The study was developed according to procedures defined by Ajzen and Fishbein.24 Data Collection Participants were individually interviewed for 45 minutes using questions in regards to their demography, physical activity beliefs, and physical activity behavior, respectively. The interviewer explained questionnaires used for data collection to the participants to prevent illiteracy or vision difficulties from affecting the study participation or findings. Instruments In order to assure the validity of the Persian version of the questionnaire, it was translated into Persian Inhibitors,research,lifescience,medical and then back into English. The translation and back translation were performed by two different linguistic students.

The translations were then compared and the questionnaire was corrected accordingly. Inhibitors,research,lifescience,medical The questionnaire was then given to 10 professionals in Health Education, sociology and Gerontology at to examine the item clarity, face validity, and content validity. The questionnaire was then modified based on their suggestions and comments. Reliability of the questionnaire was evaluated using a sample

of 20 subjects over 10 days using Inhibitors,research,lifescience,medical test-retest for physical activity behavior, and Cronbach’s alpha for other items. Participants were instructed to answer all questions based on the definition of regular physical activity. Regular physical activity was defined as a moderately intense physical activity (such as brisk walking) that is Inhibitors,research,lifescience,medical performed ideally every day for a minimum of 30 minutes. The duration of regular physical activity may be fulfilled either in a single session or accumulated in multiple bouts of at least 8–10 minutes throughout the day. Questions of TPB were based on previously used measures of TPB constructs, and were all measured on 7-point scales.13 Physical Activity Intention Inhibitors,research,lifescience,medical Physical activity intention was measured with a single item modeled after Ajzen’s work in 1999. Subjects were asked about the extent of their agreement with the statement that they intend to perform regular physical activity.

Physical Activity Behavior Physical activity was measured using the Physical Activity Scale Florfenicol for the Elderly (PASE).25 The PASE is a brief instrument designed specifically to assess the frequency and duration of recreational, leisure, and occupational physical activity in older adults over a 7-day period. Frequency was http://www.selleckchem.com/products/cobimetinib-gdc-0973-rg7420.html categorized by as never, seldom (1-2 days/week), sometimes (3-4 days/week), and often (5-7 days/week). Duration was categorized as less than 1 hour, between 1-2 hours, 2-4 hours, and more than 4 hours. The total PASE score was computed by multiplying the duration of time spent in each activity or participation (yes/no) by the empirically-derived item weights, and summing up all activities. A higher PASE score represents a greater physical activity behavior. Reliability, evaluated in 20 subjects over 10 days, was (correlation coefficient=0.76).

The baseline characteristics of the participants, including their medication use, were very similar between the groups, with only slightly greater height and weight in the loaded breathing group. The pre-training cardiovascular parameters were very similar in the three groups. The threshold loading device is very suitable for home use and has the advantage that the Paclitaxel research buy air is humidified – avoiding the unpleasant dry mouth and throat normally associated

with breathing through a mouthpiece. Such a relatively simple and inexpensive device could therefore be a valuable adjunct to conventional approaches for treatment of hypertension in all communities. Although Libraries participants and assessors were not blinded, participants were not informed that there were loaded and unloaded breathing groups, so this may have reduced some sources of bias due to lack of blinding on this comparison. The potential problems of an unblinded

study were further minimised by the nature of the measurements since blood pressure and heart rate were recorded automatically and required no particular skill or judgments to be made either by the participants at home or the experimenters in the laboratory (Wood et al 2008). Furthermore, the post-training measurements were all made without either the participants or the experimenters having access to the pretraining data measured some eight weeks earlier. The consequences of unloaded breathing training for too systolic GSK2118436 and diastolic blood pressure were very similar to previous reports where breathing has been regulated in various ways (Schein et al 2001, Grossman et al 2001, Rosenthal et al 2001, Elliot et al 2002, Viskoper et al 2003), with the mean changes being 6 to 10 mmHg for systolic and diastolic

blood pressure for all the trials, including the present one. The reductions in blood pressure achieved in this way are clinically valuable and appreciably greater than those reported for aerobic physical training reductions of 3.8 and 2.6 mmHg for systolic and diastolic blood pressure (Whelton et al 2002) which is generally recommended as an adjunct to treatment for hypertension. It is of particular interest that both training modes reduced systolic blood pressure and pulse pressure. Systolic blood pressure is considered a better predictor of cardiovascular complications than diastolic blood pressure (Lewington et al 2002). It has recently been suggested that systolic blood pressure should be the target of treatment in people aged over 50 years with hypertension (Williams et al 2008) but controlling systolic blood pressure with pharmacological measures is more difficult than controlling diastolic blood pressure (Waeber and Mourad, 2006).

