hospital transfers, defined as visits to an emergency department or hospitalization ascertained from health record reviews and caregiver interviews (aim 1). Secondary patient-centered outcomes, ascertained from 30- and 60-day health record reviews and caregiver telephone interviews, will be symptom treatment, symptom control, use of community palliative care or hospice, and new nursing home transitions (aim 2). Secondary caregiver-centered outcomes will be communication about prognosis and goals of care, shared decision-making about hospitalization and other treatments, and caregiver distress (aim 3). Analyses will use intention-to-treat, and pre-specified exploratory analyses will examine the effects of sex as a biologic variable and the GDS stage. DISCUSSION: The study results will determine the efficacy of an intervention that addresses the extraordinary public health impact of late-stage ADRD and suffering due to symptom distress, burdensome treatments, and caregiver strain. While many caregivers prioritize comfort in late-stage ADRD, shared decision-making is rare. Hospitalization creates an opportunity for dementia-specific palliative care, and the study findings will inform care redesign to advance comprehensive dementia-specific palliative care plus transitional care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04948866. Registered on July 2, 2021.

On the formation of fold-type oscillation marks in the continuous casting of steel.

Asymptotic methods are employed to revisit an earlier model for oscillation-mark formation in the continuous casting of steel. A systematic non-dimensionalization of the governing equations, which was not carried out previously, leads to a model with 12 dimensionless parameters. Analysis is provided in the same parameter regime as for the earlier model, and surprisingly simple analytical solutions are found for the oscillation-mark profiles; these are found to agree reasonably well with the numerical solution in the earlier model and very well with fold-type oscillation marks that have been obtained in more recent experimental work. The benefits of this approach, when compared with time-consuming numerical simulations, are discussed in the context of auxiliary models for macrosegregation and thermomechanical stresses and strains.

Performance of microbial identification by MALDI-TOF MS and susceptibility testing by VITEK 2 from positive blood cultures after minimal incubation on solid media.

Bloodstream infections (BSIs) are a leading cause of patient morbidity and mortality. Rapid identification of organisms from BSIs is critical for initiating targeted antimicrobial therapy. Although many methods exist for rapid identification, they do not provide detailed or definitive susceptibility information. We assessed the utility of both the VITEK MS and Bruker Biotyper MALDI-TOF mass spectrometers to identify organisms from a positive blood culture bottle after only 4 h of growth on solid media compared to identification from overnight growth using the VITEK MS. Additionally, we determined whether this limited growth could yield accurate antimicrobial susceptibility testing (AST) results compared to overnight growth using the VITEK 2 AST system. Overall, identifications using the VITEK MS and Biotyper had agreements of 127/150 (84%) and 133/150 (88%), respectively. For rapid AST, the overall categorical agreement was 1010/1017 (99.3%), where Gram-negative bacteria had concordant results for 743/750 (99.1%) organism-drug combinations and Gram-positive bacteria had concordant results for 265/267 (99.3%). Gram-negative bacteria had 4, 2, and 1 minor, major, and very major discrepancies, respectively, while Gram-positive bacteria had no minor errors, one major, and one very major discrepancy. In conclusion, organisms grown for only 4 h on solid media were accurately identified by MALDI-TOF MS and have concordant phenotypic AST profiles. This method can also be implemented using common commercial instruments, providing a way to improve upon identification and gain detailed susceptibility information without significant additional laboratory costs.

Medical student appraisal: electronic resources for inpatient pre-rounding.

BACKGROUND: Pre-rounding is essential to preparing for morning rounds. Despite its importance, pre-rounding is rarely formally taught within the medical school curriculum and more often informally learned by modeling residents. The evolution of mobile applications provides opportunities to optimize this process. OBJECTIVES: To evaluate three options available to medical students while pre-rounding and promote adoption of mobile resources in clinical care. METHODS: Six medical students formed the evaluation cohort. Students were surveyed to assess pre-rounding practices. Participants utilized paper-based pre-rounding templates for two weeks followed by two weeks of the electronic note-taking service Evernote. A review of mobile applications on the iTunes and Google Play stores was performed, with each application informally reviewed by a single student. The application Scutsheet was selected for formal review by all students. Data was collected from narrative responses supplied by students throughout the evaluation periods and aggregated to assess strengths and limitations of each application. RESULTS: Pre-study responses demonstrated two consistent processes: verbal sign-out of overnight events and template use to organize patient information. The paper-based template was praised for its organization and familiarity amongst residents, but perceived as limited by the requirement of re-copying data into the hospital's electronic medical record (EMR). Evernote excelled due to compatibility across multiple operating systems, including accessibility from clinical workstations and ability to copy notes into the hospital's EMR. Scutsheet allowed for retention of data across multiple hospital days, but was limited by inability to export data or modify the electronic template. Aggregated user feedback identified the abilities to customize templates and copy information into the EMR as two prevailing characteristics that enhanced the efficiency of pre-rounding. DISCUSSION: Mobile devices offer the potential to enhance pre-rounding efficiency for medical students and residents. A customizable Evernote-based system is described in sufficient detail for reproduction by interested students.

