Five-year patient outcomes with risperidone long-acting injection or oral aripiprazole

Background: This study examined 5-year outcomes of patients prescribed risperidone long-acting injection (RLAI) or aripiprazole in a clinical setting, using treatment discontinuation as a measure of effectiveness. Method: Patients who received RLAI or aripiprazole in the 18 months following their respective UK launches were included. Two-year outcome data were previously reported for these cohorts; this study reported an additional 3 years of follow up for each group. Data were collected from pharmacy records and by retrospective case note review. Patients were classified as continuers or discontinuers at 5 years and reasons for treatment discontinuation noted. Results: The number of patients remaining on treatment at 2 years (and included in this study) was 28/84 and 27/92 for RLAI and aripiprazole respectively. Two patients treated with RLAI and three treated with aripiprazole were lost to follow up. Therefore, 5-year outcome data were available for 50 patients. Fifteen patients from each group were continuers at 5 years. Of these, four receiving RLAI and three receiving aripiprazole were coprescribed other antipsychotics at study endpoint. Reasons for discontinuation of RLAI and aripiprazole respectively were lack of effect (n = 4; n = 4), adverse effects (n = 3; n = 1), noncompliance or patient choice (n = 2; n = 4) and patient death (n = 2; n = 0). Conclusion: There was no significant difference between the proportions of patients continuing RLAI or aripiprazole for 5 years. Continuation rates were relatively low (18% and 16% of the original RLAI and aripiprazole cohorts respectively), whilst coprescription of other antipsychotics at endpoint was relatively common. Lack of effectiveness was the most common reason for discontinuation of both compounds. These findings suggested that clinical effectiveness was somewhat disappointing, although the long period of follow up and number of patients previously treated with clozapine in the original cohorts were confounding factors

Synthetically modified bioisosteres of salicyl alcohol and their gastroulcerogenic assessment versus aspirin: biochemical and histological correlates

The present study was conducted to synthesize nitrogen containing derivatives of salicyl alcohol and to investigate in vivo their ulcerogenic potential in comparison with aspirin in rats. The compounds [4-(2-hydroxybenzyl) morpholin-4-iumchloride (I)] and [1,4-bis(2-hydroxybenzyl) piperazine-1,4-diium chloride (II)] were synthesized and their chemical structures were characterized using spectral data. In our previous study (Ali et al., Afr J Pharm Pharmacol 7:585–596, 2013), both compounds showed anti-inflammatory, antinociceptive, and antipyretic properties in standard animal models and a greater binding affinity for cyclooxygenase-2 versus cyclooxygenase-1 in molecular docking and dynamics analysis. For in vivo studies, animals were randomly divided into four groups. The synthetic compounds (both at 100 or 150 mg/kg), aspirin (150 mg/kg), or saline vehicle was administered orally, once daily for 6 days and then tested for ulcerogenic activity. At the end of the procedure, gastric juice and tissues were collected and subjected to biochemical and histological analyses. The results of the study revealed that in the case of the aspirin-treated group, there was a significant increase in gastric juice volume, free acidity, total acidity, and ulcer score and a decrease in gastric pH. Moreover, histological examination of the gastric mucosa of the aspirin-treated group indicated morphological changes while neither of the synthetic compounds showed any significant ulcerogenic or cytotoxic properties. The results of the present study suggest that both compounds are free from ulcerogenic side effects and may represent a better alternative to aspirin

The use of local anaesthesia for intrauterine device insertion by health professionals in the UK

