The outcomes of treatment for homebound adults with complex medical conditions in a hospital-at-home unit in the southern district of Israel.

BACKGROUND: A model of hospital-at-home services called the Home Care Unit ("the unit") has been implemented in the southern region of the Clalit Healthcare Services in Israel. The aim of the present study was to characterize this service model. METHODS: A retrospective cross-over study. included homebound patients 65 years of age and above who were treated for at least one month in the framework of the unit, between 2013 and 2020. We compared the hospitalization rate, the number of hospital days, the number of emergency room visits, and the cost of hospitalization for the six-month period prior to admission to the unit, the period of treatment in the unit, and the six-month period following discharge from the unit. RESULTS: The study included 623 patients with a mean age of 83.7 ± 9.2 years with a mean Mini-mental State Examination (MMSE) score of 12.0 ± 10.2, a mean Charlson Comorbidity Index (CCI) of 3.7 ± 2.2 and a Barthel Index score of 23.9 ± 25.1. The main indications for admission to the unit were various geriatric syndromes (56.7%), acute functional decline (21.2%), and heart failure (12%). 22.8% died during the treatment period and 63.4% were discharged to ongoing treatment by their family doctor after their condition stabilized. Compared to the six months prior to admission to the unit there was a significant decrease (per patient per month) in the treatment period in the number of days of hospitalization (2.84 ± 4.35 vs. 1.7 ± 3.8 days, p < 0.001) and in the cost of hospitalization (1606 ± 2170 vs. 1066 ± 2082 USD, p < 0.001). CONCLUSIONS: Treatment of homebound adults with a high disease burden in the setting of a hospital-at-home unit can significantly reduce the number of hospital days and the cost of hospitalization. This model of service for homebound patients with multiple medical problems maintained a high level of care while reducing costs. The results support the widespread adoption of this service in the community to enable the healthcare system to respond to the growing population of elderly patients with medical complexity.

Methylphenidate for Mild Cognitive Impairment: An Exploratory 3-Day, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: To evaluate the efficacy, safety and tolerability of methylphenidate (MPH) for cognitive function in older patients with mild cognitive impairment (MCI). Methods: Male and female subjects aged 65 years and older with a clinical diagnosis MCI were included in an exploratory randomized, double-blind, placebo-controlled trial. Eligible subjects were assigned to either treatment with immediate-release MPH or placebo. The active compound was administered in an increasing-dose stepwise fashion, namely 10 mg MPH on day 1, 20 mg on day 2, and 30 mg on day 3. Subjects remained under observation for 4 h following drug administration and were monitored for changes in blood pressure and for adverse events. Cognitive outcome measures included the Montreal Cognitive Assessment (MoCA) and the Neurotrax Mindstreams computerized cognitive assessment battery. Results: Of 17 subjects enrolled, 15 subjects completed the study, 7 in the active MPH group and 8 in the placebo group. The average age of the participants was 76.1 ± 6.6 years and 10 (66.7%) were men. Following the final dose a significant benefit on memory (predominantly non-verbal memory) was found in the MPH group. While 12 adverse events were reported, they were all rated as mild to moderate. Conclusions: Our finding of modest beneficial effects of MPH on memory tests in older subjects with MCI in this exploratory study is of interest and should be investigated in further studies.

Implementation of Geriatric Recommendations by Doctors: A Comparison of Models of Geriatric Assessment for Mobile and Home-Ridden Patients.

In the present study we assessed the rate of implementation of recommendations given following geriatric assessment for home-ridden patients; a retrospective review of medical records to evaluate the implementation of geriatric recommendations given to patients in the Home Geriatric Service (HGS) between 2015 and 2016. The patients were categorized into two groups: the HGS-clinic (HGS-C) group, in which the primary care physician was responsible for implementation of the recommendations, and the HGS-home care (HGS-H) group, in which the responsibility for implementation of the recommendations was on the geriatrician. The results were compared with the implementation of recommendations in other ambulatory models for mobile patients-Clinic-Based Geriatric Assessment Services (CBGAS). The study included 865 patients. The highest rate of implementation was in the HGS-H group (85.7%), compared with 66.6% in the HGS-C group and 52.7% in the CBGAS group (p < 0.0001). In the logistic regression model for prediction of patients with implementation rates above 75%, the only variable that entered the prediction model was affiliation with the HGS-H group (odds ratio [OR] = 4.8, 95% confidence interval [CI] 2.3-9.6, p < 0.0001) or the HGS-C group (OR = 1.7, 95% CI 1.0-2.9, p = 0.046). The implementation rate for geriatric recommendations is higher for home-ridden patients compared with mobile patients, with the maximum recommendation rate in the subgroup, where geriatricians implemented the recommendations themselves. These findings raise the possibility that the most successful model, in terms of the implementation of recommendations, is the model in which implementation is carried out by the same staff that conducted the assessment.

