Cemented Versus Uncemented Hemiarthroplasty for Displaced Intracapsular Neck of Femur Fractures in the Elderly: Outcomes and Costings.

Background: Hemiarthroplasty (HA) is a common form of treatment for displaced neck of femur fractures. There is ongoing debate as to whether cemented or uncemented HA is a more superior treatment modality. The aim of this study was to compare the outcomes between patients that underwent cemented HA to uncemented HA. Secondarily, we analysed the costs associated of each treatment option. Methods: This was a retrospective study conducted at a busy district general hospital. The study included 335 patients that were treated with either a cemented or uncemented HA for a displaced neck of femur fracture between January 2017 and December 2018. Data collected included age, sex, American Society of Anesthesiologist (ASA) score, treatment modality, length of stay (LOS) and general costs. Results: 197 (58.8%) of the cohort underwent cemented HA and 138 (41.2%) underwent uncemented HA. Mean age for the cemented cohort was 84.7 years and 85.9 years in the uncemented group (p = 0.31). There was no significant differences between the groups with regard to mean LOS and discharge disposition (p = 0.44). There were no significant difference in 30-day and 1-year mortality between the two groups (p = 0.2). We did find a statistically significant difference in the costings between the two procedures, with cemented HAs costing £66 more than uncemented HAs (p < 0.001). Conclusion: We found that both cemented and uncemented HAs produced comparable results. We found a statistically significant reduction in operative time and costs associated with uncemented HA. Uncemented HA implants may be considered where a shorter operation duration is essential.

Anaemia, renal dysfunction and in-hospital outcomes in patients with heart failure in Botswana

Background. Anaemia and renal dysfunction are associated with an increased morbidity and mortality in heart failure (HF) patients.Objective. To estimate the frequency and impact of anaemia and renal dysfunction on in-hospital outcomes in patients with HF.Methods. A total of 193 consecutive patients with HF admitted to Princess Marina Hospital, Gaborone, Botswana, from February 2014 to February 2015, were studied. Anaemia was defined as haemoglobin <13 g/dL for men and <12 g/dL for women. Renal dysfunction was defined by an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, calculated by the simplified Modification of Diet in Renal Disease formula. The in-hospital outcomes included length of hospital stay and mortality.Results. The mean (standard deviation (SD)) age was 54.2 (17.1) years and 53.9% of the patients were men. The overall median eGFR was 75.9 mL/min/1.73 m2 and renal dysfunction was detected in 60 (31.1%) patients. Renal dysfunction was associated with hypertension (p=0.01), diabetes mellitus (p=0.01) and a lower haemoglobin level (p=0.008). The mean (SD) haemoglobin was 12.0 (3.0) g/dL and 54.9% of the patients were anaemic. Microcytic, normocytic and macrocytic anaemia were found in 32.1%, 57.5% and 10.4% of patients, respectively. The mean (SD) haemoglobin level for males was significantly higher than for females (12.4 (3.3) g/dL v. 11.5 (2.5) g/dL; p=0.038). Anaemia was more common in patients with diabetes (p=0.028) and in those with increased left ventricular ejection fraction (p=0.005). Neither renal dysfunction nor anaemia was significantly associated with the length of hospital stay or in-hospital mortality.Conclusion. Anaemia and renal dysfunction are prevalent in HF patients, but neither was an independent predictor of length of stay or in-hospital mortality in this population. These findings indicate that HF data in developed countries may not apply to countries in sub-Saharan Africa, and call for more studies to be done in this region

Anaemia, renal dysfunction and in-hospital outcomes in patients with heart failure in Botswana.

