Organ donation by children in Australia, 2000-2019: impact of the 2009 National Reform Program. A population-based registry data study.

OBJECTIVES: To assess the impact of the 2009 National Reform Program for organ donation in Australia on the number and characteristics of organ donors under 16 years of age. DESIGN, SETTING, PARTICIPANTS: Retrospective observational time series study; analysis of Australia and New Zealand Organ Donation (ANZOD) registry data for all consented potential deceased organ donors under 16 years of age during 2000-2019, and of numbers of donors aged 16 years or more reported in ANZOD annual reports. MAIN OUTCOME MEASURES: Difference between 2000-2008 (pre-reform) and 2009-2019 (reform period) in annual organ donor rates (donors per million population), by age group (under 16 years, 16 years or more), reported as incidence rate ratio (IRR). SECONDARY OUTCOMES: Differences in child donor characteristics during 2000-2008 and 2009-2019. RESULTS: During 2000-2019, 400 children under 16 years of age were consented potential deceased organ donors, of whom 374 were actual deceased donors (94%): 146 during 2000-2008, 228 during 2009-2019. The median annual rate was 3.3 (interquartile range [IQR], 3.0-4.3) actual donors per million population during 2000-2008 and 4.2 (IQR, 3.6-5.2) donors per million population during 2009-2019 (IRR, 1.15; 95% confidence interval [CI], 0.93-1.42). In contrast, the difference between the two periods was statistically significant for donors aged 16 years or more, rising from 11.7 (IQR, 11.2-11.8) to 19.9 (IQR, 18.3-24.4) actual donors per million population (IRR, 1.75; 95% CI, 1.66-1.85). The median age of actual organ donors under 16 was similar during 2000-2008 (11 years; IQR, 7-14 years) and 2009-2019 (10 years; IQR, 4-14 years), as was the proportion of donors in this age group under 10 kg (2000-2008: four of 146, 3%; 2009-2019: 14 of 228, 6%). CONCLUSIONS: Despite its overall effect on organ donation rates, the National Reform Program was not effective in increasing the numbers of donors under 16 years of age. Relying on broad initiatives for adult donors may not be appropriate for achieving this aim.

Death determination, organ donation and the importance of the Dead Donor Rule following withdrawal of life-sustaining treatment: a survey of community opinions.

BACKGROUND: Background: Organ donation (OD) following circulatory determination of death (DCDD) is an increasing source of transplant organs but little is known about community opinions on treatment withdrawal, determination of death and acceptance of OD in DCDD. AIMS: To determine attitudes on death determination in DCDD, the importance of patient choice in treatment withdrawal and OD agreement, and the importance of the 'Dead Donor Rule'. METHODS: Scenario-based online survey of 1017 members of the Australian general public. Mean levels of agreement across respondent's responses to statements were compared by repeated measures ANOVA. RESULTS: 54% (548) of respondents agreed that a DCDD scenario patient could be declared dead 2 minutes after circulatory standstill, however over 80% nonetheless agreed OD would be appropriate, including 77% (136/176) of those disagreeing with a 2-minute death declaration. 48% (484) supported OD even if it caused the patient's death. 75% (766) would accept relatively benign ante-mortem treatments administered to improve transplant outcomes. Over 70% supported a high quadriplegic patient's request to be allowed to die, with 61% (622) agreeing that he should be allowed to donate his organs under anaesthesia, but 60% (610) also agreed that he should first be declared dead. CONCLUSIONS: We found high levels of support for treatment withdrawal in severe brain injury and when requested by a quadriplegic patient. While there was variable agreement with the timing of death determination and with OD under anaesthesia, support for OD was high in both scenarios. For many people death determination prior to OD may not be of paramount importance.

A scoping review of the perceptions of death in the context of organ donation and transplantation.

