Leveraging an established neighbourhood-level, open access wastewater monitoring network to address public health priorities: a population-based study.

BACKGROUND: Before the COVID-19 pandemic, the US opioid epidemic triggered a collaborative municipal and academic effort in Tempe, Arizona, which resulted in the world's first open access dashboard featuring neighbourhood-level trends informed by wastewater-based epidemiology (WBE). This study aimed to showcase how wastewater monitoring, once established and accepted by a community, could readily be adapted to respond to newly emerging public health priorities. METHODS: In this population-based study in Greater Tempe, Arizona, an existing opioid monitoring WBE network was modified to track SARS-CoV-2 transmission through the analysis of 11 contiguous wastewater catchments. Flow-weighted and time-weighted 24 h composite samples of untreated wastewater were collected at each sampling location within the wastewater collection system for 3 days each week (Tuesday, Thursday, and Saturday) from April 1, 2020, to March 31, 2021 (Area 7 and Tempe St Luke's Hospital were added in July, 2020). Reverse transcription quantitative PCR targeting the E gene of SARS-CoV-2 isolated from the wastewater samples was used to determine the number of genome copies in each catchment. Newly detected clinical cases of COVID-19 by zip code within the City of Tempe, Arizona were reported daily by the Arizona Department of Health Services from May 23, 2020. Maricopa County-level new positive cases, COVID-19-related hospitalisations, deaths, and long-term care facility deaths per day are publicly available and were collected from the Maricopa County Epidemic Curve Dashboard. Viral loads of SARS-CoV-2 (genome copies per day) measured in wastewater from each catchment were aggregated at the zip code level and city level and compared with the clinically reported data using root mean square error to investigate early warning capability of WBE. FINDINGS: Between April 1, 2020, and March 31, 2021, 1556 wastewater samples were analysed. Most locations showed two waves in viral levels peaking in June, 2020, and December, 2020-January, 2021. An additional wave of viral load was seen in catchments close to Arizona State University (Areas 6 and 7) at the beginning of the fall (autumn) semester in late August, 2020. Additionally, an early infection hotspot was detected in the Town of Guadalupe, Arizona, starting the week of May 4, 2020, that was successfully mitigated through targeted interventions. A shift in early warning potential of WBE was seen, from a leading (mean of 8·5 days [SD 2·1], June, 2020) to a lagging (-2·0 days [1·4], January, 2021) indicator compared with newly reported clinical cases. INTERPRETATION: Lessons learned from leveraging an existing neighbourhood-level WBE reporting dashboard include: (1) community buy-in is key, (2) public data sharing is effective, and (3) sub-ZIP-code (postal code) data can help to pinpoint populations at risk, track intervention success in real time, and reveal the effect of local clinical testing capacity on WBE's early warning capability. This successful demonstration of transitioning WBE efforts from opioids to COVID-19 encourages an expansion of WBE to tackle newly emerging and re-emerging threats (eg, mpox and polio). FUNDING: National Institutes of Health's RADx-rad initiative, National Science Foundation, Virginia G Piper Charitable Trust, J M Kaplan Fund, and The Flinn Foundation.

Impact of anaemia at discharge following colorectal cancer surgery.

