Vaccines against the zoonotic trematodes Schistosoma japonicum, Fasciola hepatica and Fasciola gigantica

Schistosoma japonicum, Fasciola hepatica and F. gigantica are digenetic trematodes and, therefore, possess similar life cycles. While schistosomiasis japonica has for a long time been recognised as a major disease of both humans and animals, infection with fasciolids has only been considered of relevance to animals. However, a number of recent reports indicate that fasciolosis is becoming a serious public health problem, especially in South America, Egypt and Iran (sporadic cases are also on the increase throughout Europe). Vaccines targeted at animals could play an important role in controlling these three diseases in animals and, by blocking transmission of infection, have a concurrent beneficial effect on disease in humans. Approaches towards identifying and producing vaccines against these parasites are similar and are discussed in this reveiw. © 2006 Cambridge University Press

Validation protocols for blood pressure measuring devices: the impact of the European Society of Hypertension International Protocol and the development of a Universal Standard

In the last three decades protocols for the validation of blood pressure measuring devices have been developed by the US Association for the Advancement of Medical Instrumentation, the British Hypertension Society, the German Hypertension League, the European Society of Hypertension Working Group on blood pressure Monitoring and the International Organization for Standardization. The European Society of Hypertension International Protocol required much smaller sample size than the other protocols, aiming to reduce the time, resources and cost of validation studies and thereby increase the number of validated devices. Given its specifications, the European Society of Hypertension International Protocol was adequate for ‘high- and low-accuracy’ devices, yet assessment of ‘moderate accuracy’ devices had high uncertainty with resultant high rate of device failure. Thus, devices validated using the European Society of Hypertension International Protocol should be considered to be as accurate as those validated with the previous Association for the Advancement of Medical Instrumentation or British Hypertension Society protocols. However, the European Society of Hypertension International Protocol did not allow subgroup evaluation (arm sizes, special populations, etc). The mission of the European Society of Hypertension International Protocol to promote the concept of validation has been well achieved, as almost double studies have been published using it than all the other protocols together. However, the maintenance of different validation protocols is confusing and therefore experts from the Association for the Advancement of Medical Instrumentation, European Society of Hypertension International Protocol and International Organization for Standardization have now developed the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018) as the recommended 21st-century procedure for worldwide application. The European Society of Hypertension Working Group has published a practical guide for using the Universal Standard. It is in the interests of all scientific bodies to propagate the Universal Standard and ensure its wide implementation

Lack of patients? – a hypothesis for understanding discrepancies between hospital resources and productivity

BACKGROUND: Despite a substantial increase in hospital resources, increased hospital admissions and out-patient visits, long waiting lists have been a significant problem in Norwegian health care. A detailed analysis of the development in resource allocation and productivity at St. Olavs University Hospital in central Norway was therefore undertaken. METHODS: Resource allocation and patient volume was analysed during the period 1995 to 2001. Data were analysed both for emergency and elective admissions as well as outpatient visits specified into new referrals and follow-up consultations. RESULTS: Full time employee equivalents for doctors and nurses increased by 36.6% and 25.9%, respectively, and all employees by 28.1%. However, admitted patients, outpatient consultations and surgical procedures only increased by 10%, 15% and 8.3%, respectively. Thus, the productivity for each hospital employee, defined as operations pr. surgeon, outpatient consultations pr. doctor etc. was significantly reduced. A striking finding was that although the number of outpatient consultations increased, the number of new referrals actually went down and the whole increase in activity at the outpatient clinics could be explained by a substantial increase in follow-up consultations. This trend was more evident in the surgical departments, where some departments actually showed a reduction in total outpatient consultations. CONCLUSION: In view of the slow increase in hospital activity in spite of a significant increase in resources, it can be speculated that patient volume might be a limiting factor for hospital activity. The health market (patient population) might not be big enough in relation to the investments in increased production capacity (equipment and manpower)

