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1.  Hospital Standardized Mortality Ratio: Consequences of Adjusting Hospital Mortality with Indirect Standardization 
PLoS ONE  2013;8(4):e59160.
The hospital standardized mortality ratio (HSMR) is developed to evaluate and improve hospital quality. Different methods can be used to standardize the hospital mortality ratio. Our aim was to assess the validity and applicability of directly and indirectly standardized hospital mortality ratios.
Retrospective scenario analysis using routinely collected hospital data to compare deaths predicted by the indirectly standardized case-mix adjustment method with observed deaths. Discharges from Dutch hospitals in the period 2003–2009 were used to estimate the underlying prediction models. We analysed variation in indirectly standardized hospital mortality ratios (HSMRs) when changing the case-mix distributions using different scenarios. Sixty-one Dutch hospitals were included in our scenario analysis.
A numerical example showed that when interaction between hospital and case-mix is present and case-mix differs between hospitals, indirectly standardized HSMRs vary between hospitals providing the same quality of care. In empirical data analysis, the differences between directly and indirectly standardized HSMRs for individual hospitals were limited.
Direct standardization is not affected by the presence of interaction between hospital and case-mix and is therefore theoretically preferable over indirect standardization. Since direct standardization is practically impossible when multiple predictors are included in the case-mix adjustment model, indirect standardization is the only available method to compute the HSMR. Before interpreting such indirectly standardized HSMRs the case-mix distributions of individual hospitals and the presence of interactions between hospital and case-mix should be assessed.
PMCID: PMC3621877  PMID: 23593133
2.  Variations in hospital standardised mortality ratios (HSMR) as a result of frequent readmissions 
We investigated the impact that variations in the frequency of readmissions had upon a hospital's standardised mortality ratio (HSMR). An adapted HSMR model was used in the study. Our calculations were based on the admissions of 70 hospitals in the Netherlands during the years 2005 to 2009.
Through a retrospective analysis of routinely collected hospital data, we calculated standardised in-hospital mortality ratios both by hospital and by diagnostic group (H/SMRs) using two different models. The first was the Dutch 2010 model while the second was the same model but with an additional adjustment for the readmission frequency. We compared H/SMR outcomes and the corresponding quality metrics in order to test discrimination (c-statistics), calibration (Hosmer-Lemeshow) and explanatory power (pseudo-R2 statistic) for both models.
The SMR outcomes for model 2 compared to model 1, varied between -39% and +110%. On the HSMR level these variations ranged from -12% to +11%. There was a substantial disagreement between the models with respect to significant death on the SMR level as well as the HSMR level (~ 20%). All quality metrics comparing both models were in favour of model 2. The susceptibility to adjustment for readmission increased for longer review periods.
The 2010 HSMR model for the Netherlands was sensitive to adjustment for the frequency of readmissions. A model without this adjustment, as opposed to a model with the adjustment, produced substantially different HSMR outcomes. The uncertainty introduced by these differences exceeded the uncertainty indicated by the 95% confidence intervals. Therefore an adjustment for the frequency of readmissions should be considered in the Netherlands, since such a model showed more favourable quality metric characteristics compared to a model without such an adjustment. Other countries could well benefit from a similar adjustment to their models. A review period of the data collected over the last three years, at least, is advisable.
PMCID: PMC3372422  PMID: 22475458
3.  Predicting hospital mortality among frequently readmitted patients: HSMR biased by readmission 
Casemix adjusted in-hospital mortality is one of the measures used to improve quality of care. The adjustment currently used does not take into account the effects of readmission, because reliable data on readmission is not readily available through routinely collected databases. We have studied the impact of readmissions by linking admissions of the same patient, and as a result were able to compare hospital mortality among frequently, as opposed to, non-frequently readmitted patients. We also formulated a method to adjust for readmission for the calculation of hospital standardised mortality ratios (HSMRs).
We conducted a longitudinal retrospective analysis of routinely collected hospital data of six large non-university teaching hospitals in the Netherlands with casemix adjusted standardised mortality ratios ranging from 65 to 114 and a combined value of 93 over a five-year period. Participants concerned 240662 patients admitted 418566 times in total during the years 2003 - 2007. Predicted deaths by the HSMR model 2008 over a five-year period were compared with observed deaths.
Numbers of readmissions per patient differ substantially between the six hospitals, up to a factor of 2. A large interaction was found between numbers of admissions per patient and HSMR-predicted risks. Observed deaths for frequently admitted patients were significantly lower than HSMR-predicted deaths, which could be explained by uncorrected factors surrounding readmissions.
Patients admitted more frequently show lower risks of dying on average per admission. This decline in risk is only partly detected by the current HSMR. Comparing frequently admitted patients to non-frequently admitted patients commits the constant risk fallacy and potentially lowers HSMRs of hospitals treating many frequently admitted patients and increases HSMRs of hospitals treating many non-frequently admitted patients. This misleading effect can only be demonstrated by an analysis over a prolonged period, but occurs, in effect, every day of the year. This finding is relevant for all countries where hospitals use HSMR for monitoring and improving hospital performance. The use of 'admission frequency' as additional adjustment variable may provide a more accurate HSMR.
PMCID: PMC3063816  PMID: 21401936
4.  The hospital standardised mortality ratio: a powerful tool for Dutch hospitals to assess their quality of care? 
Aim of the study
To use the hospital standardised mortality ratio (HSMR), as a tool for Dutch hospitals to analyse their death rates by comparing their risk-adjusted mortality with the national average.
The method uses routine administrative databases that are available nationally in The Netherlands—the National Medical Registration dataset for the years 2005–2007. Diagnostic groups that led to 80% of hospital deaths were included in the analysis. The method adjusts for a number of case-mix factors per diagnostic group determined through a logistic regression modelling process.
In The Netherlands, the case-mix factors are primary diagnosis, age, sex, urgency of admission, length of stay, comorbidity (Charlson Index), social deprivation, source of referral and month of admission. The Dutch HSMR model performs well at predicting a patient's risk of death as measured by a c statistic of the receiver operating characteristic curve of 0.91. The ratio of the HSMR of the Dutch hospital with the highest value in 2005–2007 is 2.3 times the HSMR of the hospital with the lowest value.
Overall hospital HSMRs and mortality at individual diagnostic group level can be monitored using statistical process control charts to give an early warning of possible problems with quality of care. The use of routine data in a standardised and robust model can be of value as a starting point for improvement of Dutch hospital outcomes. HSMRs have been calculated for several other countries.
PMCID: PMC2921266  PMID: 20172876
Healthcare quality improvement; quality of care; mortality; healthcare quality; control charts
5.  Trends in Canadian hospital standardised mortality ratios and palliative care coding 2004–2010: a retrospective database analysis 
BMJ Open  2012;2(6):e001729.
The hospital standardised mortality ratio (HSMR), anchored at an average score of 100, is a controversial macromeasure of hospital quality. The measure may be dependent on differences in patient coding, particularly since cases labelled as palliative are typically excluded.