OBJECTIVES: Preoperative anaemia is common in patients with colorectal cancer and increasingly optimised prior to surgery. Comparably little attention is given to the prevalence and consequences of postoperative anaemia. We aimed to investigate the frequency and short- or long-term impact of anaemia at discharge following colorectal cancer resection. METHODS: A dedicated, prospectively populated database of elective laparoscopic colorectal cancer procedures undertaken with curative intent within a fully implemented ERAS protocol was utilised. The primary endpoint was anaemia at time of discharge (haemoglobin (Hb) < 120 g/L for women and < 135 g/L for men). Patient demographics, tumour characteristics, operative details and postoperative outcomes were captured. Median follow-up was 61 months with overall survival calculated with the Kaplan-Meier log rank method and Cox proportional hazard regression based on anaemia at time of hospital discharge. RESULTS: A total of 532 patients with median 61-month follow-up were included. 46.4% were anaemic preoperatively (cohort mean Hb 129.4 g/L ± 18.7). Median surgical blood loss was 100 mL (IQR 0-200 mL). Upon discharge, most patients were anaemic (76.6%, Hb 116.3 g/L ± 14, mean 19 g/L ± 11 below lower limit of normal, p < 0.001). 16.7% experienced postoperative complications which were associated with lower discharge Hb (112 g/L ± 12 vs. 117 g/L ± 14, p = 0.001). Patients discharged anaemic had longer hospital stays (7 [5-11] vs. 6 [5-8], p = 0.037). Anaemia at discharge was independently associated with reduced overall survival (82% vs. 70%, p = 0.018; HR 1.6 (95% CI 1.04-2.5), p = 0.034). CONCLUSION: Anaemia at time of discharge following elective laparoscopic colorectal cancer surgery and ERAS care is common with associated negative impacts upon short-term clinical outcomes and long-term overall survival.

Factors Predicting Operative Difficulty of Laparoscopic Total Mesorectal Excision.

BACKGROUND: Laparoscopic total mesorectal excision is a challenging procedure requiring high-quality surgery for optimal outcomes. Patient, tumor, and pelvic factors are believed to determine difficulty, but previous studies were limited to postoperative data. OBJECTIVE: This study aimed to report factors predicting laparoscopic total mesorectal excision performance by using objective intraoperative assessment. DESIGN: Data from a multicenter laparoscopic total mesorectal excision randomized trial (ISRCTN59485808) were reviewed. SETTING: This study was conducted at 4 centers in the United Kingdom. PATIENTS AND INTERVENTION: Seventy-one patients underwent elective laparoscopic total mesorectal excision for rectal adenocarcinoma with curative intent: 53% were men, mean age was 69 years, body mass index was 27.7, tumor height was 8.5 cm, 24% underwent neoadjuvant therapy, and 25% had previous surgery. MAIN OUTCOME MEASURES: Surgical performance was assessed through the identification of intraoperative adverse events by using observational clinical human reliability analysis. Univariate analysis and multivariate binomial regression were performed to establish factors predicting the number of intraoperative errors, surgeon-reported case difficulty, and short-term clinical and histopathological outcomes. RESULTS: A total of 1331 intraoperative errors were identified from 365 hours of surgery (median, 18 per case; interquartile range, 16-22; and range, 9-49). No patient, tumor, or bony pelvimetry measurement correlated with total or pelvic error count, surgeon-reported case difficulty, cognitive load, operative data, specimen quality, number or severity of 30-day morbidity events and length of stay (all r not exceeding ±0.26, p > 0.05). Mesorectal area was associated with major intraoperative adverse events (OR, 1.09; 95%CI, 1.01-1.16; p = 0.015) and postoperative morbidity (OR, 1.1; 95% CI, 1.01-1.2; p = 0.033). Obese men were subjectively reported as harder cases (24 vs 36 mm, p = 0.042), but no detrimental effects on performance or outcomes were seen. LIMITATIONS: Our sample size is modest, risking type II errors and overfitting of the statistical models. CONCLUSION: Patient, tumor, and bony pelvic anatomical characteristics are not seen to influence laparoscopic total mesorectal excision operative difficulty. Mesorectal area is identified as a risk factor for intraoperative and postoperative morbidity. See Video Abstract at http://links.lww.com/DCR/B35. FACTORES QUE PREDICEN LA DIFICULTAD OPERATIVA DE LA ESCISIÓN MESORRECTAL TOTAL LAPAROSCÓPICA: La escisión mesorrectal total laparoscópica es un procedimiento desafiante. Para obtener resultados óptimos, se requiere cirugía de alta calidad. Se cree que, factores como el paciente, el tumor y la pelvis, determinan la dificultad, pero estudios previos solamente se han limitado a datos postoperatorios.Informar de los factores que predicen el resultado de la escisión mesorrectal total laparoscópica, mediante una evaluación intraoperatoria objetiva.Datos de un ensayo multicéntrico y randomizado de escisión mesorrectal total laparoscópica (ISRCTN59485808).Cuatro centros del Reino Unido.Un total de 71 pacientes fueron sometidos a escisión mesorrectal total laparoscópica electiva, para adenocarcinoma rectal con intención curativa. 53% hombres, edad media, índice de masa corporal y altura del tumor 69, 27.7 y 8.5 cm respectivamente, 24% terapia neoadyuvante y 25% cirugía previa.Rendimiento quirúrgico evaluado mediante la identificación de eventos intraoperatorios adversos, mediante el análisis clínico observacional de confiabilidad humana. Se realizaron análisis univariado y la regresión binomial multivariada para establecer factores que predicen el número de errores intraoperatorios, reportes del cirujano sobre la dificultad del caso y los resultados clínicos e histopatológicos a corto plazo.Se identificaron un total de 1,331 errores intraoperatorios en 365 horas de cirugía (media de 18 por caso, IQR 16-22, rango 9-49). Ningún paciente, tumor o medición de pelvimetría pélvica, se correlacionó con la cuenta de errores pélvicos o totales, reporte del cirujano sobre dificultad del caso, carga cognitiva, datos operativos, calidad de la muestra, número o gravedad de eventos de morbilidad de 30 días y duración de la estadía (todos r <± 0.26, p > 0.05). El área mesorrectal se asoció con eventos adversos intraoperatorios importantes (OR, 1.09; IC 95%, 1.01-1.16; p = 0.015) y morbilidad postoperatoria (OR, 1.1; IC 95%, 1.01-1.2; p = 0.033). Como información subjetiva, hombres obesos fueron casos más difíciles (24 mm frente a 36 mm, p = 0.042) pero no se observaron efectos perjudiciales sobre el rendimiento o los resultados.Nuestro tamaño de muestra es un modesto riesgo de errores de tipo II y el sobreajuste de los modelos estadísticos.No se observa que las características anatómicas del paciente, tumor y pelvis ósea influyan en la dificultad operatoria de la escisión mesorrectal laparoscópica total. El área mesorrectal se identifica como un factor de riesgo para la morbilidad intraoperatoria y postoperatoria. Vea el resumen del video en http://links.lww.com/DCR/B35.

