Introduction Aortic valve replacement is a class I indication for patients with severe aortic stenosis and symptoms in the ACC/AHA guidelines for the treatment of cardiac valvular disease.1 Since some patients can be judged too high a risk to undergo surgery, they may be denied aortic valve replacement. Transcatheter aortic valve replacement (TAVR) has been developed as a potential option for this patient group. To date, there are two studies that have evaluated two valve devices: The PARTNER Trial

using the Edwards SAPIEN valve, which was approved for use in nonsurgical candidates by the FDA in December 2011,2, 3 and Inhibitors,research,lifescience,medical the CoreValve US Pivotal Trial (using the Medtronic CoreValve) that is currently active and accruing patients. Both of these devices require large bore access for placement. The Edwards SAPIEN valve used in the PARTNER Trial can be inserted using an iliofemoral access or a transapical cardiac access. For the valves used in the PARTNER Trial, the small valve (23 mm) required a 22-Fr sheath and the large valve Inhibitors,research,lifescience,medical (26 mm) required a 24-Fr

sheath Inhibitors,research,lifescience,medical for iliofemoral access. Both valves used a 26-Fr sheath when click here direct transapical cardiac insertion was used in patients who were not candidates for iliofemoral access. A newer version, the SAPIEN XT, can be inserted using an 18-Fr sheath via the iliofemoral route. The Medtronic CoreValve currently comes in 23 mm, 26 mm, 29 mm, and 31 mm sizes and all are inserted through an 18-Fr sheath. For both valves, the femoral route is the preferred method of insertion whenever possible. When iliofemoral access is not possible with the CoreValve, both subclavian artery and direct aortic approaches have Inhibitors,research,lifescience,medical been used. Planning access for TAVR requires knowledge of the luminal size as well as the degree of vessel calcification and tortuosity. Inhibitors,research,lifescience,medical We consider a high-quality thin-slice

CT scan with contrast that extends from the femoral artery to the subclavian artery the cornerstone of evaluation. Arteriography and intravascular ultrasound (IVUS) can add additional data but are not considered acceptable as standalone imaging modalities. For the non-interventionist, it is important to remember that the size of the catheters to be used is listed as the outer diameter (OD), while the and size of the sheaths to be used is listed as the inner diameter (ID). In the French sizing system, 3 Fr equals 1 mm — therefore, the ID of the 18-Fr, 22-Fr, and 24-Fr sheaths are 6 mm, 7 mm, and 8 mm respectively. In general, the outer diameter is about 1 mm larger, which is important in planning access. In noncalcified arteries, we can generally insert a sheath through an artery that is about 0.75% of the sheath’s outer diameter; in a heavily or circumferentially calcified artery, we need an artery that is 1.25% of the sheath’s outer diameter.

Panitumumab has

similar indications, and is primarily used in patients intolerant to cetuximab due to hypersensitivity reactions. Biologics in the adjuvant setting Given the success of the addition of biologic agents to chemotherapy in the metastatic setting, multiple studies were attempted to investigate possible benefit of these agents in the adjuvant setting. Success of the anti-VEGF and Dorsomorphin manufacturer anti-EGFR agents in the adjuvant setting was thought by some to be a foregone conclusion, looking to the adjuvant use of 5-FU and oxaliplatin as historical examples. However, it is important to note that drugs Inhibitors,research,lifescience,medical with clinical success in the metastatic setting do not always show success adjuvantly, with irinotecan being a key example of a surprise failure in the adjuvant Inhibitors,research,lifescience,medical setting (13-15). Adjuvant bevacizumab Two large

randomized phase 3 trials investigated the use of bevacizumab with FOLFOX in the adjuvant setting. The NSABP (National Surgical Adjuvant Breast and Bowel Project) C-08 trial included 2,672 patients with resected stage II and III colon cancer Inhibitors,research,lifescience,medical (31). The standard therapy arm received mFOLFOX6 for a planned 12 cycles, and the experimental arm received the same with the addition of bevacizumab 5 mg/kg every two weeks for a year. Overall, this was a negative study. At a median follow up of 3 years, the DFS was 75.5% for the standard arm and 77.4% for the bevacizumab arm [hazard ration (HR) 0.89, 95% confidence interval (CI), 0.76-1.04, P=0.15]. Exploratory analysis found that there was a DFS benefit in favor of the bevacizumab group prior to 15 Inhibitors,research,lifescience,medical months of follow-up (HR 0.61; 95% CI, 0.48-0.78, P<0.0001), however this effect disappeared with longer follow up. The AVANT (bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer) trial (32) was a multi-center, international trial that randomized Inhibitors,research,lifescience,medical 2,867 patients with resected stage III colon cancer to mFOLFOX4 for a planned 12 cycles versus mFOLFOX4 with bevacizumab 5 mg/kg every 2 weeks for 12 cycles followed by bevacizumab 7.5 mg/kg every 3 weeks for 8 additional cycles versus XELOX with bevacizumab 7.5 mg/kg every 3 weeks for 8 cycles followed by 8 additional