BACKGROUND: Socio-cultural perceptions surrounding death have profoundly changed since the 1950s with development of modern intensive care and progress in solid organ transplantation. Despite broad support for organ transplantation, many fundamental concepts and practices including brain death, organ donation after circulatory death, and some antemortem interventions to prepare for transplantation continue to be challenged. Attitudes toward the ethical issues surrounding death and organ donation may influence support for and participation in organ donation but differences between and among diverse populations have not been studied. OBJECTIVES: In order to clarify attitudes toward brain death, organ donation after circulatory death and antemortem interventions in the context of organ donation, we conducted a scoping review of international English-language quantitative surveys in various populations. STUDY APPRAISAL: A search of literature up to October 2020 was performed, using multiple databases. After screening, 45 studies were found to meet pre-specified inclusion criteria. RESULTS: 32 studies examined attitudes to brain death, predominantly in healthcare professionals. In most, around 75% of respondents accepted brain death as equivalent to death of the person. Less common perspectives included equating death with irreversible coma and willingness to undertake organ donation even if it caused death. 14 studies examined attitudes to organ donation following circulatory death. Around half of respondents in most studies accepted that death could be confidently diagnosed after only 5 min of cardiorespiratory arrest. The predominant reason was lack of confidence in doctors or diagnostic procedures. Only 6 studies examined attitudes towards antemortem interventions in prospective organ donors. Most respondents supported minimally invasive procedures and only where specific consent was obtained. CONCLUSIONS: Our review suggests a considerable proportion of people, including healthcare professionals, have doubts about the medical and ethical validity of modern determinations of death. The prognosis of brain injury was a more common concern in the context of organ donation decision-making than certainty of death.

New blood-borne virus infections among organ transplant recipients: An Australian data-linked cohort study examining donor transmissions and other HIV, hepatitis C and hepatitis B notifications, 2000-2015.

BACKGROUND: Blood-borne viral infections can complicate organ transplantation. Systematic monitoring to distinguish donor-transmitted infections from other new infections post transplant is challenging. Administrative health data can be informative. We aimed to quantify post-transplant viral infections, specifically those transmitted by donors and those reactivating or arising new in recipients. METHODS: We linked transplant registries with administrative health data for all solid organ donor-recipient pairs in New South Wales, Australia, 2000-2015. All new recipient notifications of hepatitis B (HBV), C (HCV), or human immunodeficiency virus (HIV) after transplant were identified. Proven/probable donor transmissions within 12 months of transplant were classified using an international algorithm. RESULTS: Of 2120 organ donors, there were 72 with a viral infection (9/72 active, 63/72 past). These 72 donors donated to 173 recipients, of whom 24/173 already had the same infection as their donor, and 149/173 did not, so were at risk of donor transmission. Among those at risk, 3/149 recipients had proven/probable viral transmissions (1 HCV, 2 HBV); none were unrecognized by donation services. There were no deaths from transmissions. There were no donor transmissions from donors without known blood-borne viruses. An additional 68 recipients had new virus notifications, of whom 2/68 died, due to HBV infection. CONCLUSION: This work confirms the safety of organ donation in an Australian cohort, with no unrecognized viral transmissions and most donors with viral infections not transmitting the virus. This may support targeted increases in donation from donors with viral infections. However, other new virus notifications post transplant were substantial and are preventable. Data linkage can enhance current biovigilance systems.

Death, dying and donation: community perceptions of brain death and their relationship to decisions regarding withdrawal of vital organ support and organ donation.

Despite brain death (BD) being established as a definition of death for over 50 years, the concept remains controversial. Little is known about public perception of death determination in decision-making about withdrawal of organ support and organ donation (OD), and the importance of the 'Dead Donor Rule' (DDR). We examined perceptions about death in a BD patient and their relationship to decisions about withdrawal of vital organ support, OD and the DDR, using an online survey of 1017 Australian adults. A BD patient scenario was presented, followed by a series of questions. Statistically significant differences in responses were determined using repeated measures analyses of variance and t tests. Seven hundred and fourteen respondents (70.2%) agreed that a hypothetical BD patient was dead. Those disagreeing most commonly cited the presence of heartbeat and breathing. Seven hundred and seventy (75.7%) favoured removal of 'life support', including 136 (13.3%) who had not agreed the patient was dead. Support for OD was high, but most favoured organ removal only after heartbeat and breathing had ceased. Where OD was in keeping with the patient's known wishes, 464 (45.6%) agreed that organs could be removed even if this caused death. Forty-one (20%) of those who had indicated they considered the patient was not dead agreed to organ removal even if it caused death. Australian public views on BD, withdrawal of 'life support' and OD are complex. Emphasis on prognosis and the impact of significant brain injury may be more appropriate in these situations, rather than focussing on death determination and upholding the DDR.