To determine whether palliative coding in Canada has changed since the 2007 national introduction of publicly released HSMRs, and how such changes may have affected results.
Retrospective database analysis.
Inpatients in Canadian hospitals from April 2004 to March 2010.
12 593 329 hospital discharges recorded in the Canadian Institute for Health Information (CIHI) Discharge Abstract Database from April 2004 to March 2010.
Crude mortality and palliative care coding rates. HSMRs calculated with the same methodology as CIHI. A derived hospital standardised palliative ratio (HSPR) adjusted to a baseline average of 100 in 2004–2005. Recalculated HSMRs that included palliative cases under varying scenarios.
Crude mortality and palliative care coding rates have been increasing over time (p<0.001), in keeping with the nation's advancing overall morbidity. HSMRs in 2008–2010 were significantly lower than in 2004–2006 by 8.55 points (p<0.001). The corresponding HSPR rises dramatically between these two time periods by 48.83 points (p<0.001). Under various HSMR scenarios that included palliative cases, the HSMR would have at most decreased by 6.35 points, and may have even increased slightly.
Inability to calculate a definitively comparable HSMR that include palliative cases and to account for closely timed changes in national palliative care coding guidelines.
Palliative coding rates in Canadian hospitals have increased dramatically since the public release of HSMR results. This change may have partially contributed to the observed national decline in HSMR.
PMCID: PMC3533024  PMID: 23131397
Health Services Administration & Management; hospital; mortality rate; Palliative Care
6.  Variations in the Hospital Standardized Mortality Ratios in Korea 
The hospital standardized mortality ratio (HSMR) has been widely used because it allows for robust risk adjustment using administrative data and is important for improving the quality of patient care.
All inpatients discharged from hospitals with more than 700 beds (66 hospitals) in 2008 were eligible for inclusion. Using the claims data, 29 most responsible diagnosis (MRDx), accounting for 80% of all inpatient deaths among these hospitals, were identified, and inpatients with those MRDx were selected. The final study population included 703 571 inpatients including 27 718 (3.9% of all inpatients) in-hospital deaths. Using logistic regression, risk-adjusted models for predicting in-hospital mortality were created for each MRDx. The HSMR of individual hospitals was calculated for each MRDx using the model coefficients. The models included age, gender, income level, urgency of admission, diagnosis codes, disease-specific risk factors, and comorbidities. The Elixhauser comorbidity index was used to adjust for comorbidities.
For 26 out of 29 MRDx, the c-statistics of these mortality prediction models were higher than 0.8 indicating excellent discriminative power. The HSMR greatly varied across hospitals and disease groups. The academic status of the hospital was the only factor significantly associated with the HSMR.
We found a large variation in HSMR among hospitals; therefore, efforts to reduce these variations including continuous monitoring and regular disclosure of the HSMR are required.
PMCID: PMC4162118  PMID: 25139167
Quality of health care; Outcome assessment; Hospital mortality
7.  A Simple Insightful Approach to Investigating a Hospital Standardised Mortality Ratio: An Illustrative Case-Study 
PLoS ONE  2013;8(3):e57845.
Despite methodological concerns Hospital Standardised Mortality Ratios (HSMRs) are promoted as measures of performance. Hospitals that experience an increase in their HSMR are presented with a serious challenge but with little guidance on how to investigate this complex phenomenon. We illustrate a simple penetrating approach.
Retrospective analysis of routinely collected hospital admissions data comparing observed and expected deaths predicted by the Dr Foster Unit case mix adjustment method over three years (n = 74,860 admissions) in Shropshire and Telford NHS Trust Hospital (SaTH) constituting PRH (Princess Royal Hospital) and RSH (Royal Shrewsbury Hospital); whose HSMR increased from 99 in the year 2008/09 to 118 in the year 2009/10.
The step up in HSMR was primarily located in PRH (109 to 130 vs. 105 to 118 RSH). Disentangling the HSMR by plotting run charts of observed and expected deaths showed that observed deaths were stable in RSH and PRH but expected deaths, especially at PRH, had fallen. The fall in expected deaths has two possible explanations–genuinely lower risk admissions or that the case-mix adjustment model is underestimating the risk of admissions perhaps because of inadequate clinical coding. There was no evidence that the case-mix profile of admissions had changed but there was considerable evidence that clinical coding process at PRH was producing a lower depth of coding resulting in lower expected mortality.
Knowing whether the change (increase/decrease) in HSMR is driven by the numerator or the denominator is a crucial pivotal first step in understanding a given HSMR and so such information should be an integral part of the HSMR reporting methodology.
PMCID: PMC3589454  PMID: 23472111
8.  Palliative care coding practices in Canada since the introduction of guidelines and the HSMR indicator 
BMJ Open  2015;5(11):e008753.
This study examines palliative care (PC) coding practices since the introduction of a national coding standard and assesses a potential association with hospital standardised mortality ratio (HSMR) results.
Acute-care hospitals in Canada.
∼16 million hospital discharges recorded in Canadian Institute for Health Information (CIHI)'s Discharge Abstract Database from April 2006 to March 2013.
Primary and secondary outcome measures
In-hospital mortality, patient characteristics and service utilisation among all hospitalisations, HSMR cases and palliative patients.
We assessed all separations in the Discharge Abstract Database between fiscal years 2006–2007 and 2012–2013 for PC cases at national, provincial and facility levels. In-hospital mortality was measured among all hospitalisations (including HSMR cases) and palliative patients. We calculated a variant HSMR-PC that included PC cases.
There was an increase in the frequency of PC coding over the study period (from 0.78% to 1.12% of all separations), and year-over-year improvement in adherence to PC coding guidelines. Characteristics and resource utilisation of PC patients remained stable within provinces. Crude mortality among HSMR cases declined from 8.7% to 7.3%. National HSMR declined by 22% during the study period, compared with a 17% decline in HSMR-PC. Provincial results for HSMR-PC are not significantly different from regular HSMR calculation.
The introduction of a national coding standard resulted in increased identification of palliative patients and services. Aside from PC coding practices, we note numerous independent drivers of improving HSMR results, notably, a significant reduction of in-hospital mortality, and increase in admissions accompanied by a greater number of coded comorbidities. While PC impacts the HSMR indicator, its influence remains modest.
PMCID: PMC4663426  PMID: 26597865
HSMR; Clinical coding; Hospital mortality; Health services research; PALLIATIVE CARE
9.  Avoidability of hospital deaths and association with hospital-wide mortality ratios: retrospective case record review and regression analysis 
Objectives To determine the proportion of avoidable deaths (due to acts of omission and commission) in acute hospital trusts in England and to determine the association with the trust’s hospital-wide standardised mortality ratio assessed using the two commonly used methods - the hospital standardised mortality ratio (HSMR) and the summary hospital level mortality indicator (SHMI).
