Meta-analysis and construction of simple-to-use nomograms for approximating testosterone levels gained from weight loss in obese men.

BACKGROUND: Obesity-induced hypogonadism, which manifests as erectile dysfunction and a lack of libido, is a less visible and under-recognized obesity-related disorder in men. OBJECTIVE: We examined the impact of weight loss on total (TT) and free testosterone (FT) levels, and constructed nomograms to provide an easy-to-use visual aid for clinicians. MATERIALS AND METHODS: Meta-analysis was conducted using RevMan (v5.3) and expressed in standardized mean differences (SMD) for testosterone. Parallel-scale nomograms were constructed from baseline and target body mass index values to estimate the gain in testosterone. RESULTS: In total, 44 studies were included, comprising 1,774 participants and 2,159 datasets, as some studies included several datasets at different time points. Weight loss was controlled by low calorie diet (LCD) in 19 studies (735 participants, 988 datasets), by bariatric surgery (BS) in 26 studies (1,039 participants, 1,171 datasets), and by both in one study. The median follow-up was 26 weeks (interquartile range = 12-52). The range of baseline mean age was 21-68 yr, BMI: 26.2-71.2 kg/m2 , TT: 7-20.2 nmol/L and FT: 140-583 pmol/L. TT levels increased after weight loss by LCD: SMD (95%CI) = 2.5 nmol/L (1.9-3.1) and by BS: SMD = 7.2 nmol/L (6.0-8.4); the combined TT gain was 4.8 nmol/L (3.9-5.6). FT levels increased after weight reduction by LCD: SMD = 19.9 pmol/L (7.3-32.5) and by BS: SMD = 58.0 pmol/L (44.3-71.7); the combined gain was 42.2 pmol/L (31.4-52.9). Greater amounts of total and free testosterone could be gained by weight loss in men with higher baseline BMI, or lower levels of SHBG, TT and FT, while gain in TT was relatively greater in older and FT in younger age. Age-stratified nomograms revealed that compared to older men (> 40 yr), younger men (≤ 40 yr) gained less TT but more FT for a given weight loss. DISCUSSION AND CONCLUSION: Both TT and FT levels increased after weight loss, relatively greater with higher baseline BMI, or lower levels of SHBG, TT and FT. Nomograms constructed from a large number of participants with a wide range of BMI and testosterone values provide an evidence-based and simple-to-use tool in clinical practice.

An orthogeriatric service can reduce prolonged hospital length of stay in hospital for older adults admitted with hip fractures: a monocentric study.

BACKGROUND: The Blue Book (2005), recommended guidelines for patients care with fragility fractures. Together with introduction of a National Hip Fracture Database Audit and Best Practice Tariff model to financially incentivise hospitals by payment of a supplement for patients whose care satisfied six clinical standards), have improved hip fracture after-care. However, there is a lack of data-driven evidence to support its effectiveness. We aimed to verify the impact of an orthogeriatric service on hospital length of stay (LOS)-duration from admission to discharge. METHODS: We conducted a repeated cross-sectional study over a 10 year period of older individuals aged ≥ 60 years admitted with hip fractures to a hospital. RESULTS: Altogether 2798 patients, 741 men and 2057 women (respective mean ages; 80.5 ± 10.6 and 83.2 ± 8.9 years) were admitted from their own homes with a hip fracture and survived to discharge. Compared to 2009-2014, LOS during 2015-2019, when the orthogeriatric service was fully implemented, was shorter for all discharge destinations: 10.4 vs 17.5 days (P < 0.001). Each discharge destination showed reductions: back to own homes, 9.7 vs 17.7 days (P < 0.001); to rehabilitation units: 10.8 vs 13.1 days (P < 0.001); to residential care: 15.4 vs 26.2 days (P = 0.001); or nursing care, 24.4 vs 53.1 days (P < 0.001). During 2009-2014, the risk of staying > 3 weeks in hospital was greater by six-fold and pressure ulcers by three-fold. The number of bed days for every thousand patients per year was also shortened during 2015-2019 by: 1665 days for discharge back to own homes; 469 days with transfer to rehabilitation units; 1258 days for discharge to residential care, and 5465 days to nursing care. Estimated annual savings (2017 costs) per thousand patients after complete establishment of the service was about £2.7 m. CONCLUSIONS: Implementation of an orthogeriatric service generated significant reductions in hospital LOS for all patients, with associated cost-savings, especially for those discharged to nursing care.

