Inflammatory Cytokines Are Associated with Cognitive Dysfunction and Depressive State during Acute Bacterial Infections and the Recovery Phase.

During a bacterial infection, individuals may present with behavioral changes referred to as sickness behavior, which has been suggested is induced by the inflammatory markers that are released because of the infective immunological challenge. However, few studies have explored this multidimensional phenomenon in naturally occurring conditions. A longitudinal observational study was conducted to explore the role of inflammatory cytokines in mediating the sickness behavior during a bacterial infection. There were 13, 11 and 37 participants in the infection, hospital control and healthy groups, respectively. They were all followed up for 6 weeks and their inflammatory markers were quantified throughout those weeks. Cognitive function and depressive state were assessed by means of the Mini-Mental State Examination (MMSE) and Cornell Scale for Depression in Dementia (CSDD). Reductions in proinflammatory markers C-Reactive protein (CRP), interleukin - 6 (IL6) and tumor necrosis factor-α (TNFα) and increments in anti-inflammatory markers (interleukin - 4 (IL4)) were associated with an improvement in CSDD and MSEE in patients recovering from a bacterial infection. The correlation between inflammatory makers and CSDD was statistically significant for the CRP (r = 0.535, p = 0.001), the IL6 (r = 0.499, p < 0.001), the TNFα (r = 0.235, p = 0.007) and the IL4 (r = -0.321, p = 0.018). Inflammatory cytokines may mediate sickness behavior during acute illness. These results may enhance the understanding of the pathophysiology and potential treatment strategies to palliate this sickness behavior.

Relationship between lung function and grip strength in older hospitalized patients: a pilot study.

OBJECTIVE: Older people with reduced respiratory muscle strength may be misclassified as having COPD on the basis of spirometric results. We aimed to evaluate the relationship between lung function and grip strength in older hospitalized patients without known airways disease. METHODS: Patients in acute medical wards were recruited who were aged ≥70 years; no history, symptoms, or signs of respiratory disease; Mini Mental State Examination ≥24; willing and able to consent to participate; and able to perform hand grip and forced spirometry. Data including lung function (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], FEV1/FVC, peak expiratory flow rate [PEFR], and slow vital capacity [SVC]), grip strength, age, weight, and height were recorded. Data were analyzed using descriptive statistics and linear regression unadjusted and adjusted (for age, height, and weight). RESULTS: A total of 50 patients (20 men) were recruited. Stronger grip strength in men was significantly associated with greater FEV1, but this was attenuated by adjustment for age, height, and weight. Significant positive associations were found in women between grip strength and both PEFR and SVC, both of which remained robust to adjustment. CONCLUSION: The association between grip strength and PEFR and SVC may reflect stronger patients generating higher intrathoracic pressure at the start of spirometry and pushing harder against thoracic cage recoil at end-expiration. Conversely, patients with weaker grip strength had lower PEFR and SVC. These patients may be misclassified as having COPD on the basis of spirometric results.

Systemic Inflammation in the Genesis of Frailty and Sarcopenia: An Overview of the Preventative and Therapeutic Role of Exercise and the Potential for Drug Treatments.

The clinical, pathological and biological characteristics of frailty and sarcopenia are becoming better understood and defined, including the role of systemic inflammation. It is increasingly apparent that in older adults there is a tendency for the innate immune network to shift toward a pro-inflammatory setting, often due to the presence of chronic inflammatory diseases but also associated with age alone in some individuals. Furthermore, acute inflammation tends to resolve more slowly and less completely in many elderly people. Inflammation contributes to the pathogenesis of sarcopenia and other components of the frailty syndrome. Blood levels of inflammatory cytokines and acute phase proteins, are reduced by exercise, and there is a growing body of epidemiological, observational and intervention research that indicates that regular moderate exercise improves strength, function, morbidity and mortality in middle-aged and elderly adults. There is also an increasing awareness of the potential role of drugs to ameliorate inflammation in the context of frail old age, which might be particularly useful for people who are unable to take part in exercise programs, or as adjunctive treatment for those who can. Drugs that shift the innate immune biochemical network toward an anti-inflammatory setting, such as methyl-xanthines and 4-amino quinolones, could be of value. For example, theophylline has been shown to induce a 20 percent fall in pro-inflammatory tumor necrosis factor (TNF) and 180 percent rise in anti-inflammatory interleukin-10 production by peripheral blood monocytes, and a fall of 45 percent in interferon-gamma (IF-gamma) release. Such properties could be of therapeutic benefit, particularly to re-establish a less inflamed baseline after acute episodes such as sepsis and trauma.

