Statistical and agent-based modelling of the transmissibility of different SARS-CoV-2 variants in England and impact of different interventions.

The English SARS-CoV-2 epidemic has been affected by the emergence of new viral variants such as B.1.177, Alpha and Delta, and changing restrictions. We used statistical models and the agent-based model Covasim, in June 2021, to estimate B.1.177 to be 20% more transmissible than the wild type, Alpha to be 50-80% more transmissible than B.1.177 and Delta to be 65-90% more transmissible than Alpha. Using these estimates in Covasim (calibrated 1 September 2020 to 20 June 2021), in June 2021, we found that due to the high transmissibility of Delta, resurgence in infections driven by the Delta variant would not be prevented, but would be strongly reduced by delaying the relaxation of restrictions by one month and with continued vaccination. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

End-of-life decision making: a qualitative study of elderly individuals.

OBJECTIVE: To identify the desired features of end-of-life medical decision making from the perspective of elderly individuals. DESIGN: Qualitative study using in-depth interviews and analysis from a phenomenologic perspective. SETTING: A senior center and a multilevel retirement community in Los Angeles. PARTICIPANTS: Twenty-one elderly informants (mean age 83 years) representing a spectrum of functional status and prior experiences with end-of-life decision making. MAIN RESULTS: Informants were concerned primarily with the outcomes of serious illness rather than the medical interventions that might be used, and defined treatments as desirable to the extent they could return the patient to his or her valued life activities. Advanced age was a relevant consideration in decision making, guided by concerns about personal losses and the meaning of having lived a "full life." Decision-making authority was granted both to physicians (for their technical expertise) and family members (for their concern for the patient's interests), and shifted from physician to family as the patient's prognosis for functional recovery became grim. Expressions of care, both by patients and family members, were often important contributors to end-of-life treatment decisions. CONCLUSIONS: These findings suggest that advance directives and physician-patient discussions that focus on acceptable health states and valued life activities may be better suited to patients' end-of-life care goals than those that focus on specific medical interventions, such as cardiopulmonary resuscitation. We propose a model of collaborative surrogate decision making by families and physicians that encourages physicians to assume responsibility for recommending treatment plans, including the provision or withholding of specific life-sustaining treatments, when such recommendations are consistent with patients' and families' goals for care.

Measuring quality in end-of-life care.

Scrutiny of the quality of medical care near the end of life is increasing. Experts have begun to define and conceptualize quality of care for dying patients and are developing measurement tools to assess quality of care in this population. Definitions and conceptual models of quality of care at the end of life are reviewed. Approaches for measuring the processes and outcomes of end-of-life care are discussed. Approaches for initiating quality assessment of end-of-life care among geriatric patients are suggested.

Should air contrast computed tomography become the first investigation of the colon of frail or elderly patients?

OBJECTIVE: Air contrast computed tomography (ACCT) is an alternative test to barium enema or colonoscopy. We review our experience of this test as the first investigation of frail, elderly patients with lower gastrointestinal symptoms, and record the subsequent clinical course of these patients to evaluate the efficacy of the technique. PATIENTS AND METHODS: We performed 109 ACCT studies on frail patients aged 70 years or over with lower gastrointestinal symptoms. The findings were correlated with subsequent investigations and surgical findings. Patients with normal scans were followed up in out-patients or by their GP. Average follow up was 17 months. RESULTS: A good quality complete examination of the colon was achieved in 97% of patients. Of 109 examinations 34 (31%) were reported as normal, 65 (60%) as diverticular disease, nine (8%) as demonstrating a colonic malignancy and one (1%) showed a benign polyp. One sigmoid tumour was missed initially but diagnosed on a repeat ACCT study. CONCLUSION: ACCT is a reliable, well-tolerated technique in elderly frail patients.

Survey of intussusception reduction in England, Scotland and Wales: how and why we could do better.