COMmunication with Families regarding ORgan and Tissue donation after death in intensive care (COMFORT): protocol for an intervention study.

BACKGROUND: Discussing deceased organ donation can be difficult not only for families but for health professionals who initiate and manage the conversations. It is well recognised that the methods of communication and communication skills of health professionals are key influences on decisions made by families regarding organ donation. METHODS: This multicentre study is being performed in nine intensive care units with follow-up conducted by the Organ and Tissue Donation Service in New South Wales (NSW) Australia. The control condition is pre-intervention usual practice for at least six months before each site implements the intervention. The COMFORT intervention consists of six elements: family conversations regarding offers for organ donation to be led by a "designated requester"; family offers for donation are deferred to the designated requester; the offer of donation is separated from the end-of-life discussion that death is inevitable; it takes place within a structured family donation conversation using a "balanced" approach. Designated requesters may be intensivists, critical care nurses or social workers prepared by attending the three-day national "Family Donation Conversation" workshops, and the half-day NSW Simulation Program. The design is pre-post intervention to compare rates of family consent for organ donation six months before and under the intervention. Each ICU crosses from using the control to intervention condition after the site initiation visit. The primary endpoint is the consent rate for deceased organ donation calculated from 140 eligible next of kin families. Secondary endpoints are health professionals' adherence rates to core elements of the intervention; identification of predictors of family donation decision; and the proportion of families who regret their final donation decision at 90 days. DISCUSSION: The pragmatic design of this study may identify 'what works' in usual clinical settings when requesting organ donation in critical care areas, both in terms of changes in practice healthcare professionals are willing and able to adopt, and the effect this may have on desired outcomes. The findings of this study will be indicative of the potential benefits of the intervention and be relevant and transferrable to clinical settings in other states and countries. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613000815763 (24 July 2013). ClinicalTrials.gov: NCT01922310 (14 August 2013) (retrospectively registered).

Are potential organ donors missed on general wards? A 6-month audit of hospital deaths.

OBJECTIVE: To determine whether potential organ donors are being missed on general wards by the DonateLife Audit, which concentrates on patients dying in emergency departments and intensive care units. DESIGN, SETTING AND PATIENTS: Six-month (1 July to 31 December 2012) retrospective audit of patient deaths in a 700-bed metropolitan Australian tertiary referral and teaching hospital. MAIN OUTCOME MEASURE: Potential organ donor suitability as assessed by a panel of organ donation specialists. RESULTS: In total, 427 patients died, including nine neonates (2.1%) who were not further assessed and 175 patients (41.0%) who were excluded on the basis of age contraindicating organ donation (≥ 80 years). Seventy-eight (18.3%) were excluded on the basis of active cancer or palliative care for cancer and 143 (33.5%) were deemed otherwise not medically suitable. Twelve (2.8%) had been referred to the DonateLife team for consideration for organ donation. Ten (2.3%) were submitted for panel review, and of these only three were considered to have "potential to develop brain death within 24 hours". These patients would have required mechanical ventilation if potential organ donation were to be realised. One additional potential candidate for donation after circulatory death was identified in the intensive care unit. CONCLUSION: We identified very few potential organ donors among patients who died outside the emergency department and intensive care unit. For these patients to have progressed to organ donation, medical interventions not in keeping with standard Australian practice would have been required. The DonateLife Audit appears to be a robust tool for identifying realistic potential organ donors.

Influence of reef isostasy, dynamic topography, and glacial isostatic adjustment on sea-level records in Northeastern Australia.

