Proton-Pump Inhibitor Therapy in Patients with Gastro-Oesophageal Reflux DiseaseFass, Ronnie
doi: 10.2165/00003495-200767110-00001pmid: 17661525
Proton-pump inhibitor (PPI) failure in gastro-oesophageal reflux disease (GORD) patients has become the main reason for referral of these patients to gastroenterology specialists. It is estimated that 30% of GORD patients requiring a PPI once daily will experience treatment failure. Patients with non-erosive reflux disease are the most common GORD-related group in which once-daily PPI therapy fails. Various mechanisms have been suggested to underlie PPI failure in GORD patients. The most pertinent include weakly acidic reflux, duodenogastro-oesophageal reflux, visceral hyperalgesia, delayed gastric emptying, psychological co-morbidity and concomitant functional bowel disorders, as well as others. Because of the importance of PPI failure as a target for future drug development, further understanding of the most relevant underlying mechanisms is needed.
Immunosuppression for Lung TransplantationSnell, Gregory; Westall, Glen
doi: 10.2165/00003495-200767110-00002pmid: 17661526
With the introduction of ciclosporin (cyclosporine) into routine clinical practice 20 years ago, lung transplantation has become an established treatment for patients with advanced lung disease. Most lung transplant recipients routinely continue to receive a triple-drug maintenance immunosuppressive regimen consisting of a calcineurin inhibitor, an antimetabolite and corticosteroids. The use of antibody-based induction therapy remains common, although there has been a shift away from T cell-depleting agents, such as antithymocyte globulin, towards anti-interleukin-2 receptor monoclonal antibodies. Recent years have seen the introduction of sirolimus and everolimus, immunosuppressive drugs that act by blocking growth factor-driven cell proliferation. While the newer immunosuppressive drugs have been rigorously evaluated in large randomised trials in kidney, liver and cardiac transplantation, such studies are lacking in lung transplantation. Despite a shift towards more potent immunosuppressive regimens that incorporate tacrolimus and mycophenolate mofetil, the development of chronic allograft rejection, as manifested by the bronchiolitis obliterans syndrome continues to negatively impact on the long-term survival of lung transplant recipients. This article reviews the evidence for the immunosuppressive regimens used during induction and maintenance of patients undergoing lung transplantation, and discusses current strategies in the management of chronic rejection.
Long-Acting Injectable Risperidone for the Treatment of SchizophreniaMöller, Hans-Jürgen
doi: 10.2165/00003495-200767110-00003pmid: 17661527
Schizophrenia remains a severe disorder that is associated with a poor outcome in a large subgroup of patients. Major efforts should be made to improve treatment for all patients who have this debilitating disease. Second-generation antipsychotics were a major step forward in this respect; however, important unmet needs remain, such as a better solution for frequent noncompliance problems. Depot formulations are known to have advantages in this respect. However, for a long time, only depot formulations of conventional antipsychotics were available, with their high risk of extrapyramidal adverse effects. Therefore, there has been only very restricted use of depot antipsychotics, which mainly focused on patients with chronic disease who were difficult to treat and had a high risk of noncompliance. The situation may change with the advent of a depot formulation of an atypical antipsychotic.
Invasive AspergillosisMaschmeyer, Georg; Haas, Antje; Cornely, Oliver
doi: 10.2165/00003495-200767110-00004pmid: 17661528
Morbidity and mortality caused by invasive Aspergillus infections are increasing. This is because of the higher number of patients with malignancies treated with intensive immunosuppressive therapy regimens as well as their improved survival from formerly fatal bacterial infections, and the rising number of patients undergoing allogeneic haematopoietic stem cell or organ transplantation. Early initiation of effective systemic antifungal treatment is essential for a successful clinical outcome in these patients; however, clinical clues for diagnosis are sparse and early microbiological proof of invasive aspergillosis (IA) is rare. Clinical diagnosis is based on pulmonary CT scan findings and non-culture based diagnostic techniques such as galactomannan or DNA detection in blood or bronchoalveolar lavage samples.
Renal Transplantation in High-Risk PatientsWeimert, Nicole; Alloway, Rita
doi: 10.2165/00003495-200767110-00005pmid: 17661529
Renal transplantation in high-risk patients is a growing phenomenon. More patients are progressing to endstage renal failure, in the setting of an increased incidence of diabetes mellitus and cardiovascular disease. Current organ shortages and the use of more marginal donors have affected both patient and graft survival. Acute rejection has been minimised under modern immunosuppression; however, patient and long-term allograft outcomes have not improved concurrently. Specific understanding of donor, recipient and allograft variables associated with stratification of patients as ‘high-risk for renal transplantation’ is necessary to facilitate appropriate peri- and post-transplant pharmacotherapy. Induction and maintenance immunosuppression choices are different for high-risk patients and must be made to ensure optimal immunosuppression, while limiting patient and allograft toxicity.