Design Retrospective case record review of deaths.
Setting 34 English acute hospital trusts (10 in 2009 and 24 in 2012/13) randomly selected from across the spectrum of HSMR.
Main outcome measures Avoidable death, defined as those with at least a 50% probability of avoidability in view of trained medical reviewers. Association of avoidable death proportion with the HSMR and the SHMI assessed using regression coefficients, to estimate the increase in avoidable death proportion for a one standard deviation increase in standardised mortality ratio.
Participants 100 randomly selected hospital deaths from each trust.
Results The proportion of avoidable deaths was 3.6% (95% confidence interval 3.0% to 4.3%). It was lower in 2012/13 (3.0%, 2.4% to 3.7%) than in 2009 (5.2%, 3.8% to 6.6%). This difference is subject to several factors, including reviewers’ greater awareness in 2012/13 of orders not to resuscitate, patients being perceived as sicker on admission, minor differences in review form questions, and cultural changes that might have discouraged reviewers from criticising other clinicians. There was a small but statistically non-significant association between HSMR and the proportion of avoidable deaths (regression coefficient 0.3, 95% confidence interval −0.2 to 0.7). The regression coefficient was similar for both time periods (0.1 and 0.3). This implies that a difference in HSMR of between 105 and 115 would be associated with an increase of only 0.3% (95% confidence interval −0.2% to 0.7%) in the proportion of avoidable deaths. A similar weak non-significant association was observed for SHMI (regression coefficient 0.3, 95% confidence interval −0.3 to 1.0).
Conclusions The small proportion of deaths judged to be avoidable means that any metric based on mortality is unlikely to reflect the quality of a hospital. The lack of association between the proportion of avoidable deaths and hospital-wide SMRs partly reflects methodological shortcomings in both metrics. Instead, reviews of individual deaths should focus on identifying ways of improving the quality of care, whereas the use of standardised mortality ratios should be restricted to assessing the quality of care for conditions with high case fatality for which good quality clinical data exist.
PMCID: PMC4502415  PMID: 26174149
10.  Hospital Standardized Mortality Ratios: Sensitivity Analyses on the Impact of Coding 
Health Services Research  2011;46(6 Pt 1):1741-1761.
Hospital standardized mortality ratios (HSMRs) are derived from administrative databases and cover 80 percent of in-hospital deaths with adjustment for available case mix variables. They have been criticized for being sensitive to issues such as clinical coding but on the basis of limited quantitative evidence.
In a set of sensitivity analyses, we compared regular HSMRs with HSMRs resulting from a variety of changes, such as a patient-based measure, not adjusting for comorbidity, not adjusting for palliative care, excluding unplanned zero-day stays ending in live discharge, and using more or fewer diagnoses.
Overall, regular and variant HSMRs were highly correlated (ρ > 0.8), but differences of up to 10 points were common. Two hospitals were particularly affected when palliative care was excluded from the risk models. Excluding unplanned stays ending in same-day live discharge had the least impact despite their high frequency. The largest impacts were seen when capturing postdischarge deaths and using just five high-mortality diagnosis groups.
HSMRs in most hospitals changed by only small amounts from the various adjustment methods tried here, though small-to-medium changes were not uncommon. However, the position relative to funnel plot control limits could move in a significant minority even with modest changes in the HSMR.
PMCID: PMC3393030  PMID: 21790587
Administrative data; mortality; hospitals; quality of care
11.  Hospital mortality under surgical care 
The ‘hospital standardised mortality ratio’ (HSMR) has been used in England since 1999 to measure NHS hospital performance. Large variations in reported HSMR between English hospitals have recently led to heavy criticism of their use as a surrogate measure of hospital performance. This paper aims to review the mortality data for a consultant general surgeon contributed by his NHS trust over a 3-year period as part of the trust's HSMR calculation and evaluate the accuracy of coding the diagnoses and covariates for case mix adjustment.
The Dr Foster Intelligence database was interrogated to extract the NHS trust's HSMR benchmark data on inpatient mortality for the surgeon from 1 April 2006 to 31 March 2009 and compared to the hospital notes.
30 patients were identified of whom 12 had no evidence of being managed by the surgeon. This represents a potential 40% inaccuracy rate in designating consultant responsibility. The remaining 18 patients could be separated into ‘operative’ (11 patients) and ‘non-operative’ (7 patients) groups. Only 27% in the operative group and 43% of the non-operative mortality group respectively had a Charlson co-morbidity index recorded despite 94% of the cases having significant co-morbidities
Highlighting crude and inaccurate clinician-specific mortality data when only 1-5% of deaths under surgical care may be associated with avoidable adverse events seems potentially irresponsible.
PMCID: PMC3291133  PMID: 21477429
Hospital standardised mortality ratio; Surgical care; Inpatient mortality
12.  Patient safety and quality of care continue to improve in NHS North West following early implementation of the European Working Time Directive 
Objectives: NHS North West aimed to fully implement the European Working Time Directive (EWTD) 1 year ahead of the August 2009 national deadline. Significant debate has taken place concerning the implications of the EWTD for patient safety. This study aims to directly address this issue by comparing parameters of patient safety in NHS North West to those nationally prior to EWTD implementation, and during ‘North West-only’ EWTD implementation.
Design: Hospital standardised mortality ratio (HSMR), average length of stay (ALOS) and standardised readmission rate (SRR) in acute trusts across all specialties were calculated retrospectively throughout NHS North West for the three financial years from 2006/2007 to 2008/2009. These figures were compared to national data for the same parameters.
Results: The analysis of HSMR, ALOS and SRR reveal no significant difference in trend across three financial years when NHS North West is compared to England. HSMR and SRR within NHS North West continued to improve at a similar rate to the England average after August 2008. The ALOS analysis shows that NHS North West performed better than the national average for the majority of the study period, with no significant change in this pattern in the period following August 2008. When the HSMRs for NHS North West and England are compared against a fixed benchmark year (2005), the data shows a continuing decrease. The NHS North West figures follow the national trend closely at all times.
Conclusions: The data presented in this study quantitatively demonstrates, for the first time, that implementation of the EWTD in NHS North West in August 2008 had no obvious adverse impact on key outcomes associated with patient safety and quality of care. Continued efforts will be required to address the challenge posed nationally by the restricted working hour’s schedule.
PMCID: PMC2990025  PMID: 20739355
13.  Towards National Surgical Surveillance in the UK – A Pilot Study 
PLoS ONE  2012;7(12):e47969.
The Bristol heart inquiry in the United Kingdom (UK) highlighted the lack of standards for evaluating surgical performance and quality. In 2009, the World Health Organisation (WHO) proposed six standardised metrics for surgical surveillance. This is the first study to collect and analyse such metrics from a cohort of National Health Service (NHS) Trusts in England, helping to determine their feasibility and utility in measuring surgical performance, its impact on public health and mortality, and for tracking surgical trends over time.