A prospective observational study of outcomes from rehabilitation of elderly patients with moderate to severe cognitive impairment.

OBJECTIVES: To evaluate rehabilitation outcomes in patients with moderate to severe cognitive impairment. DESIGN: Prospective observational cohort study. SETTING: Rehabilitation unit for older people. SUBJECTS: A total of 116 patients (70F) mean age (SD) 86.3 (6.4). Group 1: 89 patients with moderate cognitive impairment (Mini-Mental State Examination 11-20); and Group 2: 27 patients with severe cognitive impairment (Mini-Mental State Examination 0-10). INTERVENTION: A personalised rehabilitation plan. MAIN MEASURES: Barthel Activity of Daily Living score on admission and discharge, length of stay and discharge destination. RESULTS: Of 116 patients, 64 (55.2%) showed an improvement in Barthel score. Mini-Mental State Examination was significantly higher in those who improved, 15.4 (SD 3.7) vs.13.2 (SD 5.1): p = 0.01. The mean Barthel score improved in both groups; Group 1 - 14.7 (SD 19.1) vs. Group 2 - 9.3 (SD 16.3): p = 0.17. Of 84 home admissions in Group 1, more patients returning home showed improvements of at least 5 points in the Barthel score compared with nursing/residential home discharges (32/37 - 86.5% vs. 10/28 - 35.7%: p = 0.0001). In Group 2 of 17 home admissions, 6/6 (100%) home discharges showed improvement compared with 3/7 (42.8%) discharges to nursing/residential home (p = 0.07). In Group 1, a discharge home was associated with significantly greater improvement in number of Barthel items than a nursing/residential home discharge (3.27 (SD 2.07) vs. 1.86 (SD 2.32): p = 0.007). A similar non-significant pattern was noted for severe cognitive impairment patients (3.5 (3.06) vs. 1.14 (1.06); p = 0.1). CONCLUSION: Patients with moderate to severe cognitive impairment demonstrated significant improvements in Barthel score and Barthel items showing that such patients can and do improve with rehabilitation.

The airflow resistance sensing threshold during tidal breathing rises in old age in patients with asthma.

BACKGROUND: in a previous study, we showed that the ability to detect a rise in airflow resistance at rest was reduced in some non-asthmatic subjects in old age. OBJECTIVE: to determine whether airflow resistance detection is attenuated in elderly subjects with asthma. METHODS: we studied 60 adult subjects with stable asthma (age range 20-88). Progressive external airflow resistance loading was used to measure the inspiratory load detection threshold (LDT) during tidal breathing at rest. RESULTS: the mean inspiratory LDT was 5.57 (4.33 SD) kPa.s/l in the 20-64 age group (n=32) and 15.6 (10.1 SD) kPa.s/l in those aged 65 and above (n=28) (P<0.0001). The inspiratory LDT was significantly correlated with age (r=0.5246, P<0.00008), mainly due to the effect of higher LDTs in about half of the subjects above the age of 65 years. Expiratory LDT values and correlations were very similar to inspiratory values. CONCLUSIONS: the threshold for detecting external resistive loads during tidal breathing rises in old age in some, but not all, asthmatic patients as was observed in non-asthmatic subjects. The finding has implications for treatment guidelines because some elderly subjects are likely to have reduced awareness of worsening airflow obstruction, and consequently delay their use of rescue treatments.

Perioperative use of nonsteroidal anti-inflammatory drugs: results of a UK regional audit.

