Pharmacological Modalities Research Articles

Neuroprotection Trials in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a significant cause of mortality and morbidity worldwide. Current treatment of acute TBI includes surgical intervention when needed, followed by supportive critical care such as optimizing cerebral perfusion, preventing pyrexia, and treating raised intracranial pressure. While effective in managing the primary injury to the brain and skull, these treatment modalities do not address the complex secondary cascades that occur at a cellular level following initial injury and greatly affect the ultimate neurologic outcome. These secondary processes involve changes in ionic flux, disruption of cellular function, derangement of blood flow and the blood-brain barrier, and elevated levels of free radicals. Over the past few decades, numerous pharmacologic agents and modalities have been investigated in an attempt to interrupt these secondary processes. No neuroprotective agents currently exist that have been proven to improve neurologic outcome following TBI. However, these trials have contributed significantly to the understanding of the clinical sequelae of TBI and to improvements in the quality of care for TBI. With the experience and insights that have been accrued with the trials to date, we will be able to optimize future trial designs and refine established neurologic endpoints to better identify new therapeutic agents and further improve neurologic outcomes from this often devastating condition.

Desensitization Strategies Pre- and Post-Cardiac Transplantation.

Panel reactive antibody (PRA) testing has become standard in the evaluation of patients prior to cardiac transplant. Sensitizing events such as blood transfusions, which result in the accumulation of pre-transplant antibodies, should be avoided as clinically feasible. Desensitization therapy might be considered in sensitized patients with cPRA > 50% although distinct cutoff PRA values for initiating therapy pre-transplant are patient and transplant program dependent. Post-cardiac transplant, quantitative antibodies should also be periodically analyzed, at intervals individualized to the patient. Donor-specific antibodies (DSA) after cardiac transplantation have been shown to be associated with worsened survival. It appears that complement fixing DSA confer the greatest risk for antibody-mediated rejection post-transplant. Desensitization strategies aim to reduce the number of clinically important antibodies prior to and after transplant, both by removal of antibodies and cessation of further production. Current desensitization regimens include pharmacologic, procedural, and surgical modalities, and must be individualized to the patient. Currently, most cardiac transplant programs tailor the post-transplant immunosuppressive regimen based on clinical factors and immunologic assays and may include the use of cytolytic induction and/or intravenous immune gammaglobulin in higher risk patients.

Strategies in clozapine-resistant schizophrenia: A literature review

Treatment resistance to what is often deemed the last line of schizophrenia treatment, clozapine, is a burgeoning problem in psychiatric practice, with estimates of clozapine resistance standing at 40–70% of the treated population. This paper, a comprehensive review of available literature, looks at augmentation strategies to clozapine for such patients, with pharmacological and nonpharmacological modalities considered and reviewed. With a preponderance of open-label trials and case reports, our conclusion is that more research in this field via randomized clinical trials is crucial. Every case of clozapine resistance should be managed in an evidence-based and multidisciplinary manner, with augmentation only used once optimal dosage and duration of clozapine monotherapy is reached, and the psychosocial environment is optimized.

Negative symptoms in schizophrenia.

The negative symptoms have been described in association with schizophrenia since the early days of it being recognized as an entity. However, their elusive nature kept them unacknowledged until there was a revival of interest in them following the development of specific quantifying measures. Over the past three decades, there has been a tremendous surge in research on their types, measurements, status in the present classificatory system, and their implications. The developments in modern investigatory methods have provided the researchers with fresh insights into the underlying mechanisms, and a distributed functioning of the neuronal networks has emerged as the major abnormality. Accordingly, a variety of pharmacological and other treatment modalities have been developed which go beyond the traditional. Nevertheless, a lot remain unanswered. The present paper summarizes important concepts with regard to negative symptoms in schizophrenia.