BACKGROUND: Anaemia and renal dysfunction are associated with an increased morbidity and mortality in heart failure (HF) patients. OBJECTIVE: To estimate the frequency and impact of anaemia and renal dysfunction on in-hospital outcomes in patients with HF. METHODS: A total of 193 consecutive patients with HF admitted to Princess Marina Hospital, Gaborone, Botswana, from February 2014 to February 2015, were studied. Anaemia was defined as haemoglobin <13 g/dL for men and <12 g/dL for women. Renal dysfunction was defined by an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, calculated by the simplified Modification of Diet in Renal Disease formula. The in-hospital outcomes included length of hospital stay and mortality. RESULTS: The mean (standard deviation (SD)) age was 54.2 (17.1) years and 53.9% of the patients were men. The overall median eGFR was 75.9 mL/min/1.73 m2 and renal dysfunction was detected in 60 (31.1%) patients. Renal dysfunction was associated with hypertension (p=0.01), diabetes mellitus (p=0.01) and a lower haemoglobin level (p=0.008). The mean (SD) haemoglobin was 12.0 (3.0) g/dL and 54.9% of the patients were anaemic. Microcytic, normocytic and macrocytic anaemia were found in 32.1%, 57.5% and 10.4% of patients, respectively. The mean (SD) haemoglobin level for males was significantly higher than for females (12.4 (3.3) g/dL v. 11.5 (2.5) g/dL; p=0.038). Anaemia was more common in patients with diabetes (p=0.028) and in those with increased left ventricular ejection fraction (p=0.005). Neither renal dysfunction nor anaemia was significantly associated with the length of hospital stay or in-hospital mortality. CONCLUSION: Anaemia and renal dysfunction are prevalent in HF patients, but neither was an independent predictor of length of stay or in-hospital mortality in this population. These findings indicate that HF data in developed countries may not apply to countries in sub-Saharan Africa, and call for more studies to be done in this region.

Presentation and mortality of patients hospitalised with acute heart failure in Botswana

Introduction: Heart failure is a common cause of hospitalisation and therefore contributes to in-hospital outcomes such as mortality. In this study we describe patient characteristics and outcomes of acute heart failure (AHF) in Botswana.Methods: Socio-demographic, clinical and laboratory data were collected from 193 consecutive patients admitted with AHF at Princess Marina Hospital in Gaborone between February 2014 and February 2015. The length of hospital stay and 30-, 90- and 180-day in-hospital mortality rates were assessed.Results: The mean age was 54 ± 17.1 years, and 53.9% of the patients were male. All patients were symptomatic (77.5% in NYHA functional class III or IV) and the majority (64.8%) presented with significant left ventricular dysfunction. The most common concomitant medical conditions were hypertension (54.9%), human immuno-deficiency virus (HIV) (33.9%), anaemia (23.3%) and prior diabetes mellitus (15.5%). Moderate to severe renal dysfunction was detected in 60 (31.1%) patients. Peripartum cardiomyopathy was one of the important causes of heart failure in female patients. The most commonly used treatment included furosemide (86%), beta-blockers (72.1%), angiotensin converting enzyme inhibitors (67.4%), spironolactone (59.9%), digoxin (22.1%), angiotensin receptor blockers (5.8%), nitrates (4.7%) and hydralazine (1.7%). The median length of stay was nine days, and the in-hospital mortality rate was 10.9%. Thirty-, 90- and 180-day case fatality rates were 14.7, 25.8 and 30.8%, respectively. Mortality at 180 days was significantly associated with increasing age, lower haemoglobin level, lower glomerular filtration rate, hyponatraemia, higher N-terminal pro-brain natriuretic peptide levels, and prolonged hospital stay.Conclusions: AHF is a major public health problem in Botswana, with high in-hospital and post-discharge mortality rates and prolonged hospital stays. Late and symptomatic presentation is common, and the most common aetiologies are preventable and/or treatable co-morbidities, including hypertension, diabetes mellitus, renal failure and HIV

A comparison of caregiver burden in older persons and persons with Parkinson's disease or dementia in sub-Saharan Africa.

BACKGROUND: Caregiver burden includes the many physical, mental and socio-economic problems arising from caring for individuals with chronic and disabling diseases. Being a carer in sub-Saharan Africa (SSA), where little is known about chronic neurological conditions, may be extremely demanding. Conversely, multigenerational living may allow sharing of care among many caregivers. We wished to determine the relative burden of caring for two chronic neurodegenerative conditions (Parkinson's disease (PD) and dementia) in rural Tanzania. METHODS: All surviving patients from a PD prevalence study, newly identified people with PD from a neurological disorders study and all people with dementia from a dementia prevalence study in Hai, rural Tanzania, were invited to participate. The Zarit Burden Interview (ZBI) was used to determine level of caregiver strain (higher score reflects more strain). RESULTS: Of 25 PD patients ZBI was recorded in 20 (14 male). Five had no identifiable carer as they were largely independent. Three had PD dementia (PDD). Of 75 people with dementia (excluding 3 PDD), 43 (32 female) completed the ZBI. For the other 32, the caregivers felt the care they provided was a normal intergenerational expectation. Median ages were 78.5 and 85 years for PD and dementia, respectively. Median ZBI was 30.5 for PD and 14 for dementia (U = 166.0, z = -3.913, p < 0.001). Disease duration and disease type (PD or dementia) were univariate predictor of ZBI score, although only disease type was predictive by multivariable linear regression. CONCLUSIONS: Caring for an individual with PD may be more burdensome than caring for an individual with dementia in SSA. People with more advanced PD had higher caregiver burden.