This caused a second dilemma: which individuals would we exclude from the study? Since all of the rating scales we employed were validated for major depressive disorder and not minor depression, it was difficult to know how individuals would score on these measures. Furthermore, we did not have any data to suggest to us what the range of symptomatology should be for individuals with minor depressive disorder on these rating measures. Therefore, we decided to require that individuals meet

Inhibitors,research,lifescience,medical the same entrance requirements for 3 out of 4 weeks in the placebo phase, including the last 2 weeks prior to randomization, in order to enter the study. This facilitated getting an accurate sense of the types of changes one would see on the ratings scales, independent

of their having a bearing on whether or not individuals were able to enter the doubleblind portion of Inhibitors,research,lifescience,medical the study. Some of the other important features of this trial included the use of the Inventory of Depressive Symptomatology – Clinician Rated (IDS-C) as well as three different forms of the HAMD (17-, 21-, and 28-item), the Hamilton Anxiety Rating Scale, the GAF, and the MOS Short Form (SF-36).20,22 The IDS-C was identified as the primary outcome measure Inhibitors,research,lifescience,medical because of the unique features of the scale. First, this scale encompasses a much broader range of depressive symptomatology, extending from various psychological symptoms through somatic symptoms. Second, this symptom scale attempts

to quantify, in a uniform way, both the severity and the intensity of symptomatology. Yet, we were Inhibitors,research,lifescience,medical not comfortable merely using existing rating scales as a way of assessing response in this trial. Therefore, we also investigated the effects of active treatment on complete resolution of symptoms of depression, Inhibitors,research,lifescience,medical plus resolution of functioning. This is a remarkably high bar to attempt to overcome. Another crucial feature, as described earlier in this article, is the length of the evaluation. Many early randomized clinical trials were 2- to 4-wcek placebo-controlled trials.23 Over time, trials have either extended to 6 to 8 weeks’ duration. Yet, as is clearly emphasized by the work of Stassen and colleagues and others, many individuals with major depressive disorder are just beginning to reach recovery at the 8- to www.selleckchem.com/products/Rapamycin.html 12-week time points.24 Therefore, we elected a 12-week acute trial particularly because we were interested in determining the number of individuals that met remission criteria, as well as a change in rating scale. The primary input, again, was the change in the IDS-C with the major outcome point being the ability to achieve complete remission for 1 month prior to the end of the trial.

There were no withdrawals related to an Libraries adverse event. An additional 9 enrolled subjects did not receive a vaccine due to withdrawal of consent (n = 7), inappropriate enrollment (n = 1) or inability to obtain baseline serology (n = 1); all subjects who received a dose of

the vaccine were included in the safety analysis to the extent that data were available. A total of 279 participants (including the 9 participants Selleckchem SRT1720 who were unvaccinated) were excluded from the per-protocol immunogenicity analysis. The main reason for exclusion was a missing prevaccination (n = 60) or postvaccination (n = 130) specimen. Ten subjects who received the wrong vaccine product were excluded from the immunogenicity analysis but included “as treated” in the safety analysis. Local or systemic adverse events after vaccination with

a single dose of MenACWY-CRM or MCV4 were common, reported by 60% and 51%, respectively (Table 3a and Table 3b). Erythema and pain were the most commonly reported injection-site reactions in both the 2–5 and 6–10 years age groups; in the 2–5 years age group, there were no differences between the vaccines. In the 6–10 years age group, significantly fewer participants reported pain after MenACWY-CRM than MCV4 (39% vs. 45%; p = 0.039). In contrast, fewer MCV4 than MenACWY-CRM recipients reported injection-site erythema (22% vs. 28%; p = 0.017). Severe pain or erythema >100 mm in the 6–10 years age group was unusual postvaccination with non significant trends toward higher rates of erythema post-MenACWY-CRM and pain post-MCV4. Rates of systemic adverse events were similar in recipients of MenACWY-CRM and MCV4 (Table click here 3a and Table 3b). In the 2–5-year-old children, irritability was the most common reported systemic adverse event (21% and 22%, respectively), followed by sleepiness (16% and 18%, respectively);

