Derivation and Validation of Clinical Prediction Rules for COVID-19 Mortality in Ontario, Canada.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a high-mortality global pandemic. The clinical spectrum of disease caused by this virus is broad, ranging from asymptomatic infection to organ failure and death. Risk stratification of individuals with coronavirus disease 2019 (COVID-19) is desirable for management, and prioritization for trial enrollment. We developed a prediction rule for COVID-19 mortality in a population-based cohort in Ontario, Canada. METHODS: Data from Ontario's provincial iPHIS system were extracted for the period from January 23 to May 15, 2020. Logistic regression-based prediction rules and a rule derived using a Cox proportional hazards model were developed and validated using split-halves validation. Sensitivity analyses were performed, with varying approaches to missing data. RESULTS: Of 21 922 COVID-19 cases, 1734 with complete data were included in the derivation set; 1796 were included in the validation set. Age and comorbidities (notably diabetes, renal disease, and immune compromise) were strong predictors of mortality. Four point-based prediction rules were derived (base case, smoking excluded, long-term care excluded, and Cox model-based). All displayed excellent discrimination (area under the curve for all rules > 0.92) and calibration (P > .50 by Hosmer-Lemeshow test) in the derivation set. All performed well in the validation set and were robust to varying approaches to replacement of missing variables. CONCLUSIONS: We used a public health case management data system to build and validate 4 accurate, well-calibrated, robust clinical prediction rules for COVID-19 mortality in Ontario, Canada. While these rules need external validation, they may be useful tools for management, risk stratification, and clinical trials.

Can enhanced screening of men with a history of prior syphilis infection stem the epidemic in men who have sex with men? A mathematical modelling study.

OBJECTIVES: The aim of this study is to determine the transmission impact of using prior syphilis infection to guide a focused syphilis screening intervention among men who have sex with men (MSM). METHODS: We parameterised a deterministic model of syphilis transmission in MSM to reflect the 2011-2015 syphilis outbreak in Winnipeg, Canada. Enhanced screening of 75% of men with prior syphilis every 3 months (A) was compared with distributing equivalent number tests to all MSM (B) or those with the highest partner number (C). We compared early syphilis incidence, diagnoses and prevalence after 10 years, relative to a base case of 30% of MSM screened annually. RESULTS: Strategy A was expected to avert 52% of incident infections, 44% of diagnosed cases and reduce early syphilis prevalence by 89%. Strategy B had the least impact. Strategy C was most effective, averting 59% of incident cases. When screening frequency was semiannual or annual, strategy A was the most effective. CONCLUSIONS: Enhanced screening of MSM with prior syphilis may efficiently reduce transmission, especially when identification of high-risk men via self-reported partner numbers or high-frequency screening is difficult to achieve.

Cost-effectiveness of enhanced syphilis screening among HIV-positive men who have sex with men: a microsimulation model.

BACKGROUND: Syphilis co-infection risk has increased substantially among HIV-infected men who have sex with men (MSM). Frequent screening for syphilis and treatment of men who test positive might be a practical means of controlling the risk of infection and disease sequelae in this population. PURPOSE: We evaluated the cost-effectiveness of strategies that increased the frequency and population coverage of syphilis screening in HIV-infected MSM receiving HIV care, relative to current standard of care. METHODS: We developed a state-transition microsimulation model of syphilis natural history and medical care in HIV-infected MSM receiving care for HIV. We performed Monte Carlo simulations using input data derived from a large observational cohort in Ontario, Canada, and from published biomedical literature. Simulations compared usual care (57% of the population screened annually) to different combinations of more frequent (3- or 6-monthly) screening and higher coverage (100% screened). We estimated expected disease-specific outcomes, quality-adjusted survival, costs, and cost-effectiveness associated with each strategy from the perspective of a public health care payer. RESULTS: Usual care was more costly and less effective than strategies with more frequent or higher coverage screening. Higher coverage strategies (with screening frequency of 3 or 6 months) were expected to be cost-effective based on usually cited willingness-to-pay thresholds. These findings were robust in the face of probabilistic sensitivity analyses, alternate cost-effectiveness thresholds, and alternate assumptions about duration of risk, program characteristics, and management of underlying HIV. CONCLUSIONS: We project that higher coverage and more frequent syphilis screening of HIV-infected MSM would be a highly cost-effective health intervention, with many potentially viable screening strategies projected to both save costs and improve health when compared to usual care. The baseline requirement for regular blood testing in this group (i.e., for viral load monitoring) makes intensification of syphilis screening appear readily practicable.

