Showing papers in "Expert Opinion on Pharmacotherapy in 2009"
TL;DR: Little is known about CLBP's economic burden and treatment guidelines, and recommended pharmacotherapies included NSAIDs, muscle relaxants, analgesics and anesthetics, and opioids.
Abstract: Objective: This study's objective was to review the literature on the epidemiological and economic burden and treatment of chronic low back pain (CLBP) in France, Germany, Italy, Spain and the UK. Methods: A literature search was conducted for 1997 – 2007, focusing on CLBP burden and treatment in the countries of interest. Results: The literature search yielded 1552 articles; 23 sources were included in this review. General population prevalence estimates for CLBP were available for two countries: 5.91% (Italy) and 6.3 – 11.1% (UK). Resource utilization estimates were available for Germany, Italy, Spain and the UK. Patients visited general practitioners and osteopaths. Annual direct costs of low back pain were available only for Germany: > € 7000 per person. Work absenteeism accounted for 75% of the total per-patient cost of low back pain in Germany. The five identified treatment guidelines recommended a multimodal approach. Recommended pharmacotherapies included NSAIDs, muscle relaxants, analgesics and a...
221 citations
TL;DR: Studies of sustained-release formulations of naltrexone suggest improved effectiveness for retention and sustained abstinence; however, randomized clinical trials are needed.
Abstract: The development of effective treatments for opioid dependence is of great importance given the devastating consequences of the disease. Pharmacotherapies for opioid addiction include opioid agonists, partial agonists, opioid antagonists, and alpha-2-adrenergic agonists, which are targeted toward either detoxification or long-term agonist maintenance. Agonist maintenance therapy is currently the recommended treatment for opioid dependence due to its superior outcomes relative to detoxification. Detoxification protocols have limited long term efficacy and patient discomfort remains a significant therapy challenge. Buprenorphine’s effectiveness relative to methadone remains a controversy and may be most appropriate for patients in need of low doses of agonist treatment. Buprenorphine appears superior to alpha-2 agonists, however, and office-based treatment with buprenorphine in the US is gaining support. Studies of sustained-release formulations of naltrexone suggest improved effectiveness for retention and sustained abstinence, however, randomized clinical trials are needed.
213 citations
TL;DR: RFA is used safely in patients with medium/large tumors and severe liver impairment; unclear tumor margins limit its curative efficacy, and RFA/LTLD can treat Child-Pugh class A-B patients with tumors up to 7 cm, a substantial increase in curable patients.
Abstract: Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide No more than 30% of HCC patients receive curative treatment Factors limiting curative therapy include tumor size and degree of liver impairment Objective: To develop a cure for medium (31 – 50 cm) and large ( > 5 cm) tumors in seriously impaired livers Method: Combine radiofrequency ablation (RFA) with lyso-thermosensitive liposomal doxorubicin (LTLD) Results/conclusions: RFA is used safely in patients with medium/large tumors and severe liver impairment; unclear tumor margins limit its curative efficacy LTLD concentrates in the liver, where the anti-HCC chemotherapeutic, doxorubicin, is released into tumor margins by hyperthermia RFA/LTLD can treat Child-Pugh class A-B patients with tumors up to 7 cm, a substantial increase in curable patients
167 citations
TL;DR: On the basis of extant data, semagacestat seems to be well tolerated, with most adverse events related to its actions on inhibition of peripheral Notch cleavage, and clinical efficacy has not been detectable because of the short duration of the current trials.
Abstract: Background: Alzheimer's disease is thought to be caused by increased formations of neurotoxic amyloid beta (Aβ) peptides, which give rise to the hallmark amyloid plaques. Therefore, pharmacological...
166 citations
TL;DR: This study shows that the fixed-ratio combination of OXN PR is superior to OXY PR alone in terms of bowel function, while providing effective equivalent analgesia.