fever ≥38 °C was only reported by 2% of participants. below Headache was the most common systemic adverse event in the 6–10-year-old children, reported by 18% of MenACWY-CRM recipients and 13% of MCV4 recipients (p = 0.049). There were no differences between the groups for any other systemic adverse events. Most adverse events in the 2–5 and 6–10 years age groups were reported as mild; rates of severe adverse events never exceeded 2% for either vaccine. There were also no differences between the groups in the rates of non solicited adverse events between the MenACWY-CRM (26%) and the MCV4 (24%) groups (data not shown). Most of these adverse events (10% and 11%, respectively) were related to minor intercurrent infectious diseases such as upper respiratory tract infection. An adverse event was reported by 72% of two-dose recipients, likely reflecting receipt of an additional dose and thus two seven-day observation periods. In the two-dose group, adverse events were reported less frequently after the second dose (47%) compared to the first dose (63%).

Additionally, chronic stimulation of the CD14/ TLR pathway by LPS was found to exacerbate disease in ALS mice and TLR4 was necessary for LPS-sensitized hypoxic-ischemic neurodegeneration in vivo (12). In our studies microglia-mediated toxicity of motoneurons was attenuated with antibodies which blocked both TLR2 and TLR4. These data suggest that extracellular mSOD1G93A is similar

to LPS, interacting with CD14, which then ligates TLR2 and TLR4, activating a proinflammatory cascade, increasing release of NO and superoxide anion, and decreasing the Inhibitors,research,lifescience,medical release of protective neurotrophic factors. Microglial release of proinflammatory factors in vitro leads to motor neuron http://www.selleckchem.com/products/Rapamycin.html injury and cell death. However, the addition of the cytokine IL-4 reversed LPS-induced and microglia-mediated motor neuron cytotoxicity; IL-4 suppressed Inhibitors,research,lifescience,medical nitric oxide and superoxide anion release, enhanced release of IGF-1, and promoted motor neuron survival (13). These data suggest that IL-4 may provide a significant immunomodulatory signal, protecting motor neurons from microglia-mediated Inhibitors,research,lifescience,medical neurotoxicity by suppressing the production and release of free radicals. Motor Neuron-Microglia Cytotoxic Signaling – The role of mSOD1 A key question is whether

any evidence demonstrates that microglia can be activated by the release of mSOD1 protein from motor neurons. An elegant series of papers have addressed this question directly. Chromogranins, components of neurosecretory vesicles, were documented to interact with mutant forms of superoxide dismutase but not with wild-type SOD1 (14). This interaction was confirmed by yeast two-hybrid screen and by co-immunoprecipitation assays using either lysates from Neuro2a cells coexpressing

chromogranins Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical and SOD1 mutants or lysates from spinal cord of ALS mice. Confocal and immunoelectron microscopy revealed a partial colocalization of mutant SOD1 with chromogranins in spinal cord of ALS mice. Mutant SOD1 was also found in immuno-isolated trans-Golgi network and in microsome preparations, suggesting that it could be secreted. Furthermore, chromogranins CYTH4 were demonstrated to act as chaperone-like proteins and promote secretion of SOD1 mutant proteins. Motor Neuron- Microglia Cytotoxic Signaling – The role of OxidizedSOD1 Recent evidence demonstrates that oxidation of WT SOD1 results in misfolded protein that may acquire the binding and toxic properties of mSOD1, suggesting a possible shared pathway between sporadic and inherited ALS cases (15). Exposure of transfected Neuro2a cells expressing WT or amyotrophic lateral sclerosis-linked SOD1 species to H2O2 resulted in oxidized SOD1. Western blot analysis of immunoprecipitates from cell lysates revealed that, like mutant SOD1, oxidized WT SOD1 was conjugated with poly-ubiquitin, interacted with Hsp70. and was co-immunoprecipitated with Chromogranin B.

