Can general practitioners use training in relaxation and management of stress to reduce mild hypertension?

To see whether general practitioners could effectively carry out training in relaxation and management of stress to reduce mild hypertension a study was carried out with a subsample of phase 2 of the Medical Research Council''s treatment of mild hypertension trial.¹ In the main mild hypertension trial patients had been receiving either an active drug or placebo for six years. In phase 2 a subsample of these patients were randomly allocated either to continue or to stop receiving the active drug or placebo. In a further subsample patients were again randomised to receive or not to receive relaxation therapy. This factorial design presented an additional opportunity to assess whether patients controlled with active drugs might have their blood pressure maintained by this behavioural therapy once drug treatment was stopped and to assess whether blood pressure might be further reduced by this therapy in patients who had been under regular medical supervision for as long as six years and who had already received non-pharmacological advice. The therapy was conducted by general practitioners in group sessions once a week for eight weeks. The training in relaxation was accompanied by galvanic skin resistance biofeedback. At one year follow up blood pressure in the relaxation subgroups was either maintained (in the group who had stopped receiving drugs) or reduced further (in the group who had continued receiving drugs and in both placebo groups), while in the control group it had increased in all the subgroups, but particularly in those who had stopped receiving drugs. Differences in changes in blood pressure between the relaxation and control groups were significant. There were five new cardiovascular events, including evidence of myocardial ischaemia in blindly coded electrocardiograms in the control group, compared with one in the treatment group.General practitioners, if motivated, can successfully apply this technique of training those with mild hypertension in relaxation and management of stress.     

Does treatment with cimetidine extended beyond initial healing of duodenal ulcer reduce the subsequent relapse rate?

Cimetidine 1 g daily is often continued for a fixed period beyond the time of healing of duodenal ulcer on the assumption that it might reduce the subsequent relapse rate. To test this, 194 patients whose ulcers had healed after one month of cimetidine 1 g daily were allocated at random to three groups for further treatment with cimetidine 1 g daily for two months (n = 63) or five months (n = 66) or placebo (n = 65). Thereafter all patients received placebo. Endoscopy was done routinely every three months, or earlier if symptoms recurred. During follow-up in the placebo phase, which lasted for up to 25 months, the estimated total proportions of patients in the three groups with symptomatic recurrences of ulcer were 80%, 90%, and 77%, respectively; the corresponding proportions with silent plus symptomatic relapses were 92%, 90%, and 100%. The relapse rates were also similar in all three groups. Statistical analysis showed a significant variation in relapse rate but the differences were regarded as clinically unimportant. These findings show that full-dose cimetidine continued for several months beyond the time of healing of duodenal ulcer dose not decrease the risk of subsequent relapse.     

How to value biodiversity in environmental management?

Biodiversity is globally recognised as a cornerstone of healthy ecosystems, and biodiversity conservation is increasingly becoming one of the important aims of environmental management. Evaluating the trade-offs of alternative management strategies requires quantitative estimates of the costs and benefits of their outcomes, including the value of biodiversity lost or preserved. This paper takes a decision-analytic standpoint, and reviews and discusses the alternative aspects of biodiversity valuation by dividing them into three categories: socio-cultural, economic, and ecological indicator approaches. We discuss the interplay between these three perspectives and suggest integrating them into an ecosystem-based management (EBM) framework, which permits us to acknowledge ecological systems as a rich mixture of interactive elements along with their social and economic aspects. In this holistic framework, socio-cultural preferences can serve as a tool to identify the ecosystem services most relevant to society, whereas monetary valuation offers more globally comparative and understandable values. Biodiversity indicators provide clear quantitative measures and information about the role of biodiversity in the functioning and health of ecosystems. In the multi-objective EBM approach proposed in the paper, biodiversity indicators serve to define threshold values (i.e., the minimum level required to maintain a healthy environment). An appropriate set of decision-making criteria and the best method for conducting the decision analysis depend on the context and the management problem in question. Therefore, we propose a sequence of steps to follow when quantitatively evaluating environmental management against biodiversity.     

Health checks in general practice: another example of inverse care?

