Description:
(1) Background: Medication adherence is a key determinant of patient health outcomes in chronic illnesses. However, adherence to long-term therapy remains poor. General beliefs about medicine are considered factors influencing medication adherence. It is essential to address the gap in the literature regarding understanding the impact of general beliefs about medicine on medication adherence to promote adherence in chronic illnesses. (2) Methods: PubMed, CINHAL, and EMBASE databases were searched. Studies were included if they examined medication beliefs using the Beliefs about Medicine Questionnaire in one of four chronic illnesses: hypertension, diabetes, chronic obstructive pulmonary disease, and/or asthma. (3) Results: From 1799 articles obtained by the search, only 11 met the inclusion criteria. Hypertension and diabetes represented 91% of included studies, while asthma represented 9%. Higher medication adherence was associated with negative general medication beliefs; 65% of the included studies found a negative association between harm beliefs and adherence, while 30% of studies found a negative association with overuse beliefs. (4) Conclusions: This review evaluated the impact of harm and overuse beliefs about medicines on medication adherence, highlighting the gap in literature regarding the impact of harm and overuse beliefs on adherence. Further research is needed to fully identify the association between general beliefs and medication adherence in people with different cultural backgrounds, and to explore these beliefs in patients diagnosed with chronic illnesses, particularly asthma and chronic obstructive pulmonary disease (COPD). Healthcare providers need to be aware of the impact of patients' cultural backgrounds on general medication beliefs and adherence.
Description:
(1) Background: Medication adherence is a key determinant of patient health outcomes in chronic illnesses. However, adherence to long-term therapy remains poor. General beliefs about medicine are considered factors influencing medication adherence. It is essential to address the gap in the literature regarding understanding the impact of general beliefs about medicine on medication adherence to promote adherence in chronic illnesses. (2) Methods: PubMed, CINHAL, and EMBASE databases were searched. Studies were included if they examined medication beliefs using the Beliefs about Medicine Questionnaire in one of four chronic illnesses: hypertension, diabetes, chronic obstructive pulmonary disease, and/or asthma. (3) Results: From 1799 articles obtained by the search, only 11 met the inclusion criteria. Hypertension and diabetes represented 91% of included studies, while asthma represented 9%. Higher medication adherence was associated with negative general medication beliefs; 65% of the included studies found a negative association between harm beliefs and adherence, while 30% of studies found a negative association with overuse beliefs. (4) Conclusions: This review evaluated the impact of harm and overuse beliefs about medicines on medication adherence, highlighting the gap in literature regarding the impact of harm and overuse beliefs on adherence. Further research is needed to fully identify the association between general beliefs and medication adherence in people with different cultural backgrounds, and to explore these beliefs in patients diagnosed with chronic illnesses, particularly asthma and chronic obstructive pulmonary disease (COPD). Healthcare providers need to be aware of the impact of patients' cultural backgrounds on general medication beliefs and adherence.
Description:
The authors thank Rebecca Sutton for her technical assistance on lamb management, and Kera Pethybridge and Ellie Wright for her technical assistance on nuclear imaging. This study is?supported by a Jack Brockhoff Foundation Early Career Research Grant and a National Health and Medical Research Council (NHMRC) Early Career Fellowship (GNT1123030) awarded to AR, and the Victorian Government?s Operational Infrastructure Support Program. PL is supported by an NHMRC Career Development Fellowship (GNT1165084).
Description:
The authors thank Rebecca Sutton for her technical assistance on lamb management, and Kera Pethybridge and Ellie Wright for her technical assistance on nuclear imaging. This study is?supported by a Jack Brockhoff Foundation Early Career Research Grant and a National Health and Medical Research Council (NHMRC) Early Career Fellowship (GNT1123030) awarded to AR, and the Victorian Government?s Operational Infrastructure Support Program. PL is supported by an NHMRC Career Development Fellowship (GNT1165084).
Description:
National voluntary reporting systems generate large volumes of clinical data pertinent to drug safety. Currently descriptive statistical techniques are used to assist in the detection of drug safety 'signals'. Australian data have been coded according to guidelines formulated almost 30 years ago and which have resulted in many drugs which are not associated with an adverse drug reaction or 'innocent bystander' drugs being recorded as 'suspected' in individual reports. In this paper we explore the application of an iterative probability filtering algorithm titled 'PROFILE'. This serves to identify the 'signals' and remove the 'innocent bystander' drugs, thus providing a clearer view of the drugs most likely to have caused the reactions. Reaction terms analysed include neutropenia, agranulocytosis, hypotension, hypertension, myocardial infarction, neuroleptic malignant syndrome, and rectal haemorrhage. In this version of PROFILE, Fishers exact test has been used as the statistical tool but other methods could be used in future. Advantages and limitations of the method and its assumptions are discussed together with the rationale underlying the method and suggestions for further enhancements.
