Are the effects of training on fat metabolism involved in the improvement of performance during high-intensity exercise?

The objective of the present study was to relate changes in certain muscle characteristics and indicators of metabolism in response to endurance training to the concomitant changes in time to exhaustion (T_lim) at a work rate corresponding to maximal oxygen uptake Eight healthy sedentary subjects pedalled on a cycle ergometer 2 h a day, 6 days a week, for 4 weeks. Training caused increases in O_2peak (by 8%), T_lim (from 299±23 s before to 486±63 s after training), citrate synthase and 3-hydroxyl-acyl-CoA dehydrogenase (HAD) activities (by 54% and 16%, respectively) and capillary density (by 31%). Decreases in activity of lactate dehydrogenase (LDH) and muscle type of LDH (by 24% and 28%, respectively) and the phosphofructokinase/citrate synthase ratio (by 37%) were also observed. Respiratory exchange ratio (RER) tended to be lower (P<0.1) at all relative work rates after training while the corresponding ventilation rates ( E) were unchanged. At the same absolute work rate, RER and E were lower after training (P<0.05). The improvement of T_lim with training was related to the increases in HAD activity (r=0.91, P=0.0043), and to the decreases in RER calculated for Pa_peak (r=0.71, P=0.0496). The present results suggest that the training-induced adaptations in fat metabolism might influence T_lim at a work rate corresponding to O_2peak and stimulate the still debated and incompletely understood role of fat metabolism during short high-intensity exercise     

What is the association between quality of treatment for depression and patient outcomes? A cohort study of adults consulting in primary care

Background

The association between adequate treatment for a Major Depressive Episode (MDE) and improvements in depressive symptoms is not well established in naturalistic practice conditions. The main objective of this study was to examine the association between receiving at least one minimally adequate treatment for MDE (i.e. according to clinical guidelines) in the previous 12 months and evolution of depressive symptoms at 6- and 12-months. Associations with receiving pharmacotherapy and/or psychotherapy and the role of severity of depression were examined.

Methods

This cohort study included 908 adults meeting criteria for previous-year MDE and consulting at one of 65 primary care clinics in Quebec, Canada. Multilevel analyses were performed.

Results

Results show that (i) receiving at least one minimally adequate treatment for depression was associated with greater improvements in depression symptoms at 6 and at 12 months; (ii) adequate pharmacotherapy and adequate psychotherapy were both associated with greater improvements in depression symptoms, and (iii) the association between adequate treatment and improvement in depression symptoms varied as a function of severity of symptoms at the time of inclusion in the cohort with worse symptoms at the time of inclusion being associated with greater reductions at 6 and 12 months.

Limitations

Measures are self-reported. Participants were recruited at different stages over the course of their MDE.

Conclusions

This study shows that adequate treatment for depression is associated with improvements in depressive symptoms in naturalistic primary care practice conditions, but that those with more severe depressive symptoms are more likely to receive adequate treatment and improve across time.     

Are early clinical effects of cholesterol lowering mediated through effects on inflammation?

In a randomized, double‐blind trial in 3086 patients with unstable angina pectoris or non‐Q wave myocardial infarction we investigated if 80 mg of atorvastatin daily could improve outcome of cardiovascular events during a short period of time (16 weeks) compared with placebo. Baseline LDL cholesterol was 3.2 mmol L⁻¹ (124 mg dL⁻¹) and decreased by 40% to 1.9 mmol L⁻¹ (72 mg dL⁻¹) during atorvastatin treatment. The primary endpoint, which was a composite of death, non‐fatal acute myocardial infarction, cardiac arrest with resuscitation or recurrent symptomatic myocardial ischaemia with objective evidence and requiring emergency rehospitalization occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group. The relative risk was0.84 and 95% confidence interval was 0.70–1.00 (P = 0.048). Thus for patients with acute coronary syndromes, lipid‐lowering therapy with high dose atorvastatin reduces recurrent ischaemic events in the short‐term. A possible mechanism behind this rapid clinical effect induced by statin treatment is on inflammatory processes. Recent studies strongly suggest that acute T‐cell activation is involved in the pathogenesis of unstable angina. In another study we investigated whether circulating T cells showed signs of activation in patients with stable angina pectoris (SA). Systemic venous blood samples were taken from 38 men with SA and 42 healthy controls. The T‐cell receptor expression was assessed by three‐colour flow cytometry using monoclonal antibodies against CD3,CD4, CD8, CD25 and human leucocyte antigen (HLA)‐DR. Soluble interleukin‐2 receptor (sIL‐2R) was measured as the circulating form in serum. Levels of circulating CD3+ and CD4+ T cells tended to be higher in patients compared with controls. Patients were also shown to have a significant increase in CD4+ T cells expressing the activation markers CD25 (P < 0.05) and HLA‐DR (P < 0.01). Furthermore, serum levels of sIL‐2R were significantly higher (P < 0.001) in patients than in controls. We also observed that the T‐cell response was more pronounced in patients without simvastatin treatment (n = 18) compared with simvastatin‐treated patients (n = 20). In conclusion, our findings indicate that a continuous immune system activation takes place in patients with chronic angina pectoris, predominantly involving proliferation of CD4+ T cells. Statin treatment seems to be able to decrease this inflammatory response.     