cycles of bevacizumab monotherapy. There was no significant difference in 3-year DFS or 5-year OS between the three groups. In fact, there were numerically more relapses and deaths due to disease progression in the two bevacizumab containing arms, though these differences did not Isotretinoin reach statistical significance. Similar to the NSABP trial, there was a decreased risk of relapse in the bevacizumab groups in the first 12 months of follow-up, however an increase in later relapses resulted in no overall differences between the groups. Much has been made of the indication of transient benefit in the bevacizumab groups in both the NSABP and the AVANT trials. Specifically, relapse risk was decreased by 39% in the first 15 months in NSABP C-08 and by 37% in the first 12 months in the AVANT trial.

We gained rich data on local context from the stakeholder FGs, particularly relating to the cultural and religious practices of the communities within the study population, which shaped the intervention design. The importance of understanding the cultural and religious

context in minority ethnic communities has been highlighted in other studies. In a childhood obesity prevention study targeting minority ethnic communities in London, Tenofovir price Rawlins reported child and parent perceptions of healthy eating and inhibitors physical activity. The findings relating to South Asian communities resonate strongly with our data, for example the influence of places of worship and the role of extended family members on healthy lifestyles (Rawlins et al., 2013). A recent comprehensive evidence synthesis review on adapting health promotion programmes (including diet and physical

activity) for minority ethnic groups also draws attention to the importance of tailoring to particular contexts. The authors concluded that such adaptation FDA approved Drug Library solubility dmso increased intervention relevance and acceptability, although whether this results in increased effectiveness is undetermined (Liu et al., 2012). The need for considering local context brings up the question of intervention transferability to different settings. Hawe and colleagues argue that a complex intervention can be standardised and transferable if it is the function and process of the intervention (e.g. mechanisms to increase children’s physical activity in school) that are standardised rather than the components (e.g. a specific curricular activity). This enables the delivery of interventions to take into account

local context (Hawe et al., 2004). This approach necessitates a theoretical understanding of the change mechanisms of local context at each intervention site. We would argue that this is a viable approach. An understanding GPX6 of the contextual factors is essential for tailoring intervention components and thus determining their success. For example, barriers to childhood obesity prevention interventions, such as lack of parental time repeatedly emerge in the literature (O’Dea, 2003, Pocock et al., 2010, Power et al., 2010 and Sonneville et al., 2009). However, this barrier can only be addressed if the precise nature of the constraints on parental time is understood. In this study mothers were likely to be constrained through obligations such as looking after extended families or attendance at places of worship (Pallan et al., 2012), whereas in a North American study of white middle class children, perceived time constraints related to parents’ work commitments (Power et al., 2010). Different approaches to intervention would be required to overcome this barrier in these two communities. The iterative development process enabled us to implicitly gain a theoretical understanding of change pathways, and use this to drive intervention development.

When the authors limited the analyses to the four high-quality trials (326 participants), the pooled SMD was -0.31 (95% CI -0.63 to 0.01) indicating a small effect in favor of exercise. Among the 32 trials identified that fulfilled the inclusion criteria, 8 studies were focused on or included adults older than 60 years.51-59 Six of the studies Depsipeptide supplier involved aerobic Inhibitors,research,lifescience,medical exercise and two studies progressive resistance training. Of the 6 studies that involved aerobic exercise, various exercise and comparator interventions were examined. Blumenthal and colleagues (1999) studied community volunteers

with major depressive disorder (MDD) (n=156) mean (SD) age of 57 (6.5) randomized to aerobic exercise (group walking or jogging 3 times per week), antidepressant pharmacologic treatment (sertraline), Inhibitors,research,lifescience,medical or the combination.58 They found that all treatment groups had statistically significant improvement in depression scores, although participants receiving medication alone had the fastest initial response. After 16 weeks of treatment,