Abstract: Background: This randomised, double-blind, double-dummy, parallel-group multicentre study assessed the impact of a total daily dose of 60-80 mg oral oxycodone prolonged-release (PR)/naloxone PR (OXN PR) as fixed-ratio combination for patients with opioid-induced constipation (OIC) having moderate-to-severe, non-malignant pain. Methods: During pre-randomisation patients receiving opioids for moderate-to-severe non-malignant pain were converted to oxycodone PR (OXY PR) and titrated to an effective analgesic dose. During randomisation 265 patients on a stable OXY PR dose (60-80 mg/day) and with OIC were included in the full analysis population to receive OXN PR or OXY PR alone. Primary outcome was improvement in symptoms of constipation as measured by the Bowel Function Index (BFI). Secondary/exploratory outcomes examined analgesic efficacy and other bowel function parameters. Results: After 4 weeks of treatment, patients receiving OXN PR showed a significant improvement in bowel function compared with those...
161 citations
TL;DR: Few good options exist or are in development for treating cephalosporin-resistant isolates, as most have had multidrug resistance.
Abstract: Gonorrhea remains an important clinical and public health problem throughout the world. Gonococcal infections have historically been diagnosed by Gram stain and culture but are increasingly diagnosed through nucleic acid tests, thereby eliminating the opportunity for antimicrobial susceptibility testing. Gonococcal infections are typically treated with single-dose therapy with an agent found to cure > 95% of cases. Unfortunately, the gonococcus has repeatedly developed resistance to antimicrobials including sulfonamides, penicillin, tetracyclines and fluoroquinolones. This has now left third-generation cephalosporins as the lone class of antimicrobials recommended as first-line therapy for gonorrhea in some regions. However, resistance to oral third-generation cephalosporins has emerged and spread in Asia, Australia and elsewhere. The mechanism of this resistance seems to be associated with a mosaic penicillin binding protein (penA) in addition to other chromosomal mutations previously found to confer res...
161 citations
TL;DR: Tiotropium was found to reduce significantly COPD-related morbidity, to improve health-related quality of life (HRQoL) irrespective of disease severity and to slow significantly lung function decline in patients not using inhaled corticosteroids or other long-acting bronchodilators.
Abstract: Background: In chronic obstructive pulmonary disease (COPD), inhaled tiotropium bromide, a long-acting anticholinergic, has been shown to exert a sustained bronchodilator effect and to be superior to ipratropium bromide, a short-acting formulation of the same pharmacological class. Objective: To discuss the effects of long-term therapy with tiotropium in COPD. Methods/results: Analysis of efficacy and safety data on tiotropium from a 4-year randomized placebo controlled study performed in moderate to very severe COPD patients. Tiotropium was found to reduce significantly COPD-related morbidity, to improve health-related quality of life (HRQoL) irrespective of disease severity and to slow significantly lung function decline in patients not using inhaled corticosteroids or other long-acting bronchodilators. The safety profile – and in particular cardiovascular safety – of tiotropium was good. Conclusions: Tiotropium bromide, alone or in combination with other inhaled therapies, can maintain an adequate cont...
151 citations
TL;DR: The aim of this review was to give an up-to-date overview on the different agents that had been studied, over the last decade, as chemopreventive agents and the current status ofChemoprevention.
Abstract: Background: Colorectal cancer (CRC) is one of the most common cancers worldwide and a prevalent cause of morbidity and mortality. CRC has a natural history of transition from a precursor lesion, ie...
148 citations
TL;DR: Increased awareness of the causes and solutions for overcoming non-adherence, including safer prescribing, improvement in physician–patient alliance and reduction in drug costs, will enhance the cost-effectiveness of the use of statins and significantly improve patient care and outcomes.