Screen more or screen more often? Using mathematical models to inform syphilis control strategies.

BACKGROUND: Syphilis incidence among men who have sex with men (MSM) continues to rise despite attempts to increase screening and treatment uptake. We examined the marginal effect of increased frequency versus increased coverage of screening on syphilis incidence in Toronto, Canada. METHODS: We developed an agent-based, network model of syphilis transmission, representing a core population of 2,000 high-risk MSM. Epidemiological and biological parameters were drawn from regional surveillance data and literature-derived estimates. The pre-intervention period of the model was calibrated using surveillance data to identify 1000 credible simulations per strategy. Evaluated strategies included: annual syphilis screening at baseline coverage, increased screening frequency at baseline coverage, and increased coverage of annual screening. Intervention impact was measured as annual prevalence of detected infectious cases and syphilis incidence per year over 10 years. RESULTS: Of the strategies evaluated, increasing the frequency of syphilis screening to every three months was most effective in reducing reported and incident syphilis infections. Increasing the fraction of individuals tested, without increasing test frequency, resulted a smaller decline in incidence, because reductions in infectious syphilis via treatment were counterbalanced by increased incident syphilis among individuals with prior latent syphilis. For an equivalent number of additional tests performed annually, increased test frequency was consistently more effective than improved coverage. CONCLUSIONS: Strategies that focus on higher frequency of testing in smaller fractions of the population were more effective in reducing syphilis incidence in a simulated MSM population. The findings highlight how treatment-induced loss of immunity can create unexpected results in screening-based control strategies.

The impact of infection on population health: results of the Ontario burden of infectious diseases study.

BACKGROUND: Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting. METHODOLOGY/PRINCIPAL FINDINGS: We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005-2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization. CONCLUSIONS/SIGNIFICANCE: Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.

Estimation of the burden of disease and costs of genital Chlamydia trachomatis infection in Canada.

BACKGROUND: Rates of Chlamydia trachomatis (CT) infection in Canada have been increasing since the mid-1990s. We sought to estimate the burden of CT in this population. METHODS: We developed an age- and sex-structured mathematical model parameterized to reproduce trends in CT prevalence between 1991 and 2009 in the Canadian population aged 10 to 39 years. Costs were identified, measured, and valued using a modified societal perspective and converted to year 2009 Canadian dollars. Cost-effectiveness of the implemented policy of enhanced screening for asymptomatic infections was estimated by comparison with model-projected trends in the absence of increased screening. Main outcome measures were current net cost and burden of illness attributable to CT infection, and incremental cost-effectiveness ratios. RESULTS: Under base case model assumptions, there was a trend of increasing detection of CT cases (due to increases in screening), despite an underlying stabilization of actual CT infections. Average estimated costs associated with CT infection over this period were $51.4 million per year. Costs of screening and treatment of asymptomatic infections as a proportion of total CT costs were estimated to have increased over time, whereas costs of long-term sequelae associated with untreated infections declined over the same period. Compared with no change in screening, enhanced screening was estimated to be highly cost-effective, with an incremental cost-effectiveness ratio of $2910 per quality-adjusted life year. CONCLUSIONS: Despite increases in screening, the economic burden of CT in Canada remains high. Further investigation of trends in chlamydia-associated complications is required to better understand the impact of screening on incidence.

Relative risk of cervical cancer in indigenous women in Australia, Canada, New Zealand, and the United States: a systematic review and meta-analysis.