Are early clinical effects of cholesterol lowering mediated through effects on inflammation?

In a randomized, double-blind trial in 3086 patients with unstable angina pectoris or non-Q wave myocardial infarction we investigated if 80 mg of atorvastatin daily could improve outcome of cardiovascular events during a short period of time (16 weeks) compared with placebo. Baseline LDL cholesterol was 3.2 mmol L-1 (124 mg dL-1) and decreased by 40% to 1.9 mmol L-1 (72 mg dL-1) during atorvastatin treatment. The primary endpoint, which was a composite of death, non-fatal acute myocardial infarction, cardiac arrest with resuscitation or recurrent symptomatic myocardial ischaemia with objective evidence and requiring emergency rehospitalization occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group. The relative risk was 0.84 and 95% confidence interval was 0.70-1.00 (P = 0.048). Thus for patients with acute coronary syndromes, lipid-lowering therapy with high dose atorvastatin reduces recurrent ischaemic events in the short-term. A possible mechanism behind this rapid clinical effect induced by statin treatment is on inflammatory processes. Recent studies strongly suggest that acute T-cell activation is involved in the pathogenesis of unstable angina. In another study we investigated whether circulating T cells showed signs of activation in patients with stable angina pectoris (SA). Systemic venous blood samples were taken from 38 men with SA and 42 healthy controls. The T-cell receptor expression was assessed by three-colour flow cytometry using monoclonal antibodies against CD3,CD4, CD8, CD25 and human leucocyte antigen (HLA)-DR. Soluble interleukin-2 receptor (sIL-2R) was measured as the circulating form in serum. Levels of circulating CD3+ and CD4+ T cells tended to be higher in patients compared with controls. Patients were also shown to have a significant increase in CD4+ T cells expressing the activation markers CD25 (P < 0.05) and HLA-DR (P < 0.01). Furthermore, serum levels of sIL-2R were significantly higher (P < 0.001) in patients than in controls. We also observed that the T-cell response was more pronounced in patients without simvastatin treatment (n = 18) compared with simvastatin-treated patients (n = 20). In conclusion, our findings indicate that a continuous immune system activation takes place in patients with chronic angina pectoris, predominantly involving proliferation of CD4+ T cells. Statin treatment seems to be able to decrease this inflammatory response.     

Does practice size matter? Review of effects on quality of care in primary care

Background

There is a trend towards consolidating smaller primary care practices into larger practices worldwide. However, the effects of practice size on quality of care remain unclear.

Aim

This review aims to systematically appraise the effects of practice size on the quality of care in primary care.

Design and setting

A systematic review and narrative synthesis of studies examining the relationship between practice size and quality of care in primary care.

Method

Quantitative studies that focused on primary care practices or practitioners were identified through PubMed, CINAHL, Embase, Cochrane Library, CRD databases, ProQuest dissertations and theses, conference proceedings, and MedNar databases, as well as the reference lists of included studies. Independent variables were team or list size; outcome variables were measures of clinical processes, clinical outcomes, or patient-reported outcomes. A narrative synthesis of the results was conducted.

Results

The database search yielded 371 articles, of which 34 underwent quality assessment, and 17 articles (13 cross-sectional studies) were included. Ten studies examined the association of practice size and clinical processes, but only five found associations of larger practices with selected process measures such as higher specialist referral rates, better adherence to guidelines, higher mammography rates, and better monitoring of haemoglobin A1c. There were mixed results for cytology and pneumococcal coverage. Only one of two studies on clinical outcomes found an effect of larger practices on lower random haemoglobin A1 value. Of the three studies on patient-reported outcomes, smaller practices were consistently found to be associated with satisfaction with access, but evidence was inconsistent for other patient-reported outcomes evaluated.