Neuropsychiatric manifestation of celiac disease: A case-control study in North India

Background: Celiac disease (CD) is an immune-mediated disease dependent on gluten. Prevalence of CD is about 1% and beside gastrointestinal complaints, neuropsychiatric symptoms may represent an atypical feature of CD. Some studies suggest that a gluten-free diet is effective in treating them. Settings and Design: This case-control study of 49 cases was done during the period of January to March 2013. Aim: To know the spectrum of psychiatric manifestations and cognitive functions in children with CD. Materials and Methods: We took 49 diagnosed cases of CD (based on the demonstration of IgA tissue transglutaminase antibodies and duodenal biopsy) and compared with demographically matched control group ( n = 50) on Seguin Form Board Test for cognitive functions and Behavioral Summarized Evaluation-Revised scale for assessment of psychiatric and behavior disturbances. All possible psychiatric diagnosis was made on the basis of International Statistical Classification of Disease and Related Health Problems-Tenth Revision criteria. Statistical Analysis: Statistical analyses were done by using Chi-square test and two-tailed P -values. Results: Neuropsychiatric manifestations were seen in 29% of cases as against 4% of controls which was statistically significant ( P =0.001). Only four cases and 1 control fount to be mild mental retardation ( P = 0.16). Autism, dyslexia, developmental delay, disruptive behavior disorder, and tic disorder present in cases were not found. Conclusion: Clinical manifestations of CD vary from typical malabsorption syndrome to neuropsychiatric manifestations. Those psychiatric patients who are not responding to standard pharmacological modalities, a diagnosis of CD should be taken into consideration. Only behavioral problem can be the sole clinical manifestation of CD.

Use of growth hormone in the treatment of pediatric burns

Hypermetabolic response is characterized by a hyperdynamic circulatory response, with increased body temperature; increased oxygen and glucose consumption; increased carbon dioxide production; hyperglycemia (raised blood sugar levels); peripheral insulin resistance; glycogenolysis, proteolysis, and lipolysis (i.e. the breakdown of glycogen, protein, and lipids, respectively); the loss of lean body mass; and muscle and bone wasting. These symptoms can last for 1-2 years after the burn injury. Failure to satisfy overwhelming energy and protein requirements results in multiorgan dysfunction and an increased susceptibility for infection and death. Immunocompromization and delayed wound healing usually result in severe sepsis, which is the most common direct cause of death in these patients. Nevertheless, providing adequate caloric and protein requirements alone was found to be insufficient to attenuate the hypermetabolic response efficiently. Thereby, various pharmacologic modalities to modulate metabolic response have become a corner stone in the management of severely burned patients. Recombinant growth hormone is the most frequently prescribed agent in pediatrics. This review will focus on the metabolic and immune responses to the use of recombinant growth hormone in pediatric burn patients. It will explore what is beyond growth hormone and the role of insulin-like growth factor-1 in modulation of immunity and apoptosis.

Whole body periodic acceleration (pGz) preserves heart rate variability after cardiac arrest

AimsHeart rate variability (HRV) is a measure of the balance between the sympathetic and parasympathetic autonomic nervous system and lack thereof an ominous sign in many cardiac and neurological conditions including post-cardiac arrest syndrome. Whole body periodic acceleration (pGz) has been shown to be cardio protective when applied prior to during and after cardiac arrest (CA). Here, we investigate whether or not pGz pre or post treatment after CA preserves HRV. MethodsEight min of unsupported ventricular fibrillation followed by CPR and defibrillation was carried out in 32 anesthetized and paralyzed male swine who were randomized to pretreatment (1h pGz prior to CA, pre-pGz [n=8]) or post-treatment (pGz beginning at 30min after return of spontaneous circulation ([ROSC], post-pGz [n=8]) or none (CONT [n=8]). pGz was applied together with conventional mechanical ventilation. In a separate group (n=8), infusion of TRIM (nNOS inhibitor) was used to determine the effects of nNOS inhibition on HRV. ResultsTime and frequency domain measures of HRV were determined along with measurements of blood gases and hemodynamics, obtained at baseline and at 30, 60, 120 and 180min after ROSC. All animals had ROSC and there were no significant differences for arterial blood gases, mean blood pressure and coronary perfusion pressure after ROSC among the groups. HRV was significantly depressed after cardiac arrest and remained depressed in CONT group. In contrast, both pre and post pGz treated groups had significantly higher and preserved time domain measures of HRV (RMSSD and SDNN) from 60 to 180min after ROSC, and nNOS inhibition markedly reduced HRV. The frequency domain of HRV did not show changes. ConclusionsIn a pig model of CA, pre or post treatment with pGz preserves HRV. Inhibition of nNOS markedly reduced HRV. Post-treatment with pGz is a novel therapeutic strategy that might serve as an adjunct to current pharmacological or hypothermia modalities to potentially improve outcomes from post-cardiac arrest syndrome.

