Search

Background: To minimize potential risk of intussusception, the World Health Organization (WHO) recommended in 2009 that rotavirus immunization should be initiated by age 15 weeks and completed before 32 weeks. These restrictions could adversely impact vaccination coverage and thereby its health impact, particularly in developing countries where delays in vaccination often occur.Methods and Findings: We conducted a modeling study to estimate the number of rotavirus deaths prevented and the number of intussusception deaths caused by vaccination when administered on the restricted schedule versus an unrestricted schedule whereby rotavirus vaccine would be administered with DTP vaccine up to age 3 years. Countries were grouped on the basis of child mortality rates, using WHO data. Inputs were estimates of WHO rotavirus mortality by week of age from a recent study, intussusception mortality based on a literature review, predicted vaccination rates by week of age from USAID Demographic and Health Surveys, the United Nations Children's Fund (UNICEF) Multiple Indicator Cluster Surveys (MICS), and WHO-UNICEF 2010 country-specific coverage estimates, and published estimates of vaccine efficacy and vaccine-associated intussusception risk. On the basis of the error estimates and distributions for model inputs, we conducted 2,000 simulations to obtain median estimates of deaths averted and caused as well as the uncertainty ranges, defined as the 5th-95th percentile, to provide an indication of the uncertainty in the estimates. We estimated that in low and low-middle income countries a restricted schedule would prevent 155,800 rotavirus deaths (5th-95th centiles, 83,300-217,700) while causing potentially 253 intussusception deaths (76-689). In contrast, vaccination without age restrictions would prevent 203,000 rotavirus deaths (102,000-281,500) while potentially causing 547 intussusception deaths (237-1,160). Thus, removing the age restrictions would avert an additional 47,200 rotavirus deaths (18,700-63,700) and cause an additional 294 (161-471) intussusception deaths, for an incremental benefit-risk ratio of 154 deaths averted for every death caused by vaccine. These extra deaths prevented under an unrestricted schedule reflect vaccination of an additional 21%-25% children, beyond the 63%-73% of the children who would be vaccinated under the restricted schedule. Importantly, these estimates err on the side of safety in that they assume high vaccine-associated risk of intussusception and do not account for potential herd immunity or non-fatal outcomes.Conclusions: Our analysis suggests that in low- and middle-income countries the additional lives saved by removing age restrictions for rotavirus vaccination would far outnumber the potential excess vaccine-associated intussusception deaths. Please see later in the article for the Editors' Summary. [ABSTRACT FROM AUTHOR]

Background: With the recent postlicensure identification of an increased risk of intussusception with rotavirus vaccine, the 14 Latin American countries currently using rotavirus vaccine must now weigh the health benefits versus risks to assess whether to continue vaccination. To inform policy considerations, we estimated excess intussusception cases and mortality potentially caused by rotavirus vaccine for each of the 14 countries and compared these estimates to hospitalizations and deaths expected to be averted through vaccination., Methods: We used regional rotavirus disease burden and rotavirus vaccine efficacy data, global natural intussusception and regional rotavirus vaccine-related risk estimates, and country-specific diphtheria, tetanus, and pertussus vaccination coverage rates to estimate rotavirus vaccine coverage rates. We performed a probabilistic sensitivity analysis to account for uncertainty in these parameters., Results: For an aggregate hypothetical birth cohort of 9.5 million infants in these 14 countries, rotavirus vaccine would annually prevent 144 746 (90% confidence interval [CI], 128 821-156 707) hospitalizations and 4124 deaths (90% CI, 3740-4239) due to rotavirus in their first 5 years of life but could cause an additional 172 hospitalizations (90% CI, 126-293) and 10 deaths (90% CI, 6-17) due to intussusception, yielding benefit-risk ratios for hospitalization and death of 841:1 (90% CI, 479:1 to 1142:1) and 395:1 (90% CI, 207:1 to 526:1), respectively. In an uncertainty analysis using 10 000 simulations of our probabilistic parameters, in comparing rotavirus disease averted to intussusception events caused, the hospitalization ratio was never below 100:1, and our death ratio fell below 100:1 only once., Conclusions: The health benefits of vaccination far outweigh the short-term risks and support continued rotavirus vaccination in Latin America.

