Geographical Variation in Underlying Social Deprivation, Cardiovascular and Other Comorbidities in Patients with Potentially Curable Cancers in England: Results from a National Registry Dataset Analysis.

AIMS: To describe the prevalence of cardiovascular disease (CVD), multiple comorbidities and social deprivation in patients with a potentially curable cancer in 20 English Cancer Alliances. MATERIALS AND METHODS: This National Registry Dataset Analysis used national cancer registry data and CVD databases to describe rates of CVD, comorbidities and social deprivation in patients diagnosed with a potentially curable malignancy (stage I-III breast cancer, stage I-III colon cancer, stage I-III rectal cancer, stage I-III prostate cancer, stage I-IIIA non-small cell lung cancer, stage I-IV diffuse large B-cell lymphoma, stage I-IV Hodgkin lymphoma) between 2013 and 2018. Outcome measures included observation of CVD prevalence, other comorbidities (evaluated by the Charlson Comorbidity Index) and deprivation (using the Index of Multiple Deprivation) according to tumour site and allocation to Cancer Alliance. Patients were allocated to CVD prevalence tertiles (minimum: <33.3rd percentile; middle: 33.3rd to 66.6th percentile; maximum: >66.6th percentile). RESULTS: In total, 634 240 patients with a potentially curable malignancy were eligible. The total CVD prevalence for all cancer sites varied between 13.4% (CVD n = 2058; 95% confidence interval 12.8, 13.9) and 19.6% (CVD n = 7818; 95% confidence interval 19.2, 20.0) between Cancer Alliances. CVD prevalence showed regional variation both for male (16-26%) and female patients (8-16%) towards higher CVD prevalence in northern Cancer Alliances. Similar variation was observed for social deprivation, with the proportion of cancer patients being identified as most deprived varying between 3.3% and 32.2%, depending on Cancer Alliance. The variation between Cancer Alliance for total comorbidities was much smaller. CONCLUSION: Social deprivation, CVD and other comorbidities in patients with a potentially curable malignancy in England show significant regional variations, which may partly contribute to differences observed in treatments and outcomes.

A service evaluation of simultaneous near-patient testing for influenza, respiratory syncytial virus, Clostridium difficile and norovirus in a UK district general hospital.

BACKGROUND: The Cepheid® GeneXpert® (GXP) can simultaneously test for norovirus (NV), Clostridium difficile (CD), influenza A/B (IFA/B) and respiratory syncytial virus (RSV). AIM: To compare centralized multiplex polymerase chain reaction (PCR) testing with localized GXP testing at a district general hospital. METHODS: From December 2017 to December 2018, samples received at Whipps Cross University Hospital (WCUH) were first tested at the local laboratory before transport centrally to the Royal London Hospital (RLH). At the RLH, a non-proprietary multiplex reverse transcriptase (RT) PCR assay was performed, which also tested for gastrointestinal or respiratory pathogens not tested for by the GXP. FINDINGS: A total of 1111 stool and respiratory samples were processed at both sites; 591 were respiratory and 520 were stool samples. Compared to centralized testing, the GXP gave sensitivity, specificity, and NPV all in excess of 97%, with the exception of RSV. The RSV assay had a sensitivity of 66.7% (95% confidence interval (CI) 24.1, 94.0) but an NPV of 99.7% (95% CI 98.6, 99.9). At the RLH, 65 (5.9%) additional respiratory or gastrointestinal viruses were detected, predominantly rhinovirus 35 (3.2%) and adenovirus 11 (1.0%). Compared to centralized testing, the median time saved for local respiratory and gastrointestinal sample testing was 19 h and 46 min and 17 h and 6 min, respectively. CONCLUSIONS: Local GXP testing compared to centralized multiplex PCR testing for IF, NV and CD, demonstrated sensitivities, specificities and NPV between 95% and 100%. Turnaround times were faster, enabling quicker infection prevention and control decision making. In our local setting (WCUH), the GXP demonstrated the potential to reduce NV and IFA/B outbreaks.

Resource use and cost of annual health checks in primary care for people with intellectual disabilities.

BACKGROUND: The annual health check (AHC) programme, as part of a Directed Enhanced Service, offers an incentive to general practitioners in England to conduct health checks for people with intellectual disabilities (IDs). The aim of this analysis was to estimate the impact on health care costs of AHCs in primary care to the National Health Service in England by comparing adults with ID who did or did not have AHCs using data obtained from The Health Improvement Network. METHODS: Two hundred eight records of people with ID from The Health Improvement Network database were analysed. Baseline health care resource use was captured at the time the first AHC was recorded (i.e. index date), or the earliest date after 1 April 2008 for those without an AHC. We examined the volume of resource use and associated costs that occurred at the time AHCs were performed, as well as before and after the index date. We then estimated the impact of AHCs on health care costs. RESULTS: The average cost of AHC was estimated at £142.57 (95%CI £135.41 to £149.74). Primary, community and secondary health care costs increased significantly after the index date in the no AHC group owing to higher increase in resource utilisation. Regression analysis showed that the expected health care cost for those who have an AHC is 56% higher than for those who did not have an AHC. Age and gender were also associated with increase in expected health care cost. CONCLUSION: The level of resource utilisation increased in both (AHC and no AHC) groups after the index date. Although the level of resource use before index date was lower in the no AHC group, it increased after the index date up to almost reaching the level of resource utilisation in the AHC group. Further research is needed to explore if the AHCs are effective in reducing health inequalities.