Orthostatic hypotension and overall mortality in 1050 older patients of the outpatient comprehensive geriatric assessment unit.

AIM: Orthostatic hypotension is a common problem in individuals aged ≥65 years. Its association with mortality is not clear. The aim of the present study was to evaluate associations between orthostatic hypotension and overall mortality in a sample of individuals aged ≥65 years who were seen at the Outpatient Comprehensive Geriatric Assessment Unit, Clalit Health Services, Beer-Sheva, Israel. METHODS: Individuals who were evaluated in the Outpatient Comprehensive Geriatric Assessment Unit between January 2005 and December 2015, and who had data on orthostatic hypotension were included in the study. The database included sociodemographic characteristics, body mass index, functional and cognitive state, geriatric syndromes reached over the course of the assessment, and comorbidity. Data on mortality were also collected. RESULTS: The study sample included 1050 people, of whom 626 underwent comprehensive geriatric assessment and 424 underwent geriatric consultation. The mean age was 77.3 ± 5.4 years and 35.7% were men. Orthostatic hypotension was diagnosed in 294 patients (28.0%). In univariate analysis, orthostatic hypotension was associated with overall mortality only in patients aged 65-75 years (HR 1.5, 95% CI 1.07-2.2), but in the multivariate model this association disappeared. CONCLUSIONS: In older frail patients, orthostatic hypotension was not an independent risk factor for overall mortality. Geriatr Gerontol Int 2018; 18: 1009-1017.

A Comparative Study of Models of Geriatric Assessment and the Implementation of Recommendations by Primary Care Physicians.

The aim of the present study was to compare implementation rates by primary care physicians of geriatric assessment recommendations given in various assessment settings. We compared Model "OCGAU," an outpatient comprehensive geriatric assessment unit where there was no direct contact between the geriatrician and the primary care physician with three "Clinic" models of in-clinic geriatric assessment: Model "Clinic A-2007" in which the primary care physician participated in the assessment, Model "Clinic A-2013" where there was no contact with the primary care physician, and Model "Clinics B-2013" where the primary care physician participated in a staff meeting with the geriatrician in the clinic. Subgroups of "OCGAU" model were composed of patients referred to the geriatric unit by primary care physicians of patients included in three "Clinic" models. Model "OCGAU" included 240 patients, Model "Clinic A-2007" 107, Model "Clinic A-2013" 127, and Model "Clinics B-2013" 133. The patients in Model "OCGAU" were older (mean age 83.2 ± 6.2 years) than in "Clinic" models where the mean age was 79.7 ± 6.5, 81.5 ± 6.1, and 80.7 ± 6.5, p < 0.001. More recommendations were given per patient (6.4) in the Model OCGAU than in the "Clinic" models (range 1.9-3.9, p < 0.05), but the implementation of recommendations by primary care physicians was lower in Model OCGAU (48.9%) than in "Clinic" models (range 56.9%-71.8%, p < 0.005). Although more recommendations were made in the geriatric unit, the implementation rate was lower. This indicates the need for organizational changes, in particular, improving communication between the geriatric staff and primary care physicians.

Which factors affect the implementation of geriatric recommendations by primary care physicians?