exercise was equally effective in reducing depression among older adults with MDD. A limitation to this study was the absence of a placebo or control intervention. In a follow-up study, Blumenthal and colleagues59 examined community-dwelling older adults with MDD (n=202), mean (SD) Inhibitors,research,lifescience,medical age 52 (8), randomly assigned to home-based exercise, supervised exercise in a group setting, sertraline, or placebo for 16 weeks. While there was a high placebo response rate, the efficacy of exercise was comparable to antidepressant

pharmacotherapy, and both were better than placebo. Brenes and colleagues studied 37 older adults with a mean (SD) age of 73.5 (7.8) with minor depression, randomized to exercise, antidepressant pharmacotherapy Inhibitors,research,lifescience,medical (sertraline), or usual care over 16 weeks.52 In the 32 participants who completed the study, they found trends for exercise and sertraline to be superior to usual care in improving emotional and physical functioning. Mather and colleagues examined whether exercise Inhibitors,research,lifescience,medical is effective as an adjunct to antidepressant pharmacotherapy in older adults. Eighty-six older adults with depression (mean age 65) were randomly assigned to attend exercise classes or health education talks for next 10 weeks.53 At 10 weeks, a significantly higher proportion of the exercise group (55% versus 33%) experienced a greater than 30% decline in depressive symptoms as measured with the Hamilton Rating Scale for Depression. McNeil and colleagues (1991) randomly assigned 30 community dwelling, moderately depressed older adults with a mean (SD) age of 72.5 (6.9) to 1 of 3 interventions: experimenter-accompanied exercise (walking), social contact control condition, and a wait-list control.54 They found that exercise and social contact both resulted in reductions in the Beck Depression Inventory. Lastly, Williams and Tappen examined the effects of exercise training for depressed older adults with Alzheimer’s disease.

We have reasons to suppose that this phenomenon occurs after stroke and other neural disorders. We will present experimental evidences to substantiate this hypothesis in the following paragraphs. In a recent study, we have described different patterns of microglial activation

over weeks after MCAO in both SVZ and striatum (Thored et al. 2009). In SVZ, microglia exhibited a more ramified or intermediate morphology, signifying a downregulated inflammatory profile, whereas amoeboid or round phagocytic microglia were frequent in the periinfarct striatum (Thored et al. 2009). In this study, SVZ microglia Inhibitors,research,lifescience,medical seem to be proneurogenic as they upregulate expression of IGF-1, a growth factor known to be neurogenic in different experimental conditions (Yan et al. 2006). In the striatum of the same experimental animals, activated microglia were more activated and often amoeboid and round at two weeks after MCAO (Thored et al. 2009). These results suggest Inhibitors,research,lifescience,medical that microglia activation is differentially regulated in SVZ and striatum. The neurogenic niche seems to modulate

microglia function toward a more neuroprotective/neurogenic phenotype. Gradients of both anti-inflammatory cytokines and growth GSK126 cost factors inside SVZ might be involved. These results illustrate Inhibitors,research,lifescience,medical well how microglial phenotype may be influenced by the molecular constitution of different anatomical niches along the ischemic environment. We have reasons to believe that both beneficial and detrimental microglia are present in different anatomical niches after MCAO. In an ongoing

investigation, we have observed that clustered SVZ microglia were spatially associated with clusters of neuroblasts several weeks Inhibitors,research,lifescience,medical after MCAO (Fig. 1). In addition, we have observed zones of abnormal aggregate (clustering) of hyperactivated Inhibitors,research,lifescience,medical microglia/macrophages (round and/amoeboid cells) as well as nonoverlapping regions of microglia displaying an intermediate morphology in the ischemic striatum weeks after MCAO (Fig. 2). Double immunofluorescence for Iba1 (a microglia marker) and DCX (a neuroblast marker) revealed a surprising spatial correlation between Non-specific serine/threonine protein kinase these two cell populations in both SVZ and ischemic striatum. A few neuroblasts were present inside abnormal striatal microglial aggregations (Fig. 2A–C), which suggest that this anatomical niche is comprised by detrimental microglia/macrophages contributing to neuroblast death or impairing their survival. Nevertheless, in the striatal regions outside aggregations, which contain microglia with a more intermediate morphology, neuroblasts were intermingled with microglia (Fig. 2D–I) prompting us to believe in a proneurogenic role for microglia in these anatomical niches. Figure 1 Spatial correlation between activated microglia and migrating neuroblasts in the subventricular zone (SVZ) after middle cerebral artery occlusion (MCAO).