Understanding sea level during the peak of the Last Interglacial (125,000 yrs ago) is important for assessing future ice-sheet dynamics in response to climate change. The coasts and continental shelves of northeastern Australia (Queensland) preserve an extensive Last Interglacial record in the facies of coastal strandplains onland and fossil reefs offshore. However, there is a discrepancy, amounting to tens of meters, in the elevation of sea-level indicators between offshore and onshore sites. Here, we assess the influence of geophysical processes that may have changed the elevation of these sea-level indicators. We modeled sea-level change due to dynamic topography, glacial isostatic adjustment, and isostatic adjustment due to coral reef loading. We find that these processes caused relative sea-level changes on the order of, respectively, 10 m, 5 m, and 0.3 m. Of these geophysical processes, the dynamic topography predictions most closely match the tilting observed between onshore and offshore sea-level markers.

Potential organ donors with primary brain tumours: missed opportunities for donation and transplantation identified in Australian cohort study 2010-2015.

BACKGROUND: Potential organ donors with primary brain tumours (PBT) frequently donate, however some may be declined due to uncertainty about tumour classification or transmission risk to transplant recipients. We sought to describe transmission risk and donation outcome of potential donors with PBT, including identifying missed opportunities for transplantation, and any PBT transmission events. METHODS: We undertook a population-based cohort study in NSW of all potential donors 2010-2015. PBT potential donors were characterized according to tumour grade and transmission risk, and whether they donated organs. Data linkage was used to determine agreement of risk assessment of potential donors to that in the Biovigilance Register, and to identify any PBT transmissions. RESULTS: Of 2957 potential donors, 76 (3%) had PBTs. There was agreement of risk assessment in 44 (58%) cases. PBT potential donors had fewer comorbidities (1.6 vs. 2.1, P = 0.006) than non-PBT potential donors. Forty-eight (63%) potential donors were declined for non-PBT reasons, 18 (24%) were declined because of perceived PBT transmission risk and 10 (13%) donated. All PBT donors had WHO-I or -II tumours, and none had a ventriculo-pertioneal shunt. No transmission events occurred. CONCLUSION: Donors with WHO-I/II PBT appear to have minimal risk of tumour transmission in solid organ transplantation; it is reassuring that no PBT transmission occurred. There is evidence of risk aversion to referrals with WHO-III/IV tumours. There exists opportunity to improve potential donor risk assessment at the time of referral using integrated data sets, and to increase organ donation and transplantation rates through greater utilization of PBT referrals.

Characteristics and Donation Outcomes of Potential Organ Donors Perceived to Be at Increased Risk for Blood-borne Virus Transmission: An Australian Cohort Study 2010-2018.

BACKGROUND: Safely increasing organ donation to meet need is a priority. Potential donors may be declined because of perceived blood-borne virus (BBV) transmission risk. With hepatitis C (HCV) curative therapy, more potential donors may now be suitable. We sought to describe potential deceased donors with increased BBV transmission risk. METHODS: We conducted a cohort study of all potential organ donors referred in NSW, Australia, 2010-2018. We compared baseline risk potential donors to potential donors with increased BBV transmission risk, due to history of HIV, HCV or hepatitis B, and/or behavioral risk factors. RESULTS: There were 624 of 5749 potential donors (10.9%) perceived to have increased BBV transmission risk. This included 298 of 5749 (5.2%) with HCV (including HBV coinfections) and 239 of 5749 (4.2%) with increased risk behaviors (no known BBV). Potential donors with HCV and those with increased risk behaviors were younger and had fewer comorbidities than baseline risk potential donors (P < 0.001). Many potential donors (82 with HCV, 38 with risk behaviors) were declined for donation purely because of perceived BBV transmission risk. Most were excluded before BBV testing. When potential donors with HCV did donate, they donated fewer organs than baseline risk donors (median 1 versus 3, P < 0.01), especially kidneys (odds ratio 0.08, P < 0.001) and lungs (odds ratio 0.11, P = 0.006). CONCLUSIONS: Many potential donors were not accepted because of perceived increased BBV transmission risk, without viral testing, and despite otherwise favorable characteristics. Transplantation could be increased from potential donors with HCV and/or increased risk behaviors.

Successful Implementation of an Increased Viral Risk Donor Waiting List for Preconsented Kidney Transplant Candidates in Victoria, Australia.