Neuromuscular blocking agents for electroconvulsive therapy: a systematic review.

Electroconvulsive therapy (ECT) is the transcutaneous application of small electrical stimuli to the brain to induce generalised seizures for the treatment of selected psychiatric disorders. The clinical indications for ECT as an effective therapeutic modality have been considerably expanded since its introduction. Anaesthesia and neuromuscular blocking agents (NMBAs) are required to ensure patients' safety during ECT. The optimal dose of muscle relaxant for ECT reduces muscle contractions without inducing complete paralysis. Slight residual motor convulsive activity is helpful in ascertaining that a seizure has occurred, while total paralysis prolongs the procedure unnecessarily. Suxamethonium is commonly used, but nondepolarising NMBAs are indicated in patients with certain comorbidities. In this review, we summarise current concepts of NMBA management for ECT.

Outcome following admission to UK intensive care units after cardiac arrest: a secondary analysis of the ICNARC Case Mix Programme Database.

Using a retrospective analysis of the Intensive Care National Audit and Research Centre Case Mix Programme Database (ICNARC CMPD), we have summarised the characteristics and outcomes for mechanically ventilated patients admitted to UK intensive care units (ICUs) after cardiac arrest. Descriptive statistics on case mix, physiology, treatment, service delivery, outcome and activity were described separately for community cardiac arrest, in-hospital cardiac arrest (peri-operative) and in-hospital cardiac arrest (not peri-operative). The impact on outcome of several patient characteristics and physiological values were analysed using multivariable logistic regression. Mechanically ventilated survivors of cardiac arrest accounted for 24,132 (5.8%) of all admissions to the 174 ICUs in the ICNARC CMP. Of these, 10,347 (42.9%) survived to leave the ICU and 6778 (28.6%) survived to acute hospital discharge. The ICNARC model gives much better discrimination than APACHE II for predicting hospital mortality after admission to ICU following cardiac arrest: the predicted hospital mortality based on the APACHE II and ICNARC model was 41.9% and 79.7%, respectively.

Hemodynamic responses to ECT in a patient with critical aortic stenosis.

We present a case study of a 46-year-old woman with a psychotic depressive illness of 2 months' duration with the coexisting medical diagnoses of critical aortic stenosis, severe labile hypertension, renal failure necessitating hemodialysis of 7-years' duration, and systemic lupus. Because of unresponsiveness to an antidepressant drug regimen, severe motor retardation, mutism, and refusal of food and fluids by mouth, an urgent indication for electroconvulsive therapy (ECT) was established. However, the patient refused ECT, and to allow its initiation, a court order was obtained. In view of the coexisting diagnoses of critical aortic stenosis, labile hypertension, and renal failure, ECT represented a substantially increased risk in this patient because of severe arterial hypertension and tachycardia. The patient was successfully managed during each ECT, using a combination of metoprolol by mouth, which was supplemented by i.v. esmolol immediately prior to the application of the ECT stimulus, and sodium nitroprusside, which was infused for several minutes prior to the seizure and thereafter to attenuate arterial hypertension. Nevertheless, sudden death, a well-known complication of critical aortic stenosis, occurred 96 hours after the fourth ECT.

Bioelectric response of human nasal epithelial cells to polycationic protein.

Polycationic proteins alter electrolyte transport by epithelium and endothelium, and in asthma are thought to disrupt the airway epithelium and contribute to hyperresponsiveness and airway plugging. In the present study, we used primary cultures of human nasal epithelial cells to investigate the response of respiratory tract epithelium to luminal presentation of a polycationic protein, protamine. Protamine (100 micrograms/ml) in the apical bathing solution had no significant effect on basal transepithelial resistance (Rt) but decreased short-circuit current (Isc) and hyperpolarized the apical membrane, indicating that Na+ absorption had been inhibited. Pretreating with amiloride inverted the response to protamine, resulting in an increase in Isc, depolarization of the apical membrane, and decrease in the fractional resistance of the apical membrane (fRa). The increase in Isc was inhibited by pretreatment with bumetanide. These results indicated that protamine augmented amiloride-induced Cl- secretion. Induction of Cl- secretion by bathing the apical surface in 3 mM Cl(-)-Ringer solution similarly resulted in protamine-induced depolarization of the apical membrane. Heparin precipitated protamine from solution and reversed the Isc responses. In summary, low concentrations of polycationic protein can alter electrolyte transport by human airway epithelium without desquamation, and the response is dependent on the secretory state of the tissue.