Abstract: Background: Hypercholesterolemia is a major risk factor for atherosclerosis and cardiovascular disease, the leading cause of death worldwide. In the last twenty years, effective lipid-lowering therapies, particularly statins, have become widely available to prevent and reverse the progression of disease. However, there is a significant gap between expected and actual benefits; this may be attributed to poor adherence to statin therapy. Objective: To define the extent, causes (including psychological aspects), consequences and management of non-adherence to statins. Methods: Literature using PubMed and Medline up to and including 30 July 2009. Results: Adherence to statin therapy is suboptimal in both primary and secondary prevention of cardiovascular disease. Causes vary, and include patient factors (e.g., comorbidities, financial constraints, psychological issues), practitioner factors (e.g., poor knowledge of adherence, time constraints, poor communication skills and patient–doctor working alliance) and...
131 citations
TL;DR: Ibudilast is a relatively nonselective phosphodiesterase inhibitor which has been marketed for almost 20 years in Japan for treating asthma and has been found to have anti-inflammatory activity in both the peripheral immune system and in the CNS via glial cell attenuation.
Abstract: Ibudilast is a relatively nonselective phosphodiesterase inhibitor which has been marketed for almost 20 years in Japan for treating asthma. More recently it has been found to have anti-inflammatory activity in both the peripheral immune system and in the CNS via glial cell attenuation. This CNS-directed anti-inflammatory activity is of potential use in the treatment of multiple sclerosis, neuropathic pain, and in the improved efficacy and safety of opioids by decreasing opioid tolerance, withdrawal and reinforcement. Its suitable pharmacokinetics and generally good tolerability make it a promising potential treatment for these conditions.
119 citations
TL;DR: The efficacy of BPO can be enhanced when used in combination with topical retinoids, antibiotics and tertiary amines and do not induce bacterial resistance and are important first-line treatments for mild to moderate acne vulgaris.
Abstract: Background: Owing to the use of topical and systemic antibiotics for acne vulgaris, the incidence of antibiotic-resistant Propionibacterium acnes is increasing worldwide. Topical benzoyl peroxide (BPO) is an alternative to antibiotics in the treatment of acne vulgaris. Objective: This review describes and evaluates recent clinical literature regarding the efficacy and tolerability of BPO. Methods: A PubMed literature search was conducted using the keywords benzoyl peroxide, acne, and combination therapy. Results: BPO is equally effective at concentrations of 2.5, 5.0 and 10%. However, a concentration-dependent irritant dermatitis can occur with higher concentrations. The efficacy of BPO can be enhanced when used in combination with topical retinoids, antibiotics and tertiary amines. BPO-containing combinations do not induce bacterial resistance and are important first-line treatments for mild to moderate acne vulgaris.
TL;DR: New antiviral agents are urgently needed with less adverse effects, good oral bioavailability and possibly novel targets or mechanisms of action to avoid cross-resistance and to improve the ability to suppress the selection of resistant virus strains by combination therapy.
Abstract: This review discusses the management of resistant cytomegalovirus and prevention strategies for fatal therapy failures. Five drugs, ganciclovir/valganciclovir, cidofovir, foscarnet and fomivirsen, ...
TL;DR: More potential options for improved TB treatment currently exist than at any other time in the last 30 years, and new classes of drugs with novel mechanisms of action, nitroimidazopyrans and a diarylquinoline, among others, may soon provide opportunities for improving treatment of drug-resistant TB or shortening treatment ofdrug-susceptible TB.
Abstract: Introduction: The treatment of tuberculosis (TB) is a mature discipline, with more than 60 years of clinical experience accrued across the globe. The requisite Multi-drug treatment of drug-susceptible TB, however, lasts 6 months and has never been optimized according to current standards. Multi-drug resistant TB and TB in individuals coinfected with HIV present additional treatment challenges. Objective: This article reviews the role that existing drugs and new compounds could have in shortening or improving treatment for TB. The key to treatment shortening seems to be sterilizing activity, or the ability of drugs to kill mycobacteria that persist after the initial days of multi-drug treatment. Results: Among existing anti-TB drugs, the rifamycins hold the greatest potential for shortening treatment and improving outcomes, in both HIV-infected and HIV-uninfected populations, without dramatic increases in toxicity. Clinical studies underway or being planned, are supported by in vitro , animal and human evi...