Medical student appraisal: applications for bedside patient education.

BACKGROUND: Medical students are often afforded the privilege of counselling patients. In the past resources were limited to pen and paper or anatomic models. The evolution of mobile applications allows for limitless access to resources that facilitate bedside patient education. OBJECTIVES: To evaluate the utility of six applications in patient education and promote awareness of implementing mobile resources in clinical care. METHODS: Six medical students rotating on various clerkships evaluated a total of six mobile applications. Strengths, limitations, and suggested uses in clinical care were identified. Applications included Meditoons™, VisiblePatient™, DrawMD™, CardioTeach™, Visual Anatomy™, and 360° Patient Education Suite™. Data was generated from narrative responses supplied by each student during their evaluation period. RESULTS: Bedside teaching was enhanced by professional illustrations and animations depicting anatomy and pathophysiology. Impromptu teaching was facilitated, as resources were conveniently available on a student's smartphone or tablet. The ability to annotate and modify images and subsequently email to patients was an extraordinary improvement in provider-patient communication. Universal limitations included small smartphone screens and the novelty of new technology. DISCUSSION: Mobile applications have the potential to greatly enhance patient education and simultaneously build rapport. Endless opportunities exist for their integration in clinical practice, particularly for new diagnoses, consent for procedures, and at time of discharge. Providers should be encouraged to try new applications and utilize them with patients.

Rapid molecular detection of tuberculosis and rifampicin drug resistance: retrospective analysis of a national U.K. molecular service over the last decade.

BACKGROUND: Fast and reliable detection of Mycobacterium tuberculosis complex (MTBC) and drug resistance is crucial in establishing effective treatment and enforcing timely public health measures. METHODS: The authors analysed the performance of a national U.K. molecular diagnostic service over a decade, based on the use of a line probe assay (Innolipa, LiPA) compared with conventional liquid and solid cultures with rapid molecular identification and culture-based drug resistance testing. FINDINGS: Data were available for 7836 consecutive patient samples using LiPA and the reference microbiological technique (conventional liquid and solid cultures with rapid molecular identification and culture-based drug resistance testing). For all sputum specimens (n=3382) the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for MTBC detection were 93.4%, 85.6%, 92.7%, 86.9% and 90.7%; the equivalent values for smear-positive sputum specimens (n=2606) were 94.7%, 80.9%, 93.9%, 83.3% and 91.3%. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for detection of rifampicin resistance in all sputum samples (n=1667) were 92.1%, 99.3%, 89.4%, 99.5% and 98.9%, respectively; the equivalent values for smear-positive sputum specimens (n=1477) were 93.3%, 99.3%, 87.5%, 99.6% and 99%. Between January 2006 and December 2008, LiPA saved 25.3 and 32.2 days for TB diagnosis and rifampicin resistance of smear-positive samples, respectively. INTERPRETATION: A molecular diagnostic service, using a non-automated line probe assay approach, provides a rapid and reliable national service for diagnosing MTBC and rifampicin resistance.

Genotyping of Mycoplasma pneumoniae isolates using real-time PCR and high-resolution melt analysis.

Mycoplasma pneumoniae is an important respiratory pathogen, accounting for up to 25% of community-acquired pneumonia, and is a common cause of hospitalized pneumonia in otherwise healthy adults and children. Mycoplasma pneumoniae isolates can be classified into two main genomic groups (type 1 and type 2) based on sequence variation within the gene encoding the major adhesion molecule P1. Although numerous publications have described real-time PCR assays for the detection of M. pneumoniae, none has been able to discriminate the two genomic types. Here, a real-time PCR assay that can distinguish each type of M. pneumoniae utilizing high-resolution melt-curve analysis is reported. Using this method, 102 isolates obtained from patients from 1965 to the present, including those from recent outbreaks, were typed along with reference strains M129 (type 1) and FH (type 2). The results show that 55 isolates (54%) can be classified as type 1 and 47 isolates (46%) as type 2, and 100% correlation was demonstrated when compared with a standard PCR-restriction fragment length polymorphism typing procedure. Typing of isolates obtained from recent outbreaks in the USA has revealed the presence of both types. This assay provides a rapid, reliable and convenient method for typing M. pneumoniae isolates and may be useful for surveillance purposes and epidemiological investigations, and may provide insight into the biology of M. pneumoniae distribution within populations.