These results are in agreement with a previous study using a unilateral dopamine depletion animal (Chudler and Lu 2008) although the authors reported minor changes in the response to mechanical stimuli. This minor difference between both studies is probably due to the magnitude of the lesion (bilateral vs. unilateral), the nature of the anatomical area lesioned (medial forebrain Quisinostat research buy bundle vs. striatum), and the type of stimuli (static vs. dynamic). Inhibitors,research,lifescience,medical This study is also in agreement with previous reports showing that dopamine depletion causes hypersensitivity to mechanical stimulus (Saadé et al. 1997;

Takeda et al. 2005). The dopaminergic lesion of SNc enhanced the pain process (decreased threshold and/or latency) in experimental pain tests (Campbell et al. 1988; Morgan and Franklin 1990; Saadé et al. 1997; Altier and Stewart 1999; Takeda et al. 2005; Ansah et al. 2007; Chudler and Lu 2008; Koszewicz et al. 2012). Moreover, pharmacological studies of D2R (agonist/antagonist) Inhibitors,research,lifescience,medical in the striatum have reported that it suppresses or enhances the pain process in animal experiments Inhibitors,research,lifescience,medical (Magnusson and Fisher 2000; Ansah et al. 2007; Barceló et al. 2010). In addition, systemic use of D2R agonists has proven their antinociceptive action (Michael-Titus et al. 1990; Morgan and Franklin 1990; Clifford et al. 1998). This finding is also supported in this study. These

reports clearly demonstrated that D2R has a general antinociceptive effect (Hagelberg et al. 2004). The mechanism by which DA depletion produces neuropathic Inhibitors,research,lifescience,medical pain has yet to be determined. To our knowledge, there is no direct projection from SNc to the MDH, therefore we can only explain the nociceptive effect of DA depletion by indirect action on the intermediary descending Inhibitors,research,lifescience,medical pain pathway, like that originating from the periaqueductal gray (PAG). The latter constitutes a central structure in the descending pain modulatory pathway

(Millan 2002). Previous studies have demonstrated different projections from SNc, SN reticula, VTA, and amygdala to the PAG. One main feature of these projections to the PAG is that they are GABAergic (Rizvi et al. 1991; Cassell et al. 1999; Gauriau and Bernard until 2002; Chieng and Christie 2010). DA depletion in these structures may decrease, in one way or another, GABA transmission at the PAG level, hence increasing descending facilitatory pain influences on the MDH. This is supported by the fact that in the 6-OHDA-lesioned animals, Fos expression increased in the PAG after mechanical stimulation or not of the hind paw (Reyes and Mitrofanis 2008). This reflected an increase in neural excitation within the PAG after dopamine depletion. The facilitatory effect of the pain descending pathway is reflected by the increase in PKCγ expression within the MDH in this study. PKCγ is known to participate in the chronicity of neuropathic pain (Malmberg et al. 1997; Martin et al. 1999; Ohsawa et al.

5±16.8 U/mL) (17), yielding a dismal positive predictive value (PPV) of only 0.9%, although the sensitivity and specificity were 100 and 98.5% respectively. Satake et al. analyzed CA 19-9 serum levels in 12,840 asymptomatic and 8,706 individuals with symptoms suspicious for pancreatic cancer such as weight loss, epigastric pain

and jaundice. These authors identified only 4 pancreatic cancers (1 resectable) among 18 asymptomatic patients (0.2%) with an elevated CA 19-9 serum level. Among the 8,706 patients with symptoms suspicious Inhibitors,research,lifescience,medical for pancreatic cancer, 198 patients (4.3%) had elevated CA 19-9 serum levels. Following extensive work up, 85 patients (1.8%) were found to have pancreatic cancer of which 28 patients (0.4%) were resectable (17). Similarly, Chang et al. have screened 5343 asymptomatic individuals

for pancreatic cancer, and identified Inhibitors,research,lifescience,medical CA 19-9 serum level elevation (>37 U/mL) in 385 patients (7.2%) (18). Among this group only 2 patients (0.004%) had pancreatic cancer and their serum CA 19-9 levels were 88.4 U/mL and 46,885 U/mL respectively. The PPV of an elevated serum CA 19-9 level in the asymptomatic population in this study was only 0.5%. False positive Inhibitors,research,lifescience,medical elevation of the CA 19-9 serum levels was noted in 325 patients (6.1%) and a total of 58 other cancers were identified (16). Table 1 Published studies evaluating the role of serum CA 19-9 level suggest that it has no utility as a Anti-cancer Compound Library cost screening Inhibitors,research,lifescience,medical marker in asymptomatic individuals given its very low positive predictive value (0.5-0.9%). CA 19-9 serum level testing in symptomatic individuals … As evident from aforementioned studies, given the suboptimal sensitivity and poor predictive value of CA 19-9 serum levels and low prevalence of pancreatic cancer in the general population, routine serum CA 19-9 level testing has no utility as a screening tool in asymptomatic patients. Even Inhibitors,research,lifescience,medical among patients with symptoms suspicious for pancreatic cancer, elevated CA 19-9 serum levels is a poor predictor of pancreatic cancer with a predictive value of 0.5-0.9%. Equally noted in all of the screening studies is that a significant