TL;DR: Preventive measures are few and uncertain; however, basic therapy includes reduction in weight in the obese and exercises to keep in shape; this is in accordance with the OARSI guidelines emphasizing the need for obese individuals with knee OA to lose weight.
Abstract: Background: Osteoarthritis (OA) is a major cause of disability, which will increase further with longer lifetime and higher average weight of the population. Objective: To review a hierarchy of interventions for OA in clinical practice, and compare it with the Strength of Recommendation (SOR) proposed by the Osteoarthritis Research Society International (OARSI). Methods: Search for relevant randomized controlled trials in databases, as well as published systematic reviews and meta-analyses. Results/conclusions: Preventive measures are few and uncertain; however, basic therapy includes reduction in weight in the obese and exercises to keep in shape; this is in accordance with the OARSI guidelines (OARSI, 100% consensus) emphasizing the need for obese individuals with knee OA to lose weight (OARSI, SOR = 96%). There are indications of an effect of some nutraceuticals, though further studies are needed for validation (OARSI, SOR = 63%). Pharmacological treatment has paracetamol as primary prescription, which...
TL;DR: Two independent Phase II clinical trials recently confirmed mecamylamine's hypothesized antidepressant activity and suggest that it may be effective as an augmentation pharmacotherapy for SSRI treatment resistant major depression.
Abstract: Mecamylamine (Inversine®), the first orally available antihypertensive agent launched in the 1950s, is rarely used today for hypertension because of its widespread ganglionic side effects at antihypertensive doses (25 – 90 mg/day). However, more recent clinical studies suggest that mecamylamine is effective at much lower doses for blocking the central and peripheral effects of nicotine. Pharmacologically, mecamylamine has been well characterized as a nonselective and noncompetitive antagonist of nicotinic acetylcholine receptors (nAChRs). Because mecamylamine easily crosses the blood – brain barrier at relatively low doses (2.5 – 10 mg), it has been used by several research groups over the past two decades investigating the role of central nAChRs in the etiology and treatment of various neuropsychiatric disorders, including addiction disorders, Tourette's syndrome, schizophrenia and various cognitive and mood disorders. Two independent Phase II clinical trials recently confirmed mecamylamine's hypothesize...
TL;DR: The most significant development for lenalidomide has been its FDA approval (US and Europe) for previously treated multiple myeloma in combination with dexamethasone.
Abstract: Over the past 5 years, lenalidomide (Revlimid®, Celgene Co., Summit, NJ, USA), a member of a class of drugs termed immunomodulatory drugs, has emerged as a significant weapon in the arsenal of canc...
TL;DR: There is an urgent need to implement strategies and to encourage physicians to take measures that increase patients' awareness of the need to use osteoporosis medications as directed in order to benefit from them fully.
Abstract: Poor therapeutic adherence is a major issue faced by physicians today. This paper summarizes the adherence rates with oral bisphosphonate (OBP) treatment in clinical practice and their impact on clinical outcomes. Studies systematically demonstrated that overall compliance and persistence with OBPs among osteoporotic women are poor. Although extending dosing intervals improved adherence, the gains are suboptimal. Most importantly, low compliance and persistence rates consistently resulted in increased rates of fractures. The results emphasize the importance of adherence to treatment to achieve optimal antifracture efficacy. There is an urgent need to implement strategies and to encourage physicians to take measures that increase patients' awareness of the need to use osteoporosis medications as directed in order to benefit from them fully.
TL;DR: These six new agents have resulted in marked progress towards the goal of being able to provide HIV-infected individuals with the drugs necessary to achieve decades of durable suppression of HIV without substantial toxicity, and a thorough understanding of their indications and limitations is critical.