Pain Relief for an Osteoarthritic Knee in the Elderly: A Practical Guide.

In view of the increasing prevalence of knee osteoarthritis (OA) in the population worldwide, optimal management is critical to decrease the burden of this condition and minimize disability and personal suffering. Current care is based on a sequence of non-pharmacological, pharmacological, and surgical modalities, targeted to improving pain and function in the elderly population. The aim of this article is to provide a practical view of the efficacy of therapeutic options available along with clinically relevant considerations on the management of knee OA in this demographic group.

The Key to Individualized Addiction Treatment is Comprehensive Assessment and Monitoring of Symptoms and Behavioral Change.

Modern health services now strive for individualized treatment. This approach has been enabled by the increase in knowledge derived from neuroscience and genomics. Substance use disorders are no exception to individualized treatment even though there are no gene-specific medications yet available. What is available is the ability to quickly and precisely assess and monitor biopsychosocial variables known to vary during addiction recovery and which place addicts at increased risk of relapse. Monitoring a broad spectrum of biopsychosocial health enables providers to address diverse genome-specific changes that might trigger withdrawal from treatment or recovery relapse in time to prevent that from occurring. This paper describes modern measurement tools contained in the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) and the NIH Toolbox and suggests how they might be applied to support recovery from alcohol and other substance use disorders in both pharmacological and abstinence-oriented modalities of care.

Should the use of pharmacological treatments still be recommended for the management of osteoarthritis?

Pharmacological treatments including acetaminophen and non-steroidal anti-inflammatory drugs are widely recommended in national and international guidelines for the management of osteoarthritis (OA) in primary care settings. Other pharmacological modalities such as intra-articular corticosteroid or hyaluronic acid injections and symptomatic slow-acting drugs remain controversial across organisations, as there are important differences in interpretation of the evidence base. Recommendations are usually based on the results of systematic reviews and meta-analysis of randomized clinical trials. These reviews are often inconclusive for the benefits of these treatments and are limited by the heterogeneity and the quality of the included studies. Furthermore, concerns have been raised about the benefit-risk profile of these drugs, including acetaminophen. Therefore, in the light of most recent evidence, one can question if the use of pharmacological treatments should still be recommended for the management of OA, especially when the level of evidence for efficacy of non-pharmacological treatments is comparable, with less concerns about side effects. Recently, network meta-analyses have been proposed as a powerful methodological approach to compare available pharmacological treatments in OA according to their relative efficacy, safety profiles and relative costs. Their results could be helpful in formulating new evidence-based rational treatment algorithms and individualized patient care decisions, in updating current guidelines, and in deciding which place pharmacological treatments should take in physician's armamentarium.

Comparative Effects of Ischemic Preconditioning and Iron Chelation in Hepatectomy

