Using a linked database for epidemiology across the primary and secondary care divide: acute kidney injury.

BACKGROUND: NHS England has mandated the use in hospital laboratories of an automated early warning algorithm to create a consistent method for the detection of acute kidney injury (AKI). It generates an 'alert' based on changes in serum creatinine level to notify attending clinicians of a possible incident case of the condition, and to provide an assessment of its severity. We aimed to explore the feasibility of secondary data analysis to reproduce the algorithm outside of the hospital laboratory, and to describe the epidemiology of AKI across primary and secondary care within a region. METHODS: Using the Hampshire Health Record Analytical database, a patient-anonymised database linking primary care, secondary care and hospital laboratory data, we applied the algorithm to one year (1st January-31st December 2014) of retrospective longitudinal data. We developed database queries to modularise the collection of data from various sectors of the local health system, recreate the functions of the algorithm and undertake data cleaning. RESULTS: Of a regional population of 642,337 patients, 176,113 (27.4%) had two or more serum creatinine test results available, with testing more common amongst older age groups. We identified 5361 (or 0.8%) with incident AKI indicated by the algorithm, generating a total of 13,845 individual AKI alerts. A cross-sectional assessment of each patient's first alert found that more than two-thirds of cases originated in the community, of which nearly half did not lead to a hospital admission. CONCLUSION: It is possible to reproduce the algorithm using linked primary care, secondary care and hospital laboratory data, although data completeness, data quality and technical issues must be overcome. Linked data is essential to follow the significant proportion of people with AKI who transition from primary to secondary care, and can be used to assess clinical outcomes and the impact of interventions across the health system. This study emphasises that the development of data systems bridging across different sectors of the health and social care system can provide benefits for researchers, clinicians, healthcare providers and commissioners.

Colostrum from cattle immunized with a vaccine based on iron regulated proteins of Mannheimia haemolytica confers partial protection.

Passive protection afforded by colostrum from cattle vaccinated prepartum with an inactivated combination vaccine against viral pathogens and Mannheimia haemolytica (M. haemolytica) was evaluated against an experimental M. haemolytica challenge. Newborn calves were either fed colostrum from vaccinated dams or control colostrum. At approximately 3 weeks of age 24 calves were experimentally infected with M. haemolytica. Animals of both groups displayed clinical signs of respiratory disease and lung damage. The survival rate was considerably higher in calves which received colostrum from vaccinated cows. Colonies consistent with M. haemolytica were recovered in large numbers from all animals, but the geometric mean recovery was more than ten-times lower in the vaccinate colostrum fed animals. It can be concluded that maternal antibodies partly protected the calves against a severe M. haemolytica challenge.

The doctor's casebook--a process of discovery.

BACKGROUND AND AIMS: A bound manuscript describing the medical cases seen by a mid-eighteenth century Scottish doctor was discovered in the possession of the first author's family. The identity of the doctor is not revealed in the book. The aims were to identify the doctor and understand the significance of this book in the context of Scottish medical history of that period. METHODS: The process of investigation involved transcribing the book in order to undertake detailed study of the text, with particular focus on style of writing, location, and the names of patients and doctors mentioned. This information was then used in searches of the Wellcome Library for the History and Understanding of Medicine, London and the Department of Special Libraries and Archives of the University of Aberdeen as well as searches of the internet. RESULTS: The author was discovered to be a doctor working in Aberdeenshire in the middle of the eighteenth century. His style of writing suggests an educational purpose, with a particular interest in midwifery, and evidence of teaching midwifery techniques to students. He associated with other prominent local doctors of the time and was aware of the current thinking being put forward by his contemporaries. He had a particular association with Dr John Gregory, with whom he not only worked, but whose extended family he also treated. CONCLUSIONS: The author of this casebook was identified as Dr David Skene, and this adds to our knowledge of this important figure of the Scottish Enlightenment who had a particular interest in midwifery and campaigned for the proper instruction of midwives.

Indicators of patient suitability for topical anesthesia.

PURPOSE: To determine whether a patient's suitability for phacoemulsification under topical anesthesia can be predicted preoperatively by their performance during tonometry and A-scan. SETTING: Whipps Cross Hospital Ophthalmology Department, London, England. METHODS: Fifty consecutive patients who were considered suitable for phacoemulsification were selected for the study. Using a scoring system we devised, observers assessed the patients for the ease with which intraocular pressure and axial length were measured. These scores were compared with an assessment of how well they tolerated phacoemulsification under topical anesthesia. Correlation between the scores was measured with Spearman's rank correlation coefficient, Kendall's rank correlation coefficient, and the Goodman-Kruskal gamma statistic. RESULTS: Phacoemulsification and posterior chamber intraocular lens implantation were completed in all patients. Statistical analysis showed that tonometry and A-scan scores correlated highly with surgery scores. Age was also a significant variable in predicting the surgery score. A significant discrepancy between tonometry and A-scan and surgery scores was found in only one patient, and it was noted that he was one of the youngest patients in the study. CONCLUSION: How well a patient performs during tonometry and A-scan was a good predictor of how well he or she tolerated having phacoemulsification under topical anesthesia. The decision about type of anesthesia should, however, also involve other factors, including communication, cooperation, and the age of the patient.

