Use Of Pharmacological Strategies Research Articles

A novel low-cost uterine balloon tamponade kit to tackle maternal mortality in low-resource settings.

The 3.1 target of the Sustainable Development Goals of the United Nations aims to reduce the global maternal mortality ratio to less than 70 maternal deaths per 100,000 live births by 2030. The last updates on this target show a significant stagnation in the data, thus reducing the chance of meeting it. What makes this negative result even more serious is that these maternal deaths could be avoided through prevention and the wider use of pharmacological strategies and devices to stop postpartum haemorrhage (PPH). PPH is the leading obstetric cause of maternal mortality in low- and middle-income countries (LMICs). Despite low-cost devices based on the uterine balloon tamponade (UBT) technique are already available, they are not safe enough to guarantee the complete stop of the bleeding. When effective, they are too expensive, especially for LMICs. To address this issue, this study presents the design, mechanical characterisation and technology assessment performed to validate a novel low-cost UBT kit, particularly a novel component, i.e., the connector, which guarantees the kit's effectiveness and represents the main novelty. Results proved the device's effectiveness in stopping PPH in a simulated scenario. Moreover, economic and manufacturing evaluations demonstrated its potential to be adopted in LMICs.

Efficacy, Safety, and Tolerability of Armodafinil Therapy for Hypersomnia Associated with Dementia with Lewy Bodies: A Pilot Study

Background/Aims: Hypersomnia is common in dementia with Lewy bodies (DLB). We assessed the efficacy, safety, and tolerability of armodafinil for hypersomnia associated with DLB. Methods: We performed a 12-week pilot trial of armodafinil therapy (125-250 mg orally daily) in DLB outpatients with hypersomnia. The patients underwent neurologic examinations, a neuropsychological battery, laboratory testing, electrocardiography, and polysomnography. Efficacy was assessed at 2, 4, 8, and 12 weeks. Safety assessment included laboratory examinations, QTc interval, and heart rate. Tolerability was assessed by analysis of adverse events. Data were analyzed using the last-observation-carried-forward method. Results: Of 20 participants, 17 completed the protocol. The median age was 72 years, most of the participants were men (80%), and most had spouses as caregivers. The Epworth Sleepiness Scale (p < 0.001), Maintenance of Wakefulness Test (p = 0.003), and Clinical Global Impression of Change (p < 0.001) scores improved at week 12. The Neuropsychiatric Inventory total score (p = 0.003), visual hallucinations (p = 0.003), and agitation (p = 0.02) improved at week 4. Caregiver overall quality of life improved at week 12 (p = 0.004). No adverse events occurred. Conclusion: These pilot data suggest improvements in hypersomnia and wakefulness and reasonable safety and tolerability of armodafinil therapy in hypersomnolent patients with DLB. Our findings inform the use of pharmacologic strategies for managing hypersomnolence in these patients.

Ability of the Pain Recognition and Treatment (PRT) Protocol to Reduce Expressions of Pain among Institutionalized Residents with Dementia: A Cluster Randomized Controlled Trial

Many strategies have been used to improve pain management in institutionalized care settings, but there is no consensus on the effects of these methods. The study purpose was to compare the effect of a Pain Recognition and Treatment (PRT) protocol coupled with basic pain education (experimental group) versus basic pain education alone (control group) in (1) improving the pain management performance of registered nurses (RNs) and (2) reducing pain-related expressions of residents with dementia postintervention and at 3-month follow up. A double-blind cluster randomized controlled trial with a 3-month follow-up period was conducted with 195 residents of six dementia special-care units. The weekly pain management performance of RNs (e.g., use of pharmacologic and nonpharmacologic strategies, use of referral) was recorded and weekly average scores of the pain-related expressions of residents were assessed using the following: the Verbal Descriptor Scale (VDS), Pain Assessment in Advanced Dementia Scale (PAINAD), and the Cohen-Mansfield Agitation Inventory (CMAI). The generalized linear mixed model analysis showed that, after intervention, the experimental group had significantly more weekly nonpharmacologic pain relief strategies and weekly referrals for pain management than the control group. Residents in the experimental group had significantly fewer verbal and behavioral expressions of pain compared to those in the control group. However, the groups did not differ significantly in the use of pharmacological strategies or the agitated behaviors expressed by residents. The PRT protocol is effective and is recommended for routine use in residents with dementia to improve the quality of pain care.

