Patients as a direct source of information on adverse drug reactions.

To determine whether patients should participate directly in detecting adverse reactions to drugs their ability to provide written reports of symptoms experienced during treatment with amoxycillin or trimethoprim-sulphamethoxazole was investigated. When compared with telephone interviews forms on which patients reported events were reliable (the observed agreement with the same statements posed during telephone calls was 85%, kappa = 0.56) and valid (sensitivity = 54%, specificity = 94%). Patients were also supplied with forms that invited them to report adverse reactions, and their perceptions were compared with those of a panel of experts, who were informed of all clinical events that had been reported during the detailed telephone interviews. Patients were more conservative than the experts in attributing clinical events to drug treatment. The extent of agreement varied and was notably poor for skin and bowel complaints (kappa = 0.13 in each case). The performance of event report forms and reaction report forms as instruments of detection was compared in a hypothetical situation in which the experts'' views represented the "truth" about adverse reactions to a new drug. Event reporting had a higher sensitivity than reaction reporting (42% v 24%) but a lower specificity (58% v 98%). National centres monitoring adverse drug reactions should probably resist pressure to accept reports of reactions directly from the public, but a system based on large scale reporting of events might be valuable in aiding the early detection of symptomatic reactions to new drugs.     

Alzheimer's disease: current knowledge,management and research

Alzheimer''s disease is a common neurological condition, appearing as early as age 40 but increasing dramatically in incidence over age 85. Different genetic factors are at play, modified by events over a lifetime. Clinical diagnosis is possible through careful history taking with a reliable informant and a minimum number of laboratory tests. A relatively predictable natural history can be observed, with progression through stages of cognitive loss, functional impairment and behavioural disinhibition or apathy. New medications such as donepezil offer hope for improving or stabilizing symptoms. Such treatment can be administered by primary care physicians with experience in the diagnosis and management of Alzheimer''s disease. Disease stabilization, or even prevention, may be possible in the future.     

Symptomatic carotid ischaemic events: safest and most cost effective way of selecting patients for angiography,before carotid endarterectomy.

OBJECTIVE: To determine the safest, least costly, and most effective way to select patients with symptomatic carotid ischaemic events for carotid angiography before carotid endarterectomy. DESIGN: Prospective cohort study. SETTING: University departments of clinical neurosciences and clinical neurology. PATIENTS: 485 Patients with carotid territory transient ischaemic attacks of the brain (n = 224) or eye (n = 162) or retinal infarction (n = 99) were referred to a single neurologist between 1976 and 1986. INTERVENTIONS: Clinical examination by auscultation over the precordium, supraclavicular fossae, and neck vessels (all patients). Cerebral angiography of patients suitable for carotid endarterectomy. MAIN OUTCOME MEASURES: Financial cost and number of disabling strokes after angiography. RESULTS: 296 Patients were investigated by cerebral angiography. Ischaemic symptoms had occurred in the distribution of 298 internal carotid arteries (symptomatic) that were imaged, two patients having bilateral symptoms. The presence or absence of a carotid bruit and the maximum percentage diameter stenosis of the origin of the symptomatic internal carotid artery were correlated. The prevalence of mild disease (diameter stenosis greater than or equal to 25%) of the symptomatic internal carotid artery was 57%, and if an ipsilateral carotid bruit was heard the probability of mild stenosis rose to 92%. The prevalence of moderate disease of the symptomatic internal carotid artery (stenosis greater than or equal to 50%) was 39%, and if a bruit was heard the probability doubled to 78%. The prevalence of severe internal carotid disease (stenosis greater than or equal to 75%) was 22%, and if a bruit was heard the probability was more than double, at 49%. The direct cost to both the NHS and the private health sector of investigating patients with symptomatic carotid ischaemia was estimated for several strategies of carotid artery imaging and expressed in terms of financial cost and number of strokes after angiography incurred in detecting all patients with diameter stenosis of the symptomatic internal carotid artery of greater than or equal to 25%, 50%, or 75%. To detect diameter stenosis of the internal carotid artery of greater than or equal to 25% it is most cost effective to proceed directly to cerebral angiography in patients with a carotid bruit over the symptomatic carotid bifurcation and to screen patients without a carotid bruit by duplex carotid ultrasonography; patients in whom duplex ultrasonography discloses stenosis of greater than or equal to 25% are then referred for cerebral angiography. To detect only more severe internal carotid disease (stenosis of greater than or equal to 50%) the same policy applies, unless the local duplex ultrasonographic service is particularly efficient and reliable, when it is probably most cost effective and safer to screen all patients by this method irrespective of the findings on cervical auscultation. To detect stenosis of 75% or greater it is most cost effective to screen all patients with duplex ultrasonography, whether a carotid bruit is present or not, because this approach reduces the number of angiograms required, is the least expensive, and results in the least number of strokes after angiography. CONCLUSIONS: Patients selection for cerebral angiography before carotid endarterectomy needs to be appropriate and cost effective. Sound clinical evaluation and duplex carotid ultrasound are required. The findings of this study should not be applied to other medical centres without first considering possible differences in the prevalence of carotid artery disease, the efficiency and reliability of duplex ultrasonography, the local complication rates of cerebral angiography, and the local costs of the imaging procedures.     

