Inadvertent P-hacking among trials and systematic reviews of the effect of progestogens in pregnancy? A systematic review and meta-analysis.

BACKGROUND: Progestogens have been evaluated in numerous trials and meta-analyses, many of which concluded they were effective. However, two large trials PROMISE and OPPTIMUM have recently concluded that progesterone was ineffective. This raises the possibility that earlier studies and reviews had been biased by either selective publication or selective choice of outcomes, so called "P-hacking". OBJECTIVES: To compare the findings all progestogen trials and systematic reviews with those of trials with pre-registered primary outcomes which avoided selective outcome reporting. SEARCH STRATEGY: Search of PubMed, the Cochrane Library and trial registries. Registration PROSPERO CRD42016035303. SELECTION CRITERIA: Systematic reviews of randomised trials comparing progestogen with placebo in pregnancy and the individual trials included in those reviews. The subset of trials reporting a pre-registered primary outcome were compared with the totality of trials and reviews. DATA COLLECTION AND ANALYSIS: For reviews all outcomes were included. For individual trials all outcomes reported in the systematic reviews were included. For the comparison group we recorded the registered primary outcome from trials that were either registered before they started, or registered during the recruitment phase and also double blind. MAIN RESULTS: Nineteen of twenty-nine meta-analyses concluded that progestogens were effective. Twenty-two trials reported their pre-registered primary outcomes. There was no effect of progesterone on primary registered dichotomous outcome RR 1.00 (95% CI 0.94-1.07). Only one of the 22 showed a nominally statistically significant benefit. AUTHOR'S CONCLUSIONS: When evaluated in registered double-blind trials with analysis restricted to predefined primary outcomes, progestational agents in pregnancy are ineffective. TWEETABLE ABSTRACT: Progestogens to prevent pregnancy loss, an example of P-hacking.

Mapping stakeholders for system evaluation - the case of the Electronic Prescription Service in England.

This paper discusses the process of identifying stakeholders for the evaluation of health information systems through a map. Defining the multiplicity of stakeholders associated with a new system as well as the nature of their relationships is an important aspect of evaluating any intervention. We report a study of the Electronic Prescription Service (EPS) in primary care in England. We describe the complexity associated with the process of identifying stakeholders and illustrating their dynamic relationships. Reflecting upon our experience of map-making and map-using, we discuss the role of a stakeholder map to generate and communicate knowledge. The EPS stakeholder map - in its variety of possible alternative representations - reveals the complexity of the electronic prescribing scenario and the challenge of its evaluation. Recognising the drawbacks of a static two dimensional representation, we argue that a dynamic use of a stakeholder map and a reflective map-making practice is useful and important for the evaluation of IT programmes in healthcare.

Can carotid ultrasound predict plaque histopathology?

AIM: European and North American studies have confirmed the benefits of carotid endarterectomy for patients with symptomatic carotid artery stenoses >70%. However, the management of asymptomatic patients and those with lesser degrees of stenosis is less certain. Several studies have suggested that, for these subgroups, the targeting of potentially unstable plaques, may help to identify those most at risk of cerebrovascular accidents and thus most likely to benefit from surgery. The aim of this study was to correlate the ultrasound features of carotid artery stenosis with the histopathological findings of the carotid endarterectomy specimens in order to identify features which will allow preoperative identification of clinically unstable plaques. METHODS: Sixty consecutive patients with symptomatic, critical carotid stenosis were prospectively studied. Plaques were classified preoperatively into one of five types based on their echogenicity and were also assessed for irregularity and ulceration. These findings were then compared with the histopathological findings of the endarterectomy specimen. RESULTS: Of 33 plaques considered on ultrasound to be uniformly or predominantly echolucent (unstable), 27 were found to be largely fatty or haemorrhagic (PPV =82%). Of 17 plaques considered to be predominantly echogenic (stable) on ultrasound, 11 were found to be predominantly fibrotic (PPV = 65%). Correlation between ultrasound irregularity or ulceration and histopathology was poor. CONCLUSION: In routine clinical practice, ultrasound can identify with reasonable accuracy, plaques that are predominantly haemorrhagic or fatty, and therefore potentially unstable. This may have future implications in selection of patients for surgery.

Electromagnetic compatibility aspects of active robotic systems for surgery: the robotic prostatectomy experience.

The paper discusses the susceptibility to electromagnetic interference (EMI) of active robots for surgery, which are safety-critical systems. The high EMI environment of an operating room in the presence of an electrosurgical generator is considered. Experience of a surgeon assistant robot for prostatectomies in improving the immunity to EMI is described. It has been found that effective isolation of the robotic system hardware from grounded metal objects provides significant improvements to safety by its immunity to EMI, in minimising the flow of high-frequency current to ground through the system hardware.

The use of ultrasound in automated prostatectomy.

