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Biomedical subjects

P McGrath

Publications and source records attributed to P McGrath.

At least 19 recordsLinked to original sources

Rapid mycobacteria drug susceptibility testing using Gel Microdrop (GMD) Growth Assay and flow cytometry.

Control of multi-drug-resistant tuberculosis has been hampered by the lack of simple, rapid and sensitive methods for assessing bacterial growth and antimicrobial susceptibility. Due to the increasing incidence and high frequency of mutations, it is unlikely that culture methods will disappear in the foreseeable future. Therefore, the need to modernize methods for rapid detection of viable clinical isolates, at a minimum as a gold standard, will persist. Previously, we confirmed the feasibility of using the Gel Microdrop (GMD) Growth Assay for identifying sub-populations of resistant Mycobacteria by testing different laboratory strains. Briefly, this assay format relies on encapsulating single bacterium in agarose microspheres and identifying clonogenic growth using flow cytometry and fluorescent staining. In this study, we modified the GMD Growth Assay to make it suitable for clinical applications. We demonstrated the effectiveness and safety of this novel approach for detecting drug susceptibility in clinically relevant laboratory strains as well as clinical isolates of Mycobacterium tuberculosis. Correlation between results using the GMD Growth Assay format and results using two well characterized methods (Broth Microdilution MIC and BACTEC 460TB) was 87.5% and 90%, respectively. However, due to the inherent sensitivity of flow cytometry and the ability to detect small (<1%) sub-populations of resistant mycobacteria, the GMD Growth Assay identified more cases of drug resistance. Using 4 clinically relevant mycobacterial strains, we assessed susceptibility to primary anti-tuberculosis drugs using both the Broth Microdilution MIC method and the GMD Growth Assay. We performed 24 tests on isoniazid-resistant BCG, Mycobacterium tuberculosis H37Ra and Mycobacterium avium strains. The Broth Microdilution MIC method identified 7 cases (29.1%) of resistance to INH and EMB compared to the GMD Growth Assay which identified resistance in 10 cases (41.6%); in 3 cases (12.5%), resistance to INH and EMB was detected only with the GMD Growth Assay. In addition, using 20 Mycobacterium tuberculosis clinical isolates, we compared results using BACTEC 460TB method performed by collaborators and the GMD Growth Assay. Eight of 20 (40%) clinical isolates, which were not identified as drug-resistant using the conventional BACTEC 460TB method, were resistant to 1, 2, or 3 different concentrations of drugs using the GMD Growth Assay (13 cases of 140 experiments). In one case (isolate 1879), resistance to 10.0 microg/ml of STR detected using BACTEC 460TB method was not confirmed by the GMD Growth Assay. Thus, the overall agreement between these methods was 90% (14 discrepant results of 140 experiments). These data demonstrate that the GMD Growth Assay is an accurate and sensitive method for rapid susceptibility testing of Mycobacterium tuberculosis for use in clinical reference laboratory settings.

Antibiotics, Antitubercular↗

Group interventions for the prevention of injuries in young children: a systematic review.

OBJECTIVE: This systematic review examined group based injury prevention interventions that targeted young children to determine the effectiveness of such strategies in enhancing children's safety behaviors. METHODS: A comprehensive (manual and electronic) search of the literature was performed using the following study selection criteria: (1) intervention engaged children under the age of 6 years; (2) included a control group; (3) used a group intervention approach; (4) study written in English language; (5) addressed unintentional injuries; and (6) outcomes included injuries, knowledge, or safety behaviors. Data abstraction was performed independently by two researchers using a standardized approach. RESULTS: Nine studies met the criteria that included safety interventions of road crossing (4), car restraint (2), spinal cord safety (1), poison safety (1), and 911/stranger danger/street crossing (1). The types of interventions included videos, interactive activities, cartoons, stories, puppets, singing, coloring, games, simulation games, demonstrations, modeling/role playing, and rehearsal practice using seat belts, models, and real street crossing. The intensity and duration of interventions varied substantially and only two studies randomly assigned participants. The review revealed a positive effect (knowledge, behaviour, and/or attitude) for five of the studies, three had mixed effect, and one reported no effect. CONCLUSIONS: Although no clear conclusions can be drawn from the limited number of studies of diverse design and rigor, researchers should attempt to minimize shortcomings occurring in community based research. Engaging community partners including teachers and parents who influence relationships and outcomes could provide opportunity for more rigorous, comprehensive, and integrated approach to longitudinal research that could identify key factors of successful strategies.

Accident Prevention↗

Reflections on serious illness as spiritual journey by survivors of haematological malignancies.

Although still in its infancy, research on spirituality is attracting increasing attention in health care. There are ongoing calls within the literature for research directed specifically toward clarifying what people mean by the word 'spiritual' and how they express this dimension in their lives. The findings presented in this article respond to that call by presenting findings from a recent qualitative study on meaning-making in relation to serious illness conducted with survivors of haematological malignancies. The findings indicate that the language of a secular spiritual journey, rather than a conventional religious or theological conceptual framework, was used for meaning-making by the survivors interviewed. Such results affirm the recent definitional move away from conflating religion with spirituality, while pointing to the richness, complexity, and contradiction that individuals bring to their meaning-making. The findings provide important insights on the interpretation of spirituality for a group of individuals surviving the confrontation with death caused by a life-threatening illness.

Adult↗

Change in rate-determining step in an E1cB mechanism during aminolysis of sulfamate esters in acetonitrile.

The kinetics of the reactions of the nitrogen-sulfur(VI) esters 4-nitrophenyl N-methylsulfamate (NPMS) with a series of pyridines and a series of alicyclic amines and of 4-nitrophenyl N-benzylsulfamate (NPBS) with pyridines, alicyclic amines, and a series of quinuclidines have been investigated in acetonitrile (ACN) in the presence of excess amine at various temperatures. Pseudo-first-order rate constants (k(obsd)) have been obtained by monitoring the release of 4-nitrophenol/4-nitrophenoxide. From the slope of a plot of k(obsd) vs [amine], second-order rate constants (k'(2)) have been obtained for the pyridinolysis of NPMS, and a Brønsted plot of log k'(2) vs pK(a) of pyridine gave a straight line with beta = 0.45. However, aminolysis with alicyclic amines of NPMS gave a biphasic Brønsted plot (beta(1) = 0.6, beta(2) approximately equal to 0). Pyridinolysis and aminolysis with alicyclic amines and quinuclidines of NPBS also gave similar biphasic Brønsted plots. This biphasic behavior has been explained in terms of a mechanistic change within the E1cB mechanism from an (E1cB)(irrev) (less basic amines) to an (E1