Factors affecting patient flow in a neurosurgery department.

INTRODUCTION: Patient flow is the process by which movement of patients and clinical productivity is achieved. The objectives of this study were to implement and evaluate the NHS Improvement SAFER patient flow bundle, evaluate the impact of the Red2Green initiative, and assess the impact of frailty on patient flow. MATERIALS AND METHODS: All patients admitted to a neurosurgery unit from 1 September to 30 November 2017 were included. Using guidance set out by NHS, data were prospectively collected from daily ward lists and patient notes, including demographics, admission and discharge details, length of stay, anticipated discharge date, red days with reasons and frailty (Rockwood Clinical Frailty Scale). NHS reference costs were used for cost analyses. RESULTS: A total of 420 patients (55% elective) were included, totalling 3909 bed days. All patients received daily senior reviews before midday, and anticipated discharge dates were set at daily multidisciplinary team meetings. Ten per cent of patients were discharged before midday. There were 21% (837) red days, significantly more (76%) for emergency patients (639 vs 198 elective; P < 0.001); 63% red days were attributed to awaiting a bed in a local hospital; 25% (106) patients were classed as frail (50 elective), which was associated with a significantly longer length of stay (17.3 vs 6; P < 0.01), and more red days (615 vs 222; p<0.01). Considering excess bed charges and lost revenue (with penalties), red days cost over £1 million per year. CONCLUSIONS: SAFER has identified areas for improvement in patient flow, with obvious cost implications. It has created a platform for discussion within the referral network and identified a role for a geriatric liaison service.

Training and accrediting international surgeons.

BACKGROUND: Formal international medical programmes (IMPs) represent an evolution away from traditional medical volunteerism, and are based on the foundation of bidirectional exchange of knowledge, experience and organizational expertise. The intent is to develop multidirectional collaborations and local capacity that is resilient in the face of limited resources. Training and accreditation of surgeons continues to be a challenge to IMPs, including the need for mutual recognition of competencies and professional certification. METHODS: MEDLINE, Embase and Google Scholar™ were searched using the following terms, alone and in combination: 'credentialing', 'education', 'global surgery', 'international medicine', 'international surgery' and 'training'. Secondary references cited by original sources were also included. The authors, all members of the American College of Academic International Medicine group, agreed advice on training and accreditation of international surgeons. RESULTS AND CONCLUSION: The following are key elements of training and accrediting international surgeons: basic framework built upon a bidirectional approach; consideration of both high-income and low- and middle-income country perspectives; sourcing funding from current sources based on existing IMPs and networks of IMPs; emphasis on predetermined cultural competencies and a common set of core surgical skills; a decentralized global system for verification and mutual recognition of medical training and certification. The global medical system of the future will require the assurance of high standards for surgical education, training and accreditation.

Indolcarboxamide is a preclinical candidate for treating multidrug-resistant tuberculosis.

New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). We have identified and characterized the indolcarboxamides as a new class of antitubercular bactericidal agent. Genetic and lipid profiling studies identified the likely molecular target of indolcarboxamides as MmpL3, a transporter of trehalose monomycolate that is essential for mycobacterial cell wall biosynthesis. Two lead candidates, NITD-304 and NITD-349, showed potent activity against both drug-sensitive and multidrug-resistant clinical isolates of Mtb. Promising pharmacokinetic profiles of both compounds after oral dosing in several species enabled further evaluation for efficacy and safety. NITD-304 and NITD-349 were efficacious in treating both acute and chronic Mtb infections in mouse efficacy models. Furthermore, dosing of NITD-304 and NITD-349 for 2 weeks in exploratory rat toxicology studies revealed a promising safety margin. Finally, neither compound inhibited the activity of major cytochrome P-450 enzymes or the hERG (human ether-a-go-go related gene) channel. These results suggest that NITD-304 and NITD-349 should undergo further development as a potential treatment for multidrug-resistant TB.

Traumatic wound microbiome workshop.