Sex differences in clinical outcomes amongst 1105 patients admitted with hip fractures.

Amongst hip fracture admissions, mortality is higher in men than in women. However, sex differences in other care-quality measures have not been well-documented. We aimed to examine sex differences in mortality as well as a wide range of underlying health indicators and clinical outcomes in adults ≥ 60 year of age admitted with hip fractures from their own homes to a single NHS hospital between April-2009 and June-2019. Sex differences in delirium, length of stay (LOS) and mortality in hospital, readmission, and discharge destination, were examined by logistic regression. There were 787 women and 318 men of similar mean age (± SD): 83.1 year (± 8.6) and 82.5 year (± 9.0), respectively (P = 0.269). There were no sex differences in history of dementia or diabetes, anticholinergic burden, pre-fracture physical function, American Society of Anesthesiologists grades, or surgical and medical management. Stroke and ischaemic heart disease, polypharmacy, and alcohol consumption were more common in men. After adjustment for these differences and age, men had greater risk of delirium (with or without cognitive impairment) within one day of surgery: OR = 1.75 (95%CI 1.14-2.68), LOS ≥ 3 weeks in hospital: OR = 1.52 (1.07-2.16), mortality in hospital: OR = 2.04 (1.14-3.64), and readmission once or more after 30 days of a discharge: OR = 1.53 (1.03-2.31). Men had a lower risk of a new discharge to residential/nursing care: OR = 0.46 (0.23-0.93). The present study revealed that, in addition to a greater risk of mortality than women, men also had many other adverse health outcomes. These findings, which have not been well-documented, serve to stimulate future targeted preventive strategies and research.

Association of Polypharmacy and Anticholinergic Burden with Length of Stay in Hospital Amongst Older Adults Admitted with Hip Fractures: A Retrospective Observational Study.

BACKGROUND: Age-associated multimorbidity and polypharmacy, predispose individuals to falls and consequent hip fractures. We examined the impact of polypharmacy (≥ 4 drugs daily), including anticholinergic agents, on hospital length of stay (LOS), mobility within 1-day of hip surgery and pressure ulcers in adults ≥ 60 years admitted with hip fractures. METHODS: In this retrospective observational study, information on medications at admission was obtained to calculate the total number of drugs taken, including those imposing an anticholinergic burden (ACB). Associations between variables were examined by logistic regression; adjusted for age, sex, co-morbidities, pre-fracture functional limitations and alcohol consumption. RESULTS: There were 787 women and 318 men of similar mean age (± SD): 83.1 years (± 8.6) and 82.5 years (± 9.0), respectively. Compared to patients with an ACB score = 0 and taking < 4 drugs daily, those with an ACB score ≥ 1 and taking ≥ 4 drugs daily had greater risk of prolonged LOS (≥ 2 weeks), OR 1.8 (1.2-2.7); failure to mobilise within 1-day of surgery, OR 1.9 (1.1-3.3); and pressure ulcers, OR 3.0 (95% CI 1.2-7.9). LOS was further prolonged by failure to mobilise within 1-day of surgery and/or pressure ulcers. Those with either an ACB score ≥ 1 or the use of ≥ 4 drugs daily had intermediate risks. CONCLUSIONS: Anticholinergic agents and polypharmacy in patients with hip fractures are associated with longer LOS in hospital, further accentuated by failure to mobilise within 1-day after surgery and pressure ulcers. This study provides further evidence of the impact of polypharmacy, including those with an ACB, on adverse health outcomes and lends support to reduce potentially inappropriate prescribing.

High LACE index scores are associated with disproportionate excess deaths in hospital amongst patients with COVID-19.