Prevalence of magnetic reconnection in the near-Sun heliospheric current sheet

During three of its first five orbits around the Sun, Parker Solar Probe (PSP) crossed the large-scale Heliospheric Current Sheet (HCS) multiple times and provided unprecedented detailed plasma and field observations of the near-Sun HCS. We report the common detections by PSP of reconnection exhaust signatures in the HCS at heliocentric distances of 29.5-107 solar radii during Encounters 1, 4 and 5. Both sunward and antisunward-directed reconnection exhausts were observed. In the sunward reconnection exhausts, PSP detected counterstreaming strahl electrons, indicating that HCS reconnection resulted in the formation of closed magnetic field lines with both ends connected to the Sun. In the antisunward exhausts, PSP observed dropouts of strahl electrons, consistent with the reconnected HCS field lines being disconnected from the Sun. The common detection of reconnection in the HCS suggests that reconnection is almost always active in the HCS near the Sun. Furthermore, the occurrence of multiple long-duration partial crossings of the HCS suggests that HCS reconnection could produce chains of large bulges with spatial dimensions of up to several solar radii. The finding of the prevalence of reconnection in the HCS is somewhat surprising since PSP has revealed that the HCS is much thicker than the kinetic scales required for reconnection onset. The observations are also in stark contrast with the apparent absence of reconnection in most of the small-scale and much more intense current sheets encountered near perihelia, many of which are associated with ‘switchbacks’. Thus, the PSP findings suggest that large-scale dynamics either locally in the solar wind or within the coronal source of the HCS (at the tip of helmet streamers) plays a critical role in triggering reconnection onset

Modeling recursive RNA interference.

An important application of the RNA interference (RNAi) pathway is its use as a small RNA-based regulatory system commonly exploited to suppress expression of target genes to test their function in vivo. In several published experiments, RNAi has been used to inactivate components of the RNAi pathway itself, a procedure termed recursive RNAi in this report. The theoretical basis of recursive RNAi is unclear since the procedure could potentially be self-defeating, and in practice the effectiveness of recursive RNAi in published experiments is highly variable. A mathematical model for recursive RNAi was developed and used to investigate the range of conditions under which the procedure should be effective. The model predicts that the effectiveness of recursive RNAi is strongly dependent on the efficacy of RNAi at knocking down target gene expression. This efficacy is known to vary highly between different cell types, and comparison of the model predictions to published experimental data suggests that variation in RNAi efficacy may be the main cause of discrepancies between published recursive RNAi experiments in different organisms. The model suggests potential ways to optimize the effectiveness of recursive RNAi both for screening of RNAi components as well as for improved temporal control of gene expression in switch off-switch on experiments

Generalizability of Blood Pressure Lowering Trials to Older Patients: Cross‐Sectional Analysis

BACKGROUND/OBJECTIVES: Randomized controlled trials are used to inform clinical guidelines on the management of hypertension in older adults, but it is unclear to what extent these trials represent the general population attending routine clinical practice. This study aimed to define the proportion and characteristics of patients eligible for hypertension trials conducted in older people. DESIGN: Cross‐sectional study. SETTING: A total of 24 general practices in England. PARTICIPANTS: Anonymized electronic health record data from all individuals aged 80 and older. MEASUREMENTS: Descriptive statistics were used to define the proportion and characteristics of patients eligible for two previous medication intensification trials (HYVET, SPRINT) and one medication reduction trial (OPTiMISE). A logistic regression model was constructed to estimate predictors of eligibility for each trial. RESULTS: Of 15,376 patients identified, 268 (1.7%; 95% confidence interval [CI] = 1.5–2.0%), 5,290 (34.4%; 95%CI = 33.7–35.2%), and 3,940 (25.6%; 95%CI = 24.9–26.3%) were eligible for the HYVET, SPRINT, and OPTiMISE trials, respectively. Between 5.6% and 30.7% of exclusions from each trial were due to eligibility criteria excluding those with high or uncontrolled blood pressure. Frailty (odds ratio [OR] = .44; 95%CI = .36–.54 [OPTiMISE]), cardiovascular polypharmacy (OR = .61; 95%CI = .55–.68 [SPRINT]) and multimorbidity (OR = .72; 95%CI = .64–.82 [SPRINT]) were associated with a lower likelihood of being eligible for one or more of the trials. CONCLUSION: A possible unintended consequence of blood pressure criteria used by trials attempting to answer different primary questions is that for many older patients, no trial evidence exists to inform treatment decisions in routine practice. Caution should be exercised when applying results from existing trials to patients with frailty or multimorbidity