Background: There are plans to introduce the oral rotavirus vaccine Rotarix (GlaxoSmithKline), 1 of 2 recently developed vaccines against rotavirus, in Peru., Methods: We modeled the cost-effectiveness of adding a rotavirus vaccine to the Peruvian immunization program under 3 scenarios for the timing of vaccination: (1) strictly according to schedule, at 2 and 4 months of age (on time); (2) distributed around the target ages in the same way as the actual timings in the program (flexible); and (3) flexible but assuming vaccination is not initiated for infants >12 weeks of age (restricted). We assumed an introductory price of US $7.50 per dose, and varied the annual rate of price decrease in sensitivity analyses., Results: The discounted cost per disability-adjusted life-year averted for restricted, flexible, and on-time schedules was $621, $615, and $581, respectively. For each of the 3 scenarios, the percentage reduction in deaths due to rotavirus infection was 53%, 66%, and 69%, respectively. The cost per disability-adjusted life-year averted for alternative "what-if" scenarios ranged from $229 (assuming a 1-dose schedule, administered on time) to $1491 (assuming a 2-dose schedule, with half the baseline vaccine efficacy rates and a restricted timing policy)., Conclusions: On the basis of current World Health Organization guidelines, rotavirus vaccination represents a highly cost-effective intervention in Peru. Withholding the vaccine from children who present for their first dose after 12 weeks of age would reduce the number of deaths averted by approximately 20%. A single dose may be more cost-effective than 2 doses, but more evidence on the protection conferred by a single dose is required.

Introduction: Recently developed rotavirus vaccines have the potential to reduce diarrhea mortality in children in developing countries. Available data to date do not indicate risk of intussusception with these new vaccines. To avoid a potential unanticipated risk post-licensure, it is recommended that rotavirus immunization be initiated before 12 weeks of age when background intussusception rates are low. This policy could exclude a substantial number of children from vaccination, especially in developing countries where delays in vaccination are common., Methods: We conducted a scenario analysis to assess the potential benefits of mortality reduction from rotavirus versus the risk of fatal intussusception when the first dose of the vaccine is strictly administered by 12 weeks of age compared with a free strategy with vaccine administered before 1 year of age using data on rotavirus disease, vaccine safety and efficacy, and current diphtheria-tetanus-pertussis vaccination rates, and by incorporating hypothetical risks of intussusception., Results: In developing countries, assuming vaccine efficacy of 50% and 75% for doses 1 and 2, respectively, and a hypothetical sixfold and threefold increased relative risk of intussusception within 7 days of doses 1 and 2, respectively, initiating rotavirus immunization before 12 weeks of age would prevent 194,564 of the 517,959 annual rotavirus-associated deaths among children <5 years, while potentially resulting in 1106 fatal intussusception events. Administration of the first dose to infants up to 1 year of age would prevent an additional 54,087 rotavirus-associated deaths (total=248,651) while potentially resulting in an additional 1226 intussusception deaths (total=2332)., Conclusion: In developing countries, the additional lives saved by broadening the age restrictions for initiation of rotavirus vaccination would far outnumber the hypothetical excess intussusception deaths that would accompany such an approach.