BACKGROUND AND OBJECTIVE: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is well established as a part of multimodal perioperative analgesia treatment, especially in day-case surgery where opioid sparing is important. The aim of this study was to assess the current perioperative use of NSAIDs, the specific drugs used, and the route by which they were administered. METHODS: A pilot study was undertaken, followed by a second, larger study. Numbered questionnaires were sent to all members of the anaesthetic departments of six target National Health Service Hospitals within the south of the UK. The questionnaires asked specific questions relating to the use of NSAIDs in their departments during the preoperative, perioperative and postoperative periods. Responses to the questionnaires were anonymous except for the identity of the hospital concerned. RESULTS: The pilot study indicated that perioperative NSAIDs continue to be used by anaesthetists and this was confirmed by the second audit. In total, 371 questionnaires were sent out, with 51% of recipients (189/371) responding. All of the respondents reported using NSAIDs (diclofenac, ibuprofen, ketorolac, ketoprofen and parecoxib), with many of the respondents using more than one NSAID. Diclofenac was the most commonly used NSAID overall. However, some of the NSAIDs - notably ketorolac (41% of respondents), diclofenac (61% of respondents) and ketoprofen (7% of respondents) were not used according to the manufacturer's recommendations. CONCLUSION: These data reveal that NSAIDs were still widely used as analgesics for many surgical procedures at the time of the audit. Intravenous (IV) NSAID administration is the preferred route because of its reliability and speed of onset. The results of this audit indicated significant use of IV NSAIDs (ketorolac, diclofenac and ketoprofen) not in accordance with manufacturers' recommendations, with some NSAIDs even being used in the absence of a product licence for use by the IV route. This may be due to a lack of a satisfactory licensed product. A new formulation of IV diclofenac may fulfil this currently unmet need.

The threshold for sensing airflow resistance during tidal breathing rises in old age: implications for elderly patients with obstructive airways diseases.

OBJECTIVE: to determine whether the ability of elderly subjects to detect a rise in airflow resistance is attenuated in old age, and to measure the magnitude and variability of such a change. METHODS: we studied 124 healthy adults aged 20-86 years. Progressive external airflow resistance loading was used to measure the inspiratory and expiratory load detection thresholds (LDTs) during tidal breathing at rest. RESULTS: the mean inspiratory LDT rose from 4.00 (3.06 SD) kPa.s/L in the 20-39 age group to 6.51 (6.20) in the 40-64 age group (NS) and 29.10 (13.58) in the 65 + age group (P < 0.00001). The inspiratory LDT was significantly correlated with age, mainly due to the higher thresholds in people over the age of 65 (r = 0.7860, P < 0.00001), but did not correlate with age-corrected forced vital capacity or respiratory rate. Expiratory LDT values and correlations were very similar. Day-to-day variability in LDTs tended to be higher in older subjects. CONCLUSION: the threshold for detecting external resistive loads during tidal breathing rises in old age. This appears to be a consequence of ageing processes rather than pathology, and might be a manifestation of a fall in proprioceptive acuity in elderly people. This finding has clinical implications for the self-management of asthma in old age. There is a need to conduct a similar study in patients with airways disease.

A comparison of four tests of cognition as predictors of inability to perform spirometry in old age.

BACKGROUND: previous studies have shown that a Mini Mental State Examination (MMSE) score of <24/30 and inability to copy intersecting pentagons (IP) predicts inability to perform spirometry. We hypothesised that clock drawing tests (CLOX 1 and 2), being validated tests of cognitive executive function, might predict spirometry performance with a higher sensitivity and specificity than the MMSE or IP. METHODS: we studied 113 (84 females) spirometry-naïve inpatients, mean age of 84 years (range 74-97). All performed the MMSE, IP, CLOX 1 and 2 and then attempted to perform assisted spirometry to the American Thoracic Society/European Respiratory Society standard. RESULTS: of 113, 49 met the criteria for adequate spirometry. Using normative thresholds for probable impairment, inability to perform spirometry was predicted by MMSE <24/30 with a sensitivity of 81% and specificity of 90% (P<0.0000); by inability to copy IP with a sensitivity of 92% and specificity of 100% (P<0.0000); by CLOX1 <10/15 with a sensitivity of 81% and specificity of 49% (P<0.001); and by CLOX2 <12/15 with a sensitivity of 63% and specificity of 65% (P<0.001). CONCLUSION: CLOX tests did not perform better than MMSE and IP to identify subjects unlikely to be able to perform spirometry. Achieving assisted spirometry from the naïve state in old age might be more determined by global cognitive function and ideo-motor praxis than by executive control function.

Perforated colonic diverticulum in old age: surgical or medical management?

Perforation of a colonic diverticulum is a common surgical emergency particularly in older people. Surgical treatments result in the best outcomes for patients with good functional and physiological status, but for frailer patients there are minimally invasive and medical alternatives. This article considers the evidence for the different options.

Neuropathic pain - the case for opioid therapy.