Background Pain associated with the insertion of an intrauterine device (IUD) is a known barrier to intrauterine contraception use in the UK. It is good practice for health professionals to discuss pain relief and use with women prior to the insertion of an IUD. Objectives This study aimed to determine the prevalence of and reasons for and against the use of local anaesthesia (LA) for IUD insertion. Methods A survey was undertaken using paper questionnaires to determine LA use for IUD insertion by UK health professionals. Results Overall, approximately one quarter (n=129) of all respondents use LA routinely, one quarter hardly ever or never use LA, while the remaining half use it sometimes. Use of LA was more prevalent among health professionals who worked in integrated sexual and reproductive health and contraception-only services, compared to general practice. UK health professionals who hardly ever or never used LA for the insertion of IUDs were more likely to be working in general practice. Conclusions The results of this survey suggest that more UK health professionals need to routinely discuss pain relief and offer this to their patients prior to IUD insertion as part of the care pathway for patients who choose to use intrauterine contraception

Patients' experiences and providers' observations on pain during intrauterine device insertion

Objective To determine women's (patients’) experiences of intrauterine device (IUD) insertion under our current practice and the extent to which these agreed with the observations of the health professionals (providers) who had performed the IUD insertion procedures. Method Questionnaires were used to collect information on women's experiences of the IUD insertion procedure from both patients and providers in a sexual and reproductive health service. Results Overall response rates were high (77%, 284 responses in total). Seventy-three percent of patients were nulliparous and over half nulligravid. The providers predominantly used local anaesthesia for IUD insertions (93%). Most patients reported being anxious before their procedure (86%). Patients mainly described the overall experience of their IUD insertion procedure as being associated with ‘minimal discomfort/nothing’ (42%) or ‘uncomfortable’ (41%). ‘Minimal discomfort/nothing’ (56%) and ‘uncomfortable’ (33%) were the main observations of providers. When responses of patients and their providers were compared, agreement was slight for reported pain levels (k = 0.167 CI [0.13–0.24]). Patients’ reported pain levels were significantly higher than those reported to have been observed by their providers (p < 0.001). Conclusion Patients’ and providers’ responses suggested that the IUD insertion procedure under our current practice appeared acceptable to most patients. However, providers were not usually accurate in their observations and tended to underestimate the degree of pain experienced by their patients during IUD insertion procedures

COMT and GAD1 gene polymorphisms are associated with impaired antisaccade task performance in schizophrenic patients

Genetic influences modulating executive functions engaging prefrontal cortical brain systems were investigated in 141 male subjects. The effects of variations in two genes implicated in dopamine and GABA activities in the prefrontal cortex: rs4680 (Val158/Met polymorphism of the catechol-o-methyltransferase gene—COMT) and rs3749034 (C/T) substitution in the promoter region of the glutamic acid decarboxylase gene (GAD1) were studied on antisaccade (AS) performance in healthy subjects and schizophrenic patients. Genotyping revealed a trend towards a reduced proportion of COMT Val/Met heterozygotes and a significantly increased frequency of the GAD1 rs3749034 C allele in schizophrenic patients relative to controls. Patients had elevated error rates, increased AS latencies and increased latency variability (coefficient of variation) compared to controls. The influence of polymorphisms was observed only in patients but not in controls. A substantial effect of the COMT genotype was noted on the coefficient of variation in latency, and this measure was higher in Val homozygotes compared to Met allele carriers (p < 0.05) in the patient group. The outcome from rs3749034 was also disclosed on the error rate (higher in T carriers relative to C homozygotes, p < 0.01) and latency (increased in C homozygotes relative to T carriers, p < 0.01). Binary logistic regression showed that inclusion of the genotype factor (i.e., selective estimation of antisaccade measures in CC carriers) considerably increased the validity of the diagnostic model based on the AS measures. These findings may well be derived from specific genetic associations with prefrontal cortex functioning in schizophrenia

Cellular efflux transporters and the potential role of natural products in combating efflux mediated drug resistance