AIM: The aim of our study was to assess the variation in technique among hospitals in England, Wales and Scotland. In addition, local in hospital variation among paediatric radiologists at our own institution was assessed. METHOD: Postal questionnaires were distributed to the radiology departments of 301 hospitals. RESULTS: 183 (60.8%) replies were received. 122 institutions reduced intussusceptions and 61 did not. A lack of paediatric surgical and/or anaesthetic cover, and a lack of radiological experience were the major reasons cited by the departments which did not attempt intussusception reduction. Sixty-five hospitals use barium for hydrostatic reduction, 43 employ pneumatic reduction, 10 use water-soluble enemas and four use ultrasound. Of the 65 centres using barium 16 (25%) reported a success rate of less than 50%, 24 (37%) had a 50-70% success rate, seven (11%) reduce greater than 70% of intussusceptions and 18 (27%) did not know. In the 43 institutions employing air reduction, one (2%) had a success rate less than 50%, 20 (47%) had a 50-70% success rate, 17 (40%) a success rate greater than 70% and five (11%) did not know. Overall, of the total number of hospitals which replied to our survey, 28 (23%) reported that they were not aware of their success rates. Within the pneumatic reduction group in particular there was marked variation in the methods and duration of attempted reduction - between different hospitals and within the same institution. In six departments the machine used for pneumatic reduction did not measure intraluminal pressure. CONCLUSIONS: Ultrasound is underutilized despite being a sensitive method in diagnosis. There is almost certainly an over-reliance on plain radiographs and on the use of sedation, antibiotics and anti-spasmodics in general. We believe a 70% or greater success rate should be achievable in most institutions whether by pneumatic or hydrostatic reduction, and all departments should strive to achieve success rates in this range. Less than a quarter of centres who replied currently achieve this standard. Successful reduction rates below 50% are unacceptable in our opinion. Not surprisingly, success rates are generally highest in those centres treating more than 20 cases per annum. Twenty-eight (23%) of hospitals performing intussusception reductions did not know their success rates. Regular audits of intussesception figures should take place in all institutions. Unacceptably wide variations in intussusception reduction techniques currently exist. An accurate pressure release valve at least, and preferably intraluminal pressure monitoring should be an integral component of all pneumatic reduction devices. The British Paediatric Radiology and Imaging Group or the Royal College of Radiology should address these issues and introduce some standardization of practice.

Platelet von Willebrand factor in Hermansky-Pudlak syndrome.

The Hermansky-Pudlak Syndrome (HPS) is an autosomal recessive inherited disorder characterized by oculocutaneous albinism, tissue accumulation of ceroid pigment, and a mild to moderate bleeding diathesis attributed to storage-pool deficient (SPD) platlets. Patients have platelet aggregation and release abnormalities. In addition, low levels of plasma von Willebrand factor (vWF) antigen in some HPS patients have been associated with a greater bleeding tendency than would be predicted from either condition alone. Other HPS patients have severe bleeding despite normal levels of plasma vWF, suggesting that at least one additional factor is responsible for their bleeding diathesis. Because platelet vWF levels have been well correlated with clinical bleeding times in patients with von Willebrand's disease, we have measured the platelet vWF activity and antigen levels in 30 HPS patients and have attempted to correlate their clinical bleeding with these values. The platelet vWF activity levels in patients was significantly lower than that of normal subjects (P < 0.0001). The patients as a group also had slightly lower values of plasma vWF activity when compared with normals (P-0.03). In 11 of the HPS patients, the multimeric structure of plasma vWF showed a decrease in the high molecular weight multimers and an increase in the low molecular weight multimers. In correlating the platelet and plasma vWF values with the bleeding histories, we were not able to show a predictable relationship in the majority of the patients.

Factors associated with change in resuscitation preference of seriously ill patients. The SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

BACKGROUND: During serious illness, patient preferences regarding life-sustaining treatments play an important role in medical decisions. However, little is known about life-sustaining preference stability in this population or about factors associated with preference change. METHODS: We evaluated 2-month cardiopulmonary resuscitation (CPR) preference stability in a cohort of 1590 seriously ill hospitalized patients at 5 acute care teaching hospitals. Using multiple logistic regression, we measured the association of patient demographic and health-related factors (quality of life, function, depression, prognosis, and diagnostic group) with change in CPR preference between interviews. RESULTS: Of 1590 patients analyzed, 73% of patients preferred CPR at baseline interview and 70% chose CPR at follow-up. Preference stability was 80% overall-85% in patients initially preferring CPR and 69% in those initially choosing do not resuscitate (DNR). For patients initially preferring CPR, older age, non-African American race, and greater depression at baseline were independently associated with a change to preferring DNR at follow-up. For patients initially preferring DNR, younger age, male gender, less depression at baseline, improvement in depression between interviews, and an initial admission diagnosis of acute respiratory failure or multiorgan system failure were associated with a change to preferring CPR at follow-up. For patients initially preferring DNR, patients with substantial improvements in depression score between interviews were more than 5 times as likely to change preference to CPR than were patients with substantial worsening in depression score. CONCLUSIONS: More than two thirds of seriously ill patients prefer CPR for cardiac arrest and 80% had stable preferences over 2 months. Factors associated with preference change suggest that depression may lead patients to refuse life-sustaining care. Providers should evaluate mood state when eliciting patients' preferences for life-sustaining treatments.