A new way of applying transurethral ultrasound scanning in the common surgical procedure of the transurethral resection of the prostate is described. The scanning is incorporated as part of a robotic procedure for surgery, so that the overall time spent in an operation can be further shortened, and a safe and accurate operation can be achieved. The prostate dimensions obtained pre-operatively by the transrectal method and those obtained operatively are compared. A robotic system, which was developed specifically to remove prostatic adenoma automatically, is discussed. The system, called a motorized frame, is briefly described, together with its predecessor, a manual frame, in relation to ultrasound measurements. Sizing of the prostate pre-operatively using transrectal ultrasound methods is discussed, using both the manual and the motorized frame. The shortcomings of transrectal ultrasound for use in a robotic procedure are highlighted.

The development of a surgeon robot for prostatectomies.

The removal of prostatic tissue through transurethral resection of the prostate (TURP) is an operation that can require considerable skill from a surgeon as well as being a lengthy procedure. The potential for using robotic techniques was investigated in a preliminary feasibility study using a standard six axis 'Puma' robot. This led to the construction of a manually operated 'safety frame' which has been shown to be effective through clinical trials on 30 patients. A special-purpose robot, based on the design of the manual frame, has now been constructed. Some of the safety issues are discussed which make this procedure an ideal candidate for a robotic device.

Severe disease in adult dairy cattle in three UK dairy herds associated with BVD virus infection.

During 1993 outbreaks of diarrhoea in adult dairy cows in three geographically unrelated herds were found to be caused by bovine viral diarrhoea virus (BVDV). The affected animals showed signs of acute watery diarrhoea, agalactia and pyrexia (39.4 to 42 degrees C). Ulceration of the buccal mucosa, a mucoid nasal discharge and stiffness were inconsistent signs. The disease spread rapidly in each case. The diagnosis was confirmed by the isolation of non-cytopathic BVDV from blood and tissues and by the demonstration of significantly rising titres to BVDV by an ELISA. The highest morbidity recorded was 40 per cent with one herd experiencing a 10 per cent mortality. There was no increased incidence of abortion in any of the herds, either at the time of or subsequent to the outbreaks of diarrhoea. In one herd the purchase of a persistently viraemic heifer 14 days before the outbreak was thought to be the source of infection, but in the other two herds the source was not established.

Active compliance in robotic surgery--the use of force control as a dynamic constraint.

Robotic surgery can be carried out automatically by using a robot to move the cutting tool under position control. However, although the surgeon can observe the procedure on a visual display and has the ability to stop the operation in an emergency, he has little direct contact with the task. An alternative approach is to involve the surgeon more directly, by his moving a robot using active force control. The robot is then used to allow motion in preprogrammed regions, by the surgeon back-driving the robot motors, while preventing motion in prohibited areas. This active constraint robot (or ACROBOT) is described in this paper applied to knee surgery, in which the knee bones are accurately machined to allow the fitting of prosthetic knee implants. The ACROBOT is, however, ideally suited to a range of surgical procedure, because it allows the surgeon to feel the forces exerted during cutting and take appropriate action. This ability to be in direct control, while being constrained to cut within a permitted region, enhances safety and makes the system more acceptable to the medical community. The system of programmable constraint also allows the ACROBOT to provide the traditional benefits of robot surgery, namely the ability to machine complex geometrical surfaces very accurately and to make repetitive motions tirelessly. The system also has a potential for minimally invasive procedures. In knee surgery, for example, the robot could operate through a small incision in the skin and excise a volume into which a small, specially designed, unicompartmental prosthesis could fit.

The Probot--an active robot for prostate resection.

As men age, their prostates can enlarge, causing urinary difficulty. Surgery to correct this [transurethral resection of the prostate (TURP)] is a skilled and time-consuming operation requiring many repetitive motions of a cutter. A robot has been developed to perform these motions, relieving the surgeon of much of the burden of surgery. This robot has been tried both in the laboratory and later on human subjects and has proved itself capable of performing prostate resection. The Probot system consists of on-line imaging and three-dimensional prostate model construction, an appropriate surgeon-computer interface, a counterbalanced mounting frame and a computer controlled robot.

Internal carotid artery occlusion: its natural history including recanalization and subsequent neurological events.

OBJECTIVE: To determine the incidence of recanalization of the occluded internal carotid artery (ICA) and establish its natural history. METHODS: Patients with duplex-confirmed ICA occlusions were identified, and a subgroup offered repeat scanning. The antemortem condition and cause of death of patients who died were recorded. RESULTS: Of 153 patients identified, 77 underwent follow-up at a median of 35 months (interquartile range [IQR]: 14-61).In all, 8 (10.3%) demonstrated recanalization at a median of 53 months (IQR: 35-114). Of 8, 7 underwent carotid endarterectomy with histopathological confirmation of recanalization. Of the 153 patients, 45 (29%) had further neurological events, and 38 (25%) were within the territory of the occluded ICA. In all, 76 patients died, and of the 53 with a confirmed cause of death, 12 (23%) were attributed to a cerebrovascular accident corresponding to the territory of the occluded artery. CONCLUSION: Recanalization of ICA occlusion is common and leads to significant neurological events. Duplex ultrasound follow-up appears mandatory.