Abstract: Background: The introduction and approval of new antiretroviral agents in the US and Canada bring new opportunities and new challenges. Arguably, for the first time ever, clinicians have the drugs necessary to achieve the goal of suppressing HIV RNA to levels less than 50 copies/mL in even the most treatment-experienced patients and in those with extensive drug-limiting resistance mutations. However, the use of these new agents is complicated by many drug–drug interactions and – to some extent – pre-existing mutations. To derive maximum durability from the use of these newer drugs, a thorough understanding of their indications and limitations is critical. Objective: To thoroughly review the six most recently approved or soon-to-be-approved antiretroviral drugs in the US and Canada: tipranavir, darunavir, etravirine, rilpivirine, maraviroc, and raltegravir. Methods: Discussion of the indications for, and pharmacokinetics, resistance profile, activity, toxicity, and clinical trials results of, the six new a...
TL;DR: The classification of antipsychotics into the two groups is no longer useful and the treatment selection for an individual patient should focus on the suitability of an individual antipsychotic for that patient rather than on the group membership of the drug.
Abstract: Background: Antipsychotic medications are conventionally divided into two groups: First-generation and second-generation antipsychotics (FGAs and SGAs). There is a disagreement about the role of th...
TL;DR: Albendazole, praziquantel and ivermectin are the most important anthelmintics available, easy to use and active against most helminths.
Abstract: Background: In the first decade of the 21st century, worm infections are still very common, especially – but not exclusively – in the developing world. Objective: To review the current pharmacotherapy of the major trematode, cestode and nematode infections of humans. Methods: A systematic search of the Cochrane Databank of Controlled Trials and PubMed with MeSH terms (anthelmint* or treatment or therapy) and (cestoda or trematoda or nematoda or specific helminth species or specific medication). Further references were obtained from article biobliographies. Results: Three hundred and twenty-six publications were selected for further review. Conclusion: Albendazole, praziquantel and ivermectin are the most important anthelmintics available, easy to use and active against most helminths. Diethylcarbamazine is used in loasis and lymphatic filariasis. Doxycycline can eliminate endosymbiotic bacteria of certain filariae, but its place in therapy needs to be further defined. In the treatment of cystic hydatid di...
TL;DR: Although further experience with this product is needed in patients at higher risk of drug reactions, ferumoxytol is likely to be highly useful in the hospital and outpatient settings for treatment of IDA and offers substantial safety and superior efficacy compared with oral iron therapy.
Abstract: Background: Iron deficiency anemia (IDA) is a common problem in patients with chronic kidney disease (CKD). Use of intravenous (i.v.) iron effectively treats the resultant anemia, but available iron products have side effects or dosing regimens that limit safety and convenience. Objective: Ferumoxytol (Feraheme™) is a new i.v. iron product recently approved for use in treatment of IDA in CKD patients. This article reviews the structure, pharmacokinetics, and clinical trial results on ferumoxytol. The author also offers his opinions on the role of this product in clinical practice. Methods: This review encompasses important information contained in clinical and preclinical studies of ferumoxytol and is supplemented with information from the US Food and Drug Administration. Results/conclusion: Ferumoxytol offers substantial safety and superior efficacy compared with oral iron therapy. As ferumoxytol can be administered as 510 mg in < 1 min, it is substantially more convenient than other iron products in non...
TL;DR: Recent publications on ASDs pathogenesis and treatment with emphasis on neuroimmune processes and new therapeutic approaches are reviewed, finding increased oxidative stress and immune dysregulation are present in ASDs.
Abstract: Background: Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by difficulties in communication and by repetitive and stereotypic behaviors, as well as by social impairment, attention, cognitive, and learning defects. ASDs present in early childhood and their prevalence has increased significantly to 1/150 children. Despite a number of theories, the actual reasons for this increase are still not clear. There is no reliable screening test, and no definite pathogenesis or curative therapy. Consequently, there is a major gap hampering development of effective treatments. Objective: To review recent publications on ASDs pathogenesis and treatment with emphasis on neuroimmune processes and new therapeutic approaches. Methods: Mostly original papers (450) on epidemiology, possible pathogenesis or treatment of ASDs in Medline from 1990 to May 2009 were reviewed. All authors contributed to this review. Results/conclusion: Increased oxidative stress and immune dysregulation are present...