Pilot study of local hyperthermia, radiation therapy, etanidazole, and cisplatin for advanced superficial tumours.

Five patients (six hyperthermia sites) with advanced superficial tumours were treated with combined etanidazole, cisplatin, local hyperthermia, and radiation therapy as part of a Phase I pilot study. Treatment was given once weekly and consisted of etanidazole 3 gm/m2 IV bolus, cisplatin 50 mg/m2 IV bolus, hyperthermia for 60 min with a target temperature of 43 degrees C, and radiation therapy 500 cGy/fraction (median total dose 3000 cGy) for a total of six weeks. Blood levels of etanidazole were taken during treatment at week 1 and week 4. Etanidazole drug exposure was calculated using the trapezoidal rule and expressed as the area under the curve (AUC) of plasma concentration x time. Five of six treatment sites had received prior irradiation. Prior chemotherapy had been given in three patients and tamoxifen therapy given in the other two patients. The median follow-up time is 34 months; 3/5 patients have died of disease. The most significant toxicity was grade I or II nausea and vomiting associated with 19/32 treatments (59%) and a second degree burn in 2/6 fields. None of the five patients experienced peripheral neuropathy, skin ulceration, or needed surgical repair. In addition, there was mild renal toxicity; pharmacokinetic analysis showed a 28-75% increase in the week 1 to week 4 AUC in three patients, all of whom had a decrease in creatinine clearance over the same time of 15-47%. This pilot study suggests this combined modality therapy can be delivered without major complications and that renal function, determined by creatinine clearance, affects clearance of etanidazole and alters the AUC. Therefore, monitoring renal function is important in patients receiving etanidazole in addition to other nephrotoxic agents such as cisplatin. The impact of etanidazole on the therapeutic index of hyperthermia, radiation therapy and cisplatin may be worth of study, especially since a positive interaction between these modalities is found in laboratory models.

Filtration of shed mediastinal blood.

Re-infusion of shed blood carries the risk of re-infusing cellular debris. All re-infusion devices have some sort of integral filtration which is variably supplemented with a second intravenous filter. Using electron microscopy we have observed what debris is collected by secondary filtration. In 12 patients studied, nine out of 12 filters had significant amounts of cellular debris present, but not clearly related to increased rates of postoperative bleeding. Noncellular debris, silicon and strands of cellulose were also observed. Although we have not detected any clinically significant embolic phenomena from re-infusion of shed mediastinal blood, it seems prudent to include a second filter prior to re-infusion.

Local hyperthermia, radiation therapy, and chemotherapy in patients with local-regional recurrence of breast carcinoma.

We retrospectively reviewed the response rate and the acute and long-term toxicity of combined treatment using radiation therapy, hyperthermia, and chemotherapy in 29 patients with locally or regionally recurrent or advanced adenocarcinoma of the breast who completed at least 4 of the 6 prescribed hyperthermia treatments as part of a Phase I-II trial. Thirty-nine separate hyperthermia treatment fields were evaluated. Cisplatin alone or cisplatin with etanidazole or bleomycin was delivered just prior to hyperthermia once weekly. Hyperthermia was delivered to a target minimum tumor temperature of 43 degrees C +/- 0.5 for 60 min. Following hyperthermia, a 400 cGy fraction of radiation was given. The radiation fraction size on other days was 200 cGy. Twenty-two fields had previously been irradiated and 17 fields had not. Prior chemotherapy had been given in 24 of 29 patients (83%) and hormonal therapy given in 21 (72%). The median follow-up time is 10 months; 16/29 patients (55%) have died of disease. The overall complete response rate for all fields was 53%. Response rate was not related to any clinical factor, radiation dose, microwave or ultrasound technique, type of chemotherapy, or tumor temperatures, but the number of patients in the study population was small. A statistically significant association between the likelihood of complications and the total radiation therapy dose (previous radiation and present radiation) was found. Persistent ulceration lasting greater than 1 month after completing treatment was seen in 67% of previously irradiated fields compared to 21% of fields that had not been previously treated (p = 0.015). Surgical wound repair was needed for 38% of fields with a history of prior irradiation versus 6% of those without prior treatment (p = 0.050). A statistically significant radiation therapy dose response was found for the likelihood of these complications. None of the hyperthermia temperature parameters studied correlated with an increased risk of complication. We conclude that the combination of radiation therapy, hyperthermia, and chemotherapy results in a high rate of complete response. However, in patients who have been treated with prior radiation therapy, this combination may be more locally toxic than treatment with hyperthermia and radiation therapy alone. The precise impact of chemotherapy on the therapeutic index of hyperthermia and radiation therapy remains to be determined in randomized clinical trials.