For many patients, neuropathic pain (NeP) is arguably more difficult to control than nociceptive or 'normal' pain. We also now recognise the great burden that NeP has on the lives of patients - it is not only a matter of treating pain in isolation, but managing all of the issues that affect the patient's quality of life. Until relatively recently we have had little understanding of the pathophysiology causing NeP and have relied on the secondary effects of non-analgesic drugs as the mainstays of treatment. Greater understanding of the pathophysiology of NeP has led to more appropriate therapy and an increased use of multiple drug therapy - 'rational polypharmacy'. Traditional opinions concerning the treatment of NeP have been challenged and it is because of this that the use of opioids in NeP has been re-evaluated. Opioids will never replace tricyclic antidepressants and anti-epileptic drugs as first-line therapy for NeP. However, they are now fully established as effective and useful second- or third-line drugs. Many patients in the past have been potentially undertreated as a result of our inertia to use opioids. The case for opioid therapy in NeP has been firmly established.

Fall risk-assessment tools compared with clinical judgment: an evaluation in a rehabilitation ward.

OBJECTIVES: to compare the use of two falls risk-identification tools (Downton and STRATIFY) with clinical judgment (based upon the observation of wandering behaviour) in predicting falls of medically stable patients in a rehabilitation ward for older people. METHODS: in a prospective observational study, with blinded end-point evaluation, 200 patients admitted to a geriatric rehabilitation hospital had a STRATIFY and Downton Fall Risk assessment and were observed for wandering behaviour. RESULTS: wandering had a predictive accuracy of 78%. A total of 157/200 were identified correctly compared to 100/200 using the Downton score (P < 0.0001 95%, CI 0.18-0.42), or 93/200 using STRATIFY (P < 0.0001; 95% CI 0.15-0.37). The Downton and STRATIFY tools demonstrated predictive accuracies of 50% and 46.5%, respectively, with no statistical significance between the two (P = 0.55; 95% CI 0.77-1.71). Sensitivity for predicting falls using wandering was 43.1% (22/51). This was significantly worse than Downton 92.2% (47/51: P < 0.001) and STRATIFY 82.3% (42/51: P < 0.001). CONCLUSIONS: this study showed that clinical observation had a higher accuracy than two used falls risk-assessment tools. However it was significantly less sensitive implying that fewer patients who fell were correctly identified as being at risk.

Predictors for falls among hospital inpatients with impaired mobility.

Gait and balance disturbances have been shown to predispose to falls in hospital. We aimed to investigate the patient characteristics associated with an unsafe gait and to determine what features predispose to falling in this group of hospital inpatients. In a prospective open observational study we studied 825 patients admitted for rehabilitation following acute medical illness or a surgical procedure. The patient's gait was assessed with the 'get up and go' test and classified into one of four categories-normal; abnormal but safe with or without mobility aids; unsafe; or unable. 72.6% of patients were assessed as having an unsafe gait. The factors independently associated with an unsafe gait were confusion, abnormal lower limbs, hearing defects and the use of tranquillizers. Patients with an unsafe gait who fell were more likely than the non-fallers within the group to have had falls in the past (85.3% versus 73.8%) and to be confused (66.2% versus 34.1%). Patients with both these characteristics had a 37.5% chance of falling compared with 15.4% in patients with one and 11.2% in patients with none of these characteristics. The presence of confusion and a history of falls identifies those patients who are at greatest risk of falls. Such patients might be the focus of special efforts at falls prevention.

Acquisition and short-term retention of inhaler techniques require intact executive function in elderly subjects.

