Community pharmacy services to optimise the use of medications for mental illness: a systematic review

The objective of this systematic review was to evaluate the impact of pharmacist delivered community-based services to optimise the use of medications for mental illness. Twenty-two controlled (randomised and non-randomised) studies of pharmacists' interventions in community and residential aged care settings identified in international scientific literature were included for review. Papers were assessed for study design, service recipient, country of origin, intervention type, number of participating pharmacists, methodological quality and outcome measurement. Three studies showed that pharmacists' medication counselling and treatment monitoring can improve adherence to antidepressant medications among those commencing treatment when calculated using an intention-to-treat analysis. Four trials demonstrated that pharmacist conducted medication reviews may reduce the number of potentially inappropriate medications prescribed to those at high risk of medication misadventure. The results of this review provide some evidence that pharmacists can contribute to optimising the use of medications for mental illness in the community setting. However, more well designed studies are needed to assess the impact of pharmacists as members of community mental health teams and as providers of comprehensive medicines information to people with schizophrenia and bipolar disorder     

Surgery for right ventricle to pulmonary artery conduit obstruction: risk factors for further reoperation.

OBJECTIVE: To identify the surgical approaches and risk factors which influence longevity of right ventricle to pulmonary artery (RV-PA) conduits following first reoperation for obstruction. METHODS: Between January 1993 and August 2003, 114 patients underwent 141 reoperations for RV-PA conduit obstruction. Diagnoses included 'Truncus Arteriosus' (n=52), 'Pulmonary atresia/Tetralogy of fallot' (n=39), 'Double outlet right ventricle' (n=10), 'Transposition of great arteries, VSD, and pulmonary atresia' (n=9), and the 'Ross operation' (n=4). All patients had undergone a previous biventricular repair. The first reoperation for conduit obstruction was performed in 112 hospital survivors by: total conduit replacement (Group A, n=73) with valved (homograft=10 and xenograft=54) or non-valved (n=9) conduit, and patch enlargement of the obstructed RV outflow tract with preservation of the posterior and sides of the conduit wall after removing of the fibrocalcific peel and degenerated valve (Group B, n=39). Mean age at first reoperation was 8.8+/-6.7 and 7.5+/-5.3 years in patients of groups A and B, respectively. Seven patients in Group A and 18 in Group B required a second reoperation and two patients in Group B a third reoperation. RESULTS: There were two hospital deaths and no late deaths. Mean follow-up was 5.8+/-3.2 years. Risk factors for second reoperation by univariate analysis were: homograft conduit use (P=0.004), Group B surgical approach (P=0.0001), higher RV-PA systolic pressure gradient at discharge (P=0.02), and age <5-years-old (P=0.01). Multivariate analysis showed that inclusion in Group B and younger age (<5-years-old) at repair were independent risk factors for second reoperation. Group B surgical approaches had higher RV-PA systolic pressure gradient at discharge (P=0.02) and required more PA bifurcation repair at the time of second reoperation (P=0.05). Freedom from second reoperation for conduit obstruction was significantly higher in Group A patients at 5 and 8 years (P<0.04) and those with xenografts rather than homograft (P=0.04). CONCLUSIONS: Our results support the optimal surgical approach for RV-PA conduit obstruction is total replacement with a xenograft. RV outflow reconstruction by other techniques without complete dissection of PA bifurcation does not completely relieve the stenosis and could cause early restenosis. Higher systolic gradients at discharge and younger age at first reoperation are predictors of earlier reoperation.     

Prostate cancer after heart transplantation: unicenter case-control study.

BACKGROUND: We have noted an unexpectedly high incidence of prostate cancer in our heart transplant recipients (HTR). METHODS: We conducted a retrospective review of patients after heart transplantation to investigate the prevalence, treatment, and outcome of prostate cancer diagnosed after systematic screening (study group). We compared them with case-matched HTR (control). RESULTS: Among 702 recipients, 15 patients had elevated prostate-specific antigen (PSA) levels. Fourteen cases of prostate cancer were diagnosed and treated. The median time between transplantation and prostate cancer diagnosis was 73 months. No patient was diagnosed in a locally advanced (>T2) or metastatic stage. Eleven patients (78.6%) received curative treatment. During follow-up (median, 44 months), 1 patient died from prostate cancer. The survival rate between the study and control groups did not differ. CONCLUSION: Routine PSA testing is recommended as a screening test for prostate cancer in patients after heart transplantation. We believe this could also result in detection of early stages of prostate cancer, thus allowing curative treatment, and achieving similar survival to other case-matched HTR with no prostate cancer.     