BACKGROUND: The overall implementation rate for outpatient comprehensive geriatric assessment (OCGAU) recommendations ranges from 48.6 to 71%. The purpose of the study was to identify factors that reduce the implementation rate of geriatric recommendations. METHODS: The medical records of patients who were assessed in the comprehensive geriatric assessment unit over an 8 year study period were surveyed. Data collected included patient's characteristics (socio-demographic, functional, cognitive, and affective condition, co-morbidity), number of recommendations, the identity of the geriatrician, and data related to the primary physician (age, sex, seniority, number of patients referred for geriatric assessment). RESULTS: Three thousand four hundred thirty-four recommendations were made for 488 patients (mean age 83.6 ± 0.6 years) of which 1,634 (47.6%) were implemented by their primary physician. In univariate analyses patients with an implementation rate < 25%, compared to patients with implementation rate ≥75%, had a higher Charlson Comorbidity Index Total Score (CCITS) (2.5 ± 1.9 vs. 1.8 ± 1.7, P < 0.05), a lower Barthel Index (82.8 ± 16.2 vs. 87.0 ± 15.3, P < 0.05), and a lower Instrumental Activity of Daily Living score (7.2 ± 3.5 vs. 8.2 ± 3.7, P < 0.05). There were no differences between these groups in other patient characteristics or the number of recommendations made during the assessment. Similarly, there were no differences in the identity of the geriatrician or the primary physician's characteristics. In the multivariate analysis only higher CCITS was associated with a lower rate of recommendation implementation by primary physicians. CONCLUSIONS: There is a need to increase the implementation rate by primary physicians by increasing and strengthening the link with them and by further training in the field of geriatrics medicine. TRIAL REGISTRATION: The Helsinki committee of the Meir Medical Center approved the study (Approval #024/2015 [k]).

Can home care for homebound patients with chronic heart failure reduce hospitalizations and costs?

BACKGROUND: Congestive heart failure (CHF), a common problem in adults, is associated with multiple hospitalizations, high mortality rates and high costs. PURPOSE: To evaluate whether home care for homebound patients with CHF reduces healthcare service utilization and overall costs. METHODS: A retrospective study of healthcare utilization among homebound patients who received home care for CHF from 2012-1015. The outcome measures were number of hospital admissions per month, total number of hospitalization days and days for CHF only, emergency room visits, and overall costs. A comparison was conducted between the 6-month period prior to entry into home care and the time in home care. RESULTS: Over the study period 196 patients were treated by home care for CHF with a mean age of 79.4±9.5 years. 113 (57.7%) were women. Compared to the six months prior to home care, there were statistically significant decreases in hospitalizations (46.3%), in the number of total in-hospital days (28.7%), in the number of in-hospital days for CHF (66.7%), in emergency room visits (47%), and in overall costs (23.9%). CONCLUSION: Home care for homebound adults with CHF can reduce healthcare utilization and healthcare costs.

Nelfinavir induces adipocyte insulin resistance through the induction of oxidative stress: differential protective effect of antioxidant agents.

BACKGROUND: Antiretroviral therapy is frequently associated with adverse metabolic effects and lipodystrophy, but the role of HIV protease inhibitors and the mechanisms involved are poorly understood. The HIV protease inhibitor nelfinavir (NFV) impairs insulin signal propagation by inducing similar signalling defects to those induced by exposure to oxidative stress. AIM: We set out to determine if oxidative stress is involved in NFV-induced insulin resistance in 3T3-L1 adipocytes, and whether antioxidant agents with unique modes of action can prevent this effect. RESULTS: Cells exposed to NFV exhibited the following markers of increased oxidative stress: a decrease in both total and low molecular weight reduced thiols, a 20-fold increase in haem oxygenase 1 (HO-1) mRNA, an increase in intracellular reactive oxygen species production (determined by 2',7'-dichlorofluorescein fluorescence), and increased markers of apoptosis. Enhancing cellular thiols with N-acetylcystein prevented the NFV-induced drop in reduced thiols and partially protected against the induction in HO-1, but failed to prevent insulin resistance or cleavage of poly ADP ribose polymerase (PARP), a process indicative of activation of pro-apoptotic caspases. Conversely, the superoxide dismutase-mimetic antioxidant MnTBAP had no effect on cellular thiols in response to NFV, but protected against HO-1 induction and against the impairment in insulin-stimulated Akt/protein kinase B activation and PARP cleavage. CONCLUSIONS: Induction of oxidative stress plays a role in adipocyte insulin resistance and apoptosis induced by NFV through a radical-dependent but thiol-independent mechanism(s). The results may suggest a new mechanism for the adverse effects of NFV on fat cells, and offer potential new intervention approaches.