On May 9-10, 2011, the Walter Reed Army Institute of Research, as the Army Center of Excellence for Infectious Disease, assembled over a dozen leaders in areas related to research into the communities of microorganisms which colonize and infect traumatic wounds. The objectives of the workshop were to obtain guidance for government researchers, to spur research community involvement in the field of traumatic wound research informed by a microbiome perspective, and to spark collaborative efforts serving the Wounded Warriors and similarly wounded civilians. During the discussions, it was made clear that the complexity of these infections will only be met by developing a new art of clinical practice that engages the numerous microbes and their ecology. It requires the support of dedicated laboratories and technologists who advance research methods such as community sequencing, as well as the kinds of data analysis expertise and facilities. These strategies already appear to be bearing fruit in the clinical management of chronic wounds. There are now funding announcements and programs supporting this area of research open to extramural collaborators.

Serum-induced macrophage activation is related to the severity of septic shock.

BACKGROUND: It seems that a balance between anti and pro-inflammatory responses must be kept to eliminate the pathogen without inducing inflammatory damage in the host. Thus we determined the relation between macrophage activation and the severity and clinical outcome in septic patients. MATERIAL AND METHODS: This was a prospective study at a tertiary general intensive care unit. Thirty-three patients admitted with sepsis, severe sepsis or septic shock were included. As a control group, healthy volunteers were included matched to septic patients by age and sex. Peritoneal rat macrophages were cultured with 2% serum from healthy volunteers or from septic patients for determination of phagocytic potential or the capacity to produce cytokines. RESULTS: TNF and IL1 secretion by macrophages activated with serum from sepsis and severe sepsis patients was higher than with serum from healthy controls. In addition, proinflammatory cytokines released in vitro from macrophages, but not determined directly in the serum from patients, were lower in non-survivor septic patients when compared to survivors. In contrast, IL-10 secretion by macrophages activated with serum from septic patients was higher in nonsurvivors. In the septic shock group we observed a diminution in the phagocytic index compared to sepsis and severe sepsis groups, and the phagocytic index was higher in sepsis survivors. CONCLUSIONS: Markers of antiinflammation are predominant in more severe types of sepsis suggesting that antiinflammation is related to mortality.

Characterization of the NIST seaweed Standard Reference Material.

The National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) for seaweed was developed through an interlaboratory comparison with 24 participants from 16 countries. After evaluating different techniques to calculate certified values for the radionuclides, the median method was found to be the most representative technique. The certified values were provided for 13 radionuclides and information values were given for 15 more radionuclides. Results for the natural decay series showed disequilibrium in both the uranium and thorium series.

Survival of patients receiving a liver transplant for hepatocellular carcinoma, and risk of tumor recurrence.

OBJECTIVE: The goal of this research has been to evaluate the survival, in long and short term, of the patient receiving liver transplant for hepatocellular carcinoma (HCC), the risk of post-transplant tumor relapse and factors related to this complication. DESIGN: Retrospective study of a consecutive series of patients having had liver transplant for HCC. PATIENTS AND METHODOLOGY: Transplant patients for HCC from 1989 to November 2003. Patients were selected due to general limitations of nodule size and quantity, which were subsequently published as Milan criteria. Also, criteria agreed in the Conference of Barcelona were followed in the pre-transplant diagnosis. RESULTS: The survival of this 81 patients group was of the 80, 61 and 52% for 1, 5 and 10 years respectively. In the 32% of the cases the HCC was an incidental finding in the explant. In the 12.3%, the tumor relapse was verified. The multivariate research identified the size of the nodule (OR=1,7944) (IC 95%=1,1332-2,8413) and the vascular invasion (OR=6,6346) (IC 95%=1,4624-30,1003) as risk factors of relapse. CONCLUSIONS: The liver transplant in selected patients with HCC has good results in medium and long term. The risk of post-transplant tumor relapse becomes notably reduced and is associated with the size of the nodule and the microscopic vascular invasion.

The angiotensin IV/AT4 receptor.