We performed a systematic review and meta-analysis of cervical cancer risk in indigenous women in Australia, Canada, New Zealand, and the United States, in order to identify whether risks of cervical dysplasia, cervical cancer, and cervical cancer-related mortality are higher in indigenous relative to non-indigenous populations. We identified 35 studies published in 1969-2008. In our findings, indigenous populations did not have an elevated risk of cervical dysplasia or carcinoma in situ relative to non-indigenous populations, but had elevated risks of invasive cervical cancer (pooled RR=1.72) and cervical cancer-related mortality (pooled RR=3.45). There was a log-linear relationship between relative risk and disease stage. In conclusion, the indigenous women have a markedly higher risk of cervical cancer morbidity and mortality than non-indigenous women, but no increased risk of early-stage disease, suggesting that structural, social, or individual barriers to screening, rather than baseline risk factors, are influencing poor health outcomes.

Pertussis resurgence in Toronto, Canada: a population-based study including test-incidence feedback modeling.

BACKGROUND: Pertussis continues to challenge medical professionals; recently described increases in incidence may be due to age-cohort effects, vaccine effectiveness, or changes in testing patterns. Toronto, Canada has recently experienced increases in pertussis incidence, and provides an ideal jurisdiction for evaluating pertussis epidemiology due to centralized testing. We evaluated pertussis trends in Toronto using all available specimen data, which allowed us to control for changing testing patterns and practices. METHODS: Data included all pertussis culture and PCR test records for Greater Toronto from 1993 to 2007. We estimated incidence trends using Poisson regression models; complex relationships between disease incidence and test submission were explored with vector autoregressive models. RESULTS: From 1993 to 2007, 26988 specimens were submitted for testing; 2545 (9.4%) were positive. Pertussis incidence was 2 per 100,000 from 1993 to 2004 and increased to 10 per 100,000 from 2005-2007, with a concomitant 6-fold surge in test specimen submissions after the introduction of a new, more sensitive PCR assay. The relative change in incidence was less marked after adjustment for testing volumes. Bidirectional feedbacks between test positivity and test submissions were identified. CONCLUSIONS: Toronto's recent surge in pertussis reflects a true increase in local disease activity; the apparent size of the outbreak has likely been magnified by increasing use of pertussis testing by clinicians, and by improved test sensitivity since 2005. These findings may be applicable to changes in pertussis epidemiology that have been noted elsewhere in North America.

The laboratory impact of changing syphilis screening from the rapid-plasma reagin to a treponemal enzyme immunoassay: a case-study from the Greater Toronto Area.

BACKGROUND: In 2005, syphilis screening in the Greater Toronto Area of Canada moved from the rapid plasma reagin (RPR) to a treponemal enzyme immunoassay (EIA). We sought to understand the consequences of this change on laboratory results and testing patterns with a population-based retrospective study of laboratory-based diagnoses of syphilis. METHODS: Samples positive under RPR (1998-2005) and EIA (2005-2008) screening were confirmed with an alternate treponemal test, and during the latter period underwent RPR testing. We compared monthly rates and the forecasting relationship between positives and future submissions with time-series methods, and assessed risk factors for EIA(+)/RPR(-) results using Poisson regression. RESULTS: A total of 3,092,938 submissions were included. Following EIA implementation, confirmed positive rates increased by 10.3 per 100,000 population (P<0.001). 0.59% of EIA(+)/RPR(-) individuals converted to RPR(+) within 2 months. EIA(+)/RPR(-) patients were more likely to be male (incidence rate ratio [IRR]: 2.3, 95% confidence interval [CI]: 1.6-2.5), asymptomatic (IRR: 1.8, 95% CI: 1.3-2.8), and aged>50 years (IRR: 2.4, 95% CI: 1.6-3.5) than those with EIA(+)/RPR(+) results. We detected a significant positive feedback loop between positive tests and subsequent submissions. This relationship was only transiently evident for EIA(+)/RPR(-) results up to 1 year following the changeover. CONCLUSIONS: EIA screening facilitates identification of probable latent syphilis and earlier serological detection of infectious syphilis, but may transiently cause increases in testing and indirectly suggests that physicians' interpretation of RPR(-) serology may lead to partner testing. In the absence of a true gold standard, implementation of EIA screening warrants careful communication regarding serological interpretation.