Changes in platelet function with inflammation in patients undergoing vascular surgery.

The role of platelets in ischaemic events is well established. Aspirin represents the default antiplatelet and blocks the metabolism of arachidonic acid (AA) at the cyclo-oxygenase enzyme (COX). AA is commonly used as a test of response to aspirin, but recent data raise uncertainty about the validity of this approach. Specifically, in some patients AA-induced clotting is not suppressed, but the level of COX-dependent AA metabolite, thromboxane B2 (TXB2) is negligible. Furthermore, AA-induced whole blood clotting varies dynamically in individuals, who are aspirin responsive according to TXB2 levels. The aim of this study was to assess the level of AA-, ADP- and thrombin-mediated platelet reactivity in patients on aspirin before, during, and after major vascular surgery, which represents a model of on/off vascular inflammation. Firstly, we hypothesized, that in association with this inflammatory episode AA-, ADP- and thrombin-induced clotting would change in a dynamic manner. Secondly, that AA-induced clotting will be modified despite complete suppression of platelet TXB2 production by aspirin throughout the periprocedural period, possibly via a lipoxygenase-mediated mechanism. Fourty patients underwent major vascular surgery (open abdominal aortic aneurysm operation, infrainguinal bypass for subcritical limb ischaemia or peripheral aneurysm repair with bypass). They were all on 75 mg of aspirin prior to and throughout the perioperative period and received 5000 units of unfractionated heparin intraoperatively. AA-, ADP-, and thrombin-induced clotting, AA metabolites (TXB2 and 12-Hyroxyeicosatetraenoic acid (12-HETE)) and inflammatory markers (CRP, IL-6, TNF-α and CD40) were measured pre-procedure and at 2, 24, 48 hours, 3 to 5 days and 3 months after surgery. AA-, ADP- and thrombin-induced platelet reactivity was assessed using thrombelastography. TXB2, 12-HETE, IL-6, TNF-α, CD40 were determined using the sequential competitive binding Enzyme-Linked ImmunoAssay technique and CRP was determined using an immune-turbidimetric test on human serum. There was a transient rise in inflammatory markers in the early perioperative period (CRP at 24, 48 hours and 3 to 5 days p < 0.001 and IL-6 at 2, 24, 48 hours and 3 to 5 days p < 0.001 as compared to baseline). Patients had negligible levels of TXB2 throughout, confirming a consistent therapeutic response to aspirin. There was a transient rise in thrombin-mediated clotting (MAThrombin at 48 hours p = 0.001 and 3 to 5 days p < 0.001) and a fall in AA- and ADP-induced clotting in the early post op period (both MAAA and MAADP p = 0.001 at 2 hours). At 3 months, the level of AA- and ADP-induced clotting was significantly higher than at baseline (p = 0.008 for MAAA and p = 0.002 for MAADP), hence demonstrating a rebound effect. These data demonstrate a novel dynamic variation in platelet aggregation with acute vascular inflammation, including AA-induced whole blood clotting which is apparently COX-1 independent.

