Search

Introduction Departmental discharge data (January 2017–January 2018) suggested a high number of “Day 1 Deaths” i.e. an individual who was readmitted 24 hours after discharge, and subsequently died during their readmission. We wondered if this was due to a lack of Advance Care Planning (ACP). Methods We undertook a retrospective case note audit of 50 cases from the “readmissions who died” (total 176/7421) subgroup, to understand whether or not they were predictably within the last days, weeks or months of life and whether there was ACP in place. We reviewed all Day 1 Deaths (16/50), and a random selection of cases across the Day 2–30 (34/50) data set. We used the Gold Standards Framework (GSF) as a prognostic tool, by use of the intuitive “surprise question” (“would you be surprised if this person died within the next days, weeks, months?”) and the disease-specific Prognostic Indictors (PI). Results Using the GSF we (retrospectively) predicted death in 94% of the Day 1 deaths and 63% of the Day 2–30 deaths. There was evidence of ACP in 32/50 patients (64%), predominantly in the form of a DNAR CPR (61%). There was very little evidence of other forms of ACP. Readmissions were justified on the basis of a medical condition in 100% of cases; this was infective in 60% (30/50). There were few interactions with secondary care in the 12 months prior to death (mode was 2 admissions in the month prior to death, 4 in the 12 months prior to death). Conclusions We must consider our discharge processes and medical decision making at the front door. A Prognostic indicator Tool would be useful to focus medical decision making. We must recognise infections as end stage disease in advanced ill health, including advanced frailty. We need to consider how we facilitate meaningful involvement of older people in their medical care towards the end of life.

Introduction Immobility can lead to rapid reductions in muscle size, strength and function. Understanding these changes could inform interventions to prevent or slow decline. This longitudinal study aimed to assess the extent of muscle changes in older patients admitted with fragility fractures where clinical management was immobilisation (non-weight bearing) of the affected limb for at least 6 weeks. Method Handgrip strength (HGS); knee extensor strength(KES); Vastus Lateralis thickness and cross-sectional area at ultrasound (VLMT, VLCSA); and skeletal mass index (SMI; bioimpedance analysis) were measured in the non-injured limb of 50 patients (88% female) aged ≥70. Pre-existing physical frailty meant patients were limited to transfers only while non-weight bearing. Measurements were performed at hospital admission, 1, 3 and 6 weeks. One-way repeated measures ANOVA was used to assess changes in measurements over time. Additionally, baseline measurements in female patients (n = 36) were compared to 11 healthy, non-frail, non-hospitalised females with comparable BMI, aged ≥70, using independent t-tests. Data are mean + SD. Results Patient Clinical Frailty Score (median, IQR) was 5 (4–6). At hospital admission, female patients were older (84 ± 7 years vs. 77 ± 6 years, p Conclusion Older patients admitted with fragility fractures were weaker and had lower VLMT compared to healthy, non-frail older people. This, together with the lack of decline in muscle strength and thickness with 6 weeks immobility strongly suggests muscle resilience was attenuated pre-admission, such that immobility had no further detrimental effect. These results differ from muscle changes seen in younger and non-frail cohorts, and warrants assessment of clinical interventions aimed at increasing muscle mass and function specifically in older people with frailty.

Additional file 1.

Introduction: Although older individuals are more prone to hypoglycaemia, it is not known if they have sufficient understanding of the risks of hypoglycaemia or the factors that predispose to it. We evaluated the effectiveness of hypoglycaemia education and examined the factors that increased susceptibility to hypoglycaemia among older people with diabetes. Methods: Forty-five patients (male/female) aged >65 years and known to have diabetes were identified through outpatient clinics at a secondary care hospital. Information relating to education received, awareness of hypoglycaemia and associated risk factors was collected using a standard questionnaire. Additionally, data regarding demographics, treatment regimes, patient attitudes, hypoglycaemic awareness and risks and barriers to self-management of diabetes was collected. Patients were categorised as low, moderate and high risk based on their responses. Independent sample t-tests and Analysis of Variance were carried out to identify factors contributing to high hypoglycaemic risk. Results: Overall, 70% of the patients reported receiving education about hypoglycaemia from health professionals and 95% of them reported good understanding of hypoglycaemia and were able to self-test. Proportion of women receiving education was, however, lower than men (52% women versus 88% men). Compared with men, women were less likely to recognise (59 versus 73%), or act appropriately to a hypoglycaemic episode (59 versus 78%). The mean number of hypoglycaemic episodes per year (41 versus 12) and the duration of hypoglycaemia (9.9 versus 6.3 min) was also greater among women compared with men. The duration of diabetes (P = 0.018), female gender, type 1 diabetes (0.002) and lack awareness of medications causing hypos (P = 0.006) were strong predictors of hypoglycaemia risk. Conclusions: There are significant gaps in education around hypoglycaemia in older people with diabetes. Women, people with longer duration and type 1 diabetes in particular, need additional attention and future educational initiatives need to address these issues.

The preparation of 3-(2-chlorethyl)-4-oxo-3H-imidazo[5,1-d]-1,2,3,5- tetrazine-8-carboxylic acid, a key derivative of mitozolomide in our exploration of the structure-activity relationships of this class of antitumor agents, is described. The facile conversion to the 8-carbonyl chloride gave a derivative that reacted preferentially with nucleophiles at the 8-position rather than at the reactive 4-oxo group, allowing the preparation of a wide range of ester, thioester, amide (including an amide derived from an amino acid), hydroxamic acid, hydrazide and sulfoximide, azide and diazoacetyl derivatives. The in vivo activity is presented of a range of these compounds against TLX5 lymphoma and L1210 leukemia cell lines.

The compound is prepared in 55–60% yield by interaction of chlorosulphonic acid on sodium 2 : 4-dinitrobenzenesulphonate obtained from 2 : 4-dinitrochlorobenzene and sodium sulphite.