Freedom of Information Act 2000 (FOI) requests for WHO standardised surgical metrics were made to 36 NHS Trusts in England during July to November 2010. Additional data on Hospital Standardised Mortality Ratio (HSMR), Patient Safety Score and Abdominal Aortic Aneurysm (AAA) volume and mortality was obtained from Dr Foster Health and The Guardian Newspaper. Analysis was performed using mixed-effect logistic regression.
30/36 trusts responded (83%). During 2005–9, 5.4 million operations were performed with a 24.2% increase in annual number of operations. This rising volume within hospitals was associated with lower mortality ratios. A 10% increase in operative volume was associated with a lower day of surgery death rate (DDR OR = 0.94, p = 0.056) and post-operative inpatient 30-day mortality (PDR30 OR = 0.93, p = 0.001). For every 10,000 more operations that an NHS Trust does, a 4% drop in PDR30 mortality was achieved. A 10% increase in the volume of elective AAAs was associated with lower elective AAA (OR = 0.96, p = 0.032) and emergency AAA (OR = 0.95, p = 0.009) PDR30 mortality. Lower DDR mortality was noted for emergency AAA mortality (OR = 0.95, p = 0.025) but not elective AAAs (OR = 0.97, p = 0.116).
Standarised surgical metrics can provide policy makers and commissioners with valuable summary data on surgical performance allowing for statistical process control of a complex intervention. This study has shown their collection is feasible albeit using FOI and the first to show a statistically significant volume-outcome relationship for surgery as a whole within hospitals. It adds weight to the argument that patients are safer in larger hospitals or those that become larger by growing their patient base. Together with other measures, such metrics can help build a picture of surgical surveillance in the UK and potentially lead us to safer surgery.
PMCID: PMC3519825  PMID: 23239962
14.  hSMR3A as a Marker for Patients With Erectile Dysfunction 
The Journal of urology  2007;178(1):338-343.
We recently reported that Vcsa1 is one of the most down-regulated genes in the corpora of rats in 3 distinct models of erectile dysfunction. Since gene transfer of plasmids expressing Vcsa1 or intracorporeal injection of its mature peptide product sialorphin into the corpora of aging rats was shown to restore erectile function, we proposed that the Vcsa1 gene has a direct role in erectile function. To determine if similar changes in gene expression occur in the corpora of human subjects with erectile dysfunction we identified a human homologue of Vcsa1 (hSMR3A) and determined the level of expression of hSMR3A in patients.
Materials and Methods
hSMR3A was identified as a homologue of Vcsa1 by searching protein databases for proteins with similarity. hSMR3A cDNA was generated and subcloned into the plasmid pVAX to generate pVAX-hSMR3A. pVAX-hSMR3A (25 or 100 μg) was intracorporeally injected into aging rats. The effect on erectile physiology was compared histologically and by measuring intracorporeal pressure/blood pressure with controls treated with the empty plasmid pVAX. Total RNA was extracted from human corporeal tissue obtained from patients undergoing previously scheduled penile surgery. Patients were grouped according to normal erectile function (3), erectile dysfunction and diabetes (5) and patients without diabetes but with erectile dysfunction (5). Quantitative reverse-transcriptase polymerase chain reaction was used to determine the hSMR3A expression level.
Intracorporeal injection of 25 μg pVAX-hSMR3A was able to significantly increase the intracorporeal pressure-to-blood pressure ratio in aging rats compared to age matched controls. Higher amounts (100 μg) of gene transfer of the plasmid caused less of an improvement in the intracorporeal pressure-to-blood pressure ratio compared to controls, although there was histological and visual evidence that the animals were post-priapitic. These physiological effects were similar to previously reported effects of intracorporeal injection of pVAX-Vcsa1 into the corpora of aging rats, establishing hSMR3A as a functional homologue of Vcsa1. More than 10-fold down-regulation in hSMR3A transcript expression was observed in the corpora of patients with vs without erectile dysfunction. In patients with diabetes associated and nondiabetes associated erectile dysfunction hSMR3A expression was found to be down-regulated.
These results suggest that hSMR3A can act as a marker for erectile dysfunction associated with diabetic and nondiabetic etiologies. Given that our previous studies demonstrated that gene transfer of the Vcsa1 gene and intracorporeal injection of its protein product in rats can restore erectile function, these results suggest that therapies that increase the hSMR3A gene and product expression could potentially have a positive impact on erectile function.
PMCID: PMC2094360  PMID: 17512016
penis; diabetes; impotence; gene transfer techniques; rats; Sprague-Dawley
15.  Did hospital mortality in England change from 2005 to 2010? A retrospective cohort analysis 
There is some evidence that hospital performance in England measured by the Dr Foster Hospital Standardised Mortality Ratio (HSMR) has improved substantially over the last 10 years. This study explores mortality in-hospital and up to 30 days post-discharge over a five year period to determine whether there have been improvements in case-mix adjusted mortality, to examine if any changes are due to changes in case-mix adjustment variables such as age, sex, method of admission and comorbidity, and to compare changes between hospital trusts.
Using Hospital Episode Statistics linked to mortality data from the Office for National Statistics the Summary Hospital-Level Mortality Index (SHMI) was calculated for all patients who were discharged or died in general acute hospital trusts in England for the period 01/04/2005 to 30/09/2010.
During this five year period the number of admissions rose by 8% but deaths fell by 5%. The SHMI fell by 24% from 112 to 85 over the period, partly due to fewer deaths but partly due to increasing numbers predicted by the SHMI model. Excluding comorbidities from the model the SHMI fell by 18% from 108 to 89 over this period. The reduction was similar in emergency and elective admissions and in all other sub-groups examined. The average quarterly change in SHMI varied considerably between trusts (range: -4.4 to −0.2).
As measured by the SHMI there has been a 24% improvement in mortality in acute general trusts in England over a period of five and a half years. Part of this improvement is an artificial effect caused by changes in the depth of coding of comorbidities and other effects due to change in case-mix or non-constant risk.
PMCID: PMC3700823  PMID: 23763942
Hospital mortality; Quality indicators; Case mix adjustment; Trends; Retrospective study
16.  The opiorphin gene (ProL1) and its homologues function in erectile physiology 
BJU international  2008;102(6):736-740.
To determine if ProL1, a member of the opiorphin family of genes, can modulate erectile physiology, as it encodes a peptide which acts as a neutral endopeptidase inhibitor, other examples of which (Vcsa1, hSMR3A) modulate erectile physiology.
We cloned members of the opiorphin family of genes into the same mammalian expression backbone (pVAX); 100 μg of these plasmids (pVAX-Vcsa1, -hSMR3A, -hSMR3B and -ProL1) were injected intracorporally into retired breeder rats and the affect on erectile physiology assessed visually, by histology and by measuring the intracavernous pressure (ICP) and blood pressure (BP). As a positive control, rats were treated with pVAX-hSlo (expressing the MaxiK potassium channel) and as a negative control the empty backbone plasmid was injected (pVAX). We also compared the level of expression of ProL1 in corporal tissue of patients not reporting erectile dysfunction (ED), ED associated with diabetes and ED not caused by diabetes.