Prevención del delirium

IntroductionDelirium is the most prevalent neuropsychiatric syndrome in the general hospital. Its presence is a marker of poor prognosis for patients. Its prevention could be the most effective strategy for reducing its frequency and its complications. ObjectiveTo review recent findings and strategies for the prevention of delirium. MethodologyA non-systematic review of scientific articles published in the last ten years in Spanish and English. A search was made in databases such as MEDLINE, Cochrane, EMBASE, Ovid, and ScienceDirect, for articles that included the terms, delirium and prevention. ResultsIdentification of predisposing and precipitating factors for delirium and a better understanding of the pathophysiological mechanisms underlying the onset of delirium have enabled the implementation of various pharmacological and non-pharmacological strategies in patients at high risk to develop hospital delirium. The studies to prevent delirium have focused on surgical patients. The current evidence supports the daily implementation of non-pharmacological measures to prevent delirium, as they are easy and cost effective. The available evidence is still limited to recommend the daily use of pharmacological strategies in delirium prophylaxis, and there is a consensus against the modest use of antipsychotic drugs in surgical patients and dexmedetomidine in patients in intensive care. ConclusionsNew high-quality clinical trials and studies involving non-surgical patients are needed to provide more evidence about this subject.

Practitioner review: Long-term pharmacological treatment of pediatric bipolar disorder.

Although long-term treatment is a core aspect of the management of children and adolescents with bipolar disorder (BD), most clinical recommendations are based on results from short-term studies or adult data. In order to guide clinical practice, we review the efficacy and safety profile of mood stabilizers, antipsychotics, and other pharmacological strategies for the long-term treatment of BD in pediatric patients. A MEDLINE, EMBASE, Cochrane and PsycInfo search (inception through November 2013) was performed to identify prospective studies longer than 12weeks assessing the use of pharmacological strategies for the long-term treatment of BD in pediatric patients (0-18years of age). Four randomized controlled trials (RCT) [three placebo-controlled (assessing aripiprazole (2) and flax oil), and one head-to-head comparison of lithium vs. divalproex], and thirteen noncontrolled studies (six open-label studies assessing lithium or anticonvulsants, five assessing second-generation antipsychotics (SGAs) and four assessing combination strategies) were included in the review. Aripiprazole has shown efficacy for relapse prevention in children with pediatric bipolar disorder (PBD) 4-9years of age in one placebo-controlled RCT. Positive results have been reported in noncontrolled studies with quetiapine and lithium for relapse prevention, as well as with lithium, quetiapine, ziprasidone, and the combination of risperidone and divalproex or lithium for long-term symptom reduction in PBD. The most frequently reported adverse events in children and adolescents treated with lithium and anticonvulsants are gastrointestinal and neurological, whereas use of SGAs is mainly related to weight gain and sedation. According to the limited empirical evidence, aripiprazole can be useful for relapse prevention in children with PBD. Given the lack of consistent efficacy data, clinical decision making should be based on individual clinical aspects and safety concerns.