Detection of individual responses to clopidogrel: Validation of a novel, rapid analysis using thrombelastography 6s.

INTRODUCTION: There is potential value in testing individual response to P2Y12 inhibitors to predict ischemic and bleeding risk in patients undergoing percutaneous coronary intervention. The aims of this study were: (1) to validate the ability of a novel point of care (POC) assay, thrombelastography (TEG) 6s, to detect changes in adenosine diphosphate (ADP)-induced whole blood clotting in volunteers and patients given clopidogrel using TEG 5000 as a reference and (2) to compare a novel, rapid parameter, area under the curve at 15 minutes (AUC15), with the traditional maximum clot amplitude (MA) in TEG 6s. METHODS: A total of 25 participants were included in whom ADP-induced clotting was measured at 4 time points: (1) 12 healthy volunteers given 600 mg of clopidogrel; (2) 12 patients with ACS given 600 mg of clopidogrel; (3) 1 healthy volunteer given 600 mg of clopidogrel on 5 separate occasions. All samples were tested using conventional TEG 5000 and the new POC TEG 6S, and a new parameter called AUC15 was compared with MA in TEG 6s. RESULTS: (1) TEG 5000 and TEG 6s both detected changes in ADP-induced platelet activation. Bland-Altman analysis demonstrated a good level of agreement between them. (2) For TEG 6S, correlation between MA and the novel AUC15 was strong for both thrombin and ADP channels (R2  = 0.867, R = .936, P < .001), and the AUC15 result was available on average 13.3 minutes earlier. CONCLUSIONS: Thrombelastography 6s is a rapid, easy to use and accurate test of ADP-induced clotting using TEG 5000 as a reference. A novel parameter, AUC15, is a viable, time-saving option for this test and has potential value in personalized P2Y12 inhibitor therapy.

Does the number of operating specialists influence the conversion rate and outcomes after laparoscopic colorectal cancer surgery?