Gene transfer of plasmids expressing all members of the opiorphin family had a similar and significant effect on erectile physiology. At the concentration used in these experiments (100 μg) they resulted in higher resting ICP, and histological and visual analysis showed evidence of a priapiclike condition. After electrostimulation of the cavernous nerve, rats had significantly better ICP/BP than the negative control (pVAX). Gene transfer of pVAX-hSlo increased the ICP/BP ratio to a similar extent to the opiorphin homologues, but with no evidence for a priapic-like condition. Corpora cavernosa tissue samples obtained from men with ED, regardless of underlying causes, had significant down-regulation of both hSMR3A and ProL1.
All members of the human opiorphin family of genes can potentially modulate erectile physiology. Both hSMR3 and ProL1 are down-regulated in the corpora of men with ED, and therefore both genes can potentially act as markers of ED.
PMCID: PMC2872073  PMID: 18410445
Vcsa1; hSMR3; ProL1; opiorphin; erectile dysfunction; priapism
17.  The most dangerous hospital or the most dangerous equation? 
Hospital mortality rates are one of the most frequently selected indicators for measuring the performance of NHS Trusts. A recent article in a national newspaper named the hospital with the highest or lowest mortality in the 2005/6 financial year; a report by the organization Dr Foster Intelligence provided information with regard to the performance of all NHS Trusts in England.
Basic statistical theory and computer simulations were used to explore the relationship between the variations in the performance of NHS Trusts and the sizes of the Trusts. Data of hospital standardised mortality ratio (HSMR) of 152 English NHS Trusts for 2005/6 were re-analysed.
A close examination of the information reveals a pattern which is consistent with a statistical phenomenon, discovered by the French mathematician de Moivre nearly 300 years ago, described in every introductory statistics textbook: namely that variation in performance indicators is expected to be greater in small Trusts and smaller in large Trusts. From a statistical viewpoint, the number of deaths in a hospital is not in proportion to the size of the hospital, but is proportional to the square root of its size. Therefore, it is not surprising to note that small hospitals are more likely to occur at the top and the bottom of league tables, whilst mortality rates are independent of hospital sizes.
This statistical phenomenon needs to be taken into account in the comparison of hospital Trusts performance, especially with regard to policy decisions.
PMCID: PMC2194686  PMID: 18005428
18.  The Dutch Hospital Standardised Mortality Ratio (HSMR) method and cardiac surgery: benchmarking in a national cohort using hospital administration data versus a clinical database 
Heart  2013;100(9):702-710.
To compare the accuracy of data from hospital administration databases and a national clinical cardiac surgery database and to compare the performance of the Dutch hospital standardised mortality ratio (HSMR) method and the logistic European System for Cardiac Operative Risk Evaluation, for the purpose of benchmarking of mortality across hospitals.
Information on all patients undergoing cardiac surgery between 1 January 2007 and 31 December 2010 in 10 centres was extracted from The Netherlands Association for Cardio-Thoracic Surgery database and the Hospital Discharge Registry. The number of cardiac surgery interventions was compared between both databases. The European System for Cardiac Operative Risk Evaluation and hospital standardised mortality ratio models were updated in the study population and compared using the C-statistic, calibration plots and the Brier-score.
The number of cardiac surgery interventions performed could not be assessed using the administrative database as the intervention code was incorrect in 1.4–26.3%, depending on the type of intervention. In 7.3% no intervention code was registered. The updated administrative model was inferior to the updated clinical model with respect to discrimination (c-statistic of 0.77 vs 0.85, p<0.001) and calibration (Brier Score of 2.8% vs 2.6%, p<0.001, maximum score 3.0%). Two average performing hospitals according to the clinical model became outliers when benchmarking was performed using the administrative model.
In cardiac surgery, administrative data are less suitable than clinical data for the purpose of benchmarking. The use of either administrative or clinical risk-adjustment models can affect the outlier status of hospitals. Risk-adjustment models including procedure-specific clinical risk factors are recommended.
PMCID: PMC3995286  PMID: 24334377
Cardiac Surgery
19.  Reductions in hospital admissions and mortality rates observed after integrating emergency care: a natural experiment 
BMJ Open  2012;2(4):e000930.
Reducing emergency admissions is a priority for the NHS. A single hospital's emergency care system was reorganised with the principles of front-loaded investigations, integration of specialties, reduced duplication, earlier decision making by senior clinicians and a combined emergency assessment area. The authors relocated our Medical Assessment Unit into our emergency department in 2006. The authors evaluated changes in admissions and mortality before and after 2006, compared with other similar hospitals.
Quasi-experimental before and after study using routinely collected data.
Setting and participants
1 acute hospital in England, the intervention site, was compared with 23 other English hospitals between 2001 and 2009.
Outcome measures
Our outcome measures were hospital standardised mortality ratios (HSMRs) for non-elective admissions and standardised admission ratios (SARs).
The authors observed a statistically and clinically significant decrease in HSMR and SAR. The intervention hospital had the lowest HSMR and SAR of all the hospitals in our sample. This was statistically significant, p=0.0149 and p=0.0002, respectively.
Integrating emergency care in one location is associated with a meaningful reduction in mortality and emergency admissions to hospital.
Article summary
Article focus
We describe the improvements that occur when a medical admissions unit is closed and relocated into an emergency department. We compared a single unit to a family of similar hospitals. We used routine data analysed by the Dr Foster healthcare intelligence unit.
Key messages
Reducing duplicate processes, centralising hospital emergency care in one area and streamlining non-elective admission pathways is associated with sustained reductions in non-elective admissions and mortality.
The Standardised Admissions Ratio is an effective way to measure the performance of non-elective admissions.
Strengths and limitations of this study
This study has compared performance against controls over a ten year period.
The study uses retrospectively analysed administrative data.
PMCID: PMC4400673  PMID: 22858459
20.  Maternal Clinical Diagnoses and Hospital Variation in the Risk of Cesarean Delivery: Analyses of a National US Hospital Discharge Database 
PLoS Medicine  2014;11(10):e1001745.
Katy Kozhimannil and colleagues use a national database to examine the extent to which variability in cesarean section rates across the US from 2009–2010 was attributable to individual women's clinical diagnoses.
Please see later in the article for the Editors' Summary
Cesarean delivery is the most common inpatient surgery in the United States, where 1.3 million cesarean sections occur annually, and rates vary widely by hospital. Identifying sources of variation in cesarean use is crucial to improving the consistency and quality of obstetric care. We used hospital discharge records to examine the extent to which variability in the likelihood of cesarean section across US hospitals was attributable to individual women's clinical diagnoses.