Controle da Dor Pós-Operatória em Cirurgia Oral: Revisão de Literatura

Objectives: To discuss effective analgesic strategies for controlling postoperative pain in oral surgery in order to support drug choice more appropriately. Material and Methods: The literature review was conducted in the databases Medline, PubMed, Science Direct, EBSCO, and Cochrane. 29 studies were selected, including 13 conventional literature reviews, 05 systematic reviews and 11 randomized controlled trials. Results: The surgical procedures in the oral cavity were found to be more invasive and with increased potential to cause postoperative pain, what requires from the professional the use of pharmacological strategies to minimize discomfort generated by such interventions. Several drugs might help in controlling pain, like opioids, non-steroidal anti-inflammatory drugs (NSAIDs) and steroidal anti-inflammatory drugs (corticosteroids). Each drug has a specific mechanism of action, associated with varying degrees of efficiency at each stage of the painful process. Conclusions: The control of postoperative pain should be made individually, choosing the drugs correctly and always taking into account the etiology of pain, type and severity of the procedure performed and patient's systemic conditions, among other factors. Strategies with the combined use of painkillers that act on different nociceptive pathways have shown a better effect in controlling postoperative pain in patients undergoing oral surgery. DESCRIPTORS: Analgesia. Pain, Postoperative. Oral Surgery.

Impact of an educational workshop upon attitudes towards pharmacotherapy for delirium

There is uncertainty regarding the optimal use of pharmacological strategies in delirium particularly regarding preferred agents, duration of treatment and effectiveness in different populations. Attitudes towards delirium pharmacotherapy were investigated before and after an educational workshop using the format of a television game show. Most respondents (65/66) reported psychotropic use with variable frequency (median 60%). Antipsychotic use was inversely related to perception of supporting evidence (p = 0.02). Respondents rated sedative (38%) and antipsychotic (33%) effects as the principal mechanism of action rather than a specific neurochemical anti-delirium effect (21%). Haloperidol was the preferred first-line agent (65%). Suggested continuation treatment after symptom resolution was three days. Eleven respondents had used psychotropics prophylactically. Antipsychotic use was influenced by concerns regarding potential for extrapyramidal (52%), sedative (32%), cerebrovascular (30%) and metabolic (8%) effects. Post-workshop concerns regarding extrapyramidal effects were reduced with a more positive general attitude towards pharmacological interventions, especially in hypoactive presentations (61%) and prophylactically in high-risk patients (56%). Attitudes towards key aspects of delirium pharmacotherapy vary considerably and relate to concerns regarding side effect potential more than perceived mechanism of action. Educational interventions can impact positively upon attitudes.

Preconditioning by Mitochondrial Reactive Oxygen Species Improves the Proangiogenic Potential of Adipose-Derived Cells-Based Therapy

Transplantation of adipose-derived stroma cells (ADSCs) stimulates neovascularization after experimental ischemic injury. ADSC proangiogenic potential is likely mediated by their ability to differentiate into endothelial cells and produce a wide array of angiogenic and antiapoptotic factors. Mitochondrial reactive oxygen species (ROS) have been shown to control ADSC differentiation. We therefore hypothesized that mitochondrial ROS production may change the ADSC proangiogenic properties. The use of pharmacological strategies (mitochondrial inhibitors, antimycin, and rotenone, with or without antioxidants) allowed us to specifically and precisely modulate mitochondrial ROS generation in ADSCs. We showed that transient stimulation of mitochondrial ROS generation in ADSCs before their injection in ischemic hindlimb strongly improved revascularization and the number of ADSC-derived CD31-positive cells in ischemic area. Mitochondrial ROS generation increased the secretion of the proangiogenic and antiapoptotic factors, VEGF and HGF, but did not affect ADSC ability to differentiate into endothelial cells, in vitro. Moreover, mitochondrial ROS-induced ADSC preconditioning greatly protect ADSCs against oxidative stress-induced cell death. Our study demonstrates that in vitro preconditioning by moderate mitochondrial ROS generation strongly increases in vivo ADSC proangiogenic properties and emphasizes the crucial role of mitochondrial ROS in ADSC fate.