Complementation group assignments of moderately UV-sensitive CHO mutants isolated by large-scale screening (FAECB).

The complementation group (CG) assignment is presented for 74 moderately sensitive (approximately 2-4x sensitivity of parental line based on ratio of D10s) UV-sensitive mutants of Chinese hamster ovary (CHO) cells from the Facility for Automated Experiments in Cell Biology (FAECB) collection. The distribution of mutants within the first five rodent UV CGs was similar to that of previously reported highly sensitive (> 4x wild-type UV sensitivity) mutants from this collection. This analysis nearly completes the identification of this large collection of over 200 mutant lines isolated after screening an estimated 3 million total colonies of mutagenized CHO cells from approximately 20 mutant hunts with up to about 400,000 colonies screened. Only eight lines with less than about 2x parental line UV sensitivity remain unassigned. One CG of UV mutants (CG6), which now has five identified representatives in the collection, has only been found among moderately UV-sensitive CHO cells. Mutant UV40, a mitomycin C (MMC)- and X-ray-sensitive line with moderate UV cross-sensitivity, is not in CGs 1-6 and apparently is not a nucleotide excision repair mutant. Also identified were new alleles of CG1 and CG4 mutants with profoundly deficient unscheduled DNA synthesis and moderate UV sensitivity but low sensitivity to MMC. The first CG5 mutant derived from MMC-sensitive MC5 cells has been identified as the second CG5 mutant in the collection. No representatives of rodent CGs 7-11 were found, suggesting that AA8 cells have a chromosomal makeup that precludes easy isolation of mutants in these CGs.

Changes in patient characteristics and surgical outcomes for coronary artery bypass surgery 1972-82.

Data from a national sample of hospitals were used to explore reasons for improved in-hospital survival rate for coronary artery bypass graft (CABG) surgery between 1972 and 1982. Increases in annual volumes of surgery explain a large fraction of the decline in death rates. The residual can be attributed to improved techniques, experience, and other factors, even though more operations were done on older patients and women in 1982 than 1972.

Association of volume with outcome of coronary artery bypass graft surgery. Scheduled vs nonscheduled operations.

Empirical evidence suggests that mortality rates for coronary artery bypass graft (CABG) surgery are lower in hospitals that perform a higher volume of the procedure. In recent years, the criteria for CABG surgery have been expanded to include patients with a wide variety of co-morbidities. To address the question of whether the volume-outcome relationship continues to exist for this new group of patients, discharge abstracts for 18,986 CABG operations at 77 hospitals in California in 1983 were analyzed using multiple-regression techniques. Higher-volume hospitals had lower in-hospital mortality (adjusted for case mix); this effect was greatest in patients who might be characterized as having "non-scheduled" CABG surgery. Higher-volume hospitals also had shorter average postoperative lengths of stay and fewer patients with extremely long stays. The results of this study suggest that the greatest improvement in average outcomes for CABG surgery would result from the closure of low-volume surgery units.

Episode-of-care physician payment: a study of coronary artery bypass graft surgery.

Paying physicians for an episode of care is a possible alternative to current fee-for-service payment. We studied physician billing patterns for 512 Medicare beneficiaries who received coronary artery bypass graft (CABG) surgery in 1983. Relatively elaborate decision rules had to be created to exclude services that were not part of a routine CABG. We found that 72% of charges for an episode were associated with services provided on the day of surgery. Forty-seven percent of charges were by the primary surgeon, 15% by the assistant surgeon(s), and 9% by the anesthesiologist. Our results suggest that episode-of-care payment is a complex, and somewhat costly, alternative to other methods of prospective payment to physicians, although selective contracting by a health insurer for an episode of care for certain procedures might both reduce costs and improve quality.

Structure and expression of a gene encoding human calcitonin and calcitonin gene related peptide.

Messenger RNAs for calcitonin (CT) and calcitonin gene related peptide (CGRP) have been detected in a human medullary thyroid carcinoma cell line. DNA sequences of their cloned cDNAs, and genomic restriction mapping, indicate that both mRNAs probably originate from a single gene; the separate mRNAs are derived by alternative processing. The calcitonin gene is expressed in 10 of 10 examined culture lines of human lung cancer; most of these lines express a higher ratio of CGRP to CT specific mRNA than does the medullary thyroid carcinoma cell line.