Methods and Findings
Using data from the 2009 and 2010 Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project—a 20% sample of US hospitals—we analyzed data for 1,475,457 births in 1,373 hospitals. We fitted multilevel logistic regression models (patients nested in hospitals). The outcome was cesarean (versus vaginal) delivery. Covariates included diagnosis of diabetes in pregnancy, hypertension in pregnancy, hemorrhage during pregnancy or placental complications, fetal distress, and fetal disproportion or obstructed labor; maternal age, race/ethnicity, and insurance status; and hospital size and location/teaching status.
The cesarean section prevalence was 22.0% (95% confidence interval 22.0% to 22.1%) among women with no prior cesareans. In unadjusted models, the between-hospital variation in the individual risk of primary cesarean section was 0.14 (95% credible interval 0.12 to 0.15). The difference in the probability of having a cesarean delivery between hospitals was 25 percentage points. Hospital variability did not decrease after adjusting for patient diagnoses, socio-demographics, and hospital characteristics (0.16 [95% credible interval 0.14 to 0.18]). A limitation is that these data, while nationally representative, did not contain information on parity or gestational age.
Variability across hospitals in the individual risk of cesarean section is not decreased by accounting for differences in maternal diagnoses. These findings highlight the need for more comprehensive or linked data including parity and gestational age as well as examination of other factors—such as hospital policies, practices, and culture—in determining cesarean section use.
Please see later in the article for the Editors' Summary
Editors' Summary
In an ideal world, all babies would be delivered safely and naturally through their mother's vagina. However, increasing numbers of babies are being delivered by cesarean section, a surgical operation in which the baby is delivered through a cut made in the mother's abdomen and womb. In the US, a third of all babies (about 1.3 million babies in 2011) are delivered this way. A cesarean section is usually performed when a vaginal birth would endanger the life of the mother or her unborn child because, for example, the baby is in the wrong position or the labor is not progressing normally. Some cesarean sections are performed as emergency procedures, but others are planned in advance when the need for the operation becomes clear during pregnancy. Although cesarean sections can save lives, women who deliver this way have higher rates of infection, pain, and complications in future pregnancies than women who deliver vaginally, and their babies can have breathing problems.
Why Was This Study Done?
Currently, cesarean section rates vary widely from country to country and from hospital to hospital within countries. Careful assessment of the risks and benefits of cesarean delivery in individual patients can help to ensure that cesarean sections are used only when necessary, but changes to clinical and policy guidelines are also needed to ensure that cesarean delivery is neither overused nor underused. To guide these changes, we need to know whether cesarean section rates vary among hospitals because of case-mix differences (some hospitals may have high rates because they admit many women with complicated pregnancies, for example) or because of differences in modifiable nonclinical factors such as hospital policies and practices. In this retrospective multilevel analysis, the researchers examine whether the current wide variation in cesarean section rates across US hospitals is attributable to differences in maternal clinical diagnoses and patient characteristics or to hospital-level differences in the use of cesarean delivery.
What Did the Researchers Do and Find?
For their study, the researchers used hospital discharge data on nearly 1.5 million births in 1,373 hospitals collected by the 2009 and 2010 US Nationwide Inpatient Sample database, which captures administrative data (for example, length of stay in hospital and clinical complications) from a representative sample of 20% of US hospitals. To assess the chances of cesarean delivery based on hospital and patient characteristics, researchers fitted these data to multilevel logistic regression statistical models. Among women with no prior cesarean deliveries, the (primary) cesarean section rate was 22%, whereas among the whole study population, it was 33% (women who have one cesarean delivery often have a cesarean section for subsequent deliveries). In unadjusted models that compared cesarean section rates between hospitals without considering patient characteristics, the between-hospital variance for primary cesarean section rate was 0.14. Put another way, the likelihood of an individual having a first cesarean delivery varied between 11% and 36% across the hospitals considered. After adjustment for maternal clinical diagnoses, maternal age and other socio-demographic factors, and hospital characteristics such as size, the between-hospital variance for the primary cesarean section rate was 0.16.
What Do These Findings Mean?
The finding that the between-hospital variance for primary cesarean section rate did not decrease after adjusting for maternal characteristics (and other findings presented by the researchers) suggests that differences in case mix or pregnancy complexity may not drive the wide variability in cesarean section rates across US hospitals. However, the lack of information in the US Nationwide Inpatient Sample database on parity (the number of babies a woman has had) or gestational age (the length of time the baby has spent developing inside its mother) limits the strength of this conclusion. Both parity and gestational age strongly predict a woman's risk of a cesarean delivery. Thus, unmeasured differences in the parity of women admitted to different hospitals and/or the gestational age of their babies may be driving some of the variability in cesarean section rates across US hospitals. The lack of hospital-level information on obstetric care policies in the database also means that the many possible administrative explanations for variations across hospitals cannot be assessed. These findings therefore highlight the need for more comprehensive patient data to be collected (including information on parity and gestational age) and on hospital policies, practices, and culture before the variation in cesarean section rate across US hospitals can be fully understood and the use of cesarean delivery can be optimized.
Additional Information
Please access these websites via the online version of this summary at
This study is further discussed in a PLOS Medicine Perspective by Gordon C. S. Smith
The American College of Obstetricians and Gynecologists provides a fact sheet for patients on cesarean birth
The American College of Nurse-Midwives provides a fact sheet for pregnant women on preventing cesarean birth
The US-based Childbirth Connection Project of the non-profit National Partnership for Women and Families has a booklet called “What Every Woman Should Know about Cesarean Section”
The US-based non-profit Nemours Foundation provides detailed information about cesarean sections (in English and Spanish)
The UK National Health Service Choices website provides information for patients about delivery by cesarean section
MedlinePlus provides links to additional resources about cesarean section (in English and Spanish)
The UK non-profit organization Healthtalkonline provides personal stories about women's experiences of cesarean delivery
Information about the US Nationwide Inpatient Sample database is available
PMCID: PMC4205118  PMID: 25333943
21.  Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD) 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at:
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients with Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at:
For more information on the economic analysis, please visit the PATH website:
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website:
The objective of this analysis was to compare hospital-at-home care with inpatient hospital care for patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) who present to the emergency department (ED).
Clinical Need: Condition and Target Population
Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease is a disease state characterized by airflow limitation that is not fully reversible. This airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. The natural history of COPD involves periods of acute-onset worsening of symptoms, particularly increased breathlessness, cough, and/or sputum, that go beyond normal day-to-day variations; these are known as acute exacerbations.
Two-thirds of COPD exacerbations are caused by an infection of the tracheobronchial tree or by air pollution; the cause in the remaining cases is unknown. On average, patients with moderate to severe COPD experience 2 or 3 exacerbations each year.
Exacerbations have an important impact on patients and on the health care system. For the patient, exacerbations result in decreased quality of life, potentially permanent losses of lung function, and an increased risk of mortality. For the health care system, exacerbations of COPD are a leading cause of ED visits and hospitalizations, particularly in winter.