Maternal position during the first stage of labor: a systematic review

BACKGROUND: Policy makers and health professionals are progressively using evidence-based rationale to guide their decisions. There has long been controversy regarding which maternal position is more appropriate during the first stage of labor. This problem has been examined often and repeatedly and the optimal recommendation remains unclear. METHODS: This is a systematic review of the effect of maternal position during the first stage of labor. The main question addressed here is: Does encouraging women to adopt an upright position or to ambulate during the first stage of labor reduce the duration of this stage? All randomized controlled trials carried out to assess this effect were taken into consideration in this review. The following electronic databases were accessed to identify studies: MEDLINE, Popline, the Scientific Electronic Library On-line and the Latin American and Caribbean Health Science Information. Citation eligibility was independently assessed by two reviewers. The methodological quality of each trial was also evaluated independently by two reviewers and a trial under consideration was included only when consensus had been attained. Allocation concealment and screening for the occurrence of attrition, performance and detection biases were considered when studies were appraised. The decision whether to perform data pooling was based on the clinical similarity of studies. RESULTS: The search strategy resulted in 260 citations, of which 18 were assessed in full-text. Nine eligible randomized controlled trials were included in the systematic review. Randomization methods were not fully described in eight studies. The allocation concealment was considered adequate in four studies and unclear in five. The investigators pooled the data from seven studies in which the length of the first stage of labor and results were in favor of the intervention, but the high level of heterogeneity (I(2 )= 88.4%) impaired the meaning of this finding. The intervention did not affect other outcomes studied (mode of delivery, use of analgesia, labor augmentation and condition of the child at birth). CONCLUSION: Adoption of the upright position or ambulation during first stage of labor may be safe, but considering the available evidence and its consistency, it cannot be recommended as an effective intervention to reduce duration of the first stage of labor

The UKCAT-12 study: educational attainment, aptitude test performance, demographic and socio-economic contextual factors as predictors of first year outcome in a cross-sectional collaborative study of 12 UK medical schools

Most UK medical schools use aptitude tests during student selection, but large-scale studies of predictive validity are rare. This study assesses the United Kingdom Clinical Aptitude Test (UKCAT), and its four sub-scales, along with measures of educational attainment, individual and contextual socio-economic background factors, as predictors of performance in the first year of medical school training

A Universal Standard for the Validation of Blood Pressure Measuring Devices

In the past 30 years, several organizations, such as the US Association for the Advancement of Medical Instrumentation (AAMI), the British Hypertension Society, the European Society of Hypertension (ESH) Working Group on Blood Pressure (BP) Monitoring, and the International Organization for Standardization (ISO), have developed protocols for clinical validation of BP measuring devices. However, it is recognized that science, as well as patients, consumers, and manufacturers, would be best served if all BP measuring devices were assessed for accuracy according to an agreed single validation protocol that had global acceptance. Therefore, an international initiative was taken by the AAMI, ESH, and ISO experts who agreed to develop a universal standard for device validation. This statement presents the key aspects of a validation procedure, which were agreed by the AAMI, ESH, and ISO representatives as the basis for a single universal validation protocol. As soon as the AAMI/ESH/ISO standard is fully developed, this will be regarded as the single universal standard and will replace all other previous standards/protocols

Prevalence and predictors of hospital prealerting in acute stroke: a mixed methods study.

BACKGROUND: Thrombolysis can significantly reduce the burden of stroke but the time window for safe and effective treatment is short. In patients travelling to hospital via ambulance, the sending of a 'prealert' message can significantly improve the timeliness of treatment. OBJECTIVE: Examine the prevalence of hospital prealerting, the extent to which prealert protocols are followed and what factors influence emergency medical services (EMS) staff's decision to send a prealert. METHODS: Cohort study of patients admitted to two acute stroke units in West Midlands (UK) hospitals using linked data from hospital and EMS records. A logistic regression model examined the association between prealert eligibility and whether a prealert message was sent. In semistructured interviews, EMS staff were asked about their experiences of patients with suspected stroke. RESULTS: Of the 539 patients eligible for this study, 271 (51%) were recruited. Of these, only 79 (29%) were eligible for prealerting according to criteria set out in local protocols but 143 (53%) were prealerted. Increasing number of Face, Arm, Speech Test symptoms (1 symptom, OR 6.14, 95% CI 2.06 to 18.30, p=0.001; 2 symptoms, OR 31.36, 95% CI 9.91 to 99.24, p<0.001; 3 symptoms, OR 75.84, 95% CI 24.68 to 233.03, p<0.001) and EMS contact within 5 h of symptom onset (OR 2.99, 95% CI 1.37 to 6.50 p=0.006) were key predictors of prealerting but eligibility for prealert as a whole was not (OR 1.92, 95% CI 0.85 to 4.34 p=0.12). In qualitative interviews, EMS staff displayed varying understanding of prealert protocols and described frustration when their interpretation of the prealert criteria was not shared by ED staff. CONCLUSIONS: Up to half of the patients presenting with suspected stroke in this study were prealerted by EMS staff, regardless of eligibility, resulting in disagreements with ED staff during handover. Aligning the expectations of EMS and ED staff, perhaps through simplified prealert protocols, could be considered to facilitate more appropriate use of hospital prealerting in acute stroke