Increased viral risk donors (IVRDs) with increased risk behaviors for blood-borne virus infection and negative nucleic acid testing have a low absolute risk of "window period" infection. Utilization and allocation of IVRD organs differ between jurisdictions. METHODS: We examined the characteristics and utilization of deceased donor IVRD kidneys and recipient outcomes within a 2-y period (July 31, 2018-July 31, 2020) postimplementation of a new opt-in allocation pathway for preconsented recipients in Victoria, Australia. RESULTS: Fifty-six kidneys from 31 IVRDs were utilized, comprising 13% of donors. Preconsent rate to accept IVRD kidneys increased to 41% of the waitlist in the 2 y postimplementation, and IVRDs having no kidneys utilized reduced to 0%. Compared with non-IVRD kidneys, kidney offer declines >10 per donor were less likely from IVRDs (3% vs 19%; P < 0.05). IVRDs were younger (median age 36 [IQR 30-44] vs 51 [35-60] y; P < 0.0001), with lower kidney donor profile index (25% [13-40%] vs 57% [29-75%]; P < 0.0001), and less hypertension (0% vs 22%; P < 0.01). Estimated glomerular filtration rate 3 mo post-transplant was superior (P < 0.01). Injecting drug use (61%) was the most common increased risk behavior. 29% of IVRDs were hepatitis C antibody positive but nucleic acid testing negative. No active infection was detected in any recipient post-transplant. CONCLUSIONS: The described opt-in system permits efficient allocation and utilization of kidneys from IVRDs, with superior quality and graft function. Education is crucial to facilitate informed consent and equity of access to this donor pool.

Effect of language and country of birth on the consent process and medical suitability of potential organ donors; a linked-data cohort study 2010-2015.

PURPOSE: Australia has unmet need for transplantation. We sought to assess the impact of cultural and linguistic diversity (CALD) on family consent and medical suitability for organ donation. METHOD: Cohort study of New South Wales donor referrals, 2010-2015. Logistic regression estimated effects of primary language other than English and birthplace outside Australia (odds ratios OR, with 95% confidence intervals, 95%CI). Outcomes were whether families were asked for consent to donation, provided consent for donation, and whether the referral was medically suitable for donation. RESULTS: Of 2977 organ donor referrals, a similar proportion of families had consent for donation was sought between non-English speakers and English speakers (p = .07), and between overseas-born compared to Australian-born referrals (p = .3). However, consent was less likely to be given for both non-English speakers than English speakers (OR 0.44, 95%CI:0.29-0.67), and those overseas-born than Australian-born (OR 0.54, 95%CI:0.41-0.72). For referrals both overseas-born and non-English speaking, families were both less likely to be asked for consent (OR 0.67; 95%CI:0.49-0.91) or give consent (OR 0.24; 95%CI0.16-0.37). There was no difference in medical suitability between English speakers and non-English speakers (p = .6), or between Australian-born and overseas-born referrals (p = .6). CONCLUSION: Intervention to improve consent rates from CALD families may increase donation.

Epidemiology and Comorbidity Burden of Organ Donor Referrals in Australia: Cohort Study 2010-2015.

Increasing organ donation rates in Australia have been exceeded by a rise in potential donor referrals not proceeding to donate. Referral evaluation is resource-intensive. We sought to characterize organ donor referrals in New South Wales, Australia, and identify predictors of referrals not proceeding to donation. METHODS: We performed a cohort study of NSW Organ and Tissue Donation Service logs 2010-2015, describing the prevalence and impact of comorbidities on referral outcome. Logistic regression was used to identify comorbidities influencing outcome and predict probability of donation. RESULTS: Of 2977 referrals, 669 (22%) donated and 2308 (78%) did not. Despite increasing donation rates, the proportion proceeding to donate declined 2010-2015. Among referrals, the prevalence of all comorbidities except cerebrovascular disease increased and was higher among nondonors. History of cardiac disease, ≥65 years of age, chronic kidney or liver disease, malignancy, and absence of cerebrovascular disease were all significantly (P < 0.01) associated with non donation. Hypertension and diabetes did not significantly impact outcome. Predicted probability of donation varied from <1% to 54% depending on comorbidity burden of the referral. CONCLUSIONS: Comorbidity burden among donor referrals is increasing. The presence of particular comorbidities may significantly impact referral outcome. A better understanding of referral characteristics associated with non donation may improve the efficiency of the referral process in the context of encouraging routine referrals.