The prevalence of neurological disorders in older people in Tanzania.

OBJECTIVES: There are few data on neurological disorders prevalence from low- and middle-income countries, particularly sub-Saharan Africa (SSA) and none specific to the African elderly. We aimed to determined the prevalence of neurological disorders in those aged 70 years and over in a rural African community. MATERIALS AND METHODS: This study was a cross-sectional two-phased community epidemiological survey set in the rural Hai district of Tanzania. Screening was performed with a validated screening questionnaire with high sensitivity and specificity. Positive responders to screening underwent full neurological history and examination to confirm or refute the presence of neurological disorders and to classify the disorder using the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10). RESULTS: Of 2232 participants, there were 384 neurological diagnoses amongst 349 people. The age-adjusted prevalence of people with neurological diagnoses was 154.1 per 1000 (95% CI 139.2-169.1). The age-adjusted prevalence per 1000 of the most common neurological disorders were tremor (48.2), headache (41.8), stroke (23.0), peripheral polyneuropathy (18.6), upper limb mononeuropathy (6.5) and parkinsonism (5.9). CONCLUSIONS: This is the first published community-based neurological disorders prevalence study specifically in the elderly in SSA. It reveals a high prevalence of neurological morbidity and demonstrates the contribution neurological disorders make to the non-communicable disease epidemic. This is likely to increase as the population of low-income countries ages constituting a public health dilemma.

The high prevalence of hypertension in rural-dwelling Tanzanian older adults and the disparity between detection, treatment and control: a rule of sixths?

There are limited, reliable data on the prevalence of hypertension in East African populations. The aim of this study was to document the prevalence of hypertension in the rural Hai district of Tanzania. All consenting individuals aged 70 years and over who were living in 12 randomly-selected villages in the district underwent three consecutive sitting blood pressure (BP) measurements. An average of the last two measurements was taken. Prior diagnosis of, and treatment for, hypertension was recorded. Of the 2223 subjects, 1553 (69.9%, 95% CI 68.0-71.8) had hypertension (BP ≥140/90). Of those with hypertension 733 (47.2%) had isolated systolic hypertension. Only 586 (37.7%) hypertensives had been previously diagnosed, 94 (6.1%) were currently treated and 14 (0.9%) were adequately controlled. This is the first large-scale prevalence study of hypertension in the elderly in sub-Saharan Africa (SSA). Our results approximate to a 'rule of sixths'; 2/6 of hypertensives were previously detected, 1/6 of those previously detected were on treatment and 1/6 of those on treatment were adequately controlled. Hypertension is a large problem in the elderly population in SSA, and there are a growing number of elderly who are at risk of hypertensive sequelae owing to lack of detection and treatment.

Accuracy of algorithms for detection of atrial fibrillation from short duration beat interval recordings.

Atrial fibrillation (AF) is characterised by highly variable beat intervals. The aims of the study were to assess the accuracy of AF detection algorithms from short analysis durations and to validate prospectively the accuracy on a large community-based cohort of elderly subjects. Three algorithms for AF detection were evaluated: coefficient of variation (CV), mean successive difference (Δ) and coefficient of sample entropy (COSEn), using two databases of beat interval recordings: 167 recordings of 300 s duration for a range of rhythms acquired in a hospital setting and 2130 recordings of 10s duration acquired in the community. Using the longer recordings receiver operating characteristic (ROC) analysis was used to identify optimal algorithm thresholds and to evaluate analysis durations ranging from 5s to 60s. An ROC area of 93% was obtained at recording duration of 60s but remained above 90% for durations as low as 5s. Prospective analysis on the 2130 recordings gave AF detector sensitivities from 90.5% (CV and Δ) to 95.2% (COSEn), specificities from 89.3% (Δ) to 93.4% (COSEn) and accuracy from 89.3% (Δ) to 93.4% (COSEn), not significantly different to those obtained on the initial database. AF detection algorithms are effective for short analysis durations, offering the prospect of a simple and rapid diagnostic test based on beat intervals alone.