A role for Th2 T-memory cells in early airway obstruction.

The role of T-cell memory in late-phase allergic lung inflammation is not well defined. To evaluate the role of systemic T-cell memory in allergic late-phase lung inflammation, BALB/c mice were injected intraperitoneally with ovalbumin (OVA) or ragweed (RW) allergens (Test I and Test II groups) or saline (control groups C I and C IV) and then challenged intratracheally with the allergen. Late-phase allergic lung inflammation was defined by: (i) recruitment of eosinophils to airways, (ii) IL-5 mRNA upregulation in BAL fluid cells, and (iii) detection of a Th2 cell cytokine profile in BAL fluids. The number of eosinophils recruited in allergic mice following intratracheal challenge with allergen was at least 300-fold higher P < or = 0.01) in mice with allergen-specific T-memory cells in BAL fluid (Test I and Test II) than in control mice without allergen-specific T-memory cells (C I and C IV). Further, the number of eosinophils recruited in Test I and II correlated with the magnitude of in vitro T-cell memory responses (r = 0.93, P < or = 0.04). Moreover, IL-5 mRNA upregulation in BAL cells and Th2 cytokine production in BAL fluids were observed only in Test I and Test II, and not in any of the control groups. Further, results from pulmonary function tests performed on the same allergic animals indicated that only animals from Test I and Test II groups had impaired lung function after allergen challenge. Taken together, these data strongly suggest that allergen-specific Th2-type T-cell memory is required for the development of allergic asthma. That is, without T-cell memory responses, no eosinophil recruitment and release of EPO (which is known to induce bronchoconstriction) occurred in the airways, and no Th2 cytokine profile was detected in the BAL fluid. Furthermore, if the Th2 cytokine profile was absent, then pulmonary functions remained normal.

Beta-adrenergic regulation of Cl- and HCO3- secretion by Clara cells.

Previous studies on beta-adrenergic agonist regulation of ion transport in distal airways yielded discordant results. The present study was performed to further investigate this process in isolated bronchiolar epithelial cells and resolve the discrepancies. Epithelial enriched in rabbit nonciliated bronchiolar epithelial (Clara) cells responded to isoproterenol with a biphasic increase in transepithelial short circuit current (Isc) and decrease in transepithelial resistance (Rt). The first phase of the Isc response consisted of a transient, 11 microA/cm2 increase in current that was inhibited by HCO3(-)-free bathing solutions, but was not inhibited by amiloride, bumetanide, or Cl(-)-free bathing solutions. The ED50 for isoproterenol stimulation of the initial peak was 81 pM. The second phase was a prolonged, 27 microA/cm2 elevation in Isc. Amiloride in the apical bath inhibited basal Isc and the prolonged change in Isc induced by isoproterenol. Bumetanide in the basolateral bath and bilateral Cl(-)-free bathing solutions likewise inhibited the plateau phase of the isoproterenol response, and the inhibition was accentuated in the presence of amiloride. HCO3(-)-free bathing solutions did not inhibit the plateau phase. The ED50 for isoproterenol stimulation of the plateau phase was 6.3 nM. The bioelectric response to isoproterenol was mimicked by isobutylmethylxanthine (IBMX) and, to a lesser degree, by dibutyryl-cAMP. Culturing the cells in medium containing cholera toxin completely inhibited the bioelectric response, yet the preparations continued to respond to isoproterenol with an increase in cAMP production. These results indicated that beta-adrenergic stimulation of Clara cells induced electrogenic transepithelial secretion of Cl- and HCO3- and resolved discrepancies between previous studies.

Comparative effects of esmolol and labetalol to attenuate hyperdynamic states after electroconvulsive therapy.

We studied 18 patients (age range, 53-90 yr) with at least one cardiovascular risk factor who were treated with electroconvulsive therapy (ECT) and compared effects of five pretreatments: no drug; esmolol, 1.3 or 4.4 mg/kg; or labetalol, 0.13 or 0.44 mg/kg. Each patient received all five treatments, during a series of five ECT sessions. Pretreatment was administered as a bolus within 10 s of induction or anesthesia. Doses of methohexital and succinylcholine were constant for the series of treatments and the assignment to no drug or to drug and dose was determined by randomized block design. Measurements of systolic and diastolic blood pressure (SBP, DBP) and heart rate (HR) were recorded during the awake state and 1, 3, 5, and 10 min after the seizure. The deviation of ST segments from baseline was measured by an electrocardiogram (ECG) monitor equipped with ST-segment analysis software. The results (mean +/- SEM) show that without pretreatment, there were significant (P < 0.05) peak increases in SBP and HR (55 +/- 5 mm Hg and 37 +/- 6 bpm, respectively), recorded 1 min after the seizure. Comparable reductions (by approximately 50%) in these peak values were achieved after esmolol (1.3 mg/kg) or labetalol (0.13 mg/kg), and cardiovascular responses were nearly eliminated after the same drugs in doses of 4.4 and 0.44 mg/kg, respectively. The deviation of ST-segment values from baseline in any lead was not measurably influenced by either antihypertensive drug. SBP values were lower after labetalol 10 min after the seizure, but not after esmolol. Asystolic time after the seizure was not significantly longer with either drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Circumcision in children beyond the neonatal period.