BACKGROUND: Laparoscopic techniques in colorectal surgery have been widely utilised due to short-term patient benefits but conversion to open surgery is associated with adverse short- and long-term patient outcomes. The aim of this study was to investigate the influence of dual specialist operating on the conversion rate and patient outcomes following laparoscopic colorectal surgery. METHODS: A prospectively populated colorectal cancer surgery database was reviewed. Cases were grouped into single or dual consultant procedures. Cluster analysis and odds ratio (OR) were used to identify risk factors for conversion. Primary outcome measures were conversion to open and five year overall survival (OS) calculated using the Kaplan-Meier log-rank method. RESULTS: 750 patients underwent laparoscopic colorectal cancer resection between 2002 and 2015 (median age 73, 319 (42.5%) female, 282 (37.6%) rectal malignancies, 135 patients (18%) had two consultants). The single surgeon conversion rate was 20.4% compared to 5.5% for dual operating (OR 4.4, 95% CI 1.87-10.2, p < 0.001). There were no demographic or tumour differences between the laparoscopic/converted and number of surgeon groups. Two-step cluster analysis identified cluster I (lower risk) 406 patients, 8% converted and cluster II (higher risk) 261 patients, conversion rate 30%. Median follow-up was 48 months (range 0-168). Five-year OS was significantly inferior for both converted and single surgeon cases (63% vs. 77%, p < 0.001 and 61% vs. 70%, p = 0.033, respectively). CONCLUSION: In selected colorectal cancer patients operated by fully trained laparoscopic surgeons, we observed a reduction in conversion with associated long-term survival benefit from dual operating specialists.

Investigation of liver dysfunction: who should we test for hepatitis E?

AIM: Hepatitis E virus (HEV) is endemic in developed countries, but unrecognized infection is common. Many national guidelines now recommend HEV testing in patients with acute hepatitis irrespective of travel history. The biochemical definition of 'hepatitis' that best predicts HEV infection has not been established. This study aimed to determine parameters of liver biochemistry that should prompt testing for acute HEV. METHODS: This was a retrospective study of serial liver function tests (LFTs) in cases of acute HEV (n=74) and three comparator groups: common bile duct stones (CBD, n=87), drug-induced liver injury (DILI, n=69) and patients testing negative for HEV (n=530). To identify the most discriminating parameters, LFTs from HEV cases, CBD and DILI were compared. Optimal LFT cutoffs for HEV testing were determined from HEV true positives and HEV true negatives using receiver operating characteristic curve analysis. RESULTS: Compared with CBD and DILI, HEV cases had a significantly higher maximum alanine aminotransferase (ALT) (P<0.001) and ALT/alkaline phosphatase (ALKP) ratio (P<0.001). For HEV cases/patients testing negative for HEV, area under receiver operating characteristic curve was 0.805 for ALT (P<0.001) and 0.749 for the ALT/ALKP ratio (P<0.001). Using an ALT of at least 300 IU/l to prompt HEV testing has a sensitivity of 98.6% and a specificity of 30.3% compared with an ALT/ALKP ratio higher than or equal to 2 (sensitivity 100%, specificity 9.4%). CONCLUSION: Patients with ALT higher than or equal to 300 IU/l should be tested for HEV. This is simple, detects nearly all cases and requires fewer samples to be tested than an ALT/ALKP ratio higher than or equal to 2. Where clinically indicated, patients with an ALT less than 300 IU/l should also be tested, particularly if HEV-associated neurological injury is suspected.

Benefits of using heterologous polyclonal antibodies and potential applications to new and undertreated infectious pathogens.

BACKGROUND: Passive immunotherapy using polyclonal antibodies (immunoglobulins) has been used for over a century in the treatment and post-exposure prophylaxis of various infections and toxins. Heterologous polyclonal antibodies are obtained from animals hyperimmunised with a pathogen or toxin. AIMS: The aims of this review are to examine the history of animal polyclonal antibody therapy use, their development into safe and effective products and the potential application to humans for emerging and neglected infectious diseases. METHODS: A literature search of OVID Medline and OVID Embase databases was undertaken to identify articles on the safety, efficacy and ongoing development of polyclonal antibodies. The search contained database-specific MeSH and EMTREE terms in combination with pertinent text-words: polyclonal antibodies and rare/neglected diseases, antivenins, immunoglobulins, serum sickness, anaphylaxis, drug safety, post marketing surveillance, rabies, human influenza, Dengue, West Nile, Nipah, Hendra, Marburg, MERS, Hemorrhagic Fever Virus, and Crimean-Congo. No language limits were applied. The final search was completed on 20.06.2015. Of 1960 articles, title searches excluded many irrelevant articles, yielding 303 articles read in full. Of these, 179 are referenced in this study. RESULTS: Serum therapy was first used in the 1890s against diphtheria. Early preparation techniques yielded products contaminated with reactogenic animal proteins. The introduction of enzymatic digestion, and purification techniques substantially improved their safety profile. The removal of the Fc fragment of antibodies further reduces hypersensitivity reactions. Clinical studies have demonstrated the efficacy of polyclonal antibodies against various infections, toxins and venoms. Products are being developed against infections for which prophylactic and therapeutic options are currently limited, such as avian influenza, Ebola and other zoonotic viruses. CONCLUSIONS: Polyclonal antibodies have been successfully applied to rabies, envenomation and intoxication. Polyclonal production provides an exciting opportunity to revolutionise the prognosis of both longstanding neglected tropical diseases as well as emerging infectious threats to humans.