Hospital-at-home programs offer an alternative for patients who present to the ED with an exacerbation of COPD and require hospital admission for their treatment. Hospital-at-home programs provide patients with visits in their home by medical professionals (typically specialist nurses) who monitor the patients, alter patients’ treatment plans if needed, and in some programs, provide additional care such as pulmonary rehabilitation, patient and caregiver education, and smoking cessation counselling.
There are 2 types of hospital-at-home programs: admission avoidance and early discharge hospital-at-home. In the former, admission avoidance hospital-at-home, after patients are assessed in the ED, they are prescribed the necessary medications and additional care needed (e.g., oxygen therapy) and then sent home where they receive regular visits from a medical professional. In early discharge hospital-at-home, after being assessed in the ED, patients are admitted to the hospital where they receive the initial phase of their treatment. These patients are discharged into a hospital-at-home program before the exacerbation has resolved. In both cases, once the exacerbation has resolved, the patient is discharged from the hospital-at-home program and no longer receives visits in his/her home.
In the models that exist to date, hospital-at-home programs differ from other home care programs because they deal with higher acuity patients who require higher acuity care, and because hospitals retain the medical and legal responsibility for patients. Furthermore, patients requiring home care services may require such services for long periods of time or indefinitely, whereas patients in hospital-at-home programs require and receive the services for a short period of time only.
Hospital-at-home care is not appropriate for all patients with acute exacerbations of COPD. Ineligible patients include: those with mild exacerbations that can be managed without admission to hospital; those who require admission to hospital; and those who cannot be safely treated in a hospital-at-home program either for medical reasons and/or because of a lack of, or poor, social support at home.
The proposed possible benefits of hospital-at-home for treatment of exacerbations of COPD include: decreased utilization of health care resources by avoiding hospital admission and/or reducing length of stay in hospital; decreased costs; increased health-related quality of life for patients and caregivers when treated at home; and reduced risk of hospital-acquired infections in this susceptible patient population.
Ontario Context
No hospital-at-home programs for the treatment of acute exacerbations of COPD were identified in Ontario. Patients requiring acute care for their exacerbations are treated in hospitals.
Research Question
What is the effectiveness, cost-effectiveness, and safety of hospital-at-home care compared with inpatient hospital care of acute exacerbations of COPD?
Research Methods
Literature Search
Search Strategy
A literature search was performed on August 5, 2010, using OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database for studies published from January 1, 1990, to August 5, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists and health technology assessment websites were also examined for any additional relevant studies not identified through the systematic search.
Inclusion Criteria
English language full-text reports;
health technology assessments, systematic reviews, meta-analyses, and randomized controlled trials (RCTs);
studies performed exclusively in patients with a diagnosis of COPD or studies including patients with COPD as well as patients with other conditions, if results are reported for COPD patients separately;
studies performed in patients with acute exacerbations of COPD who present to the ED;
studies published between January 1, 1990, and August 5, 2010;
studies comparing hospital-at-home and inpatient hospital care for patients with acute exacerbations of COPD;
studies that include at least 1 of the outcomes of interest (listed below).
Cochrane Collaboration reviews have defined hospital-at-home programs as those that provide patients with active treatment for their acute exacerbation in their home by medical professionals for a limited period of time (in this case, until the resolution of the exacerbation). If a hospital-at-home program had not been available, these patients would have been admitted to hospital for their treatment.
Exclusion Criteria
< 18 years of age
animal studies
duplicate publications
grey literature
Outcomes of Interest
Patient/clinical outcomes
lung function (forced expiratory volume in 1 second)
health-related quality of life
patient or caregiver preference
patient or caregiver satisfaction with care
Health system outcomes
hospital readmissions
length of stay in hospital and hospital-at-home
ED visits
transfer to long-term care
days to readmission
eligibility for hospital-at-home
Statistical Methods
When possible, results were pooled using Review Manager 5 Version 5.1; otherwise, results were summarized descriptively. Data from RCTs were analyzed using intention-to-treat protocols. In addition, a sensitivity analysis was done assigning all missing data/withdrawals to the event. P values less than 0.05 were considered significant. A priori subgroup analyses were planned for the acuity of hospital-at-home program, type of hospital-at-home program (early discharge or admission avoidance), and severity of the patients’ COPD. Additional subgroup analyses were conducted as needed based on the identified literature. Post hoc sample size calculations were performed using STATA 10.1.
Quality of Evidence
The quality of each included study was assessed, taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses.
The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:
Summary of Findings
Fourteen studies met the inclusion criteria and were included in this review: 1 health technology assessment, 5 systematic reviews, and 7 RCTs.
The following conclusions are based on low to very low quality of evidence. The reviewed evidence was based on RCTs that were inadequately powered to observe differences between hospital-at-home and inpatient hospital care for most outcomes, so there is a strong possibility of type II error. Given the low to very low quality of evidence, these conclusions must be considered with caution.
Approximately 21% to 37% of patients with acute exacerbations of COPD who present to the ED may be eligible for hospital-at-home care.
Of the patients who are eligible for care, some may refuse to participate in hospital-at-home care.
Eligibility for hospital-at-home care may be increased depending on the design of the hospital-at-home program, such as the size of the geographical service area for hospital-at-home and the hours of operation for patient assessment and entry into hospital-at-home.
Hospital-at-home care for acute exacerbations of COPD was associated with a nonsignificant reduction in the risk of mortality and hospital readmissions compared with inpatient hospital care during 2- to 6-month follow-up.
Limited, very low quality evidence suggests that hospital readmissions are delayed in patients who received hospital-at-home care compared with those who received inpatient hospital care (mean additional days before readmission comparing hospital-at-home to inpatient hospital care ranged from 4 to 38 days).
There is insufficient evidence to determine whether hospital-at-home care, compared with inpatient hospital care, is associated with improved lung function.
The majority of studies did not find significant differences between hospital-at-home and inpatient hospital care for a variety of health-related quality of life measures at follow-up. However, follow-up may have been too late to observe an impact of hospital-at-home care on quality of life.
A conclusion about the impact of hospital-at-home care on length of stay for the initial exacerbation (defined as days in hospital or days in hospital plus hospital-at-home care for inpatient hospital and hospital-at-home, respectively) could not be determined because of limited and inconsistent evidence.
Patient and caregiver satisfaction with care is high for both hospital-at-home and inpatient hospital care.