TL;DR: A monograph provides a brief overview on chloride channel function in the gastrointestinal tract, describes the structure, function, and pharmacokinetics of lubiprostone, and discusses the safety and efficacy of this new medication for the treatment of chronic constipation and IBS-C.
Abstract: Lubiprostone is a bicyclic fatty acid metabolite analogue of prostaglandin E1. The FDA has approved lubiprostone for the treatment of chronic constipation in men and women and the treatment of women with irritable bowel syndrome with constipation (IBS-C). Lubiprostone specifically activates type-2-chloride channels on the apical membrane of epithelial cells. Lubiprostone acts locally within the intestinal tract, is rapidly metabolized and has very low systemic bioavailability. Animal studies have demonstrated that lubiprostone increases gastrointestinal fluid secretion in a dose-dependent manner. Clinical studies performed in men and women with chronic constipation using 24 microg of lubiprostone twice-daily demonstrated objective improvement in stool frequency and consistency, as well as symptoms of straining and incomplete evacuation. A multi-center study of patients with IBS-C found that 8 microg of lubiprostone twice-daily improved both global and individual symptoms of irritable bowel syndrome. Lubiprostone is generally well tolerated and serious adverse events are rare. The most common reported side effects are nausea, headache and diarrhea. This monograph provides a brief overview on chloride channel function in the gastrointestinal tract, describes the structure, function, and pharmacokinetics of lubiprostone, and discusses the safety and efficacy of this new medication for the treatment of chronic constipation and IBS-C.
TL;DR: The molecular basis of multitarget therapies and the most relevant results obtained in different cancer types are summarized.
Abstract: Target therapies for the treatment of human cancers have revolutionized the concept of oncological medicine. This type of therapeutic approach is directed to the inhibition of molecular targets that play a pivotal role in tumor progression – such as tyrosine kinase receptors (TKIs) controlling cell proliferation and survival – mainly by means of compounds able to block their activity. In the beginning, the aim of target therapies was specifically to hit a single molecule expressed in neoplastic cells. Now the prevailing idea is that inhibiting both cancer cells and cells of the stroma supporting the tumor would gain better results in fighting the disease. Therefore, the single-target therapy is fading in favor of a multitarget approach and the new generation of TKIs is selected on the basis of their ability simultaneously to target different molecules. This review summarizes the molecular basis of multitarget therapies and the most relevant results obtained in different cancer types.
TL;DR: Although intraocular corticosteroid injections have a limited duration of action requiring frequent re-treatment, and significant side effects including cataract and glaucoma development, intraocular injections may be of benefit in certain ocular disorders.
Abstract: Background: Diabetic macular edema (DME), cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO) and uveitis are responsible for severe visual impairment worldwide. In some patients with these conditions, treatment with intraocular corticosteroids may be beneficial. Although off-label use of these agents has occurred for many years, novel agents including preservative-free and sustained-release intravitreal implants are currently being studied in clinical trials (CTs). Objective: To review the use of intraocular corticosteroids. Methods: Literature review. Results: Used alone, intravitreal corticosteroids may benefit disorders such as DME, RVO and uveitis compared with standard therapy or observation. Patients with AMD may benefit more from combination treatment with photodynamic therapy, intravitreal corticosteroid and intravitreal anti-VEGF injections. Intraoperative use of these agents may assist in visualization and manipulation of fine retinal structures...
TL;DR: It is hoped that further progress elucidating the pathophysiology and biology of MBC will continue to lead to corresponding advances in treatment.
Abstract: Metastatic breast cancer (MBC) remains an incurable disease despite ongoing therapeutic advances. Recently there has been progress extending the range of available cytotoxic chemotherapy drugs and optimizing their scheduling. In addition, a greater understanding of tumor biology has led to the development of a number of targeted therapies. Several of these newer agents, such as trastuzumab, lapatinib and bevacizumab, have demonstrated activity in combination with chemotherapy and have improved the prognosis of patients with MBC. We hope that further progress elucidating the pathophysiology and biology of MBC will continue to lead to corresponding advances in treatment.