OBJECTIVE: Although many boys are circumcised after the newborn period, there are limited data concerning the proportion of uncircumcised infants who subsequently have the procedure, as well as minimal information about characteristics of this population. POPULATION: Data and medical records of boys born in US Army hospitals from 1985 through 1992 were reviewed. General information regarding a portion of the 32,072 boys who were not circumcised during their neonatal hospitalization, but subsequently had the procedure, is reported. In addition, specific details are presented about 476 boys who were circumcised after their birth hospitalization. RESULTS: The postneonatal circumcision frequency rate of these children increased significantly over this period (P < .0001), particularly after the 1989 American Academy of Pediatrics statement on circumcision. In general, most boys were not circumcised as neonates because of parental choice (55%) or because of a complicated neonatal course (32%). "Sleeve" and "freehand" resection were the most common methods of circumcision (93%), and general anesthesia was used in 91% of the boys. The mean age at postneonatal circumcision was 2.92 years. Common reasons for the ensuing procedure included parental choice (39%), coincidence with other surgery (27%), recurrent balanoposthitis (23%), and urinary tract infections (7%). Complications occurred in 8 of the 476 boys whose specific records were reviewed. These included excessive bleeding (3), malignant hyperthermia (2), aspiration pneumonia (1), large hematoma development (1), and postoperative fever (1). CONCLUSIONS: An increasing number of boys are circumcised beyond the neonatal period, and the procedure performed at this time can be associated with substantial complications. This information may be of use when performing informed-consent counseling for neonatal circumcision.

Forging a nursing research agenda for New York State.

The Foundation of the New York State Nurses Association Inc., (hereafter Foundation), the Council on Nursing Research of the New York State Nurses Association (hereafter Council on Nursing Research), and the Delta Pi Chapter of the Sigma Theta Tau International (hereafter Delta Pi), sharing the same beliefs about nursing research and the need to take action, have worked cooperatively during the past three years to develop a nursing research agenda for New York state. Activities undertaken by these three groups to achieve this goal include co-sponsored conferences, a delphi survey to establish nursing research priorities for New York state, a research program offered at the 1989 Convention of the New York State Nurses Association, and establishment of the Foundation's Center for Nursing Research. A Planning Committee, with representatives from the three co-sponsoring organizations, has been appointed to assist the Center to further specify the action strategies for the research agenda and to oversee implementation of the agenda.

Methohexital Dosage in Electroconvulsive Therapy.

A comparison of methohexital at 0.5 mg/kg versus 1 mg/kg iv as anesthesia for unilateral brief pulse electroconvulsive therapy showed no difference in systolic or diastolic blood pressure before, immediately after, or 5 or 10 min after the seizure. Mean seizure duration was not significantly shorter using the higher methohexital dosage. These results show that methohexital can be safely used in a broad dosage range without undue effects on blood pressure or seizure duration.

Arterial hypertension and multiple cerebral aneurysms in a patient treated with electroconvulsive therapy.

The authors successfully instituted two courses of ECT at a 1-year interval for drug-resistant major depression in a patient with arterial hypertension and intracranial aneurysms. Both ECT courses required arterial and central venous cannulas, but the first course was complicated by an unusual and excessive degree of hypertension, which was not appropriately responsive to high doses of sodium nitroprusside (9 micrograms/kg/minute). Appropriate responsiveness to nitroprusside was established after therapy with timolol. The combination of sodium nitroprusside and timolol proved effective throughout the second course of ECT.

Executive functions in unipolar depression before and after electroconvulsive therapy.

A neuropsychological investigation of executive functions in patients with unipolar depression was conducted. Ten patients with unipolar depression were tested before, 48 hours after, and 3 months after ECT. Control subjects were tested at similar intervals. Measures included 10 executive and related tasks (20 variables) on which frontal lobe lesion patients have been previously shown to be differentially impaired, and 1 "nonexecutive" task. Patients were significantly inferior to controls on 9 of the executive and related variables before treatment and performed slightly worse 48 hours after treatment. Significant improvement after 3 months was absent. Depressed patients were not impaired on the "nonexecutive" task.