Lipid transfer protein: a pan-allergen in plant-derived foods that is highly resistant to pepsin digestion

BACKGROUND: Lipid transfer proteins (LTPs) are small molecules of approximately 10 kD that demonstrate high stability. They have recently been identified as allergens in the Rosaceae subfamilies of the Prunoideae (peach, apricot, plum) and of the Pomoideae (apple). They belong to a family of structurally highly conserved proteins that are also present in non-Rosaceae vegetable foods. OBJECTIVE: The aim of this study was to investigate the cross-reactivity to non-Rosaceae LTPs, and to study the role of protein stability in allergenicity. METHODS: Thirty-eight patients with a positive SPT to Rosaceae fruit extracts enriched for LTP were characterized by interview and SPT. To investigate IgE cross-reactivity between Rosaceae and non-Rosaceae LTPs, RAST and RAST inhibition as well as ELISA and ELISA inhibition were performed, using whole food extracts and purified LTPs. Both purified natural LTPs (peach, carrot and broccoli) and Pichia pastoris recombinant LTPs (carrot and wheat) were included. Pepsin digestion was used to address the role of stability in the allergenicity of LTPs. RESULTS: IgE antibodies to Rosaceae LTPs reacted to a broad range of vegetable foods, including Gramineae (cereals), Leguminosae (peanut), Juglandaceae (walnut), Anacardiaceae (pistachio), Brassicaceae (broccoli), Umbelliferae (carrot, celery), Solanaceae (tomato), Cucurbitaceae (melon), and Actinidiaceae (kiwi). Binding and inhibition studies with purified natural and recombinant LTPs confirmed their role in this cross-reactivity. Many of these cross-reactivities were accompanied by clinical food allergy, frequently including systemic reactions. Antibody binding to LTP was shown to be resistant to pepsin treatment of whole extract or purified LTP. CONCLUSION: LTP is a pan-allergen with a degree of cross-reactivity comparable to profilin. Due to its extreme resistance to pepsin digestion, LTP is a potentially severe food allergen.     

Role of the host in pathogenesis of Helicobacter-associated gastritis: H. felis infection of inbred and congenic mouse strains.

In humans, Helicobacter pylori establishes a chronic infection which can result in various degrees of gastric inflammation, peptic ulcer disease, and a predisposition to gastric cancer. It has been suggested that bacterial virulence factors such as the vacuolating toxin (VacA) and the cytotoxin-associated gene product (CagA) may play a major role in determining the clinical outcome of Helicobacter infections. The role of host responses in these varied outcomes has received little attention. Helicobacter felis, which does not express CagA or VacA, causes chronic infection and inflammation in a well-characterized mouse model. We have used this model to evaluate the role of host responses in Helicobacter infections. BALB/c, C3H, and C57BL/6 mice were orally infected with a single strain of H. felis, and 2 and 11 weeks after infection, the mice were sacrificed and evaluated histologically for magnitude of H. felis infection. Intensity and extent of inflammation, and cellular composition of the inflammatory infiltrate. All three strains of mice demonstrated comparable levels of infection at 11 weeks, but the pattern and intensity of inflammation varied from minimal in BALB/c mice to severe in C57BL/6 mice. Gastric epithelial erosions were noted in C3H mice, and mucous cell hyperplasia was observed in C3H and C57BL/6 mice. Abundant mucosal mast cells were observed in the gastric tissues of all three mouse strains. Studies using major histocompatibility complex (MHC)-congenic mice revealed probable contributions by both MHC and non-MHC genes to Helicobacter-induced inflammation. Thus, large variations in the severity of disease were observed after infection of different inbred strains and congenic mice with a single isolate of H. felis. These results demonstrate the importance of the host response in disease outcome following gastric Helicobacter infection.     

