Frailty in younger adults in hospital.

BACKGROUND: Even though frailty has been extensively measured in the acute care setting, relatively little is known about the frailty of younger adult inpatients. AIM: This study aimed to measure frailty in a sample of hospitalized adults aged 18 years and over and to examine how frailty in younger adult inpatients differs from middle-aged and older adult inpatients. DESIGN: Secondary analyses of prospectively collected cohort data. METHODS: Research nurses assessed 910 patients at admission to four Australian hospitals using the interRAI Acute Care instrument. Comparison of frailty index (FI) scores and domains was conducted across three age groups: younger (18-49 years), middle-aged (50-69 years) and older adults (≥70 years). Multivariable logistic regression examined risk of prolonged length of stay and unfavourable discharge destination. RESULTS: Younger adults (n = 214; 23.5%) had a mean (SD) FI of 0.19 (0.10). Approximately 27% (n = 57) of younger adults were frail (FI > 0.25). Mood and behaviour, health symptoms and syndromes, nutrition and pain were the most frequently affected domains in younger adults and 50% had ≥3 comorbidities. Frailty increased the risk of long length of stay (odds ratio (OR) = 1.77, P < 0.001) but not the risk of an unfavourable discharge (OR = 1.40, P = 0.20) in younger adults. CONCLUSIONS: This study showed that frailty is prevalent in younger patients admitted to acute care and is associated with adverse outcomes. This study was a critical first step towards establishing an understanding of frailty in younger hospitalized adults.

How frail is frail? A systematic scoping review and synthesis of high impact studies.

AIMS: While the frailty index (FI) is a continuous variable, an FI score of 0.25 has construct and predictive validity to categorise community-dwelling older adults as frail or non-frail. Our study aimed to explore which FI categories (FI scores and labels) were being used in high impact studies of adults across different care settings and why these categories were being chosen by study authors. METHODS: For this systematic scoping review, Medline, Cochrane and EMBASE databases were searched for studies that measured and categorised an FI. Of 1314 articles screened, 303 met the eligibility criteria (community: N = 205; residential aged care: N = 24; acute care: N = 74). For each setting, the 10 studies with the highest field-weighted citation impact (FWCI) were identified and data, including FI scores and labels and justification provided, were extracted and analysed. RESULTS: FI scores used to distinguish frail and non-frail participants varied from 0.12 to 0.45 with 0.21 and 0.25 used most frequently. Additional categories such as mildly, moderately and severely frail were defined inconsistently. The rationale for selecting particular FI scores and labels were reported in most studies, but were not always relevant. CONCLUSIONS: High impact studies vary in the way they categorise the FI and while there is some evidence in the community-dweller literature, FI categories have not been well validated in acute and residential aged care. For the time being, in those settings, the FI should be reported as a continuous variable wherever possible. It is important to continue working towards defining frailty categories as variability in FI categorisation impacts the ability to synthesise results and to translate findings into clinical practice.

Frailty: A cost incurred by reproduction?

Evolutionary theories of senescence, such as the 'disposable soma' theory, propose that natural selection trades late survival for early fecundity. 'Frailty', a multidimensional measure of health status, may help to better define the long-term consequences of reproduction. We examined the relationship between parity and later life frailty (as measured by the Frailty Index) in a sample of 3,534 adults aged 65 years and older who participated in the English Longitudinal Study of Ageing. We found that the most parous adults were the most frail and that the parity-frailty relationship was similar for both sexes. Whilst this study provided some evidence for a 'parity-frailty trade-off', there was little support for our hypothesis that the physiological costs of childbearing influence later life frailty. Rather, behavioural and social factors associated with rearing many children may have contributed to the development of frailty in both sexes.

Do sex differences in chronic disease underpin the sex-frailty paradox?

The 'male-female health-survival paradox' is a well-described clinical phenomenon. More recently, it has been conceptualized as a 'sex-frailty paradox': females may be considered to be more frail (because they have poorer health status) but also less frail (because they are less vulnerable to death) than males of the same age. Here, we review potential biological, behavioral and social mechanisms underpinning sex differences in morbidity, mortality and frailty before considering the question at the center of the sex paradox - why is it that females are able to tolerate poor health better than males? We explore, in detail, a frequently cited explanation for the sex paradox that centers on sex differences in chronic disease and conclude by presenting a new approach to this old hypothesis.

Sex differences in frailty: A systematic review and meta-analysis.