Risk factors for COVID-19-related outcomes have been variably reported. We used the standardised LACE index to examine admissions and in-hospital mortality associated with COVID-19. Data were collected in the pre-pandemic period (01-04-2019 to 29-02-2020) from 10,173 patients (47.7% men: mean age ± standard deviation = 68.3 years ± 20.0) and in the pandemic period (01-03-2019 to 31-03-2021) from 12,434 patients. With the latter, 10,982 were without COVID-19 (47.4% men: mean age = 68.3 years ± 19.6) and 1452 with COVID-19 (58.5% men: mean age = 67.0 years ± 18.4). Admissions and mortality were compared between pre-pandemic and pandemic patients, according to LACE index. Admission rates rose disproportionately with higher LACE indices amongst the COVID-19 group. Mortality rates amongst the pre-pandemic, pandemic non-COVID-19 and COVID-19 groups with LACE index scores < 4 were 0.7%, 0.5%, 0%; for scores 4-9 were 5.0%, 3.7%, 8.9%; and for scores ≥ 10 were: 24.2%, 20.4%, 43.4%, respectively. The area under the curve receiver operating characteristic for predicting mortality by LACE index was 76% for COVID-19 and 77% for all non-COVID-19 patients. The risk of age and sex-adjusted mortality did not differ from the pre-pandemic group for COVID-19 patients with LACE index scores < 4. However, risk increased drastically for scores from 4 to 9: odds ratio = 3.74 (95% confidence interval = 2.63-5.32), and for scores ≥ 10: odds ratio = 4.02 (95% confidence interval = 3.38-4.77). In conclusion, patients with LACE index scores ≥ 4 have disproportionally greater risk of COVID-19 hospital admissions and deaths, in support of previous studies in patients without COVID-19. However, of importance, our data also emphasise their increased risk in patients with COVID-19. Because the LACE index has a good predictive power of mortality, it should be considered for routine use to identify high-risk COVID-19 patients.

Does the length of stay in hospital affect healthcare outcomes of patients without COVID-19 who were admitted during the pandemic? A retrospective monocentric study.

Uncertainties remain if changes to hospital care during the coronavirus disease (COVID-19) pandemic had an adverse impact on the care-quality of non-COVID-19 patients. We examined the association of hospital length of stay (LOS) with healthcare quality indicators in patients admitted with general medical conditions (non-COVID-19). In this retrospective monocentric study at a National Health Service hospital (Surrey), data were collected from 1st April 2019 to 31st March 2021, including the pandemic from 1st March 2020. Primary admissions, in-hospital mortality, post-discharge readmission and mortality were compared between the pre-pandemic (reference group) and pandemic period, according to LOS categories. There were 10,173 (47.7% men) from the pre-pandemic and 11,019 (47.5% men) from the pandemic period; mean (SD) age 68.3 year (20.0) and 68.3 year (19.6), respectively. During the pandemic, primary admission rates for acute cardiac conditions, pulmonary embolism, cerebrovascular accident and malignancy were higher, whilst admission rates for respiratory diseases and common age-related infections, and in-hospital mortality rates were lower. Amongst 19,721 survivors, sex distribution and underlying health status did not significantly differ between admissions before the pandemic and during wave-1 and wave-2 of the pandemic. Readmission rates did not differ between pre-pandemic and pandemic groups within the LOS categories of < 7 and 7-14 days, but were lower for the pandemic group who stayed > 14 days. For patients who died within seven days of admission, in-hospital mortality rates were lower in patients admitted during the pandemic. Mortality rates within 30 days of discharge did not differ between pre-pandemic and pandemic groups, irrespective of the initial hospital LOS. Despite higher rates of admission for serious conditions during the pandemic, in-hospital mortality was lower. Discharge time was similar to that for patients admitted before the pandemic, except it was earlier during the pandemic for those who stayed > 14 days, There were no group differences in quality-care outcomes.

Comparison of characteristics and outcomes of patients admitted to hospital with COVID-19 during wave 1 and wave 2 of the current pandemic.