The hierarchy of functional loss associated with cognitive decline in older persons.

OBJECTIVES: We studied a representative cohort of community-dwelling elderly persons to (i) examine the relationship between the loss of specific functional activities and cognitive status at the time of these losses, (ii) compare the cognitive status of participants who have and have not lost independence in these functional activities, and (iii) determine whether a hierarchical scale of functional loss is associated with declining cognitive status. METHODS: A cohort of 5874 community-dwelling persons aged 65 years and older from the Canadian Study of Health and Aging I and II were analyzed. At baseline and 5 years later, cognitive status with the Modified Mini-Mental State Examination (3MS) and functional status with 14 Older American Resources and Services (OARS) items were measured. For each OARS functional item, the mean 3MS scores for persons who lost independence during the 5-year period versus those who did not were compared. RESULTS: For each functional item, the 5-year decline in 3MS scores of persons who lost independence were significantly greater than those who remained independent (e.g., ability to do finances), with an 18-point decline for those who lost independence and a 2-point decline for those who retained independence. A hierarchy of functional items existed, with instrumental activities of daily living (ADLs) (e.g., shopping, banking, and cooking) being lost at higher cognitive scores than basic ADL items (e.g., eating, dressing, and walking), although there was some overlap. CONCLUSIONS: This is the first prospective study using a large representative cohort of elderly persons to demonstrate that progressive cognitive decline is associated with a specific pattern of loss of functional tasks. Clear cognitive thresholds at which development of dependency in OARS functional items occurred. By providing estimates of the cognitive status of persons at the time at which they developed dependency in specific functional items, a natural hierarchy of functional loss associated with cognitive decline emerged. For caregivers, clinicians, and health policy makers, this information can help anticipate the pattern of functional decline and the subsequent care needs of persons with declining cognition, potentially improving the quality of life of these persons and their caregivers and playing an important part in health care planning.

Movement and sound generation by the toadfish swimbladder.

Although sound-producing (sonic) muscles attached to fish swimbladders are the fastest known vertebrate muscles, the functional requirement for such extreme speed has never been addressed. We measured movement of the swimbladder caused by sonic muscle stimulation in the oyster toadfish Opsanus tau and related it to major features of the sound waveform. The movement pattern is complex and produces sound inefficiently because the sides and bottom of the bladder move in opposite in and out directions, and both movement and sound decay rapidly. Sound amplitude is related to speed of swimbladder movement, and slow movements do not produce perceptible sound. Peak sound amplitude overlaps fundamental frequencies of the male's mating call because of muscle mechanics and not the natural frequency of the bladder. These findings suggest that rapid muscle speed evolved to generate sound from an inefficient highly damped system.

Randomized controlled trial of quadriceps training after proximal femoral fracture.

OBJECTIVE: To determine whether systematic progressive high-intensity quadriceps training increases leg extensor power and reduces disability in patients rehabilitating after proximal femoral fracture. DESIGN: Open parallel group randomized controlled trial comparing the addition of six weeks quadriceps training (40 patients) with standard physiotherapy alone (40 patients). The training group exercised twice weekly, with six sets of 12 repetitions of knee extension (both legs), progressing up to 80% of their one-repetition maximum. SETTING: Orthogeriatric unit, and community follow-up. SUBJECTS: Eighty patients rehabilitating after proximal femoral fracture. MAIN OUTCOME MEASURES: Measurements of leg extensor power (Nottingham Power Rig), functional mobility (elderly mobility score), disability (Barthel Index) and quality of life (Nottingham Health Profile) were made at baseline, after six weeks (at the end of the intervention) and at 16 weeks. RESULTS: Leg extensor power increased significantly in the quadriceps training group (fractured leg mean improvement at six weeks 157% (standard error 16), nonfractured leg 80% (12)) compared with the control group (63% (11) and 26% (8) respectively, unpaired Student's t-test p = 0.007 and p = 0.01 for between-group comparisons). Significant benefits were maintained at 16 weeks. Quadriceps training resulted in a greater increase in elderly mobility scale score compared with standard rehabilitation (between-group difference of 2.5 (95% CI 1.1,3.8) at week 6 and 1.9 (0.4,3.4) at week 16). Barthel score increased significantly from week 0 to 6 in the quadriceps training group compared with controls (Mann-Whitney U-test p = 0.05). Patients in the quadriceps training group scored significantly better in the energy subscore of the Nottingham Health Profile at the end of follow-up (Mann-Whitney U-test p = 0.0185). CONCLUSIONS: Progressive high-intensity quadriceps training in elderly proximal femoral fracture patients increased leg extensor power and reduced disability. This was accompanied by an increase in energy as measured by the Nottingham Health Profile. This intervention may provide a simple practical way of improving outcome in these patients.