Communication with Families Regarding Organ and Tissue Donation after Death in Intensive Care (COMFORT): a multicentre before-and-after study.

OBJECTIVE: To implement a best-practice intervention offering deceased organ donation, testing whether it increased family consent rates. DESIGN: A multicentre before-and-after study of a prospective cohort compared with pre-intervention controls. SETTING: Nine Australian intensive care units. PARTICIPANTS: Families and health care professionals caring for donor-eligible patients without registered donation preferences or aged ≤ 16 years. INTERVENTION: A multicomponent intervention including offers of deceased organ donation from specially trained designated requesters using a structured conversation separate to end-of-life discussions. MAIN OUTCOME MEASURE: Proportion of families consenting to organ donation. RESULTS: Consent was obtained in 87/164 cases (53%) during the intervention period compared with 14/25 cases (56%) pre-intervention (P = 0.83). The odds ratio (OR) of obtaining consent during the intervention period relative to preintervention was 1.13 (95% CI, 0.48-2.63; P = 0.78). During the intervention period, designated requesters obtained consent in 55/98 cases (56%), compared with 32/66 cases (48%) in which the medical team managing patient care raised donation (P = 0.34). Factors independently associated with increased consent were: family-raised organ donation (OR, 4.34; 95% CI, 1.79-10.52; P = 0.001), presence of an independent designated requester (OR, 3.84; 95% CI, 1.35- 10.98; P = 0.012), and multiple donation conversations per case (OR, 3.35; 95% CI, 1.93-5.81; P < 0.001). Consent decreased when patients were of non-Christian religion (OR, 0.18; 95% CI, 0.04-0.91; P = 0.038) and end-of-life and donation meetings were separate (OR, 0.38; 95% CI, 0.16-0.89; P = 0.026). CONCLUSION: Implementation of a multicomponent intervention did not increase consent rates for organ donation, although some components of the intervention exerted significant effect. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12613000815763. ClinicalTrials.gov: NCT01922310.

Hepatitis Transmission Risk in Kidney Transplantation (the HINT study): A Cross-Sectional Survey of Transplant Clinicians in Australia and New Zealand.

BACKGROUND: Interpreting hepatitis serology and virus transmission risk in transplantation can be challenging. Decisions must balance opportunity to transplant against potential infection transmission. We aimed to survey understanding among the Australian and New Zealand medical transplant workforce of hepatitis risk in kidney donors and recipients. METHODS: An anonymous, self-completed, cross-sectional survey was distributed via electronic mailing lists to Australian and New Zealand clinicians involved in kidney transplantation (2014-2015). We compared interpretation of clinical scenarios with paired donor and recipient hepatitis B virus and hepatitis C virus serology to recommendations in clinical practice guidelines. We used logistic regression modeling to investigate characteristics associated with decisions on transplant suitability in scenarios with poor (<50%) guideline concordance (odds ratios [OR]). RESULTS: One hundred ten respondents had representative workforce demographics: most were male (63%) nephrologists (74%) aged 40 to 49 years. Although donor and recipient hepatitis status was largely well understood, transplant suitability responses varied among respondents. For a hepatitis B virus surface antigen-positive donor and vaccinated recipient, 44% suggested this was unsuitable for transplant (guideline concordant) but 35% suggested this was suitable with prophylaxis (guideline divergent). In 4 scenarios with transplant suitability guideline concordance less than 50%, acute transplant care involvement predicted guideline concordant responses (OR, 1.69; P = 0.04). Guideline concordant responses were chosen less by hepatologists, intensive care doctors (OR, 0.23, 0.35, respectively; P = 0.01), and New Zealanders (guideline concordant responses OR, 0.17; P < 0.01; alternative responses OR, 4.31; P < 0.01). CONCLUSIONS: Despite broadly consistent interpretations of hepatitis serology, transplant suitability decisions varied and often diverged from guidelines. Improved decision support may reduce clinician variability.

