Sleep duration and cardiometabolic risk factors among individuals with type 2 diabetes.

OBJECTIVE: To examine the association between sleep duration and cardiometabolic risk factors among individuals with recently diagnosed type 2 diabetes (n = 391). METHODS: Sleep duration was derived using a combination of questionnaire and objective heart rate and movement sensing in the UK ADDITION-Plus study (2002-2007). Adjusted means were estimated for individual cardiometabolic risk factors and clustered cardiometabolic risk (CCMR) by five categories of sleep duration. RESULTS: We observed a J-shaped association between sleep duration and CCMR - individuals sleeping 7 to <8 h had a significantly better CCMR profile than those sleeping ≥9 h. Independent of physical activity and sedentary time, individuals sleeping 7 to <8 h had lower triacylglycerol (0.62 mmol/l (0.29, 1.06)) and higher high-density lipoprotein (HDL)-cholesterol levels (0.23 mmol/l (0.16, 0.30)) compared with those sleeping ≥9 h, and a lower waist circumference (7.87 cm (6.06, 9.68)) and body mass index (BMI) (3.47 kg/m(2) (2.69, 4.25)) than those sleeping <6 h. Although sleeping 7 to <8 h was associated with lower levels of systolic and diastolic blood pressure, HbA1c, total cholesterol, and low-density lipoprotein (LDL)-cholesterol, these associations were not statistically significant. CONCLUSIONS: Sleep duration has a J-shaped association with CCMR in individuals with diabetes, independent of potential confounding. Health promotion interventions might highlight the importance of adequate sleep in this high-risk population.The trial is supported by the Wellcome Trust, the Medical Research Council, Diabetes UK and National Health Service R&D support funding. SJG was a member of the National Institute for Health Research (NIHR) School for Primary Care Research. The General Practice and Primary Care Research Unit was supported by NIHR Research funds. SJG received support from the Department of Health NIHR Programme Grant funding scheme [RP-PG-0606-1259]. ATP is supported by the NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.sleep.2014.10.00

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium.

BACKGROUND The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. METHODS For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. FINDINGS Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. INTERPRETATION COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. FUNDING Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Drug dosing during pregnancy—opportunities for physiologically based pharmacokinetic models

Drugs can have harmful effects on the embryo or the fetus at any point during pregnancy. Not all the damaging effects of intrauterine exposure to drugs are obvious at birth, some may only manifest later in life. Thus, drugs should be prescribed in pregnancy only if the expected benefit to the mother is thought to be greater than the risk to the fetus. Dosing of drugs during pregnancy is often empirically determined and based upon evidence from studies of non-pregnant subjects, which may lead to suboptimal dosing, particularly during the third trimester. This review collates examples of drugs with known recommendations for dose adjustment during pregnancy, in addition to providing an example of the potential use of PBPK models in dose adjustment recommendation during pregnancy within the context of drug-drug interactions. For many drugs, such as antidepressants and antiretroviral drugs, dose adjustment has been recommended based on pharmacokinetic studies demonstrating a reduction in drug concentrations. However, there is relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Examples of using pregnancy PBPK models to predict feto-maternal drug exposures and their applications to facilitate and guide dose assessment throughout gestation are discussed

The Effects of Relative Changes in CEO Equity Incentives on the Cost of Corporate Debt

We examine how effort and risk incentives embedded in CEO equity incentives are related to the cost of debt and the role credit worthiness plays in this relationship. Our empirical approach addresses a number of unanswered questions in the literature by examining the sources and effects of co‐movements in CEO incentives, whether the proportionality of these movements is rationally priced, and whether the effects are concentrated among bonds with greater likelihood of default. Our findings confirm that effort and risk incentives are rationally priced by bond market participants. We also show that significant cross‐sectional effects are more pronounced for speculative bonds, implying that previously documented links between equity incentives and the cost of debt may not be generalizable to all debt issues