The angiotensin AT(4) receptor was originally defined as the specific, high-affinity binding site for the hexapeptide angiotensin IV (Ang IV). Subsequently, the peptide LVV-hemorphin 7 was also demonstrated to be a bioactive ligand of the AT(4) receptor. Central administration of Ang IV, its analogues or LVV-hemorphin 7 markedly enhance learning and memory in normal rodents and reverse memory deficits observed in animal models of amnesia. The AT(4) receptor has a broad distribution and is found in a range of tissues, including the adrenal gland, kidney, lung and heart. In the kidney Ang IV increases renal cortical blood flow and decreases Na(+) transport in isolated renal proximal tubules. The AT(4) receptor has recently been identified as the transmembrane enzyme, insulin-regulated membrane aminopeptidase (IRAP). IRAP is a type II integral membrane spanning protein belonging to the M1 family of aminopeptidases and is predominantly found in GLUT4 vesicles in insulin-responsive cells. Three hypotheses for the memory-potentiating effects of the AT(4) receptor/IRAP ligands, Ang IV and LVV-hemorphin 7, are proposed: (i) acting as potent inhibitors of IRAP, they may prolong the action of endogenous promnestic peptides; (ii) they may modulate glucose uptake by modulating trafficking of GLUT4; (iii) IRAP may act as a receptor, transducing the signal initiated by ligand binding to its C-terminal domain to the intracellular domain that interacts with several cytoplasmic proteins.

Biliopancreatic tumors: patient survival and quality of life after palliative treatment.

OBJECTIVES: to analyse survival and quality of life of patients with malignant obstructive jaundice after palliative treatment, comparing endoscopic stent insertion and palliative surgical (palliative resection and bypass surgical). PATIENTS AND METHOD: eighty and seven patients were included in a trial. They were distributed to endoscopic stent (50) and palliative surgical (37). It analysed survival, quality of life and comfort index of jaundiced patients. The good quality of life was defined by absence of jaundice, pruritus and cholangitis after the initial treatment. RESULTS: the median survival of the patients treated to endoscopic stent was 9,6 months whereas the patients to surgical treatment survived a median of 17 months. The time free of disease was 4 months in stented patients and 10,5 months in surgical patients. There was no significant difference in comfort index between the two groups (stented 34%, surgical 42,5%) Neither was there significant difference in survival and quality of life between palliative resection and bypass surgery. CONCLUSIONS: despite the survival and time free of disease being better in surgical patients, there was no significant difference in overall quality of life between the two groups. The survival and quality of life are the same after palliative resection as after bypass surgery, for this should not be performed routinely or to justify resection as a debulking procedure.

Production of melanocyte-specific antibodies to human melanosomal proteins: expression patterns in normal human skin and in cutaneous pigmented lesions.

Multiple factors affect skin pigmentation, including those that regulate melanocyte and/or keratinocyte function. Such factors, particularly those that operate at the level of the melanosome, are relatively well characterized in mice, but the expression and function of structural and enzymatic proteins in melanocytes in human skin are not as well known. Some years ago, we generated peptide-specific antibodies to murine melanosomal proteins that proved to be instrumental in elucidating melanocyte development and differentiation in mice, but cross-reactivity of those antibodies with the corresponding human proteins often was weak or absent. In an effort to characterize the roles of melanosomal proteins in human skin pigmentation, and to understand the underlying mechanism(s) of abnormal skin pigmentation, we have now generated polyclonal antibodies against the human melanocyte-specific markers, tyrosinase, tyrosinase-related protein (TYRP1), Dopachrome tautomerase (DCT) and Pmel17 (SILV, also known as GP100). We used these antibodies to determine the distribution and function of melanosomal proteins in normal human skin (adult and newborn) and in various cutaneous pigmented lesions, such as intradermal nevi, lentigo simplex, solar lentigines and malignant melanomas. We also examined cytokeratin expression in these same samples to assess keratinocyte distribution and function. Immunohistochemical staining reveals distinct patterns of melanocyte distribution and function in normal skin and in various types of cutaneous pigmented lesions. Those differences in the expression patterns of melanocyte markers provide important clues to the roles of melanocytes in normal and in disrupted skin pigmentation.

Drug physical state and drug-polymer interaction on drug release from chitosan matrix films.