Parenteral versus enteral nutrition: effect on serum cytokines and the hepatic expression of mRNA of suppressor of cytokine signaling proteins, insulin-like growth factor-1 and the growth hormone receptor in rodent sepsis.

INTRODUCTION: Early nutrition is recommended for patients with sepsis, but data are conflicting regarding the optimum route of delivery. Enteral nutrition (EN), compared with parenteral nutrition (PN), results in poorer achievement of nutritional goals but may be associated with fewer infections. Mechanisms underlying differential effects of the feeding route on patient outcomes are not understood, but probably involve the immune system and the anabolic response to nutrients. We studied the effect of nutrition and the route of delivery of nutrition on cytokine profiles, the growth hormone-insulin-like growth factor-1 (IGF-I) axis and a potential mechanism for immune and anabolic system interaction, the suppressors of cytokine signaling (SOCS), in rodents with and without sepsis. METHODS: Male Sprague-Dawley rats were randomized to laparotomy (Sham) or to cecal ligation and puncture (CLP), with postoperative saline infusion (Starve), with EN or with PN for 72 hours. Serum levels of IL-6 and IL-10 were measured by immunoassay, and hepatic expressions of cytokine-inducible SH2-containing protein, SOCS-2, SOCS-3, IGF-I and the growth hormone receptor (GHR) were measured by real-time quantitative PCR. RESULTS: IL-6 was detectable in all groups, but was only present in all animals receiving CLP-PN. IL-10 was detectable in all but one CLP-PN rat, one CLP-EN rat, approximately 50% of the CLP-Starve rats and no sham-operated rats. Cytokine-inducible SH2-containing protein mRNA was increased in the CLP-EN group compared with the Sham-EN group and the other CLP groups (P < 0.05). SOCS-2 mRNA was decreased in CLP-PN rats compared with Sham-PN rats (P = 0.07). SOCS-3 mRNA was increased with CLP compared with sham operation (P < 0.03). IGF-I mRNA (P < 0.05) and GHR mRNA (P < 0.03) were greater in the fed CLP animals and in the Sham-PN group compared with the starved rats. CONCLUSION: In established sepsis, nutrition and the route of administration of nutrition influences the circulating cytokine patterns and expression of mRNA of SOCS proteins, GHR and IGF-I. The choice of the administration route of nutrition may influence cellular mechanisms that govern the response to hormones and mediators, which further influence the response to nutrients. These findings may be important in the design and analysis of clinical trials of nutritional interventions in sepsis in man.

Measles outbreak in the Republic of the Marshall Islands, 2003.

BACKGROUND: Measles is a highly contagious viral infection. Measles transmission can be prevented through high population immunity (>or=95%) achieved by measles vaccination. In the Republic of the Marshall Islands (RMI), no measles cases were reported during 1989-2002; however, a large measles outbreak occurred in 2003. Reported 1-dose measles vaccine coverage among children aged 12-23 months varied widely (52-94%) between 1990 and 2000. METHODS: RMI is a Pacific island nation (1999 population: 50,840). A measles case was defined as fever, rash, and cough, or coryza, or conjunctivitis, in an RMI resident between July 13 and November 7, 2003. A vaccination campaign was used for outbreak control. RESULTS: Of the 826 reported measles cases, 766 (92%) occurred in the capital (Majuro). There were 186 (23%) cases in infants aged <1 year and 309 (37%) of cases in persons aged >or=15 years. The attack rate was highest among infants (Majuro atoll: 213 cases/1,000 infants). Among cases aged 1-14 years, 281 (59%) reported no measles vaccination before July 2003. There were 100 hospitalizations and 3 deaths. The measles H1 genotype was identified. The vaccination campaign resulted in 93% coverage among persons aged 6 months to 40 years. Interpretation Populations without endemic measles transmission can accumulate substantial susceptibility and be at risk for large outbreaks when measles virus is imported. 'Islands' of measles susceptibility may develop in infants, adults, and any groups with low vaccine coverage. To prevent outbreaks, high population immunity must be sustained by maintaining and documenting high vaccine coverage.