ABSTRACTPurpose/Aim: Major hepatectomies can result in severe ischemia/reperfusion (I/R) injury of the liver. The aim of this survey is to comparatively evaluate the effects of a surgical and a pharmacological hepatoprotective modality on the liver remnant in a porcine model of hepatectomy. Material and Methods: Twenty-one Landrace pigs were randomly divided into three groups: a control group (CON) (n = 7), an Ischemic Preconditioning (PRE) group (n = 7) and a Desferoxamine (DFX) treated one (n = 7). Animals were subjected to 120 min of liver ischemia with subsequent 75% hepatectomy followed by 24-hr reperfusion. In all animals, continuous intracranial pressure (ICP) monitoring was employed. Blood samples were collected at t0, t6, t12, and t24 hrs after reperfusion. Liver remnant specimens were excised for histological examination. Results: In the PRE group, ICP was statistically lower at t6 time point compared to CON group and in comparison with t0. In addition, ICP was significantly lower at all-time points after reperfusion in the DFX group. Finally, with regard to DFX and PRE group correlation, ICP was significantly lower at t0, t12, and t24 time points after reperfusion in the DFX group. In the PRE group, NH3 levels were significantly lower at t12 after reperfusion compared to CON and DFX groups. Histological evaluation elucidated significantly less hepatocellular necrosis, apoptosis, and degeneration in the PRE and DFX groups correlated to CON group. Conclusions: Both hepatoprotective modalities including PRE and DFX administration are associated with lower ICP levels and correlated with attenuated liver remnant injury.

Cholinesterase Inhibitor Induced Urinary Incontinence in Dementia:A Management Dilemma

Cholinesterase inhibitors are effective pharmacological modality of treatment in patients with Alzheimer's disease. Urinary incontinence is a relatively uncommon side effect of cholinesterase inhibitors. It is difficult to differentiate the incontinence as a result of progression of the neurodegenerative process of dementia or due to medications or due to underlying local pathology (age-related). It seems illogical to recommend anticholinergics, which are commonly recommended for treatment of urinary incontinence, in patients with dementia who have already acetylcholine-deprived brain. We here discuss the management dilemma of urinary incontinence in a patient with Alzheimer's disease with review of literature.

PrEP and Our Youth: Implications in Law and Policy

2. Minor Consent Pursuant to Emancipation Exceptions A minor who has reached the age of majority is automatically considered emancipated, but those under the age of majority who achieve legal emancipation, either by statutory mandate or judicial decree, have a greatly expanded range of rights and responsibilities. (175) All states have laws pertaining to the emancipation of minors who have not yet reached the age of majority. Emancipation may be de jure or de facto. De jure emancipation, or emancipation by law, occurs through court intervention, where a minor petitions a court to grant him or her the rights and responsibilities of adulthood. De jure emancipation, while an important tool, is of minimal significance for operationalizing PrEP for at-risk minors. Concerns about cost, privacy, and delay inherent in court intervention would likely be prohibitive for the majority of at-risk youth. Thus, operationalizing PrEP for minors without parental consent will require reviewing more economically feasible, confidential, and efficient solutions. De facto emancipation, or emancipation by right, is enabled by state statute and occurs when a minor has achieved a certain status or has certain individual or social (176) In these limited circumstances, the law presumes that the minor has the capacity to understand the risks and benefits of adult activities, and the minor may consent to general medical care (177) without court intervention. Thus, a minor who becomes a member of the armed forces, (178) enters into a marriage or receives a divorce, (179) graduates from high school, (180) is pregnant, (181) lives independently from his or her parents and is financially self-sufficient, (182) or is homeless (183) may, by virtue of this status, consent to a broad range of medical interventions. (184) No state law permits minors to consent to PrEP therapy or any other pharmacological HIV prevention modality. (185) However, some de facto emancipation exceptions that permit minors to consent to general medical care coincide with the personal, family, or social circumstances of certain at-risk minors. At-risk minors who are unaccompanied, have no contact with or live independently of caregivers, refuse to seek parental consent, or could endure mental or physical abuse should the provider seek parental consent likely comprise a great deal of PrEP candidates. Thus, it is critical to consider how state law treats minors in these circumstances. If a state permits a minor to consent to his or her own general medical care in these situations, advocates are presented with an excellent opportunity to operationalize PrEP for broad spectrum of high-risk youth who would likely eschew preventive HIV care in the event that parental consent is required. By statute, more than half of United States jurisdictions (186) permit certain minors to consent to general medical care, which by implication could include PrEP or other pharmacological HIV prevention modalities. (187) These statutory exceptions to the general rule that minors may not consent to their own medical care may be divided into six types: (1) separation and financial independence exceptions; (2) maturity exceptions; (3) mid-adolescence exceptions; (4) medical necessity exceptions; (5) parental unavailability or non-engagement exceptions; and (6) homeless youth exceptions. (188) Within this framework, I discuss each, and potential implications for operationalizing PrEP for self- consenting minors. a. Separation and Financial Independence Exceptions At least fifteen jurisdictions have statutes specifying that qualifying minors living separate and apart from their parents or guardians and managing their own financial affairs may consent on their own behalf to general medical care. (189) Some statutes do not specify the length of separation and financial independence. (190) In these jurisdictions, the exception may apply not just to those minors with sufficient financial means to live independently, but also to minors who are homeless, unstably housed, runaways, castaways, or living on the street, as long as those minors do not currently live with their parents or guardians and are not reliant upon them for financial assistance. …