A phase I-II trial of cisplatin, hyperthermia and radiation in patients with locally advanced malignancies.

A Phase I-II trial testing the addition of systemic cisplatin (CDDP) to local hyperthermia and radiation was conducted to determine the dose of cisplatin that is tolerable once weekly for 6 weeks and to estimate the therapeutic potential of this trimodality combination in patients with locally advanced malignancies. Cisplatin at 20 mg/m2 (4 patients), 30 mg/m2 (8 patients), and 40 mg/m2 (12 patients) was given rapidly (over 5-10 min) i.v. after prehydration with 1 liter of normal saline. After approximately two-thirds of the cisplatin dose had been delivered, microwave hyperthermia was begun and continued for 60 min; the target minimum tumor temperature was 43 degrees C. Following hyperthermia, a 400 cGy fraction of radiation was delivered to the tumor. On other days during the treatment weeks, additional 200 cGy fractions were given to total doses of 6,000-6600 cGy in patients with full radiation tolerance or 2400-3600 cGy in patients with limited radiation tolerance. The 24 patients in this trial had a median age of 57 years and the predominant sites/tumor types were head and neck/squamous cell carcinoma (9) and chest wall/breast adenocarcinoma (9). Seventeen of the 24 treated tumors (70%) had previously been irradiated. Eighteen patients (75%) had received prior chemotherapy and nine patients (38%) had previously been treated with cisplatin. Bone marrow suppression was dose limiting in patients heavily pretreated with chemotherapy and chest wall radiation. No significant toxicities were observed at the 20 and 30 mg/m2 dose levels, but 5 of the 12 patients (42%) treated at 40 mg/m2 required modification of the cisplatin dose because of blood count suppression in four patients and mild renal dysfunction in one patient. Each of the patients with bone marrow suppression, however, had been heavily pretreated except for one patient with thrombocytopenia due to hypersplenism. Nausea and vomiting were mild with use of a standard, multiagent antiemetic regimen. Twelve patients (50%) attained a complete regression (CR) and 12 patients (50%) a partial regression (PR). Complete regression appeared to correlate with small tumor volumes (115 cc for CR versus 199 cc for PR patients) and higher tumor temperatures (4.6 average minimum equivalent minutes at 43 degrees C in CR versus 2.0 min in PR patients). Local toxicities included second degree burns in 12 patients (50%) and third degree burns in 6 (25%), but all burns healed in 4-12 weeks without surgical intervention.(ABSTRACT TRUNCATED AT 400 WORDS)

The prevention of vitamin D deficiency in the elderly.

Vitamin D deficiency is common in the house-bound and institutionalised elderly population of Britain. A study of patients over 65 years discharged with a diagnosis of osteomalacia from Greater Glasgow Health Board hospitals between 1970 and 1981 inclusive showed a low incidence in the 65 to 74 years age group but a steeply rising incidence in older age groups. The majority (83%) of patients were female. The fortification of margarine, butter and milk with concentrations of vitamin D acceptable to the general population does not produce significant elevations in serum 25-hydroxyvitamin D (25-OHD) levels in vitamin D-deficient elderly patients. Low intensity background ultraviolet radiation (UVR) and intermittent high intensity UVR produce significant elevations in serum 25-OHD levels in elderly patients but both methods have disadvantages which limit their widespread use. Vitamin D supplements equivalent to 10 micrograms daily produce significant elevations in serum 25-OHD levels in vitamin D-deficient elderly patients. A vitamin D supplement policy for the housebound and institutionalised elderly population of Britain is required.

Effects of altered responsibility, congnitive set, and modeling on physical aggression and deindividuation.

This laboratory investigation using 64 college students as subjects assessed the role of three disinhibiting variables in producing both physical aggression and an internal state of deindividuation. Altered responsibility, congnitive set, and modeling were manipulated in a factorial design, and all three variables significantly increased physical aggression. No interaction produced significant results. The increase due to altered responsibility and varying cognitions supports Zimbardo's theory of deindividuation which relates certain input variables to wild, impulsive behavior. Questionnaire data indicated that the increase in aggression was not accompanied by internal mediational factors such as reduced self-awareness. It appears that disinhibiting forces may produce increases in antisocial behavior without necessarily producing a deindividuated internal state.