The announcement impact of seasoned equity offerings on bondholder wealth

Previous studies document a negative and significant return to equity on the announcement of a seasoned equity offering. However, the effects of such an announcement on the firms other securities has received little attention. Using a sample of seasoned equity offerings made between 1980 and 2000 we analyze the effects of an SEO on the firm’s bondholders. We find, on average, that bondholders enjoy a significantly positive return on the announcement of an SEO. This result is more pronounced for bonds with longer maturities and for bonds with lower bond ratings. We interpret these results as evidence in favor of the unanticipated leverage change hypothesis and the wealth transfer hypothesis. The results are inconsistent with the information-signaling hypothesis for SEOs. We also find strong evidence of a negative relationship between dollar losses to shareholders and dollar gains to bondholders. We interpret this as additional evidence that, at least in the case of SEOs, that the wealth transfer hypothesis best describes the data.UnpublishedNon Peer ReviewedAsquith, P. and D. Mullins, Jr., 1986, Signaling with dividends, stock repurchases, and equity issues, Financial Management 15(3), 27-44. Brous, P., 1992, Common stock offerings and earnings expectations: A test of the release of unfavorable information, Journal of Finance 47, 1517-1536. Brown, S. and J. Warner, 1980, Measuring security price performance, Journal of Financial Economics 8, 205-258. Brown, S. and J. Warner, 1985, Using daily stock returns: The case of event studies, Journal of Financial Economics 14, 3-31. Corrado, C., 1989, A non-parametric test for abnormal security-price performance in event studies, Journal of Financial Economics 23 (August), 385-395. Cowan, A., 1992, Nonparametric event study tests. Review of Quantitative Finance and Accounting 2 (Winter): 343-358. Denis, D., 1991, Shelf registration and the market for seasoned equity offerings, Journal of Business 64(2), 189-212. Eberhart, A. and A. Siddique, 2002, The long-term performance of corporate bonds (and stocks) following seasoned equity offerings, The Review of Financial Studies 15(5) (Winter), 1385-1406. Eckbo, B.E. and R. Masulis, 1995, Seasoned equity offerings: a survey. In: Jarrow, R.A. and V.M.W.T. Ziemba (Eds.), Finance, Handbooks in Operations Research and Management Science, Vol. 9, North-Holland, Amsterdam, 1017-1072 (Chapter 31). Eckbo B.E. and R. Masulis and O. Norli , 2000, Seasoned public offerings: resolution of the ‘new issues puzzle’, Journal of Financial Economics 56, 251-291. Handjinicolaou, G. and A. Kalay, 1984, Wealth redistributions or changes in firm value: An analysis of returns to bondholders and stockholders around dividend announcements, Journal of Financial Economics 13, 35-63. Hansen, R. and C. Crutchley, 1990, Corporate earnings and financing: An empricial analysis, Journal of Business 63, 347-371. Healy, P. and K. Palepu, 1990, Earnings and risk changes surrounding primary stock offers, Journal of Accounting Research 28, 25-48. Jain, P., 1992, Equity issues and changes in expectations of earnings by financial analysts, Review of Financial Studies 5, 669-683. Jayaraman, N. and K. Shastri, 1988, The valuation impacts of specially designated dividends, Journal of Financial and Quantitative Analysis 23(3), 301-312. Jensen, M. and W. Meckling, 1976, Theory of the firm: managerial behavior, agency costs, and ownership, Journal of Financial Economics 3(4), 305-360. Kalay, A. and A. Shimrat, 1987, Firm value and seasoned equity issues: Price pressure, wealth redistribution or negative information, Journal of Financial Economics 19(1), 109-126. Loughran, T. and J.R. Ritter, 1997, The operating performance of firms conducting seasoned equity offerings, The Journal of Finance 52(5)(December), 1823-1850. Loughran, T. and J.R. Ritter, 1995, The new issues puzzle, Journal of Finance 50, 23-51. Masulis, R., 1980, The effects of capital structure change on security prices: A study of exchange offers, Journal of Financial Economics 8(2), 139-177. Masulis, R. and A. Korwar, 1986, Seasoned equity offerings: An empirical investigation, Journal of Financial Economics 15, 91-118. Maxwell, W.F. and R.P. Rao, 2003, Do spinoffs expropriate wealth from bondholders?, Journal of Finance 58(5) (October), 2087-2109. Maxwell, W.F. and C. Stephens, 2003, The wealth effects of repurchases on bondholders, Journal of Finance 58(2)(April), 895-919. Mikkelson, W. and M. Parch, 1986, Valuation effects of security offerings and the issuance process, Journal of Financial Economics 15, 31-60. Miller, M. H. and K. Rock, 1985, Dividend policy under asymmetric information, Journal of Finance 40(4), 1031-1051. Myers, S. and N. Majluf, 1984, Corporate financing and investment decisions when firms have information that investors do not have, Journal of Financial Economics 13, 187-221. Spiess, K. and J. Affleck-Graves, 1995, Underperformance in long-run stock returns following seasoned equity offerings, Journal of Financial Economics 38, 243-267. Warga, A. and I. Welch, 1993, Bondholder losses in leveraged buyouts, Review of Financial Studies 6, 959-982