Efflux mediated multidrug resistance (MDR) is a major problem in the treatment of bacterial, fungal and protozoal infections in addition to cancer chemotherapy. Among other well known mechanisms, efflux pumps are significant contributors to chemo-resistance. Efflux mediated resistance generally occurs through up-regulation of genes responsible for the expression of transporter proteins extruding drugs from the cell to create intracellular sub-therapeutic concentrations leading to resistance. The rapid expansion of MDR pathogens necessitates the discovery of resistance modifying drugs, which in combination with antimicrobial or chemotherapeutic agents would tend to reinstate the action of these drugs and avert the emergence of acquired resistance. This review describes the existence of efflux pumps in prokaryotes and eukaryotes as well as their role in chemo-resistance with a special focus on natural product-derived efflux pump inhibitors

Synthetic and natural antioxidants attenuate cisplatin-induced vomiting

Background: Synthetic and natural antioxidants including Bacopa monnieri (L.) Pennell (Scrophulariaceae) which also possess anti-dopaminergic properties, have been proposed to be useful for emetogenic chemotherapy. In this study, synthetic [N-(2-mercaptopropionyl) glycine (MPG), vitamin C (Vit-C)] and natural [grape seed proanthocyanidin (GP), B. monnieri n-butanolic fraction (BM-ButFr)] antioxidants and their combinations were evaluated against cisplatin-induced emesis in pigeons during a 24 h observation period. Methods: Emesis was induced using cisplatin (7.0 mg/kg, i.v). MPG (10, 20, 30 mg/kg), Vit-C (100, 200, 300 mg/kg), GP (50, 100, 150 mg/kg) and BM-ButFr (5, 10, 20 mg/kg) and their combinations were administered i.m., 15 min before cisplatin administration. The number of vomiting bouts, retching, emetic latency and % weight loss were recorded to assess antiemetic potential. Antioxidant activity was evaluated by the DPPH free radical scavenging assay (FRSA). Results: Significant attenuation of vomiting bouts, retching, % weight loss along with an increase in latency was produced by all the antioxidants and their combinations compared to cisplatin alone and this is the first report of this activity of GP in pigeons. Low EC50 values in the FRSA for MPG (67.66 μg/mL), Vit-C (69.42 μg/mL), GP (6.498 μg/mL) and BM-ButFr (55.61 μg/mL) compared to BHT standard (98.17 μg/mL) demonstrated their radical scavenging capacity. Correlation between the antioxidant activity and antiemetic efficacy disclosed a high degree of correlation for the tested antioxidants. Conclusion: The selected synthetic and natural antioxidants and their combinations were able to attenuate cisplatin-induced vomiting, which correlated with their potent in vitro antioxidant activity

A streptozotocin-induced diabetic neuropathic pain model for static or dynamic mechanical allodynia and vulvodynia: validation using topical and systemic gabapentin

Neuropathic vulvodynia is a state of vulval discomfort characterized by a burning sensation, diffuse pain, pruritus or rawness with an acute or chronic onset. Diabetes mellitus may cause this type of vulvar pain in several ways, so this study was conducted to evaluate streptozotocin-induced diabetes as a neuropathic pain model for vulvodynia in female rats. The presence of streptozotocin (50 mg/kg i.p.)-induced diabetes was initially verified by disclosure of pancreatic tissue degeneration, blood glucose elevation and body weight loss 5–29 days after a single treatment. Dynamic (shortened paw withdrawal latency to light brushing) and static (diminished von Frey filament threshold pressure) mechanical allodynia was then confirmed on the plantar foot surface. Subsequently, both static and dynamic vulvodynia was detected by application of the paradigm to the vulval region. Systemic gabapentin (75 mg/kg, i.p.) and topical gabapentin (10 % gel) were finally tested against allodynia and vulvodynia. Topical gabapentin and the control gel vehicle significantly increased paw withdrawal threshold in the case of the static allodynia model and also paw withdrawal latency in the model for dynamic allodynia when compared with the streptozotocin-pretreated group. Likewise, in the case of static and dynamic vulvodynia, there was a significant antivulvodynia effect of systemic and topical gabapentin treatment. These outcomes substantiate the value of this model not only for allodynia but also for vulvodynia, and this was corroborated by the findings not only with systemic but also with topical gabapentin