In this study of patients admitted with COVID-19, we examined differences between the two waves in patient characteristics and outcomes. Data were collected from the first COVID-19 admission to the end of study (01/03/2020-31/03/2021). Data were adjusted for age and sex and presented as odds ratios (OR) with 95% confidence intervals (CI). Among 12,471 admissions, 1452 (11.6%) patients were diagnosed with COVID-19. On admission, the mean (± SD) age of patients with other causes was 68.3 years (± 19.8) and those with COVID-19 in wave 1 was 69.4 years (± 18.0) and wave 2 was 66.2 years (± 18.4). Corresponding ages at discharge were 67.5 years (± 19.7), 63.9 years (± 18.0) and 62.4 years (± 18.0). The highest proportion of total admissions was among the oldest group (≥ 80 years) in wave 1 (35.0%). When compared with patients admitted with other causes, those admitted with COVID-19 in wave 1 and in wave 2 were more frequent in the 40-59 year band: 20.8, 24.6 and 30.0%; consisted of more male patients: 47.5, 57.6 and 58.8%; and a high LACE (Length of stay, Acuity of admission, Comorbidity and Emergency department visits) index (score ≥ 10): 39.4, 61.3 and 50.3%. Compared to wave-2 patients, those admitted in wave 1 had greater risk of death in hospital: OR = 1.58 (1.18-2.12) and within 30 days of discharge: OR = 2.91 (1.40-6.04). Survivors of COVID-19 in wave 1 stayed longer in hospital (median = 6.5 days; interquartile range = 2.9-12.0) as compared to survivors from wave 2 (4.5 days; interquartile range = 1.9-8.7). Patient characteristics differed significantly between the two waves of COVID-19 pandemic. There was an improvement in outcomes in wave 2, including shorter length of stay in hospital and reduction of mortality.

Antenatal biological models in the characterization and research of congenital lower urinary tract disorders.

Congenital lower urinary tract disorders are a family of diseases affecting both urinary storage and voiding as well as upstream kidney function. Current treatments include surgical reconstruction but many children still fail to achieve urethral continence or progress to chronic kidney disease. New therapies can only be achieved through undertaking research studies to enhance our understanding of congenital lower urinary tract disorders. Animal models form a critical component of this research, a corner of the triangle composed of human in-vitro studies and clinical research. We describe the current animal models for two rare congenital bladder disorders, posterior urethral valves (PUV) and bladder exstrophy (BE). We highlight important areas for researchers to consider when deciding which animal model to use to address particular research questions and outline the strengths and weaknesses of current models available for PUV and BE. Finally, we present ideas for refining animal models for PUV and BE in the future to stimulate future researchers and help them formulate their thinking when working in this field.

Clinical outcomes in patients admitted to hospital with cervical spine fractures or with hip fractures.

Patients admitted with a cervical fracture are twice as likely to die within 30 days of injury than those with a hip fracture. However, guidelines for the management of cervical fractures are less available than for hip fractures. We hypothesise that outcomes may differ between these types of fractures. We analysed 1359 patients (406 men, 953 women) with mean age of 83.8 years (standard deviation = 8.7) admitted to a National Health Service hospital in 2013-2019 with a cervical (7.5%) or hip fracture (92.5%) of similar age. The association of cervical fracture (hip fracture as reference), hospital length of stay (LOS), co-morbidities, age and sex with outcomes (acute delirium, new pressure ulcer, and discharge to residential/nursing care) was assessed by stepwise multivariate logistic regression. Acute delirium without history of dementia was increased with cervical fractures: odds ratio (OR) = 2.4, 95% confidence interval (CI) = 1.3-4.7, age ≥ 80 years: OR = 3.5 (95% CI = 1.9-6.4), history of stroke: OR = 1.8 (95% CI = 1.0-3.1) and ischaemic heart disease: OR = 1.9 (95% CI = 1.1-3.6); pressure ulcers was increased with cervical fractures: OR = 10.9 (95% CI = 5.3-22.7), LOS of 2-3 weeks: OR = 3.0 (95% CI = 1.2-7.5) and LOS of ≥ 3 weeks: OR = 4.9, 95% CI = 2.2-11.0; and discharge to residential/nursing care was increased with cervical fractures: OR = 3.2 (95% CI = 1.4-7.0), LOS of ≥ 3 weeks: OR = 4.4 (95% CI = 2.5-7.6), dementia: OR = 2.7 (95% CI = 1.6-4.7), Parkinson's disease: OR = 3.4 (95% CI = 1.3-8.8), and age ≥ 80 years: OR = 2.7 (95% CI = 1.3-5.6). In conclusion, compared with hip fracture, cervical fracture is more likely to associate with acute delirium and pressure ulcers, and for discharge to residency of high level of care, independent of established risk factors.