BACKGROUND: It is a well-described clinical phenomenon that females live longer than males, yet tend to experience greater levels of co-morbidity and disability. Females can therefore be considered both more frail (because they have poorer health status) and less frail (because they have a lower risk of mortality). This systematic review aimed to determine whether this ageing paradox is demonstrated when the Frailty Index (FI) is used to measure frailty. METHODS: Medline, EMBASE and CINAHL databases were searched for observational studies that measured FI and mortality in community-dwellers over 65years of age. In five-year age groups, meta-analysis determined the sex differences in mean FI (MD=mean FIfemale-mean FImale) and mortality rate. RESULTS: Of 6482 articles screened, seven articles were included. Meta-analysis of data from five studies (37,426 participants) found that MD values were positive (p<0.001; MD range=0.02-0.06) in all age groups, indicating that females had higher FI scores than males at all ages. This finding was consistent across individual studies. Heterogeneity was high (I2=72.7%), reflecting methodological differences. Meta-analysis of mortality data (13,127 participants) showed that male mortality rates exceeded female mortality rates up until the 90 to 94-years age group. Individual studies reported higher mortality for males at each level of FI, and higher risk of death for males when controlling for age and FI. CONCLUSIONS: The pattern of sex differences in the FI and mortality of older adults was consistent across populations and confirmed a 'male-female health-survival paradox'.

The cytochrome c domain of dimeric cytochrome cd(1) of Paracoccus pantotrophus can be produced at high levels as a monomeric holoprotein using an improved c-type cytochrome expression system in Escherichia coli.

Cytochrome cd(1) nitrite reductase from Paracoccus pantotrophus is a dimer; within each monomer there is a largely alpha-helical domain that contains the c-type cytochrome centre. The structure of this domain changes significantly upon reduction of the heme iron, for which the ligands change from His17/His69 to Met106/His69. Overproduction, using an improved Escherichia coli expression system, of this c-type cytochrome domain as an independent monomer is reported here. The properties of the independent domain are compared with those when it is part of dimeric holo or semi-apo cytochrome cd(1).

Identification and characterization of a novel cytochrome c(3) from Shewanella frigidimarina that is involved in Fe(III) respiration.

Shewanella frigidimarina NCIMB400 is a non-fermenting, facultative anaerobe from the gamma group of proteobacteria. When grown anaerobically this organism produces a wide variety of periplasmic c-type cytochromes, mostly of unknown function. We have purified a small, acidic, low-potential tetrahaem cytochrome with similarities to the cytochromes c(3) from sulphate-reducing bacteria. The N-terminal sequence was used to design PCR primers and the cctA gene encoding cytochrome c(3) was isolated and sequenced. The EPR spectrum of purified cytochrome c(3) indicates that all four haem irons are ligated by two histidine residues, a conclusion supported by the presence of eight histidine residues in the polypeptide sequence, each of which is conserved in a related cytochrome c(3) and in the cytochrome domains of flavocytochromes c(3). All four haems exhibit low midpoint redox potentials that range from -207 to -58 mV at pH 7; these values are not significantly influenced by pH changes. Shewanella cytochrome c(3) consists of a mere 86 amino acid residues with a predicted molecular mass of 11780 Da, including the four attached haem groups. This corresponds closely to the value of 11778 Da estimated by electrospray MS. To examine the function of this novel cytochrome c(3) we constructed a null mutant by gene disruption. S. frigidimarina lacking cytochrome c(3) grows well aerobically and its growth rate under anaerobiosis with a variety of electron acceptors is indistinguishable from that of the wild-type parent strain, except that respiration with Fe(III) as sole acceptor is severely, although not completely, impaired.

Escherichia coli DipZ: anatomy of a transmembrane protein disulphide reductase in which three pairs of cysteine residues, one in each of three domains, contribute differentially to function.

DipZ is a bacterial cytoplasmic membrane protein that transfers reducing power from the cytoplasm to the periplasm so as to facilitate the formation of correct disulphide bonds and c-type cytochromes in the latter compartment. Topological analysis using gene fusions between the Escherichia coli dipZ and either E. coli phoA or lacZ shows that DipZ has a highly hydrophobic central domain comprising eight transmembrane alpha-helices plus periplasmic globular N-terminal and C-terminal domains. The previously assigned translational start codon for the E. coli DipZ was shown to be incorrect and the protein to be larger than previously thought. The experimentally determined translational start position indicates that an additional alpha-helix at the N-terminus acts as a cleavable signal peptide so that the N-terminus of the mature protein is located in the periplasm. The newly assigned 5' end of the dipZ gene was shown to be preceded by a functional ribosome-binding site. The hydrophobic central domain and both of the periplasmic globular domains each have a pair of highly conserved cysteine residues, and it was shown by site directed mutagenesis that all six conserved cysteine residues contribute to DipZ function.

Phylogeny of marine and freshwater Shewanella: reclassification of Shewanella putrefaciens NCIMB 400 as Shewanella frigidimarina.

Dissimilatory Fe(III) reduction by Shewanella putrefaciens and related species has generated considerable interest in biochemical characterization of the pathways for anaerobic electron transfer in this organism. Two strains, MR-1 and NCIMB 400, have been extensively used, and several respiratory enzymes have been isolated from each. It has become apparent that significant sequence differences exist between homologous proteins from these strains. The 16S rRNA from NCIMB 400 was sequenced and compared to the sequences from MR-1 and other Shewanella strains. The results indicate that NCIMB 400 is significantly more closely related to the newly identified Shewanella frigidimarina than to the S. putrefaciens type strain. It is therefore proposed that NCIMB 400 should be reclassified as S. frigidimarina.