Continuous positive airway pressure failure in preterm infants: incidence, predictors and consequences.

BACKGROUND: Preterm infants ≤32 weeks' gestation are increasingly being managed on continuous positive airway pressure (CPAP), without prior intubation and surfactant therapy. Some infants treated in this way ultimately fail on CPAP and require intubation and ventilation. OBJECTIVES: To define the incidence, predictors and consequences of CPAP failure in preterm infants managed with CPAP from the outset. METHODS: Preterm infants 25-32 weeks' gestation were included in the study if inborn and managed with CPAP as the initial respiratory support, with division into two gestation ranges and grouping according to whether they were successfully managed on CPAP (CPAP-S) or failed on CPAP and required intubation <72 h (CPAP-F). Predictors of CPAP failure were sought, and outcomes compared between the groups. RESULTS: 297 infants received CPAP, of which 65 (22%) failed, with CPAP failure being more likely at lower gestational age. Most infants failing CPAP had moderate or severe respiratory distress syndrome radiologically. In multivariate analysis, CPAP failure was found to be predicted by the highest FiO2 in the first hours of life. CPAP-F infants had a prolonged need for respiratory support and oxygen therapy, and a higher risk of death or bronchopulmonary dysplasia at 25-28 weeks' gestation (CPAP-F 53% vs. CPAP-S 14%, relative risk 3.8, 95% CI 1.6, 9.3) and a substantially higher risk of pneumothorax at 29-32 weeks. CONCLUSION: CPAP failure in preterm infants usually occurs because of unremitting respiratory distress syndrome, is predicted by an FiO2 ≥0.3 in the first hours of life, and is associated with adverse outcomes.

Variable ventilation improves ventilation and lung compliance in preterm lambs.

PURPOSE: In adult animals, ventilation with variable tidal volume and rate improves lung mechanics, arterial oxygenation and ventilation compared to a monotonously controlled ventilation pattern. We assessed the physiological consequences of variable ventilation in the immature lung. METHODS: Lambs delivered at 129 days (term = 150 days) were euthanised (n = 9) or anaesthetised, tracheostomised and suctioned prior to prophylactic intra-tracheal surfactant instillation (Curosurf(®), 100 mg/kg) and commencement of controlled ventilation (50 breaths/min, tidal volume 7.7 ± 0.8 mL/kg). Volume history was standardised at 20 min with two sustained (3 s) inflations to 30 cmH(2)O followed immediately by measurement of baseline dynamic lung mechanics (FlexiVent, Scireq, Canada). Ventilation was continued according to prior randomisation (variable or conventional ventilation). For variable ventilation (n = 9), breath-to-breath tidal volume and respiratory rate varied but intra-breath minute volume (MV) and average tidal volume were equivalent to the conventional ventilation group with fixed tidal volume and rate (n = 7). Lung mechanics and gas exchange were measured at intervals. Lambs were euthanised at 2 h. Inflammatory cell counts and protein from bronchoalveolar lavage fluid and lung tissue cytokine mRNA were quantified. RESULTS: At study completion, PaCO(2) (p = 0.026) and mean airway pressure (p = 0.002) were lower and pH (p = 0.047), ventilation efficiency index (p = 0.021) and dynamic compliance were higher (p = 0.003) in lambs on variable rather than conventional ventilation. However, oxygenation indices and post-mortem static compliances were not different between groups. CONCLUSION: Variable ventilation improves ventilation efficiency and in vivo lung compliance in the preterm lung, but unlike adult models, had no effect on arterial oxygenation.