Out of sight, out of mind? Does terminating the physical presence of a geriatric consultant in the community clinic reduce the implementation rate for geriatric recommendations.

AIM: To assess the effect of moving the geriatric consultation from the primary care clinic to another setting, on the rate of implementation of geriatric recommendations by family physicians. METHODS: A retrospective review of the computerized medical records of elderly patients in four primary care clinics. The rate of implementation of geriatric recommendations was compared between clinics in which a geriatric consultant was physically present (control clinics) and a clinic where the consultation took place elsewhere (study clinic). In addition, the results of the present study were compared to a previous study in which the geriatric consultation was carried out in the study clinic and the family doctor was an active participant. RESULTS: 127 computerized files were reviewed in the study clinic and 133 in the control clinics. The mean age of the patients was 81.1±6.3 years and 63.1% were women. The overall implementation of geriatric recommendations by family doctors in the study clinic was 55.9%, a statistically significant decrease compared to the previous study where the rate was 73.9% (p<0.0001). In contrast, there was no change in the implementation rate in the control clinics at 65.0% in the present study and 59.9% in the previous one (p=0.205). CONCLUSIONS: Direct, person-to-person contact between the geriatric consultant and the family doctor has a beneficial effect on the implementation of geriatric recommendations. This should be considered by healthcare policy makers when planning geriatric services in the community.

The diagnosis of delirium among elderly patients presenting to the emergency department of an acute hospital.

Delirium is prevalent among elderly people presenting to an emergency department (ED). However, despite the fact that delirium is associated with longer hospital stays, an increased rate of institutionalization and higher mortality (especially in the case of undiagnosed delirium), this condition often goes undiagnosed by ED doctors. We examined the rate of mental status assessment and the prevalence of delirium in the ED among patients older than 65 years in a large teaching hospital in Southern Israel via a retrospective chart review. Surprisingly we found no diagnosis of delirium in the medical charts of representative sample of 319 elderly people. Furthermore, only 12.5% of people received either an adequate or even a partially adequate mental status assessment by the ED doctors. We attribute these negative findings not to a low incidence of delirium but probably to a combination of a heavy workload along with a lack of adequate training of ED physicians. We suggest that part of the solution involves providing appropriate education to ED physicians as well as adding a geriatric consultant to the ED roster.

Comparison of antigen constructs and carrier molecules for augmenting the immunogenicity of the monosaccharide epithelial cancer antigen Tn.

We have demonstrated previously that the optimal method for inducing an antibody response against defined cancer antigens is covalent conjugation of the antigen to keyhole limpet hemocyanin (KLH) and use of the potent saponin adjuvant QS-21. Single molecules of glycolipids (tetrasaccharides, pentasaccharides, or hexasaccharides) and MUC1 peptides (containing between one and five MUC1 tandem repeats) conjugated to KLH have proven sufficient for antibody recognition and vaccine construction. However, cancer specificity of monoclonal antibodies against the monosaccharide Tn and disaccharide sTn comes largely from recognition of clusters (c) of these molecules on the cell surface. Tn consists of a monosaccharide (GalNAc) O-linked to serine or threonine on epithelial cancer mucins which are uniquely rich in serines and threonines. We test here several Tn constructs: Tn monosaccharide, Tn(c) prepared on a triple threonine backbone, and Tn prepared on a partially or fully glycosylated MUC1 backbone. We determine that Tn(c) is more effective than Tn, and conjugation to KLH is more effective than conjugation to BSA or polystyrene beads for inducing ELISA reactivity against Tn, and FACS reactivity against Tn-positive tumor cells. Surprisingly, MUC1 glycosylated with Tn at three or five sites per 20 amino acid MUC1 tandem repeat and conjugated to KLH, induced the strongest antibody response against Tn and tumor cells expressing Tn, and had the additional advantage of inducing antibodies against MUC1.