OBJECTIVE--To assess attendance at and the characteristics of patients attending health checks for cardiovascular disease offered in a general practice over a period of five years (1984-9). DESIGN--Medical record audit and postal questionnaire survey. SETTING--One general practice in Oxfordshire with a socially diverse population. PARTICIPANTS--1101 Men and 1110 women aged 35-64 registered with the practice. MAIN OUTCOME MEASURES--Age, sex, marital state, social class, smoking habits, alcohol consumption, and diet. RESULTS--Of the 2211 men and women in the target age group (35-64) in 1989, 1458 (65.9%) had been offered screening and 963 (43.6%) had attended for a health check. Attenders were more likely to be women, aged greater than or equal to 45, married, non-smokers, and of higher social class than patients who did not respond to the invitation. The relative likelihood of non-attendance was 1.24 for smokers, 1.20 for the overweight, 1.16 for heavy drinkers, and 1.28 for those with a less healthy diet, even after adjustment for age, sex, marital state, and social class. CONCLUSIONS--After five years of offering health checks, opportunistically (to men) and in the context of cervical smear tests (to women), less than half of the eligible patients had attended. The likelihood of acceptance of an invitation to attend was inversely related to the patient''s cardiovascular risk for all factors measured except age. A coherent strategy to reduce cardiovascular disease depends on more careful targeting of scarce health service resources and more emphasis on public health measures (such as dietary regulation and tobacco taxation). Doctors should be careful not to absolve the government of its public health obligations by substituting unproved preventive interventions aimed at the individual patient.     

Do clinical guidelines improve general practice management and referral of infertile couples?

OBJECTIVE--To evaluate guidelines for general practice management and referral of infertile couples. Guidelines were implemented with a disease specific reminder at the time of consultation (the guidelines were embedded within a structured infertility management sheet for each couple). DESIGN--Pragmatic randomised controlled trial. Participating practices were randomised to a group that received the guidelines and a control group. SETTING--82 general practices in Grampian region. SUBJECTS--100 couples referred by general practitioners receiving the guideline and 100 couples referred by control general practitioners. MAIN OUTCOME MEASURES--Whether the general practitioner had taken a full sexual history and examined and investigated both partners appropriately. RESULTS--Characteristics of patients referred by study and control general practitioners did not differ significantly at baseline. Compliance with the guidelines increased for all targeted activities. General practitioners in the study group were more likely to take a sexual history (for example, couples'' use of fertile period, 85% v 69%, p < 0.01); examine both partners (female partner, 68% v 52%, p < 0.05; male partner 39% v 13%, p < 0.01); and investigate both partners (day 21 progesterone, 72% v 41%, p < 0.001; semen analysis, 51% v 41%, p > 0.05). Improvements were greater when general practitioners used the disease specific reminder. CONCLUSION--Receiving guidelines led to improvements in the process of care of infertile couples within general practice. This effect was enhanced when the guidelines were embedded in a structured infertility management sheet for each couple.     

Long term effects of ART: What do animals tell us?

Early stages of mammalian embryonic development are now known to be very sensitive to their microenvironment, with long term effects on fetal, postnatal, and adult health, thus extending to these early stages the concept of Developmental Origin of Health and Disease (DoHaD). In this scientific context, and with 3% of births in developed countries, safety of Assisted Reproductive Techniques procedures becomes a matter of concern. Besides, embryo technologies in domestic mammals, using huge number of embryos, do not seem to evidence heavy impacts on adult phenotypes. This paper first discusses what can or cannot be concluded from farm animal data, then develops long term effects of ART procedures (ovarian stimulation, in vitro fertilization and embryo culture) evidenced in model species (mainly mouse model). Recent literature demonstrates both individual and cumulative effects of each ART procedure on fetal and postnatal phenotypes. In a second part, because they are sources for further perturbations, immediate effects of ART on early embryo phenotypes at the cellular and molecular levels are described in both farm animals and model species. Mechanistic hypotheses supporting these ART induced phenotypic alterations are subsequently considered. Finally, taking into account interspecies differences in the mechanisms likely to be involved, the relevance of results obtained in animal models for human ART are discussed.     

On the Inference of Large Phylogenies with Long Branches: How Long Is Too Long?

The accurate reconstruction of phylogenies from short molecular sequences is an important problem in computational biology. Recent work has highlighted deep connections between sequence-length requirements for high-probability phylogeny reconstruction and the related problem of the estimation of ancestral sequences. In Daskalakis et al. (in Probab. Theory Relat. Fields 2010), building on the work of Mossel (Trans. Am. Math. Soc. 356(6):2379–2404, 2004), a tight sequence-length requirement was obtained for the simple CFN model of substitution, that is, the case of a two-state symmetric rate matrix Q. In particular the required sequence length for high-probability reconstruction was shown to undergo a sharp transition (from O(log n) to poly(n), where n is the number of leaves) at the “critical” branch length g _ML(Q) (if it exists) of the ancestral reconstruction problem defined roughly as follows: below g _ML(Q) the sequence at the root can be accurately estimated from sequences at the leaves on deep trees, whereas above g _ML(Q) information decays exponentially quickly down the tree.     

How to account for habitat suitability in weed management programmes?