Molecular pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts: mutations in MLC1 cause folding defects

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy, most often caused by mutations in the MLC1 gene. MLC1 is an oligomeric plasma membrane (PM) protein of unknown function expressed mainly in glial cells and neurons. Most disease-causing missense mutations dramatically reduced the total and PM MLC1 expression levels in Xenopus oocytes and mammalian cells. The impaired expression of the mutants was verified in primary cultures of rat astrocytes, as well as human monocytes, cell types that endogenously express MLC1, demonstrating the relevance of the tissue culture models. Using a combination of biochemical, pharmacological and imaging methods, we also demonstrated that increased endoplasmatic reticulum-associated degradation and endo-lysosomal-associated degradation can contribute to the cell surface expression defect of the mutants. Based on these results, we suggest that MLC1 mutations reduce protein levels in vivo. Since the expression defect of the mutants could be rescued by exposing the mutant-protein expressing cells to low temperature and glycerol, a chemical chaperone, we propose that MLC belongs to the class of conformational diseases. Therefore, we suggest the use of pharmacological strategies that improve MLC1 expression to treat MLC patients.

P.2.094 Risperidone reduces symptoms of psychosisin Alzheimer's Disease: Results from 3 double-blind controlled clinical trials

Many strategies have been used to improve pain management in institutionalized care settings, but there is no consensus on the effects of these methods. The study purpose was to compare the effect of a Pain Recognition and Treatment (PRT) protocol coupled with basic pain education (experimental group) versus basic pain education alone (control group) in (1) improving the pain management performance of registered nurses (RNs) and (2) reducing pain-related expressions of residents with dementia postintervention and at 3-month follow up. A double-blind cluster randomized controlled trial with a 3-month follow-up period was conducted with 195 residents of six dementia special-care units. The weekly pain management performance of RNs (e.g., use of pharmacologic and nonpharmacologic strategies, use of referral) was recorded and weekly average scores of the pain-related expressions of residents were assessed using the following: the Verbal Descriptor Scale (VDS), Pain Assessment in Advanced Dementia Scale (PAINAD), and the Cohen-Mansfield Agitation Inventory (CMAI). The generalized linear mixed model analysis showed that, after intervention, the experimental group had significantly more weekly nonpharmacologic pain relief strategies and weekly referrals for pain management than the control group. Residents in the experimental group had significantly fewer verbal and behavioral expressions of pain compared to those in the control group. However, the groups did not differ significantly in the use of pharmacological strategies or the agitated behaviors expressed by residents. The PRT protocol is effective and is recommended for routine use in residents with dementia to improve the quality of pain care.

P.2.096Atypical antipsychotics and driving-related psychomotor skills in schizophrenic patents

Many strategies have been used to improve pain management in institutionalized care settings, but there is no consensus on the effects of these methods. The study purpose was to compare the effect of a Pain Recognition and Treatment (PRT) protocol coupled with basic pain education (experimental group) versus basic pain education alone (control group) in (1) improving the pain management performance of registered nurses (RNs) and (2) reducing pain-related expressions of residents with dementia postintervention and at 3-month follow up. A double-blind cluster randomized controlled trial with a 3-month follow-up period was conducted with 195 residents of six dementia special-care units. The weekly pain management performance of RNs (e.g., use of pharmacologic and nonpharmacologic strategies, use of referral) was recorded and weekly average scores of the pain-related expressions of residents were assessed using the following: the Verbal Descriptor Scale (VDS), Pain Assessment in Advanced Dementia Scale (PAINAD), and the Cohen-Mansfield Agitation Inventory (CMAI). The generalized linear mixed model analysis showed that, after intervention, the experimental group had significantly more weekly nonpharmacologic pain relief strategies and weekly referrals for pain management than the control group. Residents in the experimental group had significantly fewer verbal and behavioral expressions of pain compared to those in the control group. However, the groups did not differ significantly in the use of pharmacological strategies or the agitated behaviors expressed by residents. The PRT protocol is effective and is recommended for routine use in residents with dementia to improve the quality of pain care.

Safety and tolerability of atypical antipsychotics in patients with bipolar disorder: prevalence, monitoring and management.