QA interval as an indirect measure of cardiac contractility in the conscious telemeterised rat: model optimisation and evaluation.

INTRODUCTION: Conscious telemeterised rats are used for early assessment of cardiovascular drug safety. This paper details the surgery required to allow key cardiovascular parameters to be determined and describes how QA interval (QAI), a surrogate measure of cardiac contractility, is related to a more direct measure of cardiac contractility, dP/dt(max) (LVdP/dt(max)). Experimental studies examining the effect of both positive and negative inotropes are described. METHODS: Eight rats were surgically implanted with telemetry probes for measuring blood pressure, heart rate, activity, body temperature and ECG parameters. Initial studies focussed on evaluating surgical procedures aimed at improving the ECG signal to allow QAI quantification. Once achieved, experimental studies were undertaken with verapamil, salmeterol, milrinone or vehicle. Following treatment, data was collected for approximately 20 h from pair-housed animals to establish effects on QAI or LVdP/dt(max), which was measured directly from the left ventricle in a separate group of rats. RESULTS: The modified ECG lead placement produced both a qualitative and quantitative improvement in ECGs. Increases in cardiac contractility (measured directly) were paralleled by a decrease in QAI (measured indirectly). Salmeterol and milrinone increased (all p<0.05) LVdP/dt(max) (1942+/-452 and 2333+/-506 mmHg/s, respectively) and decreased QAI (3.5+/-0.54 and 2.9+/-0.43 ms, respectively). In contrast, the negative inotrope verapamil decreased LVdP/dtmax (-2119+/-300 mmHg/s) and increased QAI (4.9+/-0.46 ms). A statistically significant (p<0.001) linear relationship was identified between log(10)(QAI) and log(10)(LVdP/dt(max)). DISCUSSION: Improvements in ECG signal quality, resulting from refinements in surgical techniques allowed for the reliable quantification of ECG parameters. The linear relationship demonstrated between log(10)(QAI) and log(10)(LVdP/dt(max)) indicates that QAI may be a useful index of cardiac contractility in routine rat cardiovascular safety studies. These limited studies support the use of QAI as an indirect measure of cardiac contractility in the rat.

Reduced nerve blood flow in diabetic rats: relationship to nitric oxide production and inhibition of aldose reductase.

This study examined links between impaired nitric oxide production in the sciatic endoneurium, nerve blood flow, and polyol pathway flux, to test the hypothesis that reduced nerve blood flow might be compromised by competition for NADPH between aldose reductase and nitric oxide synthase. Sciatic nerves of streptozotocin-diabetic rats showed reduced laser Doppler flux (by 51% or 63%; both p<0.05)-indicative of reduced nerve blood flow-and reduced motor nerve conduction velocity (17% in two experiments; p<0.05). Acute interruption of nitric oxide production in the sciatic nerves of control rats, via endoneurial injection of N omega-nitro-D-arginine methyl ester (L-NAME), caused a local reduction (of 64%; p<0.001) in nerve Doppler flux. This was reversed by either L-arginine or sodium nitroprusside. The response to L-NAME was greatly reduced in diabetic rats (only 22% reduction; p<0.01), though both L-arginine and SNP caused marked increases in flux. Chronic inhibition of aldose reductase in diabetic rats (with either sorbinil or imirestat at a range of doses) had little effect on resting sciatic nerve Doppler flux, though both inhibitors normalized conduction velocity. Both aldose reductase inhibitors reduced sorbitol pathway intermediates in a dose-related manner. These findings do not support the proposition that aldose reductase inhibitors normalise conduction velocity by mechanisms dependent upon either normalization of endoneurial nitric oxide or nerve blood flow. Instead, a mechanism based upon more direct effects on axon or Schwann cell function is favoured.