May spa therapy be a valid opportunity to treat hand osteoarthritis? A review of clinical trials and mechanisms of action.

Osteoarthritis (OA) is the most common form of arthritis and its current treatment includes non-pharmacological and pharmacological modalities. Spa therapy represents a popular treatment for many rheumatic diseases. The aim of this review was to summarize the currently available information on clinical effects and mechanisms of action of spa therapy in OA of the hand. We conducted a search of the literature to extract articles describing randomized clinical trials (RCTs) in hand OA published in the period 1952-2015. We identified three assessable articles reporting RCTs on spa therapy in hand OA. Data from these clinical trials support a beneficial effect of spa therapy on pain, function and quality of life in hand OA. Spa therapy seems to have a role in the treatment of hand OA. However, additional RCTs are necessary to clarify the mechanisms of action and the effects of the application of thermal treatments.

How to do a stress echocardiography?

Stress echocardiography (SE) is a powerful functional imaging technique to assess cardiac performance under work conditions. The main indication is the detection of myocardial ischemia due to coronary artery disease (CAD), however it can also be used in patients with structural heart disease (e. g. valvular disease, hypertrophic obstructive cardiomyopathy). Dynamic or pharmacological (dobutamine / adenosine) modalities are available to induce cardiac stress, basically depending on the clinical problem and the patient's ability to exercise. Exercise on a treadmill or a semi-supine bicycle is the most physiological way to induce stress. Dobutamine stimulation is useful in patients who are unable to exercise and for detection of viable myocardium in hypo- or akinetic segments. Adenosin-induced hyperaemia causes steal effects in myocardial segments with significant CAD. Main limitations of SE are the need for an appropriate acoustic window and the user-dependent variability with regard to the interpretation of the results.

Complementary and alternative medicine approaches in the treatment of PTSD.

Complementary and alternative medicine is a diverse set of practices and treatments that has seen a significant increase among Americans over the past decade. These approaches have been applied to a myriad of medical and mental health disorders with varying levels of efficacy. Recent years have seen an increased interest in the use of complementary and alternative medicine to address the growing numbers of individuals suffering from post-traumatic stress disorder and other trauma-related disorders. These approaches include pharmacologic and non-pharmacologic modalities. This article will review some of the most widely used non-pharmacologic complementary and alternative medicine practices used to treat post-traumatic stress disorder such as recreational therapy, animal-assisted therapy, yoga, and acupuncture as well as alternative delivery methods for psychotherapy.

Optimal management of digital ulcers in systemic sclerosis.

Raynaud’s phenomenon and digital ulcerations are two common clinical features seen in patients with systemic sclerosis. They are painful and lead to significant morbidity and altered hand function within this patient population. While currently there are no US Food and Drug Administration (FDA)-approved medications for the treatment of digital ulcerations in the United States, clinical trials have supported the use of pharmacologic and nonpharmacologic modalities in facilitating healing of existing digital ulcers and preventing formation of new ulcers. This article reviews the published data on these therapeutic options.