The announcement impact of seasoned equity offerings on bondholder wealth

Previous studies document a negative and significant return to equity on the announcement of a seasoned equity offering. However, the effects of such an announcement on the firms other securities has received little attention. Using a sample of seasoned equity offerings made between 1980 and 2000 we analyze the effects of an SEO on the firm’s bondholders. We find, on average, that bondholders enjoy a significantly positive return on the announcement of an SEO. This result is more pronounced for bonds with longer maturities and for bonds with lower bond ratings. We interpret these results as evidence in favor of the unanticipated leverage change hypothesis and the wealth transfer hypothesis. The results are inconsistent with the information-signaling hypothesis for SEOs. We also find strong evidence of a negative relationship between dollar losses to shareholders and dollar gains to bondholders. We interpret this as additional evidence that, at least in the case of SEOs, that the wealth transfer hypothesis best describes the data.UnpublishedNon Peer ReviewedAsquith, P. and D. Mullins, Jr., 1986, Signaling with dividends, stock repurchases, and equity issues, Financial Management 15(3), 27-44. Brous, P., 1992, Common stock offerings and earnings expectations: A test of the release of unfavorable information, Journal of Finance 47, 1517-1536. Brown, S. and J. Warner, 1980, Measuring security price performance, Journal of Financial Economics 8, 205-258. Brown, S. and J. Warner, 1985, Using daily stock returns: The case of event studies, Journal of Financial Economics 14, 3-31. Corrado, C., 1989, A non-parametric test for abnormal security-price performance in event studies, Journal of Financial Economics 23 (August), 385-395. Cowan, A., 1992, Nonparametric event study tests. Review of Quantitative Finance and Accounting 2 (Winter): 343-358. Denis, D., 1991, Shelf registration and the market for seasoned equity offerings, Journal of Business 64(2), 189-212. Eberhart, A. and A. Siddique, 2002, The long-term performance of corporate bonds (and stocks) following seasoned equity offerings, The Review of Financial Studies 15(5) (Winter), 1385-1406. Eckbo, B.E. and R. Masulis, 1995, Seasoned equity offerings: a survey. In: Jarrow, R.A. and V.M.W.T. Ziemba (Eds.), Finance, Handbooks in Operations Research and Management Science, Vol. 9, North-Holland, Amsterdam, 1017-1072 (Chapter 31). Eckbo B.E. and R. Masulis and O. Norli , 2000, Seasoned public offerings: resolution of the ‘new issues puzzle’, Journal of Financial Economics 56, 251-291. Handjinicolaou, G. and A. Kalay, 1984, Wealth redistributions or changes in firm value: An analysis of returns to bondholders and stockholders around dividend announcements, Journal of Financial Economics 13, 35-63. Hansen, R. and C. Crutchley, 1990, Corporate earnings and financing: An empricial analysis, Journal of Business 63, 347-371. Healy, P. and K. Palepu, 1990, Earnings and risk changes surrounding primary stock offers, Journal of Accounting Research 28, 25-48. Jain, P., 1992, Equity issues and changes in expectations of earnings by financial analysts, Review of Financial Studies 5, 669-683. Jayaraman, N. and K. Shastri, 1988, The valuation impacts of specially designated dividends, Journal of Financial and Quantitative Analysis 23(3), 301-312. Jensen, M. and W. Meckling, 1976, Theory of the firm: managerial behavior, agency costs, and ownership, Journal of Financial Economics 3(4), 305-360. Kalay, A. and A. Shimrat, 1987, Firm value and seasoned equity issues: Price pressure, wealth redistribution or negative information, Journal of Financial Economics 19(1), 109-126. Loughran, T. and J.R. Ritter, 1997, The operating performance of firms conducting seasoned equity offerings, The Journal of Finance 52(5)(December), 1823-1850. Loughran, T. and J.R. Ritter, 1995, The new issues puzzle, Journal of Finance 50, 23-51. Masulis, R., 1980, The effects of capital structure change on security prices: A study of exchange offers, Journal of Financial Economics 8(2), 139-177. Masulis, R. and A. Korwar, 1986, Seasoned equity offerings: An empirical investigation, Journal of Financial Economics 15, 91-118. Maxwell, W.F. and R.P. Rao, 2003, Do spinoffs expropriate wealth from bondholders?, Journal of Finance 58(5) (October), 2087-2109. Maxwell, W.F. and C. Stephens, 2003, The wealth effects of repurchases on bondholders, Journal of Finance 58(2)(April), 895-919. Mikkelson, W. and M. Parch, 1986, Valuation effects of security offerings and the issuance process, Journal of Financial Economics 15, 31-60. Miller, M. H. and K. Rock, 1985, Dividend policy under asymmetric information, Journal of Finance 40(4), 1031-1051. Myers, S. and N. Majluf, 1984, Corporate financing and investment decisions when firms have information that investors do not have, Journal of Financial Economics 13, 187-221. Spiess, K. and J. Affleck-Graves, 1995, Underperformance in long-run stock returns following seasoned equity offerings, Journal of Financial Economics 38, 243-267. Warga, A. and I. Welch, 1993, Bondholder losses in leveraged buyouts, Review of Financial Studies 6, 959-982

Board Composition in New Zealand: An Agency Perspective

This paper looks at board composition determinants in New Zealand. We document that the proportion of outside board members is inversely related to insider equity ownership supporting the notion that these variables are substitute mechanisms in controlling agency problems. We also find that board composition is directly related to debt, ownership concentration, and profitability and inversely related to growth and firm size. There is evidence that firms with influential CEOs have lower outside board representation. Finally, we document that the passage of the legislation reforming company and securities laws in 1993 was associated with increased outside members on the board. Copyright Blackwell Publishers Ltd 2002.

Block Trade Price Asymmetry and Changes in Depth: Evidence from the Australian Stock Exchange

This paper examines the price response to large block transactions on the Australian Stock Exchange during the 1999 sample period. We find asymmetry in the price reaction between buyer- and seller-initiated trades with respect to size and resiliency following the trade. We extend previous research by examining order book changes surrounding block trades and relating price effects to changes in book depth. Purchases are associated with persistent order book imbalance, while the sales imbalance is insignificant. Cross-sectional analysis demonstrates that price resiliency following a trade is related to the speed at which limit orders arrive to replenish book depth. Copyright 2006, The Eastern Finance Association.