Description:
The purpose of this study was to evaluate the treatment integrity of Family-focused Grief Therapy (FFGT), a preventive intervention designed for families at high risk of poor functioning during palliative care and bereavement. From the 81 families participating in a randomized controlled trial (53 assigned to therapy), 28 were randomly selected for this study of treatment fidelity using the ITGT integrity measure. A total of 109 family sessions were appraised. This represented a review of 62 % of treated families, 38 % of total therapy sessions, and 87% of the 15 participating therapists. Weighted mean percentage occurences therapist behaviors permitted trends in therapy application to be observed. Inter-rater reliability using the FFGT integrity measure was satisfactory, with 88 % overall agreement. Eighty-six percent of therapists adhered faithfully to core elements of the model. Therapist competence was evidenced by a strong therapeutic alliance (94 %), affirmation of family strengths in over 90%, and focus on agreed themes in 76 % of sessions. Therapists averaged 10 grief-related questions per session, 7 on communication-related issues during assessment, 7 on conflict late in therapy, and 4 on cohesiveness across the course of therapy. Consistent application of FFGT, with attention to its low-key themes of family communication, cohesiveness, conflict resolution, and shared grief has been demonstrated. The model is generalizable when applied by family therapists. (C) 2004 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
Description:
Microglia are the immune cells in the central nervous system and can produce cytokines when they are activated by an insult or injury. In the present study, we investigated in detail the time frame of the activation of microglia in the hypothalamic paraventricular nucleus (PVN) following myocardial infarction in rats. Morphological changes and immunohistochemistry to detect CD11b (clone OX-42) were used to identify activated microglia. Compared to rats that had undergone sham surgical procedures, there was a significant increase of between 40 and 50% in the proportion of activated microglia in the PVN 4–16 weeks following myocardial infarction (P < 0.001, One way ANOVA). At 24 h or 1 week post myocardial infarction, however, there was no significant increase in the proportion of activated microglia. Echocardiography and haemodynamic parameters after myocardial infarction indicated significantly reduced left ventricular function. In conclusion, following myocardial infarction, activation of microglia in the PVN does not occur immediately but once manifested, activation is sustained. Thus, activated microglia may contribute to the chronic elevation in cytokine levels observed following myocardial infarction. Since cytokines elicit sympatho-excitatory effects when locally microinjected into the PVN, activated microglia may contribute to the mechanisms mediating the chronic increase in sympathetic nerve activity in animals with reduced left ventricular function induced following myocardial infarction.
Description:
Objectives The efflux inhibitor 1-(1-naphthylmethyl)-piperazine (NMP) has been demonstrated to reverse multidrug resistance in Acinetobacter baumannii. We investigated the interaction of NMP with tigecycline and three other tetracyclines on clinical isolates of A. baumannii. Methods One hundred and four clinical isolates of Acinetobacter were tested for susceptibility to tigecycline, minocycline, doxycycline and tetracycline by disc diffusion, and tigecycline MICs were determined by Etest, both in the presence and absence of NMP. Tigecycline MICs and zones of inhibition were interpreted using the BSAC guidelines. An OXA carbapenemase multiplex PCR was also performed on each isolate. Results Mean zones of inhibition for tetracycline, doxycycline and minocycline increased by 11.3%, 22.9% and 11.2%, respectively, in the presence of NMP. In contrast, tigecycline susceptibility was decreased in the presence of NMP, with mean zones of inhibition decreasing by 8.4%. Based on PCR results, all but six isolates belonged to the OXA-23 clone 1. Conclusions Susceptibility to tigecycline of the A. baumannii OXA-23 clone 1 prevalent in the UK is reduced (∼2-fold) by the presence of the efflux inhibitor NMP. NMP does not have the same effect on susceptibility to other tetracyclines.