Effects of aminoguanidine and N(G)-nitro-L-arginine methyl ester on vascular responses of aortae and lungs from streptozotocin-diabetic rats.

Aminoguanidine (AG) treatment can prevent the development of some functional anomalies in experimentally diabetic rats, possibly via the prevention of a diabetes-induced vascular dysfunction. The acute effects of AG on endothelium-dependent relaxation of aortae in the presence of indomethacin and on pressor responses and prostacyclin release in isolated perfused lungs, were therefore investigated using tissues from control and streptozotocin-diabetic rats. Endothelium-dependent relaxations of aortae were reduced by aminoguanidine (control 20%, and diabetic 25%). For lungs, angiotensin II-induced pressor responses were unaffected by AG, whereas the nitric oxide synthase inhibitor L-NAME caused integrated pressor responses to be increased in lungs from control and diabetic rats (2.0 and 1.8 fold respectively). Individually, AG (1 mM) and L-NAME (10 microM) did not affect total cumulative prostacyclin release by control lungs, whereas significant increases for both were observed for diabetic lungs. In summary, these studies firstly provide evidence that AG can increase prostacyclin release from tissues in vitro, with little effect upon endothelium-dependent vasodilatation, and secondly, that the regulation of vasodilator prostanoid release by the pulmonary circulation of the rat may be altered in experimental diabetes.

Aminoguanidine--effects on endoneurial vasoactive nitric oxide and on motor nerve conduction velocity in control and streptozotocin-diabetic rats.

1. The effects of aminoguanidine (AG) treatment on reductions in motor nerve conduction velocity (MNCV) and sciatic nerve blood flow, indexed by laser Doppler flux (LDF), were investigated in rats with experimental diabetes (streptozotocin-induced; 8-10 weeks duration). The contribution of endoneurial vasoactive nitric oxide to the LDF of these animals was also investigated by the direct micro-injection of NG-nitro-L-arginine methyl ester (L-NAME; 1 nmol in 1 microliter), followed by L-arginine (100 nmol in 1 microliter), into the sciatic nerve endoneurium. 2. The MNCV (m s-1, mean +/- 1 s.d.) of diabetic rats (38.2 +/- 1.5) was lower (P < 0.01) than that of age-matched controls (47.2 +/- 4.2). AG treatment (50 mg kg-1 day-1, i.p.) attenuated the diabetes-induced deficits in MNCV (43.4 +/- 5.9; P < 0.01), but had no effect in controls (48.8 +/- 3.8) or, if administered via drinking water (1 gl-1), diabetics (37.4 +/- 4.1). 3. L-NAME markedly reduced the resting LDF (arbitrary units; mean +/- s.e.mean) of controls (209 +/- 13 to 120 +/- 18; P < 0.005), an effect reversed by subsequent L-arginine (to 206 +/- 27). In diabetic rats the LDF reduction following L-NAME was much smaller (111 +/- 11 to 84 +/- 6; P < 0.05), but the change with L-arginine was significantly increased (to 145 +/- 12; P < 0.001). 4. AG treatment increased the resting LDF of control (265 +/- 34) and diabetic rats (133 +/- 14 for daily injection and 119 +/- 13 for drinking water). The responses to L-NAME and L-arginine were not changed markedly by AG treatment. However, L-arginine appeared to be less effective. 5. In conclusion, these data suggest that AG treatment may affect nitric oxide production in the vasa nervorum of peripheral nerves. However, the effects of AG-treatment are not consistent with the prevention of a diabetes-associated reduction in endoneurial nitric oxide production. The mechanisms by which AG attenuates nerve conduction slowing in streptozotocin-diabetic rats therefore remain unclear.

alpha-Lipoic acid corrects neuropeptide deficits in diabetic rats via induction of trophic support.