Conclusion

There is limited evidence to support an association between practice size and quality of care in primary care.     

Does patient education modify behaviour in the management of COPD?

With respect to the beneficial health effects of patient education in the treatment of asthma it might be expected that the active participation of COPD-patients in the management of their disease may reduce the burden of the disease. Self-management of chronic obstructive pulmonary disease (COPD) includes sufficient coping behaviour, compliance with inhaled medication, attention to changes in the severity of the disease, adequate inhalation technique, and self-adjustment of the medication in case of exacerbations. In contrast to the conflicting results of the current literature, the evaluation of our structured education programme for patients with mild to moderate COPD revealed a significant improvement of inhalation technique and self-control of the disease as well as a significant reduction of exacerbations. Therefore, it may be concluded that education may modify the behaviour of patients in the management of COPD by improving self-control and self-management of the disease and thus reducing morbidity.     

Are proinflammatory cytokines involved in an increased risk for depression by unhealthy diets?

Depression is a highly prevalent mental illness, which is associated with substantial functional impairment. Many factors, like especially genetic risk and stressful life events, are being discussed to be involved in the pathogenesis of the disease. There is also evidence that elevated levels of proinflammatory cytokines, which are frequently found in depressed individuals, could contribute to the development of the disease. Patients with metabolic syndrome also show a chronic low grade of inflammation. In addition, epidemiological studies suggest that an unhealthy dietary eating pattern, consisting of high amounts of refined grains and softdrinks, red and processed meat, fatty dairy products, and little amounts of vegetables, fruits and fish is associated with higher levels of major inflammatory cytokines, like Interleukin-6, and the acute phase C-reactive protein, even after controlling for body mass index. Furthermore, several recent studies suggest that an unhealthy diet quality is associated with an increased risk of depression. Therefore the connection between regular consumption of unhealthy foods, chronic inflammation, and increased risk for depression seems plausible.     

Is the silvering process similar to the effects of pressure acclimatization on yellow eels?

To reproduce eels need to migrate over 6000 km and at pressure but before this migration they metamorphose into silver eels (silvering). The question raised in this study is to determine whether and how the silvering process contributes to pressure resistance. As migration represents a long swimming activity mainly performed with slow muscles, the red muscle energetics of pressure exposed silver eels was studied. By comparing these results to what has already been shown in yellow eels, we point out that the effects of the silvering process on pressure resistance are similar to the effects of pressure acclimatization in yellow eels. As previously shown, success of pressure acclimatization depends on membrane fluidity, but we raise the hypothesis that the high-pressure resistance of silver eels is due to more fluid membranes.     

Is the association between depression and blunted cardiovascular stress reactions mediated by perceptions of stress?

Symptoms of depression are related to blunted cardiovascular reactions to acute stress tasks. However, it is unclear what factors might mediate this association and whether blunted responses are specific to mental stress tasks or are also evident with other forms of stress. The present study assessed cardiovascular reactivity to both mental and postural stress and the role of background stress exposure and stress perception. Undergraduate students (N = 119, 81 females) were screened for depressive symptoms using the Beck Depression Inventory. Twenty-six participants with probable depression and 26 non-depressed controls underwent cardiovascular stress testing. Heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure were measured at rest and in response to a 5 min orthostatic challenge and an 8 min mental arithmetic task. Stress exposure was measured using the Undergraduate Stress Questionnaire. Perceptions of general life stress were assessed using the Perceived Stress Scale (PSS) and perceptions of the stress task impact were measured using Threat Appraisal (TA). Symptoms of depression were associated with blunted HR, F(2,98) = 5.26, p = .010, η² = .097, and SBP, F(2,98) = 6.47, p = .008, η² = .117, reactions to the mental stress but not to postural challenge. HR reactions were mediated by PSS score, while both PSS score and TA emerged independently as mediators of SBP reactions. These results confirm a negative relationship between depressive symptoms and cardiovascular reactions to acute stress, suggest that this association may be stress task-specific, and may be mediated by perceptions of stress.     

How much does trust really matter? A study of the longitudinal effects of trust and decision-making preferences on diabetic patient outcomes

Objective

To examine the impact of trust on patient outcomes (satisfaction, HbA_1C, physical and mental health-related quality of life (HRQoL)) and to investigate the role of decision-making preferences in the trust-outcome relationship.