Hypertrophic osteoarthropathy in cystic fibrosis.

Seven adult patients with cystic fibrosis who had radiological evidence of hypertrophic osteoarthropathy were reviewed. In five of the patients symptoms were particularly pronounced at times of acute infective exacerbations; appropriate treatment of the infective episodes resulted in reduction or resolution of the bone pain and joint effusions. Despite this symptomatic relief periosteal changes persisted radiologically and their chronic nature was indicated by changes in the midshafts of long bones. Four of the seven patients had transient gynaecomastia or mastalgia related to infective exacerbations. It is hypothesised that a neuroendocrine mechanism--namely, release of vasoactive intestinal polypeptide--might account for the osteoarthropathy.     

Late Ventricular Dysrhythmias after Myocardial Infarction

Serious ventricular dysrhythmias occurred in hospital after discharge from a coronary intensive care unit in 11 out of 142 patients with myocardial infarction. Previous rhythm changes, hypotension, and left ventricular failure were common findings; only one of these patients had an uneventful previous course. Four patients were resuscitated and left hospital; six were resuscitated but died at varying periods up to eight days after the event; one patient could not be resuscitated. Recent coronary occlusion or further myocardial infarction was demonstrated in 7 of these 11 patients and presumably accounted for the dysrhythmia.     

Effects of Bois noir on carbon assimilation, transpiration, stomatal conductance of leaves and yield of grapevine (Vitis vinifera) cv. Chardonnay

Bois noir (BN) is one of the main phytoplasma diseases of grapevine (Vitis vinifera). It is widespread, and can cause severe losses in European vineyards. The infective agent colonizes phloem elements and induces visible symptoms of leaf yellowing or reddening after a relatively long incubation period. As the most sensitive cultivars to BN, Chardonnay plants were grouped as healthy or symptomatic in spring, based on the records from the previous year. Leaf gas exchange and chlorophyll a fluorescence were measured weekly from July to September in healthy plants, and in symptomatic and asymptomatic leaves from symptomatic plants. The midday relative water content (mRWC) was measured once per month. The detection of phytoplasma DNA by nested-polymerase chain reaction revealed BN infection in symptomatic leaf samples at the end of September. A significant decrease in pigment content and maximum quantum efficiency of photosystem II (Fv/Fm) of these symptomatic leaves was detected from July to September, although in the asymptomatic leaves of the symptomatic plants the net photosynthesis (Pn) decrease was not significant. In the leaves from the healthy plants, Pn and transpiration were relatively stable. Of note, in July, an initially healthy plant showed a strong Pn reduction that was followed by visible leaf yellowing symptoms only in August. The phytoplasma infection also stimulated significant reductions in mRWC of the symptomatic leaves, with a final large decrease in yield.     

COVID-19 modeling and non-pharmaceutical interventions in an outpatient dialysis unit