A comparison of mobility assessments in a geriatric day hospital.

OBJECTIVE: To assess the sensitivity of the Elderly Mobility Scale (EMS) to detect improvements in mobility after physiotherapy in comparison with the Barthel Index (BI) and Functional Ambulation Category (FAC) in routine clinical day hospital practice. SUBJECTS: Eighty-three patients who completed a course of physiotherapy were studied. METHODS: Each was assessed by an independent physiotherapist before and after a programme of physiotherapy, using the EMS, BI and FAC. RESULTS: The mean age was 79 years (SD 7.7). Fifty-three out of 83 (64%) patients were female and 92% were community dwelling. The median number of physiotherapy sessions undergone by each patient was 9 (range 3-51). All three scales detected an improvement in mobility with physiotherapy (p < 0.001). However, using the EMS, 68 out of 82 (83%) patients had a detectable improvement in mobility compared with only 34 out of 80 (42%) using the BI and 28 out of 81 (35%) using the FAC. Using a matched-pairs comparison, the EMS was significantly more likely to detect an improvement in mobility following physiotherapy within the study group than the BI (p < 0.001) or the FAC (p < 0.001). CONCLUSION: Although all three scales detected improvements in mobility, the EMS detected mobility improvements in a significantly greater number of patients.

Compressive properties of cancellous bone defects in a rabbit model treated with particles of natural bone mineral and synthetic hydroxyapatite.

A rabbit model was developed to evaluate the compressive mechanical properties of cancellous bone defects treated with particles of selected bone graft substitute materials. A novel feature of the model was the precise retrieval of the site of implantation. A notable finding was a 9-fold increase in the modulus of elasticity of the defect implanted with a synthetic hydroxyapatite material after 26 weeks when compared to the modulus of the trabecular bone normally at the site. The compressive modulus of lesions treated with particles of a natural bovine bone mineral (anorganic bovine bone) was closer to the normal modulus of the cancellous bone at the site. While the compressive strength of the anorganic bone particles was less than that of normal bone, the site implanted with the bone mineral particles achieved compressive strength greater than normal after 6 weeks. Moreover, the anorganic bone particles accelerated the increase in strength of the lesion, at 6 weeks exceeding the strength achieved by the untreated defect after 26 weeks. The potential problem associated with the disparity in the compressive modulus between sites implanted with the synthetic HA particles and surrounding bone is discussed.

The association between antiulcer medication and initiation of cobalamin replacement in older persons.

As chronic use of antiulcer medications might predispose older persons to cobalamin deficiency, we studied participants (> 65 years) in the clinical examination of the Canadian Study of Health and Aging to test the association between the use of an antiulcer medication (histamine-2 blocker or proton pump inhibitor) at baseline with initiation of cobalamin replacement during the 5 year follow-up period. Of 1054 eligible subjects, 125 (11.7%) were taking an antiulcer medication at baseline. At follow-up, 49 (4.6%) had started cobalamin replacement. Antiulcer medication use at baseline was significantly associated with the initiation of cobalamin therapy (odds ratio 2.56, 95% confidence interval 1.30-5.05), even after adjusting for age, gender and institutional residence (odds ratio 2.61, 95% confidence interval 1.31-5.23). There is an independent association between the use of antiulcer medication and initiation of cobalamin therapy. While the relationship is not unambiguously causal, this finding underscores the need for judicious prescribing of antiulcer medications for older persons.

A decision aid for long-term tube feeding in cognitively impaired older persons.

OBJECTIVE: To describe the development and evaluation of a decision aid for long-term tube feeding in cognitively impaired older people. DESIGN: Before-and-after study. SETTING: Acute care hospitals in Ottawa, Canada. PARTICIPANTS: Substitute decision makers for 15 cognitively impaired inpatients 65 years and older being considered for placement of a percutaneous endoscopic gastrostomy tube. MEASUREMENTS: Questionnaires were used to compare the substitute decision makers' knowledge, decisional conflict, and predisposition regarding feeding tube placement before and after exposure to the decision aid. The acceptability of the decision aid was also assessed. RESULTS: Substitute decision makers significantly increased their knowledge (P = .004) and decreased their decisional conflict (P = .004) regarding long-term tube feeding after using the decision aid. The impact of the decision aid on predisposition toward the intervention was greatest for those who were unsure of their preferences at baseline. All substitute decision makers found the decision aid helpful and acceptable despite very difficult and emotional circumstances. CONCLUSIONS: A decision aid improves the decision-making process for long-term tube feeding in cognitively impaired older patients by decreasing decisional conflict and by promoting decisions that are informed and consistent with personal values. There are particular challenges for developing and evaluating these tools in the context of end-of-life decisions.