Background: Non-invasive ventilation is first-line treatment for patients with acutely decompensated chronic obstructive pulmonary disease (COPD), but endotracheal intubation, involving admission to an intensive care unit, may sometimes be required. Decisions to admit to an intensive care unit are commonly based on predicted survival and quality of life, but the information base for these decisions is limited and there is some evidence that clinicians tend to be pessimistic. This study examined the outcomes in patients with COPD admitted to the intensive care unit for decompensated type II respiratory failure., Methods: A prospective cohort study was carried out in 92 intensive care units and 3 respiratory high dependency units in the UK. Patients aged 45 years and older with breathlessness, respiratory failure or change in mental status due to an exacerbation of COPD, asthma or a combination of the two were recruited. Outcomes included survival and quality of life at 180 days., Results: Of the 832 patients recruited, 517 (62%) survived to 180 days. Of the survivors, 421 (81%) responded to a questionnaire. Of the respondents, 73% considered their quality of life to be the same as or better than it had been in the stable period before they were admitted, and 96% would choose similar treatment again. Function during the stable pre-admission period was a reasonable indicator of function reported by those who survived 180 days., Conclusions: Most patients with COPD who survive to 180 days after treatment in an intensive care unit have a heavy burden of symptoms, but almost all of them-including those who have been intubated-would want similar intensive care again under similar circumstances.

Objective: Estimates of vaccination costs usually provide only point estimates at national level with no information on cost variation. In practice, however, such information is necessary for programme managers. This paper presents information on the variations in costs of delivering routine immunization services in three diverse districts of Peru: Ayacucho (a mountainous area), San Martin (a jungle area) and Lima (a coastal area)., Methods: We consider the impact of variability on predictions of cost and reflect on the likely impact on expected cost-effectiveness ratios, policy decisions and future research practice. All costs are in 2002 prices in US dollars and include the costs of providing vaccination services incurred by 19 government health facilities during the January-December 2002 financial year. Vaccine wastage rates have been estimated using stock records., Findings: The cost per fully vaccinated child ranged from 16.63-24.52 U.S. Dollars in Ayacucho, 21.79-36.69 U.S. Dollars in San Martin and 9.58-20.31 U.S. Dollars in Lima. The volume of vaccines administered and wastage rates are determinants of the variation in costs of delivering routine immunization services., Conclusion: This study shows there is considerable variation in the costs of providing vaccines across geographical regions and different types of facilities. Information on how costs vary can be used as a basis from which to generalize to other settings and provide more accurate estimates for decision-makers who do not have disaggregated data on local costs. Future studies should include sufficiently large sample sizes and ensure that regions are carefully selected in order to maximize the interpretation of cost variation.

Objectives: The aim of this study was to make epidemiologically based estimates of the prevalent and incident "need" for prostatectomy for lower urinary tract symptoms, defined as the numbers of men who would both benefit from and want the operation., Methods: The methods involved a consensus panel, a two-stage postal survey of 1,480 men aged 55 years or older from eight general practices to the northwest of London, United Kingdom, and a multistate life table., Results: The overall response rate was 69% (initial survey: 78%, follow-up survey: 88%). A trial-based estimate of number of candidates for prostatectomy (men with symptoms that were at least moderately severe and bothersome and who would probably or definitely want surgery) was 610 men in a population of 250,000. The corresponding incidence estimate (including men with symptoms recurring after spontaneous remission or surgery) was approximately 200 per year, including approximately 110 new cases. Consensus-based estimation, including categories of patients who have not yet been subject to a trial, gave much higher figures of approximately 3,000, 650, and 200 candidates, respectively. Adding the number of men who said they were "inclined to" choose surgery would almost double these figures., Conclusions: Estimates of need were highly sensitive to choice of indications and assumptions about patients' attitudes toward surgery. Population needs assessment for specific procedures will always involve judgment as well as epidemiological data and modeling.

Our objective was to determine the extent to which lower urinary tract symptoms affect the general health status of men and contribute to the decision to undergo surgery. A cross-sectional population survey using postal questionnaires was conducted in the North West Thames health region, followed by a prospective cohort study of men undergoing prostatectomy (North West Thames and Oxford regions). The subjects in the first survey were 221 men aged 55 and over with previously reported mild, moderate or severe urinary symptoms; subjects in the second study were 388 men undergoing prostatectomy. Main outcome measures were self-reported symptom severity, bothersomeness and general health status (Nottingham Health Profile, Part 1). The response rate among eligible responders in the population survey was 85.7%. Increasing symptom severity was associated with worsening NHP scores for energy, emotional reactions, sleep and physical mobility (p < 0.01). Increasing bothersomeness of symptoms was associated with emotional reactions, sleep and pain (p < 0.05). Men undergoing surgery reported worse health status than men in the population with the same severity of symptoms as regards emotional reactions, energy and pain. For a given level of symptom severity, the impact of those symptoms on aspects of a man's general health status may be the determinant of seeking and undergoing surgery. Greater understanding of the factors that affect a man's response to his symptoms is needed in interpreting the decision to seek and accept treatment.