Description:
Cytotoxicity of the two pesticides, thiram and endosulfan, have been studied in Ehrlich ascites tumor cells. Thiram cytotoxicity was much lower than that of endosulfan with LC50 (1 h exposure) of 4.02 and 1.12 mM, respectively. The cytotoxic action of the pesticides on the cells were characterised by glutathione depletion, induction of reactive oxygen species (ROS). The cell death induced by the pesticides was of necrotic type as confirmed by lactate dehydrogenase (LDH) leakage. At non-cytotoxic concentration, thiram potentiated the cytotoxicity of endosulfan when cells were exposed to a mixture of both chemicals. The mechanisms involved in the potentiation of cytotoxicity include excessive glutathione depletion and induction ROS which were higher than the additive effects of individual chemicals. The study demonstrates the importance of pesticide interactions in toxicity risk assessment.
Description:
Recently, we have discovered that the registered pesticide, tolfenpyrad, unexpectedly and potently inhibits the development of the L4 larval stage of the parasitic nematode Haemonchus contortus with an IC50 value of 0.03 mu M while displaying good selectivity, with an IC50 of 37.9 mu M for cytotoxicity. As a promising molecular template for medicinal chemistry optimization, we undertook anthelmintic structure-activity relationships for this chemical. Modifications of the left-hand side (LHS), right-hand side (RHS), and middle section of the scaffold were explored to produce a set of 57 analogues. Analogues 25, 29, and 33 were shown to be the most potent compounds of the series, with IC50 values at a subnanomolar level of potency against the chemotherapeutically relevant fourth larval (L4) stage of H. contortus. Selected compounds from the series also showed promising activity against a panel of other different parasitic nematodes, such as hookworms and whipworms.
Description:
A contemporary influenza type B virus was passaged in vitro in the presence of increasing concentrations of the neuraminidase inhibitors, zanamivir and oseltamivir carboxylate (0.1-1000 μM over nine passages). After the fifth passage in the presence of zanamivir (10 μM), the virus acquired a Glu 119 Asp neuraminidase mutation (influenza A N2 subtype numbering) in the enzyme active site. After a further three passages, in which growth occurred in 100 μM of zanamivir, a Gln 218 Lys mutation (A (H3) numbering) in the HA1 domain of the haemagglutinin was found. In a fluorescence-based neuraminidase inhibition assay, viruses with the Glu 119 Asp NA mutation had a 32,000-fold reduction in sensitivity to the NA inhibitor zanamivir compared to the wild-type virus, while the mutation resulted in a 105-fold reduction in sensitivity to oseltamivir carboxylate. Viruses grown in the presence of 1000 μM oseltamivir carboxylate did not acquire any neuraminidase mutations but did have a His 103 Gln substitution (A (H3) numbering) in the HA1 region of the haemagglutinin which was demonstrated to significantly reduce receptor binding strength in vitro. Tissue culture assays demonstrated that the HA mutation caused a seven-fold reduction in sensitivity to oseltamivir carboxylate, and a 90-fold reduction in sensitivity to zanamivir.
Description:
Introduction: Significant effort has been invested in looking at the antimicrobial activity of plant extracts from tropical regions of Australia, with less interest in those from more temperate environments. We sought to redress this imbalance by examining antimicrobial activities of extracts from native plants of Victoria. Methods: Sixteen plant samples were obtained around the Ballarat region of Victoria. Plant material was desiccated, ground and extracted with methanol at room temperature. Methanol extracts were subsequently dissolved in water, filtered and freeze dried. Extracts were dissolved in water and their activity determined against eight bacterial species. Plant extracts that showed appreciable antibacterial activity in the initial antimicrobial screen were examined further with both their MICs and MBCs determined. Results: Ten of the sixteen plant extracts showed antimicrobial activity. Extracts of Eucalyptus, Melaleuca, Prostanthera and Westringia were particularly active with MICs as low as 0.25 mg/ml against organisms including P. aeruginosa and S. aureus. Conclusion: The current study demonstrates the antimicrobial activity of plant extracts from temperate Australia. These may serve as precursors for future chemotherapy agents.