Derivation and validation of a clinical prediction rule for nosocomial pneumonia after coronary artery bypass graft surgery.

BACKGROUND: Nosocomial pneumonia is an important cause of morbidity and mortality among surgical patients in the United States. The emergence of effective but potentially costly or risky preventive interventions makes perioperative risk stratification desirable. We sought to develop a prediction rule for pneumonia after coronary artery bypass grafting (CABG), a common surgical procedure. METHODS: Data on individuals undergoing CABG at 32 hospitals in 6 states were extracted from Tenet Healthcare's Quality and Resource Management System. A logistic regression-based prediction rule was developed in half of the study sample and validated in the remaining patients. RESULTS: Of 17,143 individuals undergoing CABG from January 1999 through February 2004, 361 (2%) developed pneumonia without a known aspiration etiology. Thirteen independent predictors of pneumonia were identified in the derivation subset of the sample: body mass index <18.5 (defined as the weight in kilograms divided by the square of the height in meters), smoking history, admission from a nonresidential setting, cancer history, chronic obstructive pulmonary disease, Canadian Cardiovascular Society score 3, prior internal mammary artery CABG, emergency status, serum creatinine level >1.2 mg/dL, percutaneous transluminal coronary angioplasty, blood transfusion, preoperative vancomycin administration, and receipt of mechanical ventilation for >1 day. The model-based rule was well calibrated (Hosmer-Lemeshow X(2)=5.51; P=.70) and demonstrated good discrimination (area under the receiver-operating characteristic curve [ROC AUC], 0.78) in the derivation group. Discriminatory ability was also reasonable in the validation cohort (ROC AUC, 0.75; P=.18, for difference in ROC AUC between groups). CONCLUSIONS: Using a large cohort of patients treated at community and teaching hospitals, we derived and validated a prediction rule for pneumonia after CABG. This index may prove to be useful in prioritizing receipt of preventive interventions.

Let the sun shine in: effects of ultraviolet radiation on invasive pneumococcal disease risk in Philadelphia, Pennsylvania.

BACKGROUND: Streptococcus pneumoniae is a common cause of community acquired pneumonia and bacteremia. Excess wintertime mortality related to pneumonia has been noted for over a century, but the seasonality of invasive pneumococcal disease (IPD) has been described relatively recently and is poorly understood. Improved understanding of environmental influence on disease seasonality has taken on new urgency due to global climate change. METHODS: We evaluated 602 cases of IPD reported in Philadelphia County, Pennsylvania, from 2002 to 2007. Poisson regression models incorporating seasonal smoothers were used to identify associations between weekly weather patterns and case counts. Associations between acute (day-to-day) environmental fluctuations and IPD occurrence were evaluated using a case-crossover approach. Effect modification across age and sex strata was explored, and meta-regression models were created using stratum-specific estimates for effect. RESULTS: IPD incidence was greatest in the wintertime, and spectral decomposition revealed a peak at 51.0 weeks, consistent with annual periodicity. After adjustment for seasonality, yearly increases in reporting, and temperature, weekly incidence was found to be associated with clear-sky UV index (IRR per unit increase in index: 0.70 [95% CI 0.54-0.91]). The effect of UV index was highest among young strata and decreased with age. At shorter time scales, only an association with increases in ambient sulphur oxides was linked to disease risk (OR for highest tertile of exposure 0.75, 95% CI 0.60 to 0.93). CONCLUSION: We confirmed the wintertime predominance of IPD in a major urban center. The major predictor of IPD in Philadelphia is extended periods of low UV radiation, which may explain observed wintertime seasonality. The mechanism of action of diminished light exposure on disease occurrence may be due to direct effects on pathogen survival or host immune function via altered 1,25-(OH)2-vitamin-D metabolism. These findings may suggest less diminution in future IPD risk with climate change than would be expected if wintertime seasonality was driven by temperature.