Objectives: To determine the extent to which urinary symptoms, and resulting bothersomeness interfere with daily activities and affect health status, as measured using the Medical Outcomes Study 36-item short form health survey (SF-36)., Methods: Postal population survey in a British health region of 217 men aged 55 years and over known to have reported mild, moderate, or severe lower urinary tract symptoms. Outcome measures are self-reported urinary symptoms, their bothersomeness, general health status, and quality of life (measured using the SF-36)., Results: Response rate among eligible subjects was 84%. Depending on the activity, between 9% and 49% of men with moderate or severe urinary symptoms reported interference with some of their daily activities. Increasing symptom severity was associated with worsening physical role, social functioning, vitality, mental health, and perception of general health, and increasing bothersomeness was associated with worsening of all dimensions of general health status and quality of life. The association between these measures and bothersomeness was stronger than with symptom score. Compared with the general population, men bothered by their symptoms to the extent that they were a medium or a large problem have worse health status for all dimensions except physical functioning., Conclusions: The SF-36 demonstrates a deterioration in general health status and quality of life with increasing lower urinary tract symptoms and the extent to which those symptoms are bothersome. As such, it provides a generic measure of the burden of ill health arising from these symptoms at a population level. There is, however, considerable individual variation in the way that men respond to their symptoms.

Background: Urinary symptoms are common among middle aged and elderly men., Aim: A study was undertaken to describe the health care sought by men aged 55 years and over with urinary symptoms, the action taken by general practitioners and urologists, and the men's views on prostatectomy., Method: A postal questionnaire was sent to 516 men aged 55 years and over in the North West Thames Regional Health Authority, with previously identified mild, moderate or severe urinary symptoms., Results: The response rate among eligible subjects was 83%. Of 420 respondents 45% had seen their general practitioner for their symptoms. General practitioners had referred 62% of these men to a urologist, reassured 21% and prescribed medication to 17%. The probability of a man seeking medical advice increased with increasing symptom severity. In contrast, the decision to refer was independent of symptom severity. Of the men referred to a urologist, the majority (71%) were offered and accepted surgery. The remainder were reassured (17%), or received a prescription (4%). Eight per cent were offered surgery but declined. When presented with details and information on the risks and benefits of prostatectomy, 22% of men with symptoms would probably or definitely refuse treatment, while a further 47% of men were unsure., Conclusion: There are many men who do not seek treatment for urinary symptoms and, of those who do, subsequent referral is not associated with symptom severity. There is scope for improving the referral process through the shared development of guidelines between general practitioners, hospitals and commissioning agencies.

Objective: To measure the prevalence and severity of urinary symptoms among men aged 55 and over in the British population., Design: Cross sectional population survey using a postal questionnaire., Setting: North West Thames health region., Subjects: 1480 men aged 55 years and over randomly selected from 8 general practices., Main Outcome Measures: Self reported frequency and severity of urinary symptoms, their bothersomeness and previous prostate surgery., Results: The response rate among eligible subjects was 78%. The prevalence of moderate and severe symptoms was 204 per 1000, rising from 160 per 1000 in the 55-59 age group to 259 per 1000 in the 70-74 age group and declining after the age of 80 to 119 per thousand in the 85+ age group. Twelve per cent of men reported previous prostate surgery, and the probability of having had surgery increases steadily with age. About a third of those undergoing surgery have recurrence or persistence of symptoms after surgery. Of men with moderate and severe symptoms, 27.9% reported that their symptoms were a medium or big problem, 36.9% reported that their symptoms interfered with their daily activities at least some of the time, and 43.1% were unhappy or 'felt terrible' about the prospect of a future with their current symptoms., Conclusion: The prevalence of urinary symptoms in men is lower than previously reported, although there is a substantial number of men who are bothered by, or who find their lives adversely effected by them.