Cardiopulmonary haemodynamics in lambs during induced capillary leakage immediately after preterm birth.

1. Early postnatal events might play a critical role in the development of cardiorespiratory diseases of prematurity. Although the exact mechanism is unknown, capillary leakage resulting in increased interstitial fluid volume has been postulated to play a critical role. We investigated the effects of capillary leakage, induced by a volume load, on cardiopulmonary and systemic haemodynamics immediately after preterm delivery. 2. Fetal sheep were instrumented at 129 days gestation, delivered and ventilated. After 15 min, lambs in the volume load group received intravenous saline (50 mL/kg) infused over 10 min; control lambs received no infusion. At 30 min, lambs underwent a pulmonary challenge by increasing positive end-expiratory pressure (PEEP) by 2 cmH(2)O every 10 min to 10 cmH(2)O, with similar decrements back to baseline PEEP. Pulmonary blood flow (PBF) and arterial pressures were recorded in real-time and cardiovascular variables were measured by Doppler echocardiography. 3. Total protein concentration in the bronchoalveolar-lavage fluid was higher in volume load lambs compared with controls, and histological interstitial fluid retention was evident in volume load lambs, both indicative of capillary leak. PBF increased immediately after the volume load, but PBF, pulmonary and systemic arterial pressures, and oxygenation all deteriorated during the PEEP challenge compared with controls, coinciding with an increase in downstream pulmonary resistance. Three of six volume load lambs had pulmonary haemorrhage, which was not observed in control lambs. 4. Capillary leakage had moderate effects, but subsequent high levels of PEEP had significant negative effects on cardiopulmonary and respiratory function in preterm lambs. Capillary leakage might contribute to postnatal cardiopulmonary failure in preterm infants.

Pulmonary vascular and alveolar development in preterm lambs chronically colonized with Ureaplasma parvum.

Ureaplasma species, the most commonly isolated microorganisms in women with chorioamnionitis, are associated with preterm delivery. Chorioamnionitis increases the risk and severity of bronchopulmonary dysplasia and persistent pulmonary hypertension in newborns. It is not known whether the timing of exposure to inflammation in utero is an important contributor to the pathogenesis of bronchopulmonary dysplasia. We hypothesized that chronic inflammation would alter the pulmonary air space and vascular development after 70 days of exposure to infection. Pregnant ewes were given intra-amniotic injection of Ureaplasma parvum serovars 3 or 6 at low (2 x 10(4) cfu) or high doses (2 x 10(7) cfu) or media (controls) at 55 days gestational age. Fetuses were delivered at 125 days (term = 150 days). U. parvum was grown from the lungs of all exposed fetuses, and neutrophils and monocytes were increased in the air spaces. Lung mRNA expression of IL-1beta and IL-8, but not IL-6, was modestly increased in U. parvum-exposed fetuses. U. parvum exposure increased surfactant and improved lung gas volumes. The changes in lung inflammation and maturation were independent of serovar or dose. Exposure to U. parvum did not change multiple indices of air space or vascular development. Parenchymal elastin and collagen content were similar between groups. Expression of several endothelial proteins and pulmonary resistance arteriolar media thickness were also not different between groups. We conclude that chronic exposure to U. parvum does not cause sustained effects on air space or vascular development in premature lambs.

An examination of treatment completers and non-completers at a child and adolescent community mental health clinic.