Atypical antipsychotics are associated with fewer movement disorders and a lower risk of tardive dyskinesia than conventional antipsychotics, but are not without side-effects. Metabolic side-effects associated with some of the atypical antipsychotics are a concern for both clinicians and patients. Adverse events related to central nervous system effects, weight gain, and alterations in glucose, lipid, and prolactin levels in patients with depression, bipolar, and anxiety disorders have been reported. Balancing the significant benefits of treatment with these agents against the potential risks of metabolic disturbances and other adverse effects is crucial. Emerging data are making it possible to determine the risk-benefit analysis for specific atypical antipsychotics in individual patients and allow for targeted selection of treatment. A new concept of effectiveness is emerging that attempts to balance adverse effects of treatment with patient quality of life. Patients treated with atypical antipsychotics should have their weight, waist circumference, glucose, and lipids monitored on a regular basis. Monitoring of prolactin levels is not suggested; however, a baseline measurement before initiating treatment can be useful, with subsequent assessment only if a patient demonstrates symptoms. Prevention of weight gain is important. Diet and exercise should be considered for prevention and management, with the use of pharmacologic strategies approached with caution in patients with mood disorders. If a patient is at high risk of developing diabetes, certain pharmacologic agents have been shown to delay the onset of overt diabetes. Once diabetes or dyslipidemia are diagnosed, management should proceed in accordance with approved guidelines for these conditions.

Dentists’ perceived stress and its relation to perceptions about anxious patients

Dentists' perceptions about the stressfulness of dental practice, their perceptions about dental anxiety and its management were surveyed in a descriptive study. A mailed questionnaire was completed by 216 randomly selected Danish private dentists. Of these, nearly 60% perceived dentistry as more stressful than other professions. Dentist perceptions of the most intense stressors were (ranked): 1) running behind schedule, 2) causing pain, 3) heavy work load, 4) late patients and 5) anxious patients. Bivariate odds ratio (OR) analyses were undertaken to check for associations of perceived stress and other dentist variables with perceptual outcomes about anxious patients. Signs of dental anxiety were reported to be less often spotted by older (> or = 52 yr) dentists (OR=3.1) who perceived their job stress to be greater than that of other professionals (OR=3.2). Perceived causes of dental anxiety (1st, 2nd or 3rd choices tallied and then ranked) were 1) fear of pain, 2) trauma in dental treatment, 3) general psychological problems, 4) shame about dental status and 5) economic excuses. Dentists who reported that dental anxiety was primarily the result of general psychological problems in patients, usually had solo (OR=2.4) practices older than 18 years (OR=2.6) and reported high perceived stress (OR=2.2). Adjusted odds ratios for these two dentist perception outcomes about anxious patients generally improved strength of associations and confidence intervals. There were no meaningful differences by practice location or perceived public image. Also, there was no significant association between the use of pharmacological strategies for anxiety and the perceived stress of dentists. Nearly all dentists talked with anxious patients as their main treatment strategy. It was concluded that psychosocial aspects of dental practice have meaningful and often adverse associations with dentist perceptions about anxious patients. Some dentists appeared to require more knowledge about dental anxiety and managing their own stress.

Implications of the links between hypertension and myocardial infarction for choice of drug therapy in patients with hypertension

Meta-analyses of major outcome trials have demonstrated that the benefits of antihypertensive treatment for reduction of the incidence of stroke are entirely consistent with the benefits predicted from epidemiologic data; however, there remains a shortfall in the expected reduction of the incidence of coronary heart disease. Several explanations have been proffered to account for this shortfall, including the potential deleterious metabolic effects of long-term antihypertensive treatment; this has led to the speculation that antihypertensive agents with beneficial ancillary properties might confer additional significant advantage. However, with the exception of the angiotensin-converting enzyme inhibitors, few of these agents have translated into clinical benefit for humans. In addition, sound reasons exist to justify a focus on maintaining and improving the "quality" of blood pressure control. Current evidence suggests that optimal benefit is likely to result from the use of pharmacologic strategies that lower blood pressure consistently over a 24-hour period while at the same time maintaining the "normal" circadian pattern of blood pressure. This result will only be achieved with drugs and drug regimens that genuinely offer long duration of action with the additional potential benefit of maintaining a significant blood pressure lowering effect beyond the end of the dosage interval. This factor is particularly important because many patients with hypertension demonstrate poor adherence to prescribed dosage regimens.