Four different grades of chitosan varying in molecular weight and degree of deacetylation were used to prepare chitosan films. Salicylic acid and theophylline were incorporated into cast chitosan films as model acidic and basic drugs, respectively. Crystalline characteristics, thermal behavior, drug-polymer interaction and drug release behaviors of the films were studied. The results of Fourier transform infrared and solid-state 13C NMR spectroscopy demonstrated the drug-polymer interaction between salicylic acid and chitosan, resulting in salicylate formation, whereas no drug-polymer interaction was observed in theophylline-loaded chitosan films. Most chitosan films loaded with either salicylic acid or theophylline exhibited a fast release pattern, whereas the high viscosity chitosan films incorporated with salicylic acid showed sustained release patterns in distilled water. The sustained release action of salicylic acid from the high viscosity chitosan films was due to the drug-polymer interaction. The mechanism of release was Fickian diffusion control with subsequent zero order release. It was suggested that the swelling property, dissolution characteristics of the polymer films, pK(a) of drugs and especially drug-polymer interaction were important factors governing drug release patterns from chitosan films.

Physical properties and molecular behavior of chitosan films.

Chitosan films, varying in molecular weight and degree of deacetylation, were prepared by a casting technique using acetic acid as a dissolving vehicle. The physicochemical properties of the films were characterized. Both molecular weight and degree of deaceylation affected the film properties. Powder X-ray diffraction patterns and differential scanning calorimetry thermograms of all chitosan films indicated their amorphous state to partially crystalline state with thermal degradation temperature lower than 280-300 degrees C. The increase in molecular weight of chitosan would increase the tensile strength and elongation as well as moisture absorption of the films, whereas the increase in degree of deacetylation of chitosan would either increase or decrease the tensile strength of the films depending on its molecular weight. Moreover, the higher the degree of deacetylation of chitosan the more brittle and the less moisture absorption the films became. All chitosan films were soluble in HCl-KCl buffer (pH 1.2), normal saline, and distilled water. They swelled in phosphate buffer (pH 7.4), and cross-linking between chitosan and phosphate anions might occur Finally, transmission infrared and 13C-NMR spectra supported that chitosan films prepared by using acetic acid as a dissolving were chitosonium acetate films.

Automatic differentiation of melanoma from melanocytic nevi with multispectral digital dermoscopy: a feasibility study.

BACKGROUND: Differentiation of melanoma from melanocytic nevi is difficult even for skin cancer specialists. This motivates interest in computer-assisted analysis of lesion images. OBJECTIVE: Our purpose was to offer fully automatic differentiation of melanoma from dysplastic and other melanocytic nevi through multispectral digital dermoscopy. METHOD: At 4 clinical centers, images were taken of pigmented lesions suspected of being melanoma before biopsy. Ten gray-level (MelaFind) images of each lesion were acquired, each in a different portion of the visible and near-infrared spectrum. The images of 63 melanomas (33 invasive, 30 in situ) and 183 melanocytic nevi (of which 111 were dysplastic) were processed automatically through a computer expert system to separate melanomas from nevi. The expert system used either a linear or a nonlinear classifier. The "gold standard" for training and testing these classifiers was concordant diagnosis by two dermatopathologists. RESULTS: On resubstitution, 100% sensitivity was achieved at 85% specificity with a 13-parameter linear classifier and 100%/73% with a 12-parameter nonlinear classifier. Under leave-one-out cross-validation, the linear classifier gave 100%/84% (sensitivity/specificity), whereas the nonlinear classifier gave 95%/68%. Infrared image features were significant, as were features based on wavelet analysis. CONCLUSION: Automatic differentiation of invasive and in situ melanomas from melanocytic nevi is feasible, through multispectral digital dermoscopy.

Accelerated fluid bed drying using NIR monitoring and phenomenological modeling.

A "fast-drying" method to accelerate the fluid bed drying process is presented. It relies on concepts of heat and mass transfer with real-time near-infrared (NIR) monitoring of moisture. Triplicate trials show that fast drying can reduce granulation drying time by half over single-temperature cycles. The product is equivalent in every way tested to material made using a conventional cycle even though the inlet temperature throughout the constant-rate stage was higher than the melting point of the compound. Tablets made from the fast-dried granulation exhibit equivalent physical characteristics to tablets made from granulations dried at a single, lower temperature.