Description:
Introduction: Significant effort has been invested in looking at the antimicrobial activity of plant extracts from tropical regions of Australia, with less interest in those from more temperate environments. We sought to redress this imbalance by examining antimicrobial activities of extracts from native plants of Victoria. Methods: Sixteen plant samples were obtained around the Ballarat region of Victoria. Plant material was desiccated, ground and extracted with methanol at room temperature. Methanol extracts were subsequently dissolved in water, filtered and freeze dried. Extracts were dissolved in water and their activity determined against eight bacterial species. Plant extracts that showed appreciable antibacterial activity in the initial antimicrobial screen were examined further with both their MICs and MBCs determined. Results: Ten of the sixteen plant extracts showed antimicrobial activity. Extracts of Eucalyptus, Melaleuca, Prostanthera and Westringia were particularly active with MICs as low as 0.25 mg/ml against organisms including P. aeruginosa and S. aureus. Conclusion: The current study demonstrates the antimicrobial activity of plant extracts from temperate Australia. These may serve as precursors for future chemotherapy agents.
Description:
Androgenic anabolic steroid (AAS) abuse is associated with changes in cardiac electrophysiology. Recently heart rate corrected QT interval (QTc) has been suggested as a method of screening for AAS use in athletes despite conflicting reports. This study aimed to further investigate the effect of AAS on QTc in a cohort of long-term AAS users in whom the affects may be more pronounced. Using a cross-sectional cohort design with AAS using resistance trained athletes (AS n = 15) and a group of non-AAS using resistance trained, age matched controls (C n = 15). AS had a long history of AAS use (18 +/- 2 yrs) and AS and C both had >19 years of resistance training. Participants underwent a resting electrocardiogram (ECG), from which, the QTc interval was calculated using the Bazett formula. The main outcome measure was significant differences in mean corrected QTc between groups. A secondary outcome was to calculate a QTc that best differentiated between C and AS. Results indicated that QTc was shorter in AS than in C (382.0 +/- 21.01 ms versus 409 +/- 18.77 ms for AS and C respectively p < 0.001). Chi squared analyses revealed a greater incidence of QTc < 380 ms in AS versus C p < 0.01, specificity 93% sensitivity 60%). In conclusion these results supports previous findings that AAS use causes a reduction in QTc, however, the specificity and sensitivity in our sample is lower than reported previously and precludes use as a screening tool.
Description:
Objectives: The burden of disease due to influenza B is often underestimated. Clinical studies have shown that oseltamivir, a widely used neuraminidase inhibitor (NAI) antiviral drug, may have reduced effectiveness against influenza B viruses. Therefore, it is important to study the effect of neuraminidase mutations in influenza B viruses that may further reduce NAI susceptibility, and to determine whether these mutations have the same effect in the two lineages of influenza B viruses that are currently circulating (B/Yamagata-like and B/Victoria-like). Methods: We characterized the effect of 16 amino acid substitutions across five framework residues and four monomeric interface residues on the susceptibility to four different NAIs (oseltamivir, zanamivir, peramivir and laninamivir). Results: Framework residue mutations E117A and E117G conferred highly reduced inhibition to three of the four NAIs, but substantially reduced neuraminidase activity, whereas other framework mutations retained a greater level of NA activity. Mutations E105K, P139S and G140R of the monomeric interface were also found to cause highly reduced inhibition, but, interestingly, their effect was substantially greater in a B/Victoria-like neuraminidase than in a B/Yamagata-like neuraminidase, with some susceptibility values being up to 1000-fold different between lineages. Conclusions: The frequency and the effect of key neuraminidase mutations on neuraminidase activity and NAI susceptibility can differ substantially between the two influenza B lineages. Therefore, future surveillance, analysis and interpretation of influenza B virus NAI susceptibility should consider the B lineage of the neuraminidase in the same manner as already occurs for different influenza A neuraminidase subtypes.
Description:
In Papua New Guinean (PNG) children with acute bacterial meningitis (ABM), all Haemophilus influenzae isolates were resistant to chloramphenicol. Although Streptococcus pneumoniae isolates had a median chloramphenicol MIC of 3 μg/ml, it was ≥4 μg/ml in 42.8%, and the likelihood of an area under the 24-hour concentration-time curve/MIC ratio of >100 h at a MIC of ≥4 μg/ml was approximately 50%. All isolates were ceftriaxone sensitive. These data support ceftriaxone rather than conventional chloramphenicol for all PNG children with suspected ABM.