Mechanisms of cold sensitivity of paramyotonia congenita mutation R1448H and overlap syndrome mutation M1360V

Missense mutations of the human skeletal muscle voltage-gated Na⁺ channel (hSkM1) cause a variety of neuromuscular disorders. The mutation R1448H results in paramyotonia congenita and causes cold-induced myotonia with subsequent paralysis. The mutation M1360V causes an overlapping syndrome with both K⁺-induced muscle weakness and cold-induced myotonia. The molecular mechanisms of the temperature dependence of these disorders are not well understood. Therefore we investigated physiological parameters of these Na⁺ channel mutations at different temperatures. Channel proteins were recombinantly expressed in human embryonic kidney cells and studied electrophysiologically, using the whole-cell patch-clamp technique. We compared the wild-type (WT) channel with both mutants at different temperatures. Both mutations had slower inactivation and faster recovery from inactivation compared to WT channels. This effect was more pronounced at the R1448H mutation, leading to a larger depolarization of the cell membrane causing myotonia and paralysis. The voltage dependence of activation of R1448H was shifted to more negative membrane potentials at lower temperature but not at the M1360V mutation or in the WT. The window current by mutation R1448H was increased at lower temperatures. The results of this study may explain the stronger cold-induced clinical symptoms resulting from the R1448H mutation in contrast to the M1360V mutation.     

Probiotic Supplementation and High-Intensity Interval Training Modify Anxiety-Like Behaviors and Corticosterone in High-Fat Diet-Induced Obesity Mice

Evidence supports the role of exercise training and probiotics on reducing obesity. Considering the relationship between obesity and high-fat diet with anxiety indices, the aim of this study was to assess the effect of probiotic supplementation and high-intensity interval training (HIIT) on anxiety-like behaviors, corticosterone and obesity indices in high-fat diet (HFD)-induced obesity mice. Thirty male adult C57BL/6 mice were randomly divided into five groups: (1) Control with normal diet (CON), (2) High-fat diet (HFD), (3) HFD + exercise training (HT), (4) HFD + probiotics supplement (HP) and (5) HFD + exercise training +probiotics (HTP). Exercise training consisted of 8 weeks of high-intensity interval training (HIIT) programs. Probiotics supplement included 0.2 mL Lactobacillus rhamnosus GG. Anxiety-like behaviors were measured by open field (OF) and Elevated plus maze (EPM). OF and EPM tests, visceral fat mass (VFM) measurement, and blood sampling for corticosterone were performed after the intervention. Bodyweight was measured at different stages during the intervention. HFD regime in C57BL/6 mice increased bodyweight, VFM, and serum corticosterone levels and anxiety-like behaviors (p < 0.05). HIIT, probiotic and their combination, decreased bodyweight, VFM, and serum corticosterone levels and improved anxiety-like behavior in the HFD mice (p < 0.05). The effect of a combination of HIIT and probiotic on most of the anxiety indices was more than each one separately (p < 0.5). HIIT and probiotic supplements separately or above all in combination, may have beneficial effects in reducing obesity and anxiety indices.     

Medical and dental implications of cocaine abuse

With the ever-increasing supply of cocaine and use of "crack," the potent and smokeable form of cocaine, the dangers of cocaine abuse, with its high morbidity and mortality, have become recognized. Oral and maxillofacial surgeons may frequently and unknowingly be treating patients who use cocaine, and, therefore, they must be educated about cocaine-related problems and be prepared to deal with the complications. This article discusses the nature of cocaine, its pharmacology, systemic affects, the oral manifestations of cocaine abuse, and recommended clinical management of the patient.     

Interaction of topiramate with glycine receptor channels

Glycine receptor channels are pentameric ligand-gated ion channels that respond to the application of inhibitory neurotransmitters by opening of a chloride-selective central pore. Topiramate (TPM) is a broad-spectrum antiepileptic drug used as add-on or monotherapy for focal seizures. In the present study the interaction of TPM with glycine receptor channels was studied on outside-out patches from HEK293 cells expressing alpha1beta glycine receptor channels. The patch clamp techniques combined with ultra fast solution exchange enabled us to investigate the kinetics of receptor channels in presence of TPM. Our study showed no agonistic or potentiating effect for TPM on glycine receptor channels. However, in presence of 1 mM glycine + 1 mM TPM, the desensitization got faster and the peak current amplitude decreased. After the end of glycine + TPM pulses, off-currents occurred, suggestive for a specific channel block mechanism.