Consistent with the hypothesized therapeutic impact of mACh receptor activation is a small clinical trial in schizophrenia showing antipsychotic efficacy of the putative M1/M4 selective mACh receptor agonist xanomaline.185 Current cholinergic

therapeutics are limited in their applicability because of aversive side-effect profiles that are attributed to peripheral activation of M2 and M3 mACh receptors.186,187 For this reason, Inhibitors,research,lifescience,medical the development of subtype selective ligands has been a major interest. M1 and M4 subtypes are of greatest interest in schizophrenia, given the efficacy of xanomaline (an M1/M4-pref erring agonist) and postmortem findings of reduced M1 and M4 receptor densities in schizophrenia.188,189 Studies with mutant mice support the targeting of M1 and M4 receptors. Null deletion mutants of M1 receptors display deficits in working memory and social memory,190 as well as elevated baseline dopamine turnover and increased sensitivity to the behavioral and neurochemical effects of amphetamine.191 Inhibitors,research,lifescience,medical Likewise M4 null mutant mice display hypersensitivity to amphetamine and PCP-induced increases in nucleus acccumbens dopamine, consistent with an involvement of NMDA receptors.192 In the Rigosertib chemical structure absence of selective pharmacological tools, mutant animal studies have been used to improve our understanding of the neurophysiological Inhibitors,research,lifescience,medical role of mACh receptors.187 M4 null mutant mice display enhanced baseline ACh efflux with in vivo dialysis

in various brain regions, consistent with a prominent role as an autoreceptor193 The finding that M1 null mutation abolishes ACh-mediated LTP of pyramidal neurons in the hippocampus194 complements earlier work suggesting a similar role for M1 receptors in the potentiation of NMDA receptor currents.195 Taken together, Inhibitors,research,lifescience,medical these Inhibitors,research,lifescience,medical studies suggest that M1 mACh receptors possess

activity similar to that of mGlu5 receptors, modulating NMDA receptor signaling postsynaptically mACh receptors, like mGluRs, have proven to be difficult to selectively target at the orthosteric site. The agonist xanomaline, though often touted as M1/M4-selective, possesses prominent affinity for other tuclazepam subtypes. Recent progress has been made in the development of M1 and M4 PAMs and allosteric agonists for mACh receptors.196 As with mGlu receptors, allosteric modulation appears to be a promising route for achieving pharmacological selectivity. Recent studies describe the activity of a M1-selective allosteric agonist, 1-(1′-2-methylbenzyl)-1,4′-bipiperidin4-yl)-1H-benzo[ d]imidazol-2(3H)-one (TBPB) and a PAM, benzylquinolone carboxylic acid (BQCA). In experiments that further elucidate the physiological roles of M1 receptors, TBPB enhances NMDA receptor currents; BQCA enhances the frequency and amplitude of spontaneous excitatory neurotransmission in the cortex.197 In evidence of in vivo activity, TBPB reduced amphetamineinduced hyperactivity198 and BQCA enhanced reversal learning in a murine transgenic model of Alzheimers’ disease.

41,61 As previously discussed, according to the ANLS hypothesis, this lactate can then be used as an energy substrate by neurons.40,41 Alternatively, protons released into the extracellular space may also be reconverted to CO2 and water by the action of extracellular CA at the expense of one HCO3 -.61 This model suggests that pH buffering taking

place in glial cells during neuronal activation may also act cooperatively to: i) contribute, via the Na+- HCO3 – cotransporter, to the extrusion against its concentration gradient of the excess intracellular Na+ resulting Inhibitors,research,lifescience,medical from glutamate uptake in astrocytes, thereby alleviating the metabolic burden on the glial Na+/K+ ATPase; and ii) drive the efflux of lactate which is produced in response