Description:
Summary Background: Patients with advanced liver disease may develop portal hypertensionthat can result in variceal haemorrhage. Beta-blockers reduce portal pressure andminimise haemorrhage risk. These medications may attenuate measures of car-diopulmonary performance, such as the ventilatory threshold and peak oxygenuptake measured via cardiopulmonary exercise testing. Aim: To determine the effect of beta-blockers on cardiopulmonary exercise testingvariables in patients with advanced liver disease. Methods: This was a cross-sectional analysis of 72 participants who completed acardiopulmonary exercise test before liver transplantation. All participants remainedon their usual beta-blocker dose and timing prior to the test. Variables measuredduring cardiopulmonary exercise testing included the ventilatory threshold, peakoxygen uptake, heart rate, oxygen pulse, the oxygen uptake efficiency slope and theventilatory equivalents for carbon dioxide slope. Results: Participants taking beta-blockers (n = 28) had a lower ventilatory threshold(P <.01) and peak oxygen uptake (P = .02), compared to participants not takingbeta-blockers. After adjusting for age, the model of end-stage liver-disease score,liver-disease aetiology, presence of refractory ascites and ventilatory thresholdremained significantly lower in the beta-blocker group (P = .04). The oxygen uptakeefficiency slope was not impacted by beta-blocker use. Conclusions: Ventilatory threshold is reduced in patients with advanced liver dis-ease taking beta-blockers compared to those not taking the medication. This mayincorrectly risk stratify patients on beta-blockers and has implications for patientmanagement before and after liver transplantation. The oxygen uptake efficiencyslope was not influenced by beta-blockers and may therefore be a better measureof cardiopulmonary performance in this patient population.
Description:
Boxing exposes participants to the physiological response to high intensity exercise and also to direct body and brain trauma. Amateur boxing is increasing and females have also been included in the Olympics. The aim of this study is to assess the stress response and possible brain injury incurred during a match by measuring serum biomarkers associated with stress and cellular brain injury before and after combat. Sixteen male amateur boxers were studied retrospectively. The study population was divided into two groups: (a) a group that received predominantly punches to the head (PTH) and (b) a group that received predominantly punches to the body (PTB). Blood samples were taken before and five minutes after each contest. They were analysed for S-100B, neuron-specific enolase (NSE), creatine kinase (CK) and cortisol. The PTH group received direct contacts to the head (not blocked, parried or avoided) and to the body (n=8, age: 17.6 +/- 5.3, years; height: 1.68 +/- 0.13, meters; mass: 65.4 +/- 20.3, kg). The PTB group received punches to the body including blocked and parried punches, but received no direct punches to the head, (n=8, mean +/- SD, age: 19.1 +/- 3.2 years; height: 1.70 +/- 0.75, meters; mass: 68.5 +/- 15 kg). Significant increases (P<0.05) were observed between pre- and post-combat serum concentrations in serum concentrations in PTH of S-100B (0.35 +/- 0.61 vs. 0.54 +/- 0.73, mug.L-1) NSE (19.7 +/- 14 vs.31.1 +/- 26.6, ng.ml-1) and cortisol (373 +/- 202 vs. 756 +/- 93, nmol.L-1). Significant increases (P<0.05) of creatine kinase were recorded in both groups. This study demonstrates significant elevations in neurochemical biomarkers in boxers who received direct blows to the head. However, further work is required to quantify this volumetric brain damage and long term clinical sequelae.
Description:
Neuraminidase (NA) inhibitors are a class of antivirals designed to target the conserved residues of the influenza NA active site. While there are many conserved residues in the NA active site that are involved in NA inhibitor binding, only a few have been demonstrated to confer resistance. As such, little is known regarding the potential of the other conserved residues in the NA active site to cause NA inhibitor resistance. Two conserved residues (E227 and E276) of an N1 NA that have not previously been associated with resistance to NA inhibitors were investigated. Site-directed mutagenesis was used to generate three alternative amino acids at each residue. Reverse genetics was used to generate recombinant mutant viruses which were characterized for growth, NA activity and NA inhibitor sensitivity. Of the six recombinant viruses expressing NA with mutations at either E227 or E276, only the E227D and E276D viruses were able to grow without supplementary NA activity, and all mutant viruses had a significant reduction in NA activity. The E227D virus demonstrated significantly reduced sensitivity to zanamivir while the E276D virus did not demonstrate any significant changes in NA inhibitor sensitivity. Interestingly, the resistance profiles of E227D and E276D in N1 NA were significantly different from these sites that have been reported for N2 NA. This study confirmed the essential role of NA active site residues in viral fitness, and identified clear differences in the role of residues E227 and E276 in NA inhibitor resistance with N1 and N2 neuraminidases.