Of gastro and the gold standard: evaluation and policy implications of norovirus test performance for outbreak detection.

BACKGROUND: The norovirus group (NVG) of caliciviruses are the etiological agents of most institutional outbreaks of gastroenteritis in North America and Europe. Identification of NVG is complicated by the non-culturable nature of this virus, and the absence of a diagnostic gold standard makes traditional evaluation of test characteristics problematic. METHODS: We evaluated 189 specimens derived from 440 acute gastroenteritis outbreaks investigated in Ontario in 2006-07. Parallel testing for NVG was performed with real-time reverse-transcriptase polymerase chain reaction (RT2-PCR), enzyme immunoassay (EIA) and electron microscopy (EM). Test characteristics (sensitivity and specificity) were estimated using latent class models and composite reference standard methods. The practical implications of test characteristics were evaluated using binomial probability models. RESULTS: Latent class modelling estimated sensitivities of RT2-PCR, EIA, and EM as 100%, 86%, and 17% respectively; specificities were 84%, 92%, and 100%; estimates obtained using a composite reference standard were similar. If all specimens contained norovirus, RT2-PCR or EIA would be associated with > 99.9% likelihood of at least one test being positive after three specimens tested. Testing of more than 5 true negative specimens with RT2-PCR would be associated with a greater than 50% likelihood of a false positive test. CONCLUSION: Our findings support the characterization of EM as lacking sensitivity for NVG outbreaks. The high sensitivity of RT2-PCR and EIA permit identification of NVG outbreaks with testing of limited numbers of clinical specimens. Given risks of false positive test results, it is reasonable to limit the number of specimens tested when RT2-PCR or EIA are available.

Environmental exposures and invasive meningococcal disease: an evaluation of effects on varying time scales.

Invasive meningococcal disease (IMD) is an important cause of meningitis and bacteremia worldwide. Seasonal variation in IMD incidence has long been recognized, but mechanisms responsible for this phenomenon remain poorly understood. The authors sought to evaluate the effect of environmental factors on IMD risk in Philadelphia, Pennsylvania, a major urban center. Associations between monthly weather patterns and IMD incidence were evaluated using multivariable Poisson regression models controlling for seasonal oscillation. Short-term weather effects were identified using a case-crossover approach. Both study designs control for seasonal factors that might otherwise confound the relation between environment and IMD. Incidence displayed significant wintertime seasonality (for oscillation, P < 0.001), and Poisson regression identified elevated monthly risk with increasing relative humidity (per 1% increase, incidence rate ratio = 1.04, 95% confidence interval: 1.004, 1.08). Case-crossover methods identified an inverse relation between ultraviolet B radiation index 1-4 days prior to onset and disease risk (odds ratio = 0.54, 95% confidence interval: 0.34, 0.85). Extended periods of high humidity and acute changes in ambient ultraviolet B radiation predict IMD occurrence in Philadelphia. The latter effect may be due to decreased pathogen survival or virulence and may explain the wintertime seasonality of IMD in temperate regions of North America.

The relative test performance characteristics of two commercial assays for the detection of Mycobacterium tuberculosis complex in paraffin-fixed human biopsy specimens.

The Seeplex TB Detection-2 assay (Rockville, MD) is a nested endpoint PCR for the Mycobacterium tuberculosis complex (MTBC) targets IS6110 and MPB64 that utilizes dual priming oligonucleotide technology. When used to detect the presence of MTBC DNA in formalin-fixed paraffin-embedded tissue specimens, the sensitivity and specificity of this assay is equivalent to a labor-intensive traditional endpoint PCR assay and is more sensitive than a commercial real-time PCR assay.