to glutamate uptake in astrocytes, thus providing an energy substrate for the neuronal TCA cycle,61,65 Defense against oxidative stress Oxidative stress occurs as a result of an Inhibitors,research,lifescience,medical imbalance between the production of reactive oxygen species (ROS) and antioxidant processes. It is known to be selleck products involved in a number of neuropathological conditions, including neurodegenerative diseases, traumatic brain Inhibitors,research,lifescience,medical injury, and stroke,66 suggesting that the CNS is particularly vulnerable to oxidative injury. This can be explained by the brain’s high rate of oxidative energy metabolism (which inevitably generates ROS), combined with a relatively low intrinsic antioxidant capacity.67 Compared with neurons, astrocytes display a much more effective artillery against Inhibitors,research,lifescience,medical ROS. Accordingly, cooperative astrocyte-neuron

defense mechanisms against oxidative stress seem to be essential for neuronal viability.68 This is supported by a number of studies demonstrating that when cultured in the presence of astrocytes, neurons show increased resistance to toxic doses of nitric oxide,69,70 hydrogen peroxide,71-73 superoxide anion combined with nitric Inhibitors,research,lifescience,medical oxide,69,74 or iron.69,74 This neuroprotective capacity of astrocytes may derive from the fact that they possess significantly higher levels of a variety of antioxidant molecules (including glutathione, ascorbate, and vitamin E) and display greater activities ADAMTS5 for ROS-detoxifying enzymes (including glutathione S-transferase, glutathione peroxidase, and catalase).68,72,75,78 In addition, it appears that astrocytes may also play an active role in preventing the generation of free radicals by redox active metals, as they participate in metal sequestration in the brain.79 This is achieved in part through their high expression levels of metallothioneins and ceruloplasmin, which are involved in metal binding and iron trafficking, respectively.80-82 Glutathione (GSII) is the most important antioxidant molecule found in the brain.

During these years he hebraized his name to “Dan Yaalon”, something that signaled an established life in Israel, and married Rita Singer. Together Rita and Dan shared nearly six decades and established a family that includes two sons and daughters-in-law, and seven grandchildren. As a PhD student in the early 1950s, the soil chemist Avraham Adolf Reifenberg became Yaalon’s advisor. Yaalon was impressed by the RG7204 small Department of Soil Science’s focus on arid zone soils, common worldwide but vastly understudied at that time with significant questions and needs that ranged from the local to global. In day-to-day terms however, Yaalon commented, “Doing

research in those early days, with meager resources, involved overcoming many difficulties. Essentially self-taught we did our best to establish the research and teaching laboratories. These comments reveal perspectives strongly held by Yaalon about life and work. To Yaalon, “ingrained curiosity” was the basis for successful engagement with science. Yaalon’s university education, in Denmark, Sweden, and Israel, challenged him in ways that fed his native curiosity and gave him confidence that Earth’s soil was well worth a life’s work. The making of a scientist according to Yaalon, included much that is fortuitous, unplanned, and even unfair, but what makes

a successful scientist is selleck chemical “grabbing an opportunity when it arises.” Whether in science or in life, he said, “much is due to accidental events but what you make of it is very much subject to your choice and efforts.” Given the gravity of the “accidental events” in Yaalon’s life, these words underscore an incredibly positive message about science, life, and living. Soil Science has no age but will always be remembered through its history. These words were used in Endonuclease 2000 at the Ghent University to honor Dan Yaalon’s

contributions to the history of soil science (Gabriels 2000). Dan was born in 1924 in a small town in the former Czechoslovakia. His original name was Hardy Berger but he changed it shortly after coming to Israel. “Yaalon” was a play on the German meaning of Berger (a mountain dweller), his mother’s Czech surname Jellinek (a mountain goat) and the Hebrew word “Aliyah” (literally, ascent), which united the three concepts. Now it is our time to say good-bye to Dan and to honor his achievements. Dan was not the first to study the history of soil science, but he contributed richly and uniquely to its growing archive of scholarship, and was the moving force in creating a community in which it could Modulators prosper. And Dan saw history as but one component of the study of soils in the context of the human experience. While the philosophy and sociology of soil science remain in the incipient stage, Dan’s vision made a place for them at the table and he actively encouraged other scientists to take up study of these topics.