number of individuals with elevated CA 19-9 serum levels have actually harbored non-pancreatic neoplastic pathology which further undermines the applicability of serum CA 19-9 levels as a screening tool. Among patients who present with a pancreatic mass, elevated CA 19-9 serum levels yield a much higher predictive value however for diagnosing pancreatic cancer. Tessler et al. studied 150 patients undergoing surgery for suspected pancreatic cancer without a preoperative tissue diagnosis. Multivariate analysis identified that a combination of weight loss >20 lbs, bilirubin >3 mg/dL, and CA 19-9 >37 U/mL provided an almost 100% specificity and positive predictive value for pancreatic cancer regardless of the extent of imaging abnormalities (19).

Although observational studies do not use randomized treatment assignment, evaluation of interventions is possible with an appropriate statistical adjustment, but only if the plausibility of statistical assumptions is carefully evaluated. This data analytic strategy was illustrated with evaluations of acute and maintenance antidepressant effectiveness using the NIMH CDS data for longitudinal, observational analyses of ordered www.selleckchem.com/products/Gefitinib.html categorical antidepressant doses. Propensity score adjusted Inhibitors,research,lifescience,medical analyses demonstrated that participants receiving higher doses during an episode were significantly more likely to recover, even though subjects

who received higher doses Inhibitors,research,lifescience,medical tended to be more severely ill. Similarly, participants who received a higher dose of maintenance antidepressant therapy were significantlyless likely to have a recurrence. The propensity adjustment provides an opportunity to examine treatment effects in lieu of randomization. However, there are critical assumptions of this approach. First, it is useful to examine the degree to which between-treatment group Inhibitors,research,lifescience,medical balance has been achieved with the propensity adjustment. Second,

it is essential that the treatment by propensity quintile interaction is tested before pooling quintile specific results. This is because an interaction would signify that the treatment effect varied across quintiles and those quintile-specific results must be reported separately. Third, Rubin highlighted the importance of selection of variables for a propensity score prior to seeing the outcome data.21 This parallels the practice of designating a primary outcome variable and a primary data analytic procedure in Inhibitors,research,lifescience,medical an RCT protocol, prior to collecting data. Finally, D’Agostino and D’Agostino provide an overview of the propensity adjustment Inhibitors,research,lifescience,medical and emphasize make that it is not a panacea, particularly with the assumption of no unmeasured confounding variables.22 A mis-specified propensity model will not reduce

as much bias as a model that includes all confounding variables. Simulation studies have shown this with cross-sectional23 and longitudinal data.24 It is therefore important to conduct sensitivity only analyses.25 Randomization, in and of itself, does not insulate an RCT from threats to internal validity. Two common features ol antidepressant RCT implementation introduce an observational aspect to group assignment. First, attrition, which is highly prevalent in trials ol psychiatric interventions, introduces bias and reduces statistical power, feasibility, and generalizability. There are wellaccepted strategies for reducing the impact of attrition. Adherence to the principle of intention to treat, in which all randomized subjects are included in the primaryanalyses, is critically important.