Designing efficient management strategies for already established invasive alien species is challenging. Here, we ask whether environmental suitability, as predicted by species distribution models, is a useful basis of cost-effective spatial prioritization in large-scale surveillance and eradication programmes. We do so by means of spatially and temporarily explicit simulations of the spread of a case study species (Ambrosia artemisiifolia L.) in Austria and southern Germany under different management regimes. We ran these simulations on a contiguous grid of the study area with each grid cell (~35 km²) characterized by a habitat suitability value derived from the predictions of a species distribution model. The management regimes differed in terms of (a) a minimum habitat suitability rank p (suitability threshold) used to separate cells for surveillance from those which are not controlled; and (b) the strategy for selecting cells for annual campaigns from the pool defined by p. According to the results (i.e., number of cells infested in 2050 as well as infested on average per year) the most efficient way to base surveillance on suitability is to define the temporal sequence of management according to the grid cells’ suitability ranks. Management success declines sharply when the suitability threshold is set too high, but only moderately when it is set too low. We conclude that accounting for environmental suitability is important for large-scale management programmes of invasive alien species and that species distribution models are hence useful tools for designing such programmes.     

How to use the paradigm of ischemic preconditioning to protect the heart?

Ischemic preconditioning affords the most powerful protection to a heart submitted to a prolonged ischemia-reperfusion. During the past decade, a huge amount of work allowed to better understand the features of this protective effect as well as the molecular mechanisms. Ischemic preconditioning reduces infarct size and improves functional recovery; its effects on arrhythmias remain debated. Triggering of the protection involves cell surface receptors that activate pro-survival pathways including protein kinase C, PI3-kinase, possibly Akt and ERK1/2, whose downstream targets remain to be determined. Much attention has been recently focused on the role of mitochondrial K(+)ATP channels and the permeability transition pore that seem to play a major role in the progression toward irreversible cellular injury. Based on these experimental studies attempts have been made to transfer preconditioning from bench to bedside. Human experimental models of ischemic preconditioning have been set up, including cardiac surgery, coronary angioplasty or treadmill exercise, to perform pathophysiological studies. Yet, protecting the heart of CAD (coronary artery disease) patients requires a pharmacological approach. The IONA trial has been an example of the clinical utility of preconditioning. It helped to demonstrate that chronic administration of nicorandil, a K(+)ATP opener that mimics ischemic preconditioning in experimental preparations, improves the cardiovascular prognosis in CAD patients. Recent experimental studies appear further encouraging. It appears that "postconditioning" the heart (i.e. performing brief episodes of ischemia-reperfusion at the time of reperfusion) is as protective as preconditioning. In other words, a therapeutic intervention performed as late as at the time of reflow can still significantly limit infarct size. Further work is needed to determine whether this may be transferred to the clinical practice.     

Highly selective vagotomy for duodenal ulcer: do hypersecretors need antrectomy?

Two to five years after highly selective vagotomy (H.S.V.) for duodenal ulcer the results were similar in patients with high preoperative maximal acid outputs and those with lower acid outputs. Pain of ulcer type was experienced at some time by 6% of patients from each group, but it was mild and transient in some. No patients had recurrent ulceration at endoscopy or laparotomy, while incidence of individual symptoms was about equal in the two groups. Hence H.S.V. is adequate surgical treatment for patients with both duodenal ulceration and high levels of acid secretion. Antrectomy in such patients is not necessary provided that the incidence of incomplete vagotomy can be kept low.     

Detrending climate data prior to climate–growth analyses in dendroecology: A common best practice?

Tree growth varies closely with high–frequency climate variability. Since the 1930s detrending climate data prior to comparing them with tree growth data has been shown to better capture tree growth sensitivity to climate. However, in a context of increasingly pronounced trends in climate, this practice remains surprisingly rare in dendroecology. In a review of Dendrochronologia over the 2018–2021 period, we found that less than 20 % of dendroecological studies detrended climate data prior to climate-growth analyses. With an illustrative study, we want to remind the dendroecology community that such a procedure is still, if not more than ever, rational and relevant. We investigated the effects of detrending climate data on climate–growth relationships across North America over the 1951–2000 period. We used a network of 2536 tree individual ring-width series from the Canadian and Western US forest inventories. We compared correlations between tree growth and seasonal climate data (Tmin, Tmax, Prec) both raw and detrended. Detrending approaches included a linear regression, 30-yr and 100-yr cubic smoothing splines. Our results indicate that on average the detrending of climate data increased climate–growth correlations. In addition, we observed that strong trends in climate data translated to higher variability in inferred correlations based on raw vs. detrended climate data. We provide further evidence that our results hold true for the entire spectrum of dendroecological studies using either mean site chronologies and correlations coefficients, or individual tree time series within a mixed-effects model framework where regression coefficients are used more commonly. We show that even without a change in correlation, regression coefficients can change a lot and we tend to underestimate the true climate impact on growth in case of climate variables containing trends. This study demonstrates that treating climate and tree-ring time series “like-for-like” is a necessary procedure to reduce false negatives and positives in dendroecological studies. Concluding, we recommend using the same detrending for climate and tree growth data when tree-ring time series are detrended with splines or similar frequency-based filters.