Chromatography was performed on 10 × 10 cm2 aluminum HPTLC plates precoated with 0.2 mm layers of silica gel (E. Merck, Darmstadt, Germany; supplied by Merck India, Mumbai, India). Before chromatography, the plates were prewashed with

methanol and dried in an oven at 50 °C for 5 min. Samples were applied as 6-mm wide bands, under a continuous flow of nitrogen, Tyrosine Kinase Inhibitor Library concentration by means of a CAMAG (Muttenz, Switzerland) Linomat V sample applicator equipped with an applicator microsyringe (Hamilton, Bonaduz, Switzerland). A constant application rate of 0.1 μL s−1 was used. The plates were then conditioned for 20 min in a presaturated twin-trough glass chamber (10 × 10 cm2) with the mobile phase of chloroform–toluene–methanol–acetic acid (8:1:1:1, v/v/v/v). The plates were then placed in the mobile phase and ascending development was performed to a distance of 70 mm from the point of application at ambient temperature, buy Crizotinib and the development time was 12 min. Subsequent to the development, the plates were dried in a current of air with the help of an air dryer and spots were visualized in CAMAG UV cabinet with dual wavelength UV lamp (254 and 366 nm); densitometric scanning was performed at 365 nm with CAMAG TLC scanner III operated in reflectance–absorbance mode and controlled by Wincats V software. The concentrations of compound were studied from the intensity of diffusely

reflected light. Evaluation was based on linear regression of peak areas. A stock solution containing 1 mg mL−1 LER was prepared in methanol. Calibration solutions were prepared by diluting the stock solution so that application of 1 μL volumes gave a series of spots covering the range 30–210 ng LER. The developed method was validated for linearity and range, specificity, precision, accuracy

and robustness as per ICH guidelines.7 and 8 Each concentration 3-mercaptopyruvate sulfurtransferase in the range of 30–210 ng per spot was spotted five times on individual plates and response was measured after scanning. For evaluation of linearity, peak area and concentrations were subjected to least square regression analysis to calculate calibration equation and correlation coefficient. The specificity of the method was ascertained by analyzing LER in presence of excipients of LER tablet formulations. The bands of LER in the sample were confirmed by comparing RF values and respective spectra of the sample with those of the standard. The peak purity of LER was assured by comparing the spectra at three Modulators different levels, that is, peak-start (s), peak-apex (m) and peak-end (e) positions. Precision was measured by using standard solutions containing LER at concentrations covering the entire calibration range. The precision of the method was evaluated by calculating the percent relative standard deviation (%RSD) of mean peak areas obtained from each spot of sample. Same procedure was performed at different time intervals on the same day, on different days and by different analysts.

63 The presence of comorbid medical conditions or abnormal laboratory tests has also become an increasing concern given the potentially high rates of metabolic syndrome, smoking, etc. among people with schizophrenia. Randomization strategies Most RCTs use even randomization strategies, which assign equal numbers of patients to each treatment arm. This makes sense since the smallest arm will determine Inhibitors,research,lifescience,medical the statistical power involved in the comparison between treatments. However, there are some situations

where equal randomization might not be appropriate. Equipoise randomization64 has been used in some trials and can provide patient and physician input into the potential options involved in the treatment assignment without doing away with randomization altogether. Adaptive design is another strategy which entails the use of data already collected to influence Inhibitors,research,lifescience,medical subsequent randomization of treatment groups.65 This can be particularly useful in studies involving dose-finding; however, it can also lead to premature closure of a study arm or an entire study based on relatively small amounts of data. Sequential design allows pairing of individuals who are assigned to alternate treatments

with the results of each subsequent pair contributing to an ongoing find more analysis of the Inhibitors,research,lifescience,medical odds of reaching a significant effect or not.65 This can provide statistical significance with a small number of patients if Inhibitors,research,lifescience,medical the treatment effect is substantial, or it can provide an initial confirmation of the null hypothesis. Such a design has rarely been used in RCTs in schizophrenia,66 but should be considered. Stratified randomization is an important tool to ensure that the treatment arms are balanced

on a small Inhibitors,research,lifescience,medical number of potentially important mediating or moderating variables. The number of such variables will be determined by the overall sample size. Crossover studies are also conducted in some situations, enough but given potential medication carryover effects and uncertainty as to how vulnerable patients are to returning to their baseline state make placebo-controlled crossover trials less informative in psychiatry than they might be in some medical conditions. So-called “switch” studies are often done in psychiatry, but unless there is a control group they cannot be considered RCTs. Switch studies are obviously much more informative if patients are randomized to be switched or to stay on the original treatment, in a double-blind fashion. Blinding While blinding/masking is an important feature to minimize expectation biases, blinding patients and providers to the treatment does not match clinical practice.