BACKGROUND: patients with dementia are almost invariably unable to use any form of inhaler. Some elderly patients are unable to learn to use a metered dose inhaler or Turbohaler despite a normal abbreviated mental test score. Studies have shown that in many people this is due to unrecognised cognitive impairment and/or dyspraxia. The executive domains of cognition are particularly important in planning and sequencing; it might be expected therefore that disordered frontal (executive) function could be a predictor of poor inhaler technique in subjects with no overt features of dementia. OBJECTIVE: to explore the relationship between cognitive, and executive, function and the ability to acquire metered dose inhaler and Turbohaler technique in old age. DESIGN: a prospective randomised observational study with blinded evaluation. SUBJECTS: 30 inhaler-naive inpatients (21 female) with a mean age of 85 (range 75-94) and having a normal (8-10) abbreviated mental test score. METHODS: subjects received standardised metered dose inhaler and Turbohaler training and were scored on an analogue scale (for metered dose inhaler) or for competence (Turbohaler) the following day. The Mini-Mental State Examination and EXIT25 (for executive function) were performed by separate observers. RESULTS: significant correlation was found between the metered dose inhaler score and Mini-Mental State Examination (r 0.540, P<0.002) and EXIT25 (r -0.702, P<0.0001). Threshold effects emerged for the metered dose inhaler in that 18/19 with a competent score compared to 2/11 scored as incompetent had a Mini-Mental State Examination of >23 (P<0.01) and 19/19 compared to 0/11 had an EXIT25 of <15 (P<0.01). Similarly, for the Turbohaler 21/21 of the competent subjects had a Mini-Mental State Examination of >23 compared with 3/9 incompetent subjects (P<0.01), with 21/21 competent compared with 0/9 incompetent having an EXIT25 <15 (P<0.01). CONCLUSION: acquisition and short-term retention of metered dose inhaler and Turbohaler techniques is unlikely to be successful in frail elderly people who have an abnormal Mini-Mental State Examination and/or EXIT25 test. The latter test, when abnormal, is probably the superior predictor of inability to learn inhaler techniques.

Characteristics of early fallers on elderly patient rehabilitation wards.

BACKGROUND: falls are one of the most frequent complications on rehabilitation wards for elderly patients. OBJECTIVE: to study the characteristics of early and late fallers. DESIGN: prospective observational study with blinded end-point evaluation. SETTING: a non-acute geriatric hospital. SUBJECTS: 1025 consecutive patients admitted for rehabilitation following treatment for an acute illness. MAIN OUTCOME MEASURES: early/late fallers and time to first fall from admission. RESULTS: we identified 824 non-fallers and 201 fallers. Seventy seven (38.3%) fell during the first week. The incidence decreased progressively in subsequent weeks. Early fallers were more likely to have a past history of falls (P=0.0009), an unsafe gait (P=0.001), confusion (P<0.0001) and be admitted from medical wards (P=0.03). Patients admitted from orthopaedic wards having sustained a lower limb fracture were significantly less likely to have an early fall compared to all other patients (P=0.027). When compared to later fallers, early fallers were more likely to have a past history of falls (P=0.045). They were less likely to be admitted from an orthopaedic ward (P=0.01) or to have sustained a fracture of the lower limbs (P=0.002). Logistic regression analysis showed that a past history of falls, confusion and an unsafe gait were independent risk factors predisposing to early falls. The Kaplan-Meier survival analysis showed a significantly higher cumulative risk of falling associated with these characteristics. CONCLUSION: the initial week of patients' rehabilitation is associated with the greatest risk of falling. Early fallers can be predicted by easily identifiable characteristics. This highlights the need for early fall risk assessment.

Characteristics of single fallers and recurrent fallers among hospital in-patients.

BACKGROUND: Recurrent fallers constitute a minority of patients who fall but contribute considerably to the total number of falls recorded. OBJECTIVE: To study the characteristics of recurrent fallers in a hospital setting. METHODS: In a prospective observational study we investigated the characteristics of 1,025 patients admitted to a geriatric non-acute hospital. Patients were followed until discharge and were classified as non-fallers, single fallers or recurrent fallers. RESULTS: We identified 824 non-fallers, 136 single fallers and 65 recurrent fallers contributing 175 falls. Compared to non-fallers, recurrent fallers were more likely to have pre-admission falls (p = 0.004), confusion (p < 0.0001), an unsafe gait (p = 0.0001) and be on tranquillisers (p = 0.018) and antidepressants (p = 0.006). They had longer stays in hospital (p < 0.0001) and more nursing home discharges (p = 0.0001). There was considerable overlap with risk factors for single fallers but compared to this group they were more likely to be confused (p = 0.027), and on antidepressant medication (p = 0.009). They also had a longer length of stay (p < 0.001) and more nursing home discharges (p = 0.03). Confusion (p = 0.0001), unsafe gait (p = 0.0006) and antidepressants (p = 0.018) were independently associated with recurrent falls. CONCLUSIONS: It is important to recognise the risk factors that prospectively identify a recurrent faller because of the significant contribution to total falls by a relatively small number of patients. This may be useful not only in trying to reduce total falls but also in trying to reduce injury.