Methods

We conducted a one-year longitudinal analysis of 614 type 2 diabetic patients (mean age: 59.3 years; mean disease duration: 6.7 years). Patients’ self-administered questionnaires and medical record were used for the research. Multiple regression analyses were conducted to investigate the relationship among variables during a 12-month follow-up. Further, we used latent growth modeling (LGM) to assess changes in health outcomes and to examine how these changes were related to trust.

Results

Regression analyses revealed that trust was positively related to glycemic control, physical HRQoL, and satisfaction at 12 months. Patients with higher decision-making preferences experienced a greater increase in subsequent satisfaction. The results of LGM showed that higher levels of trust were associated with greater increases in physical HRQoL.

Conclusion

Trust contributes to improvements in health outcomes. The relationship between trust and satisfaction may be stronger among patients with higher decision-making preferences.

Practice implications

For healthcare providers, efforts should be made to cultivate patients’ trust and enhance their decision-making preferences to maximize satisfaction and improve outcomes.     

Is there a role for palmitoylethanolamide in the treatment of depression?

Depression is a common brain disorder affecting about 350 million people worldwide. Although the pharmacological treatment currently available can produce benefits in the majority of cases, residual depressive symptoms, cognitive deficits, functional impairment, and increase in frequency of relapses are frequently present in unipolar and bipolar depressed patients correctly treated. In the last years, numerous evidences have demonstrated the involvement of endocannabinoid system in the pathophysiology of mood disorders. Considering the recent findings about the antidepressant effect of palmitoylethanolamide in animal model, we have hypothesized the potential antidepressant effect of this fatty acid amide in unipolar and bipolar depressed patients.     

“Can we have a little humanity here?”: Patient perspectives on the impact of a standardized care process for patients who use opioids for the management of chronic pain

ObjectiveStandardized processes have evolved in response to the opioid epidemic. The impact of standardized processes on patients has not been adequately described.MethodsFive focus groups were held at four affiliated academic family medicine clinics. All participants experienced a transition to a standardized process for their ongoing opioid use for chronic, non-cancer pain. Data was analyzed and coded using a grounded theory approach with NVivo12 (QSR International).ResultsThirty patients participated. Five main themes emerged: experience of pain; view of opioid medications; view of opioid prescribing process changes; “good patients” and trust; and experience with medical clinicians and clinics.ConclusionsStandardized processes created to improve the safety of opioid prescribing have burdened patients and resulted in a loss of trust and autonomy. Patients perceived greater risks for other patients prescribed opioids and processes are a result of their actions.Practice ImplicationsHealthcare systems must acknowledge patients’ burden, shift away from interventions that are limited in supporting data, reinforce patient agency and shift the conversation to unsafe medications rather than supervision of “bad actors”.     

Are psychiatrists' characteristics related to how they care for depression in the medically ill? Results from a national case-vignette survey

The authors' goal was to examine the relationship between psychiatrists' characteristics and their decisions regarding depression care. A national sampling of 278 psychiatrists answered diagnosis and treatment questions for one of four case vignettes with depression and various degrees of medical comorbidity. They also responded to a questionnaire assessing practice and demographic characteristics. Tendency to diagnose major depression was significantly associated with being board certified, being in practice for less time, having a greater percentage of patients with managed care, and having a greater percentage of patients on psychotropic medications. Tendency to recommend an antidepressant was significantly associated with the psychiatrist being male, being less satisfied with practice, and having a greater percentage of patients on psychotropic medications. These findings remained significant even after controlling for case characteristics. Diagnostic and prescribing tendencies of psychiatrists appear to be associated with specific physician characteristics and not simply case characteristics. These findings have implications for further studies of predictors of quality of care.     

Recommendations from the EGAPP Working Group: does PCA3 testing for the diagnosis and management of prostate cancer improve patient health outcomes?