The impact of open cholecystectomy on patients' symptoms and health status and their level of satisfaction has been examined to provide a basis for comparison with newer rival treatments. A prospective cohort study using patient and surgeon completed questionnaires before and six weeks after surgery was carried out in 14 general hospitals in eight European countries. Five hundred and eighty three patients were recruited consecutively in 1990 to 1991. Information on their symptoms, general health status, activities of daily living, and satisfaction with their care were collected. After surgery 42.8% of patients reported that they were free of symptoms. Symptoms varied in their responsiveness to surgery--six weeks after surgery 89% of those who had complained of vomiting had improved, 81% of nausea, 69% of loss of appetite, 65% of abdominal pain, and 51% of flatulence. In contrast 28.1% of patients still suffered from flatulence and 23.5% continued to complain of abdominal pain. Most patients' (62.7%) general health improved, 28% were unchanged, and 9.3% were worse. After surgery most patients reported no restrictions in their normal social activities (75-90% depending on the activity) and most (89.5%) felt the results of their operation had been as expected or better than expected. Most patients undergoing open cholecystectomy reported an improvement in their symptoms, health status, and social functioning. This was reflected in their high level of satisfaction. Some patients, however, gained no benefit and a small proportion were worse than before surgery.

Study Objective: The use of formal consensus development to determine appropriate indications for prostatectomy and to identify factors underlying clinical decisions about appropriateness is described., Design: A nominal group technique was used., Settings: The study took place in an academic research institution., Participants: The panel consisted of six urologists and three general practitioners., Measurements and Main Results: The panel identified agreed indications for prostatectomy, expressed in terms of different combinations of type of retention, type and severity of symptoms, and level of comorbidity. Agreement was reached for 67% of the indications considered. For acute on chronic retention, surgery is indicated, regardless of symptom severity, if life expectancy is greater than one year. For acute or chronic retention, surgery is generally indicated if symptoms are severe, or if symptoms are moderate and life expectancy is greater than five years. For patients with neither acute nor chronic retention, surgery is indicated if symptoms are severe, or if these are moderate and life expectancy is greater than five years. For chronic or acute retention surgery is inappropriate if symptoms are mild and life expectancy is less than one year, or if there is no retention and only mild symptoms. An "appropriateness score" was developed. This confirmed that in general the ratings were internally consistent, that the panel attached little weight to mild symptoms, that a combination of irritative and obstructive symptoms was no more indicative of surgery than obstructive symptoms alone, and that the type of symptom was less important than the other factors considered., Conclusions: The results provide a basis for population based surveys of the need for prostatectomy.

Relative changes in disease incidence for different population groups can shed light on two questions: if they can be linked to groups exposed to contrasting types or intensities of intervention in a disease prevention program, they provide a way to assess the program's effectiveness; if they can be linked to groups with different levels of risk factors, they can provide information on the etiological relationships upon which prevention programs can be based. Sweden's registers and databases are reviewed as potential sources of cancer incidence data. In principle, these data may be used to evaluate the Stockholm Cancer Prevention Programme if "place of residence" is a sufficiently valid indicator of exposure to intervention. Through record linkage, the effect of socioeconomic status can be examined and controlled for. For etiological studies, differential changes in cancer incidence between geographical areas can be linked to, for example, local changes in diet, although data on this may be limited. However, given the "prospective" design and the expected lag between habit change and effect on morbidity, the sizes of the groups and the length of the period studied will have to be very substantial.