Non-dipping circadian blood pressure and renal impairment are associated with increased mortality in diabetes mellitus.

AIMS: To assess the relevance of circadian blood pressure variation to future morbidity and mortality in patients with diabetes mellitus. METHODS: A retrospective descriptive 4 year follow-up study of data collected after ambulatory blood pressure monitoring in a clinic setting. RESULTS: Seventy-five patients (46 male; 29 female) of whom 41 % had Type 1 diabetes and 59% Type 2 were followed up for a median of 42 months (11-56). The median creatinine for the whole group at baseline was 101 (56-501) micromol/l. The median circadian blood pressures for the total study population were 147 (110-194)/87 (66-109) mmHg during daytime and 132 (86-190)/77 (50-122) mmHg during night-time. Half of the patients exhibited a fall in night-time pressures to 10% lower than daytime pressures (dippers). Dippers were younger, 47 (32-75) years, than non-dippers, 57 (35-79) years, P = 0.03. Over time, dippers had a lower mortality than non-dippers, with 8% deaths in the cohort of dippers, 26% deaths in the cohort of non-dippers, P = 0.04. Cox regression analysis revealed significant contributions from age, duration of diabetes and baseline renal function to subsequent mortality in non-dippers. Analysing current degree of renal impairment and original dipper status together revealed that, of those patients whose creatinine remained normal, 7% of patients whose blood pressure dipped had subsequently died and 10% of non-dipping patients had died; of those patients whose creatinine unequivocally rose, 10% of dipping patients had died and 42% of non-dipping patients had died, P = 0.03 CONCLUSIONS: Loss of circadian variation in blood pressure is associated with an increased mortality rate, regardless of diabetes type. The combination of non-dipping and subsequent renal impairment leads to the highest mortality rate. The study suggests a role for ambulatory blood pressure monitoring in day-to-day clinical practice to select patients with nephropathy who are at greatest risk, in an effort to alter outcome.

Multifactorial analysis of exchanger efficiency and liquid conservation during perfluorochemical liquid-assisted ventilation.

Liquid-assisted ventilation (LAV) of the lung with perfluorochemical (PFC) requires a method of oxygenating and removing CO2 from the liquid. Current PFC LAV techniques consist of total liquid ventilation, PFC lavage, and partial liquid ventilation. Because PFC liquid is volatile, it may be lost from the lung or ventilator circuit in the expired gas. This study evaluated the efficiencies of two types of exchangers (spray bubbler and membrane oxygenator) with respect to CO2 elimination from the PFC liquid and prevention of the loss of PFC liquid. A multifactorial analysis of exchanger efficiency was performed with respect to liquid conservation and CO2 removal. PFC losses and relative efficiencies of two types of exchangers to eliminate CO2 from expired PFC liquid were evaluated, along with two types of PFC liquids. Gas (100% O2 at 4 and 8 L/min) and PFC liquid were circulated countercurrently through the exchangers (oxygenator and bubbler) through a temperature-controlled (25 degrees or 37 degrees C) open circuit. To evaluate effectiveness of CO2 elimination, an exchanger efficiency index (EEI) for CO2 was calculated applying mass-transfer theory to characterize gas transport down a concentration gradient where EEI equals: [PPFCCO2 out--PPFCCO2 in]/PgasCO2 in--PPFCCO2 in]. Rate of PFC loss from the circuit was calculated from mixed expired gas samples using a thermal detector analyzer. EEI and PFC loss rate were analyzed with respect to gas: PFC liquid flow ratios (analogous to the V/Q ratio). The results showed that 1) PFC loss rate and exchanger efficiency to remove CO2 increased with increasing gas: PFC liquid flow rates independent of the type of exchanger or PFC liquid; 2) PFC loss rate at any gas or liquid flow rate was greater for the bubbler than for the oxygenator; 3) the oxygenator was more efficient than the bubbler with respect to CO2 elimination; 4) although PFC loss rate increased with temperature and vapor pressure, there was little difference in the EEIs for the temperatures studied. These results 1) identify exchanger requirements necessary to maintain effective CO2 elimination up to four times normal CO2 loading conditions during LAV; 2) suggest that using a membrane oxygenator as the gas exchanger, in concert with stringent fluid temperature control, improves PFC liquid conservation and CO2 elimination relative to bubbler exchanger configurations; 3) highlight the importance of matching the exchanger type to the physiocochemical properties of the specific PFC liquid to optimize CO2 elimination while reducing PFC liquid loss by minimizing gas relative to PFC liquid flow rates. Because PFC liquid loss occurs with all current means of oxygenating and removing CO2, this study raises the importance of developing alternative, bulk-gas-flow-independent, means to recondition PFC liquids.