Summary of recommendationsThe Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group found insufficient evidence to recommend prostate cancer antigen 3 (PCA3) testing to inform decisions for when to rebiopsy previously biopsy-negative patients for prostate cancer or to inform decisions to conduct initial biopsies for prostate cancer in at-risk men (e.g., previous elevated prostate-specific antigen test or suspicious digital rectal examination).The EGAPP Working Group found insufficient evidence to recommend PCA3 testing in men with cancer-positive biopsies to determine if the disease is indolent or aggressive in order to develop an optimal treatment plan.Based on the available evidence, the overall certainty of clinical validity to predict the diagnosis of prostate cancer using PCA3 is deemed “low.” The EGAPP Working Group discourages clinical use for diagnosis unless further evidence supports improved clinical validity.Based on the available evidence, the overall certainty of net health benefit is deemed “low.” The EGAPP Working Group discourages clinical use unless further evidence supports improved clinical outcomes.RationaleIt has been suggested that PCA3 testing in the general male population might lead to earlier diagnosis and management changes (e.g., earlier detection and earlier initiation or higher rates of medical interventions) that improve outcomes. EGAPP Working Group found no direct evidence to support this possibility, so we sought indirect evidence aimed at documenting the extent to which PCA3 testing alters prostate cancer diagnosis or management, alone and in combination with traditional clinical management factors, and the extent to which this testing improves health outcomes.Analytic validityAssay-related evidence was deemed adequate for the PROGENSA PCA3 assay approved by the US Food and Drug Administration, available from Gen-Probe. Very few studies were available that investigated preanalytical effects, analytical performance, and diagnostic accuracy of other quantitative assays for PCA3.Clinical validityEvidence on clinical validity was rated inadequate to derive any conclusions about performance of PCA3 testing to inform decisions for when to rebiopsy previously biopsy-negative patients for prostate cancer, or to inform decisions to conduct initial biopsies for prostate cancer in at-risk men (e.g., previous elevated prostate-specific antigen test or suspicious digital rectal examination). Furthermore, there was little evidence to derive any conclusions about performance of PCA3 testing in men with cancer-positive biopsies to determine if the disease is indolent or aggressive in order to develop an optimal treatment plan.Clinical utilityNo studies were available to provide direct evidence on the balance of benefits and harms related to PCA3 testing for diagnosis and management in the general male population. Evidence for other populations (e.g., high risk) was not evaluated in the review.Contextual issuesEarly diagnosis of prostate cancer is central to minimizing morbidity and mortality. Prevention of prostate cancer mortality is a public health priority. Improvements in outcomes associated with PCA3 testing could have important impacts.Genet Med 2014:16(4):338–346.     

Are we estimating the adverse effects of shock-wave lithotripsy on a faulty scale?

The adverse effect of shock-wave lithotripsy (SWL) for renal stones on blood pressure is currently defined as its post-treatment increase. On the contrary, we hypothesize that even mild, unilateral renal obstruction initiates an increase in blood pressure. Then, in absence of treatment-induced injury, the stone removal should decrease the blood pressure. We derived the formula to assess the expected change in the mean arterial pressure following relief of renal obstruction without affecting the kidney functions. The predictions were well replicated in the cohort of patients with renal stone treated with parenchyma-saving open surgery, with 6.4 mmHg decrease at 3 months. On the contrary, in SWL cohort, instead of the expected 4.7 mmHg decrease, the blood pressure was unchanged. In conclusion, the absence of decrease in blood pressure is a very common adverse effect of SWL, leading to an epidemiologically significant increase in the risk of arterial vascular events.     

Effect of a discordant opinion offered by a second opinion physician on the patient’s decision for management of spinal disc disease

BackgroundFactors that influence a patient’s decision for spinal surgery and selection of the spine surgeon have not been studied in the context of a Second Opinion (SO). Providing insight into these factors will guide surgeons in their discussion of treatment options with patients.ObjectiveThis study aims to assess the impact of a discordant SO on the final decision of patients as compared to their initial preference regarding spinal disc disease treatment for chronic neck and low back pain.Patient involvementPatients in this study engage in clinical vignettes designed to induce decisional conflict.MethodsA cross-sectional study using clinical vignette-based questionnaires was presented to patients at the Family Medicine, Orthopedic, and Neurosurgery clinics at a university-based tertiary academic medical center.ResultsA total of 246 patients participated in the study (response rate, 66.8%). Irrespective of the initial offered treatment, most patients wanted to consult a SO (64.2%). Most patients preferred conservative treatment to surgery after getting the initial recommendation (78.5%) and after getting a discordant SO (56.5%). There was an association between the agreement of the patient with the initial recommendation and the effect of the SO on the final decision of patients (p < 0.001). Patients who disagreed with the initially offered treatment were more likely to abide by their initial decision after the SO (80.8%) as compared to those who were in agreement (17.7%), while those who agreed with the initially offered treatment were more likely to change their decision (39.5%) or to take a third opinion (42.9%).DiscussionA discordant SO may validate patients’ wishes when they disagree with the initially offered treatment and may lead to confusion when they agree with the initial physicians’ recommendations.Practical valueAs patients tend to abide by their initial preference, physicians should explicitly consider patients’ wishes when discussing options for management of spinal disc disease.