Early emergency readmission frequency as an indicator of short-, medium- and long-term mortality post-discharge from hospital.

Frequent emergency readmissions, an indicator of quality of care, has been rising in England but the underlying reasons remain unclear. We examined the association of early readmissions with subsequent mortality in adults, taking into account the underlying presenting diagnoses and hospital length of stay (LOS). Data of alive-discharge episodes were prospectively collected between 01/04/2017 and 31/03/2019 in an National Health Service hospital, comprising 32,270 patients (46.1% men) aged 18-107 years (mean = 64.0, ± SD = 20.5 years). The associations of readmission frequency within 28 days of discharge and mortality within 30 days and 6 months of hospital discharge, and over a 2-year period were evaluated, adjusted for presenting diagnoses, LOS, age and sex during the first admission. Analysis of all patients 18-107 years (reference: no readmission) showed mortality within 30 days was increased for 1 readmission: event rate = 9.2%, odds ratio (OR) = 3.4 (95% confidence interval (CI) = 2.9-4.0), and ≥ 2 readmissions: event rate = 10.0%, OR = 2.6 (95%CI = 2.0-3.3), and within 6 months for 1 readmission: event rate = 19.6%, OR = 3.0 (95%CI = 2.7-3.4), and ≥ 2 readmissions: event rate = 27.4%, OR = 3.4 (95%CI = 2.9-4.0), and over a 2-year period for 1 readmission: event rate = 25.5%, hazard ratio = 2.2 (95%CI = 2.0-2.4), and ≥ 2 readmissions: event rate = 36.1%, hazard ratio = 2.5 (95%CI = 2.2-2.8). Within the age groups 18-49, 50-59, 60-69, 70-79 and ≥ 80 years, readmissions were also associated with increased risk of mortality within 3 months and 6 months of discharge, and over 2-year period. In conclusion, early hospital readmission predicts short-, medium- and long-term mortality post-discharge from hospital in adults aged 18-107 years, independent of underlying presenting conditions, LOS, age and sex. Further research focussing on safe discharge and follow-up patient care may help reduce preventable readmissions and post-discharge mortality.

Derivation of age-adjusted LACE index thresholds in the prediction of mortality and frequent hospital readmissions in adults.

The LACE index has been shown to predict hospital readmissions and death with variable accuracy. A LACE index ≥ 10 is considered as high risk in the existing literature. We aimed to derive age-specific LACE index thresholds in the prediction of mortality and frequent readmissions. Analysis of prospectively collected data of consecutive alive-discharge episodes between 01/04/2017 and 31/03/2019 to a single hospital was conducted. The derivation of LACE index thresholds for predicting all-cause mortality within 6 months of hospital discharge or frequent readmissions (≥ 2 times within 28 days) was examined by receiver operating characteristics (ROC) in 32270 patients (14878 men, 17392 women) aged 18-107 year (mean = 64.0 years, SD = 20.5). For all patients with a LACE index ≥ 10, the area under the curve (AUC) for predicting mortality was 80.5% (95% CI 79.7-81.3) and for frequent readmissions was 84.0% (83.0-85.1). Two-graph ROC plots showed that the LACE index threshold where sensitivity equates specificity was 9.5 (95% intermediate range = 5.6-13.5) for predicting mortality and 10.3 (95% intermediate range = 6.6-13.6) for frequent readmissions. These thresholds were lowest among youngest individuals and rose progressively with age for mortality prediction: 18-49 years = 5.0, 50-59 years = 6.5, 60-69 years = 8.0, 70-79 years = 9.8 and ≥ 80 years = 11.6, and similarly for frequent readmissions: 18-49 years = 5.1, 50-59 years = 7.5, 60-69 years = 9.1, 70-79 years = 10.6 and ≥ 80 years = 12.0. Positive and negative likelihood ratios (LRs) ranged 1.5-3.3 and 0.4-0.6 for predicting mortality, and 2.5-4.4 and 0.3-0.6 for frequent readmissions, respectively, with stronger evidence in younger than in older individuals (LRs further from unity). In conclusion, the LACE index predicts mortality and frequent readmissions at lower thresholds and stronger in younger than in older individuals. Age should be taken into account when using the LACE index for identifying patients at high risk.