Osteoporosis in steroid-dependent asthma.

BACKGROUND: Patients on prolonged corticosteroid therapy are at risk of developing osteoporosis. Some patients with severe asthma are difficult to wean off corticosteroids and are therefore at risk of developing bony complications due to steroids. OBJECTIVE: The purpose of this study was to examine the relationship of cumulative steroid dosage and duration of therapy with osteoporosis. METHODS: We obtained bone mineral density studies using dual photon absorptiometry, and radiographs of the lumbar spine of 16 steroid-dependent patients with asthma. Patients with conditions affecting bone metabolism were excluded. RESULTS: We studied 16 male steroid-dependent patients with asthma who received 4 to 41 grams equivalent dose of prednisone over a period of 1 to 15 years. The overall prevalence rate for abnormal age-matched bone mineral density was 50%. Abnormal bone mineral density was more commonly noted in the lumbar spine (38%) than in the femoral neck (19%). The lowest dose of corticosteroid associated with a decrease in bone mineral density was a cumulative steroid dose of 5.6 equivalent grams-prednisone. CONCLUSION: Prolonged corticosteroid therapy can cause significant osteoporosis among male patients with steroid-dependent asthma. Bone loss due to corticosteroid therapy occurs at different rates at different bony sites.

Utility of additional skin testing in "nonallergic" asthma.

It has been suggested that asthma almost always as an allergic basis. In this study we tried to determine whether an additional limited skin test panel would be useful in revealing hidden allergies in our "nonallergic" asthmatic patients. In 127 consecutive asthmatic adults, a survey panel of seven tests (rat, mouse, cockroach, Helminthosporium, Chaetomium, Pullularia, and Penicillium) was used in addition to our routine skin test panel (local pollens, Alternaria, Aspergillus, Hormodendrum, dog; and standardized cat, D. pteronyssinus, and D. farinae). On the basis of the routine test panel, 111 patients (87%) were allergic and 16 patients (13%) were nonallergic. Only one nonallergic patient (6%) had any positive survey test results (to cockroach only) while 69 allergic patients (62%) had at least one positive survey test result (p less than .00002). With the possible exception of cockroach, additional skin testing with our survey panel to search for hidden allergies in otherwise nonallergic asthmatic adults is not worthwhile.

Comparison of nifedipine with a new calcium channel blocker, flordipine, in exercise-induced asthma.

Four patients with documented exercise-induced asthma (EIA) were pretreated orally in random, double-blind fashion with the calcium channel blockers nifedipine 20 mg and flordipine 25 and 50 mg and placebo, then subjected to exercise challenge on a cycloergometer. Each patient served as his own control, undergoing exercise challenge with the different pretreatments on 4 separate days. No statistically significant protection from EIA was found with either nifedipine or flordipine.

The effect of high dose glucocorticoid therapy on immunoglobulin E in asthma.

Serum IgE levels were measured before and after high dose intravenous methylprednisolone therapy in 14 patients with severe asthma. Eight patients received methylprednisolone 125 mg every 6 hours, four received methylprednisolone 60 mg every 6 hours, and two patients received hydrocortisone 100 mg every 6 hours. In patients receiving the higher dose, in extrinsic asthma, and in those not recently receiving corticosteroids, total serum IgE levels tended to decrease within a short interval after corticosteroid therapy.

Delayed cutaneous hypersensitivity in normals: choice of antigens and comparison to in vitro assays of cell-mediated immunity.

In 81 normal subjects, ages 19 to 100 yr (mean 52), we studied the prevalence of positive 48 hr skin reactions to six antigens: fluid tetanus toxoid, Candida albicans, SK/SD, Trichophyton, PPD, and coccidioidin. Of these, C. albicans was most frequently reactive (92%); SK/SD (51%) and tetanus (49%) were less so. Each of the remaining three antigens was reactive in less than 42% of the subjects. The minimum number of antigens required to detect delayed hypersensitivity in 100% of subjects was two: C. albicans and tetanus. We found no correlation between skin reactivity at 20 min, 6 hr, and 48 hr for most of the antigens studied, suggesting different mechanisms for reactions occurring at each time. In 60 of the subjects, lymphocyte stimulation index (LSI) with tetanus toxoid and monocyte chemotaxis (MC) assays were done. The natural log of the area of induration at 48 hr after tetanus skin testing (I48) increased as a function of LSI (p less than 0.005) and MC (p less than 0.025) by multiple regression analysis. Skin testing was less sensitive than LSI as a test for cell-mediated immunity in our population. However, because of availability and correlation with LSI, delayed cutaneous hypersensitivity should be tested initially. For this purpose, tetanus toxoid appears to be a useful antigen when used in combination with C. albicans.

Primary amoebic meningo-encephalitis in an indoor heat-exchange swimming pool.

The case history, identification and isolation of the aetiological agent of a case of primary amoebic meningo-encephalitis (PAM) contracted in an indoor heat-exchange pool are presented. The isolated strain (MsM) is compared with known strains of pathogenic and non-pathogenic Naegleria.