This study examined sociodemographic and clinical characteristics of treatment completers (N = 114) and non-completers (N = 136) at a child and adolescent community mental health clinic. Results indicated that children who completed treatment significantly differ from those who prematurely drop out of treatment. Non-completers presented with considerably more impairment in functioning and psychiatric symptoms, and their caregiver reported experiencing significantly more parenting stress and depressive symptoms. Results suggest that mental health treatment is not readily provided to the most difficult to reach and most at-risk youth and their families.

Acute giant gastric volvulus causing cardiac tamponade.

INTRODUCTION: Acute gastric volvulus is an uncommon condition which is rarely associated with cardiac impairment. DISCUSSION: We report a patient with an acute giant gastric volvulus causing cardiac tamponade. Prompt decompression was unsuccessful and the patient died prior to definitive treatment.

The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) prisons project pilot study: protocol for a randomised controlled trial comparing dihydrocodeine and buprenorphine for opiate detoxification.

BACKGROUND: In the United Kingdom (UK), there is an extensive market for the class 'A' drug heroin. Many heroin users spend time in prison. People addicted to heroin often require prescribed medication when attempting to cease their drug use. The most commonly used detoxification agents in UK prisons are buprenorphine, dihydrocodeine and methadone. However, national guidelines do not state a detoxification drug of choice. Indeed, there is a paucity of research evaluating the most effective treatment for opiate detoxification in prisons. This study seeks to address the paucity by evaluating routinely used interventions amongst drug using prisoners within UK prisons. METHODS/DESIGN: The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) Prisons Pilot Study will use randomised controlled trial methodology to compare the open use of buprenorphine and dihydrocodeine for opiate detoxification, given in the context of routine care, within HMP Leeds. Prisoners who are eligible and give informed consent will be entered into the trial. The primary outcome measure will be abstinence status at five days post detoxification, as determined by a urine test. Secondary outcomes during the detoxification and then at one, three and six months post detoxification will be recorded.

Physiologic impact of low-dose dopamine on renal function in the early post renal transplant period.

BACKGROUND: Low-dose dopamine (LDD) (< or =5.0 microg/kg/min) is often used in the early postrenal transplant period for its perceived improvements in renal function parameters. However, there is little published evidence to support its use. The aim of this study was to evaluate the effects of LDD on the physiologic parameters of the transplanted kidney. METHODS: With local ethics approval, 20 consecutive adult patients (age range, 27-74 years), who underwent cadaveric renal transplantation with cyclosporine immunosuppression, were randomized into two study groups, each with 10 patients. The study period was over 9 hrs on the first postoperative day. This 9-hr block was divided into three 3-hr periods. Patient group 1 received a dopamine infusion over the second 3-hr period only, and patient group 2 received a dopamine infusion over both the first and third 3-hr periods. During these periods, urine flow rate (UFR), effective renal plasma flow (ERPF), creatinine clearance (CC), and total urinary sodium excretion rate (tUNa) were measured. RESULTS: In both groups, there were significant (P<0.05, Wilcoxon rank sum test) increases in ERPF, UFR, CC, and tUNa during LDD infusion periods compared with periods of no LDD infusion. No changes in heart rate or mean arterial blood pressure were seen with LDD administration. CONCLUSIONS: LDD significantly increases ERPF, UFR, CC, and tUNa in the transplanted allograft kidney treated with cyclosporine immunosuppression in the early posttransplant period.

Adolescent treatment outcome in a community mental health center.

To assess the effectiveness of a community mental health center outpatient adolescent treatment program, outcome measures were completed by the parents of 50 consecutively admitted adolescent patients who were evaluated and treated with one of three therapy modalities. Their results were compared to outcome measures of 29 non-treated adolescent control subjects. Also, self-report outcome measures were completed by 30 treatment subjects. The results demonstrated a significant positive change in the study group following treatment as compared with the control group. Each of the treatment modalities used with the study group was associated with improvement. The staffing referral mechanism used to determine the particular treatment modality for each patient was shown to be consistently and appropriately implemented.