New targets for overactive bladder-ICI-RS 2109.

AIM: To review evidence for novel drug targets that can manage overactive bladder (OAB) symptoms. METHODS: A think tank considered evidence from the literature and their own research experience to propose new drug targets in the urinary bladder to characterize their use to treat OAB. RESULTS: Five classes of agents or cellular pathways were considered. (a) Cyclic nucleotide-dependent (cyclic adenosine monophosphate and cyclic guanosine monophosphate) pathways that modulate adenosine triphosphate release from motor nerves and urothelium. (b) Novel targets for ß3 agonists, including the bladder wall vasculature and muscularis mucosa. (c) Several TRP channels (TRPV1 , TRPV4 , TRPA1 , and TRPM4 ) and their modulators in affecting detrusor overactivity. (d) Small conductance Ca2+ -activated K+ channels and their influence on spontaneous contractions. (e) Antifibrosis agents that act to modulate directly or indirectly the TGF-ß pathway-the canonical fibrosis pathway. CONCLUSIONS: The specificity of action remains a consideration if particular classes of agents can be considered for future development as receptors or pathways that mediate actions of the above mentioned potential agents are distributed among most organ systems. The tasks are to determine more detail of the pathological changes that occur in the OAB and how the specificity of potential drugs may be directed to bladder pathological changes. An important conclusion was that the storage, not the voiding, phase in the micturition cycle should be investigated and potential targets lie in the whole range of tissue in the bladder wall and not just detrusor.

Anticoagulation therapy in patients with stroke and atrial fibrillation: a registry-based study of acute stroke care in Surrey, UK.

INTRODUCTION: Because of their high risk of stroke, anticoagulation therapy is recommended for most patients with atrial fibrillation (AF). The present study evaluated the use of anticoagulants in the community and in a hospital setting for patients with AF and its associations with stroke. METHODS: Patients admitted with stroke to four major hospitals in County of Surrey, England were surveyed in the 2014-2016 Sentinel Stroke National Audit Programme. Descriptive statistics was used to summarise subject characteristics and χ² test to assess differences between categorical variables. RESULTS: A total of 3309 patients, 1656 men (mean age: 73.1 years±SD 13.2) and 1653 women (79.3 years±13.0) were admitted with stroke (83.3% with ischaemic, 15.7% haemorrhagic stroke and 1% unspecified). AF occurred more frequently (χ2=62.4; p<0.001) among patients admitted with recurrent (30.2%) rather than with first stroke (17.1%). There were 666 (20.1%) patients admitted with a history of AF, among whom 304 (45.3%) were anticoagulated, 279 (41.9%) were untreated and 85 (12.8%) deemed unsuitable for anticoagulation. Of the 453 patients with history of AF admitted with a first ischaemic stroke, 138 (37.2%) were on anticoagulation and 41 (49.6%) were not (χ2 = 6.3; p<0.043) and thrombolysis was given more frequently for those without prior anticoagulation treatment (16.1%) or unsuitable for anticoagulation (23.6%) compared with those already on anticoagulation treatment (8.3%; χ2=10.0; p=0.007). Of 2643 patients without a previous history of AF, 171 (6.5%) were identified with AF during hospitalisation. Of patients with AF who presented with ischaemic stroke who were not anticoagulated or deemed unsuitable for anticoagulation prior to admission, 91.8% and 75.0%, respectively, were anticoagulated on discharge. CONCLUSIONS: The study highlights an existing burden for patients with stroke and reflects inadequate treatment of AF which results in an increased stroke burden. There is significant scope to improve the rates of anticoagulation.