During the course of a larger study aimed at relating staffing levels of junior doctors in general medicine to the safety of the care provided, it became clear that consultant doctors considered the quality of their junior staff as being at least as important as the quantity. This paper describes several attempts to develop a feasible and valid method of measuring the quality of senior house officers (SHOs) and registrars using routinely available data. Having rejected three methods and had difficulties with three other methods, a modified Delphi survey was used to explore the extent to which consultants agreed on the key attributes of a high quality SHO or registrar. Sixty-seven (60%) of all consultants in the South-West Thames and Trent regions responded to two rounds of questionnaires which revealed communication skills as being consistently the most significant factor. This was confirmed in a second, anonymous survey of 198 (78%) SHO and registrar posts in the North-West Thames region. It also became clear that consultants viewed the quality of their own SHOs and registrars as generally high. This being so it is argued that the requirement to adjust for quality, when comparing SHO and registrar levels between hospitals, is of minor importance. These results also suggest that the explicit teaching of communication skills should have a high priority in undergraduate and postgraduate education.

Objective: To assess the effect of five different surgical treatments for glue ear (secretory otitis media) on improvement in hearing and, assuming one or more treatments to be effective, to identify the appropriate indications for surgery., Design: Randomised controlled trial of children receiving (a) adenoidectomy, bilateral myringotomy, and insertion of a unilateral grommet; (b) adenoidectomy, unilateral myringotomy, and insertion of a unilateral grommet; (c) bilateral myringotomy and insertion of a unilateral grommet; and (d) unilateral myringotomy and insertion of a grommet. Children were followed up at seven weeks, six months, 12 months, and 24 months by symptom history and clinical investigations., Setting: Otolaryngology department in an urban hospital., Patients: 149 Children aged 4-9 years who were admitted for surgery for glue ear and who had no history of previous operations on tonsils, adenoids, or ears and no evidence of sensorineural deafness. Inadequate follow up information on levels of hearing and on middle ear function was obtained from 22., Main Outcome Measures: Mean hearing loss (dB) of the three worst heard frequencies between 250 and 4000 Hz, results of impedance tympanometry, and parental views on their child's progress., Results: In the 127 children for whom adequate information was available ears in which a grommet had been inserted performed better in the short term (for at least six months) than those in which no grommet had been inserted, irrespective of any accompanying procedure. Most of the benefit had disappeared by 12 months. Adenoidectomy produced a slight improvement that was not significant, though was sustained for at least two years. The ears of children who had had an adenoidectomy with myringotomy and grommet insertion, however, continued to improve so that two years after surgery about 50% had abnormal tympanometry compared with 83% of those who had had only myringotomy and grommet insertion, and 93% of the group that had had no treatment. Logistic regression analyses identified preoperative hearing level as the single best predictor of good outcome from surgery. Other variables contributed little additional predictive power., Conclusions: If the principal objective of surgery for glue ear is to restore hearing then our study shows that insertion of grommets is the treatment of choice. The addition of an adenoidectomy will increase the likelihood of restoration of normal function of the middle ear but will not improve hearing. When deciding appropriate indications for surgery, a balance has to be made between performing unnecessary operations and failing to treat patients who might benefit from surgical intervention. Preoperative audiometry scores might be the best predictor in helping to make this decision.

The incidence of myocardial infarction and the return to work for survivors were studied among the employees of an English car assembly plant by analysing 12 811 medical records of persons employed during the seven years between January 1966 and December 1972. The standardized morbidity ratio of myocardial infarction found in this study calculated on the basis of incidence rates reported by Kinlen )1973) for the Oxford community in which the factory was situated was 90. The standardized morbidity ratio from production line workers only was 66 and that for the monthly paid staff 272. Of the production line workers who survived the attack 22 (90%) returned to their previous jobs without undue difficulty and with two exceptions within four months of the onset of their illness; there was no relation between length of absence and age at the time of attack. These findings suggest that workers in mass production jobs such as car assembly are not special risk from myocardial infarction, and most of those who survive a heart attack are able to return to their former work. Taken with Kinlen's (1973) study and that of Armstrong et al. (1972) in Edinburgh, they also bear out mortality data by indicating that in Oxfordshire the incidence of coronary heart disease is lower than the British average.