This paper describes a data-driven simulation study that explores the relative impact of several low-cost and practical non-pharmaceutical interventions on the spread of COVID-19 in an outpatient hospital dialysis unit. The interventions considered include: (i) voluntary self-isolation of healthcare personnel (HCPs) with symptoms; (ii) a program of active syndromic surveillance and compulsory isolation of HCPs; (iii) the use of masks or respirators by patients and HCPs; (iv) improved social distancing among HCPs; (v) increased physical separation of dialysis stations; and (vi) patient isolation combined with preemptive isolation of exposed HCPs. Our simulations show that under conditions that existed prior to the COVID-19 outbreak, extremely high rates of COVID-19 infection can result in a dialysis unit. In simulations under worst-case modeling assumptions, a combination of relatively inexpensive interventions such as requiring surgical masks for everyone, encouraging social distancing between healthcare professionals (HCPs), slightly increasing the physical distance between dialysis stations, and—once the first symptomatic patient is detected—isolating that patient, replacing the HCP having had the most exposure to that patient, and relatively short-term use of N95 respirators by other HCPs can lead to a substantial reduction in both the attack rate and the likelihood of any spread beyond patient zero. For example, in a scenario with R₀ = 3.0, 60% presymptomatic viral shedding, and a dialysis patient being the infection source, the attack rate falls from 87.8% at baseline to 34.6% with this intervention bundle. Furthermore, the likelihood of having no additional infections increases from 6.2% at baseline to 32.4% with this intervention bundle.     

The lightning heart: a case report and brief review of the cardiovascular complications of lightning injury

Lightning strike is a rare natural phenomenon, which carries a risk of dramatic medical complications to multiple organ systems and a high risk of fatality. The known complications include but are not limited to: myocardial infarction, arrhythmia, cardiac contusion, stroke, cutaneous burns, respiratory disorders, neurological disorders, acute kidney injury and death. We report a case of a healthy young man who suffered a lightning injury and discuss the cardiovascular complications of lightning injury, ranging from ECG changes to death. The patient in our case, a 27-year old previously healthy male, developed a syndrome of rhabdomyolysis and symptomatic cardiogenic pulmonary edema. Electrocardiographic findings included transient T-wave inversions, late transition shift and long QT. His clinical condition improved with supportive measures.Early recognition of lightning injury syndromes and anticipation of complications may help us improve outcomes for these patients. Evaluation of patients having experienced a lightning injury should include a minimum of a detailed history and physical examination, 12-lead ECG and drawing of baseline troponins. Prolonged electrocardiographical monitoring (for monitoring of ventricular arrhythmias) and assessment for signs and symptoms of hemodynamic compromise may be warranted.     

Cardiac rhythm abnormalities in patients presenting with transient non-focal neurological symptoms: a diagnostic grey area?

Eighty-nine patients attending neurology clinics with transient non-focal neurological symptoms were studied by routine electrocardiography and 24-hour monitoring of the electrocardiography and 24-hour monitoring of the electrocardiogram. In comparison with 109 control subjects there was no significant overall excess of arrhythmias (age-adjusted odds ratio 1.7, kappa2 = 2.67) except in the subgroup of patients under the age of 30 (odds ratio 11.6, p less than 0.05). Bradyarrhythmias, but not tachyarrhythmias, were significantly more common in the patients (odds ratio 7.4, p less than 0.001),. Since patients can rarely be studied while they are having symptoms a working diagnosis must be based on a balance of probabilities: arrhythmias in young patients, or bradyarrhythmias in any patient, are likely to be clinically relevant. Ambulatory electrocardiographic monitoring contributed to the diagnosis in at least 25 of the patients, Nevertheless, the extent to which further investigations are pursued, and the form of treatment ultimately adopted, must also be influenced by the frequency and severity of the patients'' symptoms.     

Assessing long term backache after childbirth.

OBJECTIVES--To investigate the factors associated with long term backache after childbirth, to assess all women reporting new onset long term backache, and to investigate any relation with pain relief in labour. DESIGN--Data collected from obstetric records and postal questionnaires or telephone interviews on morbidity after childbirth from all women delivering their first baby between March 1990 and February 1991, followed by analysis of data collected from outpatient consultations. SETTING--St Thomas''s Hospital, London. SUBJECTS--Questionnaires were sent to 1615 women who had delivered their first baby in the defined period; 1015 either replied by post or were contacted by telephone. RESULTS--299 women (29.5% of responders) reported backache lasting more than six months and of these 156 (15.4%) said they had had no back problems previously. Those women who had received epidural analgesia in labour were significantly more likely to report new onset backache (17.8%; 95% confidence interval 14.8% to 20.8%) than those who did not (11.7%; 8.6% to 14.8%). Younger women, unmarried women, and those reporting other antenatal symptoms were significantly more likely to report new long term backache. The 156 women reporting new backache were asked to attend an outpatient clinic and 36 (23%) did so. The majority had a postural backache which was not severe. Psychological factors were present in 14 women. CONCLUSIONS--Though new long term backache is reported more commonly after epidural analgesia in labour, it tends to be postural and not severe. There were no differences in the nature of the backache between those who had or had not received epidural analgesia in labour.     