Treatment Strategies for Cannabis Use in Schizophrenia

Cannabis is used by more than 25 % of schizophrenia patients and is associated with symptom exacerbation and poorer clinical outcome. To date, evidence is scarce for treating cannabis use disorders among schizophrenia patients. Psychosocial interventions such as cognitive behavioral therapy, motivational interviewing, or contingency management have been evaluated as potential treatments for cannabis use disorders (CUD) among schizophrenia patients and in the general population. However, results are somewhat inconsistent, and efficacy appears to wane after treatment concludes. Pharmacotherapy has also been examined as a potential treatment for CUD but has not yet demonstrated consistent efficacy in the general population. The administration of second-generation antipsychotic medications is the pharmacological standard of care for schizophrenia as well as the treatment of choice for comorbid cannabis use among schizophrenia patients. Recent preliminary trials of pharmacotherapy agents in the general population must be further tested to confirm their potential efficacy at treating CUD. Based on the current evidence, we recommend a multi-faceted approach to treatment for CUD in the schizophrenia population, employing pharmacological and psychosocial modalities. We recommend using a second-generation antipsychotic medication; to date risperidone, olanzapine, and clozapine show the most promise for this population. We also recommend engaging patients in a combination of motivation-based treatment (motivational interviewing or motivation enhancement therapy) and cognitive behavioral treatment directed at cannabis use. When family systems allow, multidimensional family therapy should also be considered, particularly for adolescent patients. The available evidence suggests that CUDs will require ongoing treatment in order to maintain long-term efficacy.

2015 AAHA/AAFP pain management guidelines for dogs and cats.

The robust advances in pain management for companion animals underlie the decision of the American Animal Hospital Association (AAHA) and American Association of Feline Practitioners (AAFP) to expand on the information provided in the 2007 AAHA/AAFP Pain Management Guidelines. The 2015 Guidelines summarize and offer a discriminating review of much of this new knowledge. Pain management is central to veterinary practice, alleviating pain, improving patient outcomes, and enhancing both quality of life and the veterinarian-client-patient relationship. These Guidelines support veterinarians in incorporating pain management into practice, improving patient care. The management of pain requires a continuum of care that includes anticipation, early intervention, and evaluation of response on an individual patient basis. A team-oriented approach, including the owner, is essential for maximizing the recognition, prevention and treatment of pain in animals. The Guidelines include both pharmacologic and non-pharmacologic modalities to manage pain; they are evidence-based insofar as possible and otherwise represent a consensus of expert opinion. Behavioral changes are currently the principal indicator of pain and its course of improvement or progression, and the basis for recently validated pain scores. Post-surgical pain is eminently predictable but a strong body of evidence exists supporting strategies to mitigate adaptive as well as maladaptive forms. Chronic pain is dominated by degenerative joint disease (DJD), which is one of the most significant and under-diagnosed diseases of cats and dogs. DJD is ubiquitous, found in pets of all ages, and inevitably progresses over time; evidence-based strategies for management are established in dogs, and emerging in cats.

A promising future for peptides in ophthalmology: work effectively and smartly.

Despite progress in pharmacological modalities, treatments for ocular diseases are inconvenient, traumatic, costly and often end in poor final visual results. Peptides, considered as protein fragments, can adequately mimic protein binding and thus are used as therapeutic agents. Chemical modifications and bioengineering techniques are being frequently introduced to improve efficacy and stability of peptides, thereby improving their druggability. Cell-penetrating peptides (CPPs), peptides characterized by penetrating plasma membrane, are famous barrier- passers. They are good candidates for carrying drugs through ocular barriers. Therapeutic peptide and CPP perfectly complement each other. Once united, they may form an optimal formula for ocular topical administration, which can work both effectively and smartly. The consequent noninvasive delivery and economical cost would actualize prophylactic intervention, early treatment and long-term therapy to avoid chronic irreversible vision loss. The aim of the current review is a) to summarize recent therapeutic peptides, both anti-angiogenic and anti-inflammation, evidenced by animal experiments in vivo; b) to discuss the discovery strategies for therapeutic peptide; c) to present current delivery strategies for ophthalmic therapeutic peptide; and d) to introduce CPPs which are capable to deliver cargos to intraocular space via ocular surface administration.