New 1,2-diaryl- and 1,2,6-triarylpyridinium salts, containing various five- and six-membered heteroaromatic substituents in the 1, 2, and 6-positions of the pyridinium ring, were synthesized. New tetra- and hexacyclic compounds were prepared by photocyclization of the cations of these salts. Photocyclization proceeds through a singlet excited state with nonadiabatic formation of a dihydro intermediate, followed by its oxidative dehydrogenation. The structure and quantum yield of the formation of photoproducts are determined by steric and electronic effects of the substituents, and in bichromophore compounds by the presence of S-S intramolecular interfragment energy transfer.

On the basis of data obtained from microscopic examination, melting observations, cooling curves, X-ray analyses, and resistance measurements, phase diagrams have been proposed for the Th-Cb and Th-Ti alloy systems. Both are simple eutectic systems and have no terminal solid solubility or intermediate phases. The eutectic between thorium and columbium occurs at a composition of about 8 wt pet Cb and a temperature of 1435°C. The Th-Ti eutectic occurs at 1190°C at the composition 12 wt pet Ti. No change was observed in the transformation temperature of thorium in either system or in the titanium transformation.

RESEARCH in these Laboratories on new hypotensive drugs has in recent years centred on the development of compounds exhibiting both a high level of ganglion-blocking activity and good absorption after oral administration. The first phase of this work culminated in the discovery of 1:2:2:6:6:-pentamethylpiperidine, pempidine1. In clinical use the good absorption and conveniently rapid excretion characteristics of this drug combine to make it a useful advance in the management of essential hypertension2.

The in vitro cytotoxicity, stability, and metabolism of the 8-(N,N-dimethylcarboxamide) and 8-(N-methylcarboxamide) analogues of the experimental antitumor drug mitozolomide have been investigated in conjunction with their in vivo murine pharmacokinetics and metabolism. When tested against the TLX5 lymphoma in vitro the ID50 values for dimethylmitozolomide, methylmitozolomide, and mitozolomide were 14.6, 3.0, and 2.3 microM, respectively. The cytotoxicity of dimethylmitozolomide was dramatically increased when it was incubated with murine hepatic microsomes. There was no significant difference in the in vitro stabilities of dimethylmitozolomide and methylmitozolamide with half-lives of 43.5 and 45.8 min, respectively, in RPMI at 37 degrees C. The in vitro microsomal incubation of dimethylmitozolomide produced significant amounts of methylmitozolomide, which suggests that methylmitozolomide contributed to the cytotoxicity of dimethylmitozolomide in the presence of microsomes. The pharmacokinetics of both dimethylmitozolomide and methylmitozolomide, given i.p. at 10 mg/kg, were investigated in CBA/Ca mice bearing the s.c. solid TLX5 lymphoma. Methylmitozolomide was absorbed rapidly with maximum plasma and tumor concentrations of 10.66 mg/liter and 8.01 mg/kg, respectively, achieved 0.17 h following dosing. Dimethylmitozolomide was also rapidly absorbed with maximum plasma and tumor concentrations of 9.34 mg/liter and 5.00 mg/kg, respectively, achieved within 0.18 h of dosing. Following administration of dimethylmitozolomide, methylmitozolomide was found in both plasma and tumor tissue. The plasma and tumor area under the curves of methylmitozolomide were 87.7% and 120.8%, respectively, of those seen when mice were dosed with authentic methylmitozolomide. By comparison of the area under the curves and clearance values, it was demonstrated that 89% of the administered dimethylmitozolomide was metabolized via methylmitozolomide.

Die Photocyclisierung des Tetraphenylpyridiniumsalzes (I) liefert ein Benzo[ 1,2]chinolizino[3,4,5,6-def]phenanthridin (II).

8-Carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H) -one (mitozolomide) demonstrates curative action against a range of murine tumor model systems. At single doses of between 20 and 40 mg/kg, the latter of which approximates the 10% lethal dose value in mice, the compound elicited cures against the L1210 and P388 leukemias irrespective of the route of tumor and/or drug administration; in these tests, animals receiving 10(5) cells i.p. survived greater than 60 days after treatment. Potent effects were also observed against the TLX5 lymphoma (s.c.) and B16 melanoma (i.p.). In other experiments, 7 of 10 animals implanted with 2 X 10(5) Lewis lung carcinoma cells survived greater than 60 days while 10 of 10 animals survived greater than 60 days after implantation of the Colon 26 tumor. Potent inhibition of the solid tumor models was also observed with complete cures of the Colon 38, M5076 sarcoma, and ADJ/PC6A plasmacytoma. In cross-resistance studies, the compound was ineffective against an L1210 leukemia made resistant to 1,3-bis(2-chloroethyl)-1-nitrosourea and against a TLX5 lymphoma resistant to dimethyltriazenes but cured animals bearing the L1210 leukemia with derived resistance to cyclophosphamide.

4-Mercaptocinnolines are obtained in good yield from the 4-hydroxy-compounds by reaction with phosphorus pentasulphide in pyridine. The corresponding amines are prepared readily from the mercapto-compounds by treatment with ammonia or primary amines. The amination reaction fails with nitro-4-mercaptocinnolines. The reaction of the 4-mercapto-derivatives with hydrazine, methylating agents, and Raney nickel is described. Treatment of 6-chloro-4-mercaptocinnoline with chlorine in acetic acid gave a good yield of 4,6-dichlorocinnoline and not the expected 4-sulphonyl chloride.

Das 1-Amino-pyridiniumkation (Ia) befindet sich in wasriger Losung bei hohem pH im Gleichgewicht mit Pyridin-( 1)-imid (II), das sich langsam zersetzt.

n/a