The Philadelphia High-School STD Screening Program: key insights from dynamic transmission modeling.

BACKGROUND: The Philadelphia high-school STD Screening Program (PHSSP) represents an innovative approach to screening-based control of Chlamydia trachomatis infection. The program has been associated with significant reductions in Chlamydia trachomatis prevalence in young females in Philadelphia. We sought to assess program cost-effectiveness in a manner that allowed us to quantify the impact of including males students in the screened population. METHODS: We created a dynamic transmission model using a susceptible-infectious-resistant-susceptible framework. The model was parameterized using PHSSP program data, supplemented by available data from the medical and public health literature, and was used to project the impact of screening on disease burden, quality adjusted survival, and costs. RESULTS: A well-calibrated model suggests that high-school based screening is highly cost-effective in the Philadelphia context. Five important insights are gained through dynamic transmission modeling of the PHSSP: (i) the importance of screening males can be appreciated using a dynamic transmission model; (ii) the attractiveness of screening males is inversely related to equilibrium prevalence in males; (iii) including males enhances both effectiveness and economic attractiveness of screening; (iv) rebound in prevalence does not greatly diminish the cost-effectiveness of screening; and (v) increasing program expenditures via increased screening coverage decreases net societal costs, due to diminished disease transmission. CONCLUSIONS: The current PHSSP is highly cost-effective relative to other commonly accepted interventions. Effectiveness and cost-effectiveness of this program are enhanced by including males. This, and other important attributes of the program, is best appreciated when a dynamic transmission model is used for program evaluation.

Cost-effectiveness of competing strategies for the treatment of pediatric empyema.

BACKGROUND: The optimal management of pediatric empyema is controversial. The purpose of this decision analysis was to assess the relative merits in terms of costs and clinical outcomes associated with competing treatment strategies. METHODS: A cost-effectiveness analysis was conducted using a Bayesian tree approach. Probability and outcome estimates were derived from the published literature, with preference given to data derived from randomized trials. Costing was based on published estimates from Great Ormond Street Hospital (London, United Kingdom), supplemented by American and Canadian data. Five strategies were evaluated: (1) nonoperative; (2) chest tube insertion; (3) repeated thoracentesis; (4) chest tube insertion with instillation of fibrinolytics; or (5) video-assisted thorascopic surgery. The model was used to project overall costs, survival in life-years, and incremental cost-effectiveness ratios for competing strategies. RESULTS: In the base-case analysis, chest tube with instillation of fibrinolytics was the least expensive therapy, at $7787 per episode. This strategy was projected to cost less but provide equivalent health benefit when compared with all of the competing strategies except repeated thoracentesis, which had an incremental cost-effectiveness ratio of approximately $6,422,699 per life-year gained relative to chest tube with instillation of fibrinolytics. In univariable and multivariable sensitivity analyses, thorascopic surgery was preferred only when the length of stay associated with chest tube with instillation of fibrinolytics exceeded 10.3 days or when the probability of dying as a result of this strategy exceeded 0.2%, assuming a threshold willingness to pay of $75,000 per life-year gained. Chest tube with instillation of fibrinolytics was preferred in >58% of Monte Carlo simulations. CONCLUSIONS: On the basis of the best available data, chest tube with instillation of fibrinolytics is the most cost-effective strategy for treating pediatric empyema. Video-assisted thorascopic surgery would be preferred to chest tube with instillation of fibrinolytics if the differential in length of stay between these 2 strategies were proven to be greater than that suggested by currently available data.

Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes.