On the power of chemical synthesis: immunological evaluation of models for multiantigenic carbohydrate-based cancer vaccines.

Synthetic carbohydrate cancer vaccines have been shown to stimulate antibody-based immune responses in both preclinical and clinical settings. The antibodies have been observed to react in vitro with the corresponding natural carbohydrate antigens expressed on the surface of tumor cells, and are able to mediate complement-dependent and/or antibody-dependent cell-mediated cytotoxicity. Furthermore, these vaccines have proven to be safe when administered to cancer patients. Until recently, only monovalent antigen constructs had been prepared and evaluated. Advances in total synthesis have now enabled the preparation of multivalent vaccine constructs, which contain several different tumor-associated carbohydrate antigens. Such constructs could, in principle, serve as superior mimics of cell surface antigens and, hence, as potent cancer vaccines. Here we report preclinical ELISA-based evaluation of a TF-Le(y)-Tn bearing construct (compound 3) with native mucin glycopeptide architecture and a Globo-H-Le(y)-Tn glycopeptide (compound 4) with a nonnative structure. Mice were immunized with one or the other of these constructs as free glycopeptides or as keyhole lymphet hemocyanin conjugates. Either QS-21 or the related GPI-0100 were coadministered as adjuvants. Both keyhole lymphet hemocyanin conjugates induced IgM and IgG antibodies against each carbohydrate antigen, however, the mucin-based TF-Le(y)-Tn construct was shown to be less antigenic than the unnatural Globo-H-Le(y)-Tn construct. The adjuvants, although related, proved significantly different, in that GPI-0100 consistently induced higher titers of antibodies than QS-21. The presence of multiple glycans in these constructs did not appear to suppress the response against any of the constituent antigens. Compound 4, the more antigenic of the two constructs, was also examined by fluorescence activated cell sorter analysis. Significantly, from these studies it was shown that antibodies stimulated in response to compound 4 reacted with tumor cells known to selectively express the individual antigens. The results demonstrate that single vaccine constructs bearing several different carbohydrate antigens have the potential to stimulate a multifaceted immune response.

A preclinical study comparing approaches for augmenting the immunogenicity of a heptavalent KLH-conjugate vaccine against epithelial cancers.

Previously using a series of monovalent vaccines, we demonstrated that the optimal method for inducing an antibody response against cancer cell-surface antigens is covalent conjugation of the antigens to keyhole limpet hemocyanin (KLH) and the use of a saponin adjuvant. We have prepared a heptavalent-KLH conjugate vaccine containing the seven epithelial cancer antigens GM2, Globo H, Lewis(y), TF(c), Tn(c), STn(c), and glycosylated MUC1. In preparation for testing this vaccine in the clinic, we tested the impact on antibody induction of administering the individual conjugates plus adjuvant compared with a mixture of the seven conjugates plus adjuvant, and of several variables thought to augment immunogenicity. These include approaches for decreasing suppressor cell activity or increasing helper T-lymphocyte activity (low dose cyclophosphamide or anti-CTLA-4 MAb), different saponin adjuvants at various doses (QS-21 and GPI-0100), and different methods of formulation (lyophilization and use of polysorbate 80). We find that: (1). Immunization with the heptavalent-KLH conjugate plus GPI-0100 vaccine induces antibodies against the seven antigens of comparable titer to those induced by the individual-KLH conjugate vaccines, high titers of antibodies against Tn (median ELISA titer IgM/IgG 320/10240), STn (640/5120), TF (320/10240), MUC1 (80/20480), and globo H (640/40); while lower titers of antibodies against Lewis(y)()(160/0) and only occasional antibodies against GM2 are induced. (2). These antibodies reacted with the purified synthetic antigens by ELISA, and with naturally expressed antigens on the cancer cell surface by FACS. (3). None of the approaches for further altering the suppressor cell/helper T-cell balance nor changes to the standard formulation by lyophilization or use of polysorbate 80 had any impact on antibody titers. (4). An optimal dose of saponin adjuvant, QS-21 (50 microg) or GPI-0100 (1000 microg), is required for optimal antibody titers. This heptavalent vaccine is sufficiently optimized for testing in the clinic.