Multi-centre randomised controlled trial of a smart phone-based event recorder alongside standard care versus standard care for patients presenting to the Emergency Department with palpitations and pre-syncope - the IPED (Investigation of Palpitations in the ED) study: study protocol for a randomised controlled trial

Background

Palpitations and pre-syncope are together responsible for 300,000 annual Emergency Department (ED) attendances in the United Kingdom (UK). Diagnosis of the underlying rhythm is difficult as many patients are fully recovered on ED arrival; and examination and presenting electrocardiogram (ECG) are commonly normal. The only way to establish the underlying heart rhythm is to capture an ECG during symptoms. Recent technology advances have led to several novel ECG monitoring devices appearing on the market. This trial aims to compare the symptomatic rhythm detection rate at 90?days of one such smart phone-based event recorder (AliveCor Heart Monitor and AliveECG) with standard care for participants presenting to the ED with palpitations and pre-syncope and no obvious cause in the ED.

Methods/Design

This is a multi-centre hospital ED / Acute Medical Unit (AMU) open label, randomised controlled trial. Participants will be recruited in 10 tertiary and district general hospitals in the UK. Participants aged ≥?16?years presenting with an episode of palpitations or pre-syncope with no obvious cause and whose underlying ECG rhythm during these episodes remains undiagnosed after clinical assessment will be included. Participants will be randomised to either: (1) the intervention arm, standard care plus the use of a smart phone-based event recorder; or (2) the control arm, standard care. Primary endpoint will be symptomatic rhythm detection rate at 90?days. A number of secondary clinical, process and cost-effectiveness endpoints will be collected and analysed. Analysis will be on an intention-to-treat basis.

Discussion

The Investigation of Palpitations in the ED (IPED) study aims to recruit 242 participants across 10 hospital sites. It will be the first study to investigate the ability of a smart phone-based event recorder to detect symptomatic cardiac rhythms compared to standard care for ED patients with palpitations and pre-syncope with no obvious cause in the ED. This smart phone event recorder will allow ED patients who have presented with palpitations or pre-syncope to record their ECG tracing if they have a further episode and may increase the rate of underlying rhythm diagnosis.

Trial registration

ClinicalTrials.gov, NCT02783898. Registered on 26 May 2016.

     

Long-Branch Attraction Bias and Inconsistency in Bayesian Phylogenetics

Bayesian inference (BI) of phylogenetic relationships uses the same probabilistic models of evolution as its precursor maximum likelihood (ML), so BI has generally been assumed to share ML''s desirable statistical properties, such as largely unbiased inference of topology given an accurate model and increasingly reliable inferences as the amount of data increases. Here we show that BI, unlike ML, is biased in favor of topologies that group long branches together, even when the true model and prior distributions of evolutionary parameters over a group of phylogenies are known. Using experimental simulation studies and numerical and mathematical analyses, we show that this bias becomes more severe as more data are analyzed, causing BI to infer an incorrect tree as the maximum a posteriori phylogeny with asymptotically high support as sequence length approaches infinity. BI''s long branch attraction bias is relatively weak when the true model is simple but becomes pronounced when sequence sites evolve heterogeneously, even when this complexity is incorporated in the model. This bias—which is apparent under both controlled simulation conditions and in analyses of empirical sequence data—also makes BI less efficient and less robust to the use of an incorrect evolutionary model than ML. Surprisingly, BI''s bias is caused by one of the method''s stated advantages—that it incorporates uncertainty about branch lengths by integrating over a distribution of possible values instead of estimating them from the data, as ML does. Our findings suggest that trees inferred using BI should be interpreted with caution and that ML may be a more reliable framework for modern phylogenetic analysis.     

Development in the red alga,Griffithsia pacifica: Control by internal and external factors

Summary Development in the red alga Griffithsia pacifica is affected by both external and internal factors. Under 16:8 photoperiods, both cell division and cell elongation show a diurnal rhythm. The rhythm of division persists for at least 7 cycles in continuous light, and can be reset; this indicates that the timing of cell division is controlled by an endogenous rhythm. Both cell division and elongation require light, but the rate of division of apical cells and the rate of cell elongation are both relatively insensitive to either light intensity or photoperiod. In contrast. division in nodal cells, which leads to branch formation, is strongly promoted by high light intensity or long photoperiods. By manipulating the conditions of illumination, one can obtain Griffithsia plants varying from unbranched to highly branched.     