This study compared the effects of treatment of diabetic rats with either alpha-lipoic acid (100 mg/kg/day i.p. 5 days/week) or with recombinant human nerve growth factor (rhNGF; 0.2 mg/kg s.c. 3 days/week) on NGF-like immunoreactivity (NGFLI) and neuropeptide Y-like immunoreactivity (NPYLI) levels in the sciatic nerve and on the release of substance P-like immunoreactivity (SPLI) from the spinal cord in response to electrical stimulation of the dorsal roots in vitro. Diabetic rats showed depletion of NGFLI and NPYLI, together with reduced release of SPLI. Treatment with NGF increased the sciatic nerve NGFLI (to four times that seen in untreated diabetic rats) and normalised stimulus-evoked release of SPLI, but did not affect the sciatic nerve NPYLI. Treatment with alpha-lipoic acid caused a small non-significant increase in sciatic nerve NGFLI, but normalised both NPYLI levels and stimulus-evoked release of SPLI. These findings indicate that alpha-lipoic acid can boost neurotrophic support in diabetic rats, with effects beyond those related to NGF.

Deficient nitric oxide responsible for reduced nerve blood flow in diabetic rats: effects of L-NAME, L-arginine, sodium nitroprusside and evening primrose oil.

1. This study examined the potential role of impaired nitric oxide production and response in the development of endoneurial ischaemia in experimental diabetes. Rats were anaesthetized (Na pentobarbitone 45 mg kg-1, diazepam 2 mg kg-1) for measurement of sciatic nerve laser Doppler flux and systemic arterial pressure. Drugs were administered into the sciatic endoneurium via a microinjector attached to a glass micropipette. 2. In two separate studies comparing diabetic rats (streptozotocin-induced; 8-10 wk duration) with controls, nerve Doppler flux in diabetic rats (Study 1, 116.6 +/- 40.4 and Study 2, 90.1 +/- 34.7 (s.d.) in arbitrary units) was about half that measured in controls (219.6 +/- 52.4 and 212.8 +/- 95.5 respectively; P < 0.005 for both). There were no significant differences between the two in systemic arterial pressure. 3. Inhibition of nitric oxide production by microinjection of 1 nmol L-NAME into the endoneurium halved flux in controls (to 126.3 +/- 41.3 in Study 1 and 102.1 +/- 38.9 in Study 2; both P < 0.001), with no significant effect in diabetic rats, indicating markedly diminished tonic nitric oxide production in the latter. D-NAME was without effect on nerve Doppler flux. 4. L-Arginine (100 nmol), injected after L-NAME, markedly increased flux in controls (by 65.8% (P < 0.03) and 97.8% (P < 0.01) in the two studies) and by proportionally similar amounts in diabetic rats [75.8% (P < 0.001) and 60.2% (P < 0.02)]. The nitro-donor, sodium nitroprusside (SNP; 10 nmol) had similar effects to L-arginine in both groups (increases of 66.0% in controls and 77.5% in diabetics; both P < 0.002). 5. A second diabetic group, treated with evening primrose oil performed exactly like control rats in respect of responses to L-NAME, L-arginine and SNP. 6. These findings implicate deficient nitric oxide in nerve ischaemia of diabetes and suggest correction thereof as a mechanism of action of evening primrose oil.

Effects of anti-oxidant treatment on sciatic nerve dysfunction in streptozotocin-diabetic rats; comparison with essential fatty acids.

In Study 1, the effects of treatment of streptozotocin-diabetic rats with the antioxidants, probucol or vitamin E were compared. Untreated diabetic rats showed a reduction of 45% (p < 0.01) in nerve laser Doppler flux, which was used as an index of nerve blood flow. In diabetic rats treated with either probucol or vitamin E nerve Doppler flux was reduced by only 13 or 16%, respectively (p < 0.01 for either compared to untreated diabetic rats). A second study examined the effects of treatment with evening primrose oil either alone or in combination with probucol. Reduced nerve Doppler flux was reproduced in untreated diabetic rats (47%; p < 0.01). In parallel diabetic groups, nerve Doppler flux was reduced by only 14% with evening primrose oil alone and by 8% with evening primrose oil plus probucol (both p < 0.01 vs untreated diabetic rats). Both treatments were also associated with marked attenuation of motor and sensory nerve conduction velocity deficits. Measurements on plasma from rats showed normalisation of triglyceride levels by probucol treatment without an effect on those of cholesterol in Study 1. In Study 2, the converse was true for evening primrose oil treatment, whilst the combined treatment lowered both plasma triglycerides and cholesterol. This work indicates similar effects of antioxidants and evening primrose oil against reduced nerve Doppler flux and conduction velocity in diabetic rats, with dissimilar actions on plasma triglycerides and cholesterol.