31 Oxygen therapy should be titrated to achieve oxyhaemoglobin saturation (SpO2) between 88 and 92%,31 and is usually administered via nasal prongs or a venturi mask. Oxygen can also be delivered using high flow nasal cannulae, which may better CB-839 in vivo meet the

inspiratory flow demands of severely dyspnoeic patients and is more tolerable than a face mask. Such systems can also provide humidification, which may be important to prevent sputum retention in patients with excess secretions; however, there is no evidence to guide practice in this area. Non-invasive ventilation is highly effective as a supportive therapy for people with AECOPD complicated by type-II respiratory failure. It unloads the respiratory muscles, restores acid-base balance and provides time for pharmaceutical therapies to be effective. A systematic review and meta-analysis showed that in patients with COPD and acute hypercapnic respiratory failure (PaCO2 > 45 mmHg, pH < 7.35), non-invasive ventilation reduced mortality compared to usual care

(RR 0.52, 95% CI 0.36 to 0.76) and reduced the need for intubation MK-1775 in vivo (RR 0.41, 95% CI 0.33 to 0.53).32 There are also benefits for the health system, with reduced length of stay in those treated with non-invasive ventilation (MD – 3.24 days, 95% CI –4.41 to –2.06).32 Physiotherapists are frequently Libraries involved in the delivery of non-invasive ventilation, including assessment and referral of appropriate patients, establishing patients on treatment, titration of pressures, optimising patient

4-Aminobutyrate aminotransferase tolerance and monitoring treatment effects.33 Non-invasive ventilation may assist in delivery of other physiotherapy treatments such as early mobilisation. In a group of hospitalised patients who were recovering from acute-on-chronic respiratory failure, most of whom had COPD, the use of non-invasive ventilation and oxygen during walking resulted in clinically significant improvements in walking distance, oxyhaemoglobin saturation and exercise-induced dyspnoea compared to walking on oxygen alone.34 Non-invasive ventilation also improved endurance time for unsupported upper limb exercise. These results were obtained from patients who were as early as 2 days into their hospital admission, using inspiratory positive airway pressure ranging from 15 to 18 cmH2O and expiratory positive airway pressure ranging from 4 to 5 cmH2O. Physiotherapists frequently use breathing exercises to relieve dyspnoea, improve thoraco-abdominal co-ordination and enhance functional capacity in people with acute exacerbations of COPD. Commonly used techniques include breathing control (also known as diaphragmatic or abdominal breathing) and pursed lip breathing (gentle exhalation through lips that are pressed together).

It might be argued that the lack of a fixed and coherent model is due to the relevance of unavoidable context issues in palliative care, such as specific cultural settings, patient-centred variables, and family specificity. The implication is that palliative care staff have continuously to adapt

their model of caring to the specific needs and values of each patient, more than applying a fixed, although maybe comprehensive, care model. Competing interests The authors declare that they have no competing interests. Authors’ contributions GB performed the search and analysis of the documents. CB and GM participated in the analysis and wrote Inhibitors,research,lifescience,medical the different versions of the paper. FT discussed the results and wrote the background section. All authors read and approved

the final manuscript. Pre-publication history The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1472-684X/9/1/prepub Supplementary Material Additional file 1: list of documents. Inhibitors,research,lifescience,medical list of documents with name and level of representativeness of the organizations, and code assigned for the text analysis. Click here for file(61K, DOC) Additional file 2: quotations. Inhibitors,research,lifescience,medical quotations from selected documents sorted by areas and subareas. Click here for file(310K, DOC) Acknowledgements Funding The study was supported Inhibitors,research,lifescience,medical by the Istituto di Ricerca in Medicina Palliativa “Lino Maestroni”- ONLUS – Cremona (Italy). The first Author received a specific funding in order to perform the search and the analysis of the documents. The Istituto di Ricerca in Medicina Palliativa “Lino Maestroni” made the payment for the online publication too. The Istituto di Ricerca in Medicina Palliativa

“Lino Maestroni” did not interfere in any way in the collection, analysis and interpretation of data, neither in the writing of the manuscript or in the decision to submit the manuscript for publication
Chronic Inhibitors,research,lifescience,medical severe pain is a Calpain common complication of buy TSA HDAC cancer [1]. Opioid analgesics are highly effective at treating cancer pain and are typically used after maximum doses of non-opioid analgesics have failed [2-5]. The European Association for Palliative Care [6] and the American Pain Society [7] support the use of long-term analgesics for maintaining pain relief once individual dose requirements have been established. Hydromorphone hydrochloride is a hydrogenated semi-synthetic potent μ-opioid agonist that has been used for many years to treat moderate-to-severe cancer pain. Numerous studies have demonstrated an efficacy and safety profile similar to that of morphine and other opioids [8-10]. For oral administration, it is available as short-acting immediate-release (IR) and long-acting controlled-release (CR).