Twenty-Four-Hour Blood Pressure Control: An Intraarterial Review

Intraarterial blood pressure monitoring has shown the circadian rhythm of blood pressure control. Blood pressures tend to be highest in the morning before falling gradually during the day to a nadir at 3:00 a.m. There is a slight rise in the late afternoon that may correspond to patients' attendance at hospital for calibration of the equipment. There is a small rise in the blood pressure before awakening, and after arousal there is a rise in blood pressure to the peak level of the morning. In this article, we examine the effect of a variety of antihypertensive agents on this rhythm. In general, β-adrenoceptor blockers appear to have less effect on nocturnal blood pressure and surge in pressure after arousal, while vasodilators, particularly α-adrenoceptor blockers, have a pronounced effect. These findings indicate that the rise in blood pressure before awakening and the rapid rise upon arousal appear to be due to increased α-adrenoceptor activity.     

Recent Advances in Artificial Pacemakers

Electronic pacing is now the accepted therapy for patients with symptomatic slow ventricular heart rates. Pacing may be temporary or permanent, epicardial or endocardial, fixed, synchronous or demand. The choice of pacing mode is dictated by the clinical status of the patient, his progress during temporary pacing, and the presence or absence of competitive rhythm.     

Never Out of the Woods: Onset of Events in Long QT Syndrome Late in Life Provoked by Atrial Arrhythmias

The assessment of risk in the asymptomatic patient with long QT syndrome can often be a challenging task, particularly when the available evidence is limited to relatively small retrospective registries, not to mention the need to consider the effect of individual patient factors which are often difficult to quantitate. We describe the relatively uncommon case of a man with a long-standing diagnosis of Long QT 2 syndrome who suffered his first cardiac event in his late 60''s, likely precipitated by the development of paroxysmal atrial tachycardia. A brief review of the available literature on risk assessment in adults with genetically confirmed long QT syndrome who have remained asymptomatic late into adulthood will follow the case.     

Perceptual echoes at 10 Hz in the human brain

The occipital alpha rhythm (～10 Hz) is the most prominent electrophysiological activity in the awake human brain, yet its functional role and relation to visual perception are little understood. Transient stimuli normally elicit a short series of positive and negative deflections lasting between 300 and 500 ms: the visual-evoked potential (VEP). Alpha oscillations, on the other hand, are generally suppressed by transient visual input; they only augment in response to periodic ("steady-state") inputs around 10 Hz. Here, we applied reverse-correlation techniques to the visual presentation of random, nonperiodic dynamic stimulation sequences and found that the brain response to each stimulus transient was not merely a short-lived VEP but also included a strong ～10 Hz oscillation that lasted for more than 1 s. In other words, the alpha rhythm implements an "echo" or reverberation of the input sequence. These echoes are correlated in magnitude and frequency with the observer's occipital alpha rhythm, are enhanced by visual attention, and can be rendered perceptually apparent in the form of ～10 Hz flicker. These findings suggest a role for the alpha rhythm in the maintenance of sensory representations over time.     

根田鼠粪便皮质酮的检测效能

为验证根田鼠粪便皮质酮的可检测效能,本研究检测根田鼠粪便皮质酮含量的昼夜变化,并检测急性应激后和慢性应激期间根田鼠粪便皮质酮含量变化,及其慢性应激个体的HPA 轴负反馈功能。结果表明,根田鼠粪便皮质酮水平具有明显的似昼夜节律,粪便中皮质酮含量的最高点出现在08:00 和24:00,最低点在12:00 和16:00;在终止急性应激12 h 后,根田鼠粪便皮质酮含量显著增加,且有性别间差异;慢性应激根田鼠粪便皮质酮含量始终保持在高水平;再次急性应激,慢性应激根田鼠个体的粪便皮质酮含量较对照个体升高的时间延后。上述结果说明,根田鼠的粪便皮质酮含量能够反映机体所处的生理状态及应激水平,因此,该方法可用于野外根田鼠种群的相关研究并具有可靠性。