Influence of bone densitometry results on the treatment of osteoporosis.

BACKGROUND: Measurement of bone mineral density is widely used to diagnose osteoporosis. The objectives of this study are to determine how bone densitometry affects subsequent treatment of osteopenia and osteoporosis with either hormone replacement therapy or bisphosphonates and to examine clinical factors associated with starting either therapy after bone densitometry. METHODS: We conducted a prospective study involving women over 50 years of age who were referred to a tertiary care hospital for the first time to undergo bone density measurement using dual-energy x-ray absorptiometry (DXA). Baseline clinical data were collected through face-to-face interviews before the test. Subsequently, the scans were reviewed and categorized as showing no bone loss, osteopenia or osteoporosis, based on World Health Organization criteria. Three months after DXA, subjects were contacted by telephone to determine their understanding of the test results and any new treatments started or recommended since the scan. RESULTS: Of 383 women recruited at the time of their DXA, 335 (87.5%) completed the 3-month follow-up. Among those reached at follow-up, DXA results showed no bone loss in 119 (35.5%), osteopenia in 137 (40.9%) and osteoporosis in 79 (23.6%). The proportion of subjects with osteoporosis receiving either hormone replacement therapy or bisphosphonate therapy was 15.2% before the test, increasing to 63.3% after the scan. The following factors were independently associated with the initiation of either therapy: actual DXA result showing osteoporosis (odds ratio [OR] 7.2; 95% confidence interval [CI] 1.7-30.3), compared with a normal scan; subjects' perception that their scan showed bone loss (osteopenia, or osteoporosis) (OR 13.5; 95% CI 4.0-45.5) or that they were unclear about the results (OR 5.4; 95% CI 1.6-18.8), compared with the perception that the results were normal; and discussion of the DXA results with a physician (OR 5.5; 95% CI 1.9-16.0). INTERPRETATION: The proportion of women with osteoporosis receiving hormone replacement therapy or bisphosphonate therapy increases after diagnosis with densitometry. However, communication by physicians so that patients understand their test results is a critical component in the initiation of therapy after bone densitometry.

Racial and state differences in the designation of advance directives in nursing home residents.

OBJECTIVES: To examine racial and state differences in the use of advance directives and surrogate decision-making in a nursing home population. DESIGN: A retrospective cohort study. SETTING: Nursing homes in the states of California (CA), Massachusetts (MA), New York (NY), and Ohio (OH). PARTICIPANTS: Nursing home residents: 130,308 in CA, 59,691 in MA, 112,080 in NY, and 98,954 in OH. MEASUREMENTS: Minimum Data Set information concerning resident race and whether or not residents have a living will (LW), a do not resuscitate (DNR) order, or a surrogate decision-maker (SDM). RESULTS: The proportion of LWs, DNR orders, and SDMs varied significantly (P < .0001) by racial categories in each state. In general, whites were distinctly different from other racial categories. Whites were significantly more likely to have a LW (odds ratio (OR) = 1.9 (CA), OR = 2.2 (NY), OR = 4.9 (OH)), a DNR order (OR = 2.4 (CA), OR = 2.4 (MA), OR = 3.3 (NY), OR = 3.2 (OH)), and a SDM (OR = 1.1 (CA), OR = 1.2 (NY), OR = 1.6 (OH)) than were nonwhites, after adjusting for potentially confounding factors. Significant state differences (P < .0001) were observed in LWs, DNR orders, and SDMs and were most pronounced in residents of Ohio, who were significantly more likely to have a LW than were residents in other states (OR = 9.3). CONCLUSIONS: Various resident characteristics explain some of the racial differences, although whites are still more likely to have a LW, a DNR order, or an SDM independent of various resident characteristics included in the adjusted analyses. This pattern is observed in all states, although the ORs varied by state. Some of these differences may be due to distinct cultural approaches to end-of-life care and lack of knowledge and understanding of advance directives. The distinctly higher rates of LWs among all racial groups in Ohio than in other states suggest that states can potentially increase the use of advance directives through intervention.