PMCID: PMC3384361  PMID: 23074420
22.  Drug Efflux by a Small Multidrug Resistance Protein Is Inhibited by a Transmembrane Peptide 
Drug-resistant bacteria use several families of membrane-embedded transporters to remove antibiotics from the cell. One such family is the small multidrug resistance proteins (SMRs) that, because of their relatively small size (ca. 110 residues with four transmembrane [TM] helices), must form (at least) dimers to efflux drugs. Here, we use a Lys-tagged synthetic peptide with exactly the same sequence as TM4 of the full-length SMR Hsmr from Halobacterium salinarum [TM4 sequence: AcA(Sar)3-VAGVVGLALIVAGVVVLNVAS-KKK (Sar = N-methylglycine)] to compete with and disrupt the native TM4-TM4 interactions believed to constitute the locus of Hsmr dimerization. Using a cellular efflux assay of the fluorescent SMR substrate ethidium bromide, we determined that bacterial cells containing Hsmr are able to remove cellular ethidium via first-order exponential decay with a rate constant (k) of 10.1 × 10−3 ± 0.7 × 10−3 s−1. Upon treatment of the cells with the TM4 peptide, we observed a saturable ∼60% decrease in the efflux rate constant to 3.7 × 10−3 ± 0.2 × 10−3 s−1. In corresponding experiments with control peptides, including scrambled sequences and a sequence with d-chirality, a decrease in ethidium efflux either was not observed or was marginal, likely from nonspecific effects. The designed peptides did not evoke bacterial lysis, indicating that they act via the α-helicity and membrane insertion propensities of the native TM4 helix. Our overall results suggest that this approach could conceivably be used to design hydrophobic peptides for disruption of key TM-TM interactions of membrane proteins and represent a valuable route to the discovery of new therapeutics.
PMCID: PMC3393413  PMID: 22526304
23.  Modulation of Substrate Efflux in Bacterial Small Multidrug Resistance Proteins by Mutations at the Dimer Interface ▿ 
Journal of Bacteriology  2011;193(21):5929-5935.
Bacteria evade the effects of cytotoxic compounds through the efflux activity of membrane-bound transporters such as the small multidrug resistance (SMR) proteins. Consisting typically of ca. 110 residues with four transmembrane (TM) α-helices, crystallographic studies have shown that TM helix 1 (TM1) through TM helix 3 (TM3) of each monomer create a substrate binding “pocket” within the membrane bilayer, while a TM4-TM4 interaction accounts for the primary dimer formation. Previous work from our lab has characterized a highly conserved small-residue heptad motif in the Halobacterium salinarum transporter Hsmr as 90GLXLIXXGV98 that lies along the TM4-TM4 dimer interface of SMR proteins as required for function. Focusing on conserved positions 91, 93, 94, and 98, we substituted the naturally occurring Hsmr residue for Ala, Phe, Ile, Leu, Met, and Val at each position in the Hsmr TM4-TM4 interface. Large-residue replacements were studied for their ability to dimerize on SDS-polyacrylamide gels, to bind the cytotoxic compound ethidium bromide, and to confer resistance by efflux. Although the relative activity of mutants did not correlate with dimer strength for all mutants, all functional mutants lay within 10% of dimerization relative to the wild type (WT), suggesting that the optimal dimer strength at TM4 is required for proper efflux. Furthermore, nonfunctional substitutions at the center of the dimerization interface that do not alter dimer strength suggest a dynamic TM4-TM4 “pivot point” that responds to the efflux requirements of different substrates. This functionally critical region represents a potential target for inhibiting the ability of bacteria to evade the effects of cytotoxic compounds.
PMCID: PMC3194897  PMID: 21890698
24.  The impact on neonatal mortality of shifting childbirth services among levels of hospitals: Taiwan's experience 
There is considerable discussion surrounding whether advanced hospitals provide better childbirth care than local community hospitals. This study examines the effect of shifting childbirth services from advanced hospitals (i.e., medical centers and regional hospitals) to local community hospitals (i.e., clinics and district hospitals). The sample population was tracked over a seven-year period, which includes the four months of the 2003 severe acute respiratory syndrome (SARS) epidemic in Taiwan. During the SARS epidemic, pregnant women avoided using maternity services in advanced hospitals. Concerns have been raised about maintaining the quality of maternity care with increased demands on childbirth services in local community hospitals. In this study, we analyzed the impact of shifting maternity services among hospitals of different levels on neonatal mortality and maternal deaths.
A population-based study was conducted using data from Taiwan's National Health Insurance annual statistics of monthly county neonatal morality rates. Based on a pre-SARS sample from January 1998 to December 2002, we estimated a linear regression model which included "trend," a continuous variable representing the effect of yearly changes, and two binary variables, "month" and "county," controlling for seasonal and county-specific effects. With the estimated coefficients, we obtained predicted neonatal mortality rates for each county-month. We compared the differences between observed mortality rates of the SARS period and predicted rates to examine whether the shifting in maternity services during the SARS epidemic significantly affected neonatal mortality rates.
With an analysis of a total of 1,848 observations between 1998 and 2004, an insignificantly negative mean of standardized predicted errors during the SARS period was found. The result of a sub-sample containing areas with advanced hospitals showed a significant negative mean of standardized predicted errors during the SARS period. These findings indicate that despite increased use of local community hospitals, neonatal mortality during the SARS epidemic did not increase, and even decreased in areas with advanced hospitals.
An increased use of maternity services in local community hospitals occurred during the SARS epidemic in Taiwan. However, we observed no increase in neonatal and maternity mortality associated with these increased demands on local community hospitals.
PMCID: PMC2703635  PMID: 19505330
25.  The US hospital standardised mortality ratio: Retrospective database study of Massachusetts hospitals 
JRSM Open  2015;6(1):2054270414559083.
To present a case-mix adjustment model that can be used to calculate Massachusetts hospital standardised mortality ratios and can be further adapted for other state-wide data-sets.
We used binary logistic regression models to predict the probability of death and to calculate the hospital standardised mortality ratios. Independent variables were patient sociodemographic characteristics (such as age, gender) and healthcare details (such as admission source). Statistical performance was evaluated using c statistics, Brier score and the Hosmer–Lemeshow test.
Massachusetts hospitals providing care to patients over financial years 2005/6 to 2007/8.
1,073,122 patients admitted to Massachusetts hospitals corresponding to 36 hospital standardised mortality ratio diagnosis groups that account for 80% of in-hospital deaths nationally.
Main outcome measures
Adjusted in-hospital mortality rates and hospital standardised mortality ratios.
The significant factors determining in-hospital mortality included age, admission type, primary diagnosis, the Charlson index and do-not-resuscitate status. The Massachusetts hospital standardised mortality ratios for acute (non-specialist) hospitals ranged from 60.3 (95% confidence limits 52.7–68.6) to 130.3 (116.1–145.8). The reference standard hospital standardised mortality ratio is 100 with the values below and above 100 suggesting either random or special cause variation. The model was characterised by excellent discrimination (c statistic 0.87), high accuracy (Brier statistics 0.03) and close agreement between predicted and observed mortality rates.
We have developed a case-mix model to give insight into mortality rates for patients served by hospitals in Massachusetts. Our analysis indicates that this technique would be applicable and relevant to Massachusetts hospital care as well as to other US hospitals.
PMCID: PMC4304889  PMID: 25852951
hospital standardised mortality ratio; logistic regression; Massachusetts

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