TL;DR: Terbinafine has established itself as a drug of choice for dermatophytic infections; it must be considered in combination with other antifungal agents for the management of nondermatophytic refractory or resistant yeast/mold infections as well.
Abstract: Terbinafine (TRB) is an allylamine antifungal agent that has been available for more than a decade. It is now used for the treatment of dermatophytic infections and onychomycosis. Despite several studies having demonstrated the efficacy of terbinafine against nondermatophytic infections including azole-resistant candidiasis, invasive aspergillosis, disseminated fusariosis and scedosporiosis, the role of TRB in the management of these infections remains greatly underappreciated. A brief review of pharmacodynamic, pharmacokinetic, in vitro and in vivo data and published case reports provides insight into the use of terbinafine as a potential adjunct in combination with azoles, polyenes or echinocandins in the management of severe drug-resistant or refractory mycoses. Despite the lack of intrinsic fungicidal activity against several nondermatophytes, when used in combination, particularly with azoles, TRB has demonstrated good antifungal efficacy that could be exploited in clinical practice. As comprehensive human clinical studies are not feasible with the rare occurence of these mycoses, experiments using animal models are essential to evaluate the in vivo efficacy of drug combinations. In summary, terbinafine has established itself as a drug of choice for dermatophytic infections; it must be considered in combination with other antifungal agents for the management of nondermatophytic refractory or resistant yeast/mold infections as well.
TL;DR: The manufacturer, Eli Lilly Co., has received an approvable letter from the FDA for the prevention of vision loss in patients with diabetic retinopathy with RBX, pending results of additional clinical trials for this indication.
Abstract: Diabetes mellitus is the most common cause of blindness among working-age adults, with a prevalence of 7 – 8% of adults in the USA, and is one of the most common causes of renal failure requiring kidney transplant and the most common cause of non-traumatic lower limb amputation in developed nations . The role of the intracellular signaling enzyme protein kinase C (PKC) in the development of diabetic complications has become a field of intense research interest. An inhibitor of the PKC-β isoform ruboxistaurin (RBX) has in vitro and in vivo benefits in ameliorating disturbances of cell regulation and blood flow related to hyperglycemia. The benefit of RBX for peripheral neuropathy has not been successfully demonstrated in Phase III trials. Although there was a beneficial effect of RBX on nephropathy in a pilot study, there has been no further clinical development for this indication. The major cause of visual disability – diabetic macular edema – seems to respond to RBX treatment with both anatomic and func...
TL;DR: Bromfenac and other NSAIDs are seeing expanded use for the treatment and prevention of cystoid macular edema, and could have clinical utility in other diseases of vascular permeability.
Abstract: Topical nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibiting the formation of prostaglandin by cyclooxygenases. Several agents in this class have been approved for the treatment of postoperative pain and inflammation following cataract surgery. Bromfenac 0.09% (Xibrom™, ISTA Pharmaceuticals, USA) is a relatively new topical NSAID that exhibits ocular penetration and duration of action sufficient to permit twice-daily dosing. Bromfenac dosed twice-daily was clearly superior to placebo for postoperative pain and inflammation in a large, controlled trial and compares favorably with other NSAIDs in smaller studies. Adverse events associated with use have been minimal in large studies, although there are reports of corneal compromise with bromfenac use in cases of preexisting corneal disease. The comfort and reduced frequency of use offered by bromfenac would be expected to improve patient compliance, which would in turn be expected to result in adoption of bromfenac over other NSAIDs by many physic...
TL;DR: The pros and cons of combination therapies, and the ongoing research in this area are discussed.
Abstract: The anti-obesity medications available at present achieve a rather modest degree of weight loss that falls below the expectations of clinicians as well as consumers. Several combination drug therapies are in development with the aim of achieving better results that would be clinically more meaningful in the reduction of obesity-related health risks. This paper discusses the pros and cons of combination therapies, and the ongoing research in this area.