The effect of formulation on radioiodide thyroid uptake in the hyperthyroid cat.

This investigation was designed to compare in vitro dissolution profiles from sodium iodide capsules with radioiodide thyroid uptake in hyperthyroid cats using sodium iodide capsules prepared with a formulation exhibiting a complete release of radioiodide (I-123) in vitro and a formulation with an incomplete release of radioiodide. In vitro dissolution profiles for I-123 sodium iodide capsules with two different formulations were determined using the USP XXIII dissolution test. The two formulations studied in vitro were sodium phosphate dibasic powder with 1% magnesium stearate and calcium phosphate dibasic powder with 3% magnesium stearate. By 20 min after initiation of the dissolution test, over 95% of the I-123 was released from capsules of sodium phosphate dibasic powder. The capsules of calcium phosphate dibasic powder reached 75% at 65 min, with no further release occurring thereafter. There was a statistically significant difference in the dissolution profiles of the two formulations. The thyroid uptake of I-123 from capsules exhibiting complete release and incomplete release of radioiodide was determined in hyperthyroid cats. At 4 hr, the mean percentage thyroid uptake value for sodium phosphate dibasic powder with 1% magnesium stearate (complete release formulation) was 12.0% compared to 9.4% for calcium phosphate dibasic powder with 3% magnesium stearate (incomplete release formulation); at 24 hr, the values were 34.4% compared to 23.7%. The data suggest that the incomplete dissolution profile observed in vitro may correlate with a reduction in the bioavailability of the radioiodide in vivo. However, using the Wilcoxon signed rank test, statistically significant differences did not occur between the complete release formulation and incomplete release formulation at either 4 hr or 24 hr (p > .05). The results of the in vivo study with five hyperthyroid cats were not conclusive due to the variability in response between individual cats.

[Prospective and randomized study on the usefulness of octreotide in the prevention of complications after cephalic duodeno-pancreatectomy]. / Estudio prospectivo y randomizado sobre la utilidad del Octreótido en la prevención de complicaciones tras duodeno-pancreatectomía cefálica.

OBJECTIVE: This study seeks to evaluate the role of the somatostatin analogue Octreotide as postoperative prophylaxis in the prevention of pancreatic fistula following Pancreaticoduodenectomy (PD). METHODS: A prospective and randomized study has been completed in 34 patients undergoing PD. Sixteen patients were randomly assigned to receive Octreotide 0.1 cc (100 mcg) three times daily subcutaneously during the first seven days of the post-operative period and the remaining 18 constituted the control group. All patients were fed parenterally until normal oral feeding was restored (mean 8 days). Fisher's exact test was used to compare complications in both groups. Pancreatic fistula was defined as the persistence of an amylase-rich discharge at least 50 ml daily during a minimum period of two weeks. RESULTS: The mortality rate was 3% and the morbidity 26%. No significant differences were observed regarding the total number of complications. The appearance of pancreatic fistula was considerably smaller (p = 0.03) in the Octreotide group than in control group. Postoperative hospital stay and the number of subsequent surgical interventions were significantly higher (p < 0.05) in the control group. CONCLUSION: Octreotide prevents the occurrence of pancreatic fistula after PD when it is administered prophylactically during the immediate postoperative period.