Subthalamic nucleus (STN) deep brain stimulation (DBS) is currently the most common therapeutic surgical procedure for patients with Parkinson's disease (PD) who have failed medical management. However, a recent summary of clinical evidence on the effectiveness of STN DBS is lacking. We report the results of such a systematic review and meta-analysis. A comprehensive review of the literature using Medline and Ovid databases from 1993 until 2004 was conducted. Estimates of change in absolute Unified Parkinson's Disease Rating Scale (UPDRS) scores after surgery were generated using random-effects models. Sources of heterogeneity were explored with meta-regression models, and the possibility of publication bias was evaluated. Patient demographics, reduction in medication requirements, change in dyskinesia, daily offs, quality of life, and a ratio of postoperative improvement from stimulation compared to preoperative improvement by medication from each study were tabulated and average scores were calculated. Adverse effects from each study were summarized. Thirty-seven cohorts were included in the review. Twenty-two studies with estimates of standard errors were included in the meta-analysis. The estimated decreases in absolute UPDRS II (activities of daily living) and III (motor) scores after surgery in the stimulation ON/medication off state compared to preoperative medication off state were 13.35 (95% CI: 10.85-15.85; 50%) and 27.55 (95% CI: 24.23-30.87; 52%), respectively. Average reduction in L-dopa equivalents following surgery was 55.9% (95% CI: 50%-61.8%). Average reduction in dyskinesia following surgery was 69.1% (95% CI: 62.0%-76.2%). Average reduction in daily off periods was 68.2% (95% CI: 57.6%-78.9%). Average improvement in quality of life using PDQ-39 was 34.5% +/- 15.3%. Univariable regression showed improvements in UPDRS III scores were significantly greater in studies with higher baseline UPDRS III off scores, increasing disease duration prior to surgery, earlier year of publication, and higher baseline L-dopa responsiveness. Average baseline UPDRS III off scores were significantly lower (i.e., suggesting milder disease) in later than in earlier studies. In multivariable regression, L-dopa responsiveness, higher baseline motor scores, and disease duration were independent predictors of greater change in motor score. No evidence of publication bias in the available literature was found. The most common serious adverse event related to surgery was intracranial hemorrhage in 3.9% of patients. Psychiatric sequelae were common. Synthesis of the available literature indicates that STN DBS improves motor activity and activities of daily living in advanced PD. Differences between available studies likely reflect differences in patient populations and follow-up periods. These data provide an estimate of the magnitude of the treatment effects and emphasize the need for controlled and randomized studies.

Prior pneumococcal vaccination is associated with reduced death, complications, and length of stay among hospitalized adults with community-acquired pneumonia.

BACKGROUND: Vaccination with pneumococcal polysaccharide reduces the incidence of bacteremic pneumococcal disease in adults. We investigated the impact of prior pneumococcal vaccination on in-hospital mortality and the probability of respiratory failure among hospitalized adults with community-acquired pneumonia. METHODS: Consecutive individuals hospitalized with community-acquired pneumonia (diagnosed by International Classification of Diseases, Ninth Revision, Clinical Modification codes 480.0-487.0) at 109 community and teaching hospitals in the United States were identified using the Quality and Resource Management System, a database constructed by Tenet HealthCare to improve the quality of patient care. Vaccination status, comorbidities, and outcomes were abstracted by case managers concurrently with patient care. Associations between vaccination, survival, and respiratory failure were defined using multivariable logistic regression models. RESULTS: Of 62,918 adults hospitalized with community-acquired pneumonia between 1999 and 2003, 7390 (12%) had a record of prior pneumococcal vaccination. Vaccine recipients were less likely to die of any cause during hospitalization than were individuals with no record of vaccination (adjusted odds ratio [OR], 0.50; 95% confidence interval [CI], 0.43-0.59), even after adjustment for the presence of comorbid illnesses, age, smoking, and influenza vaccination and under varying assumptions about missing vaccination data. Vaccination also lowered the risk of respiratory failure (adjusted OR, 0.67; 95% CI, 0.59-0.76) and other complications and reduced median length of stay by 2 days, compared with nonvaccination (P<.001). CONCLUSIONS: Prior vaccination against pneumococcus is associated with improved survival, decreased chance of respiratory failure or other complications, and decreased length of stay among hospitalized patients with community-acquired pneumonia. These observations reinforce current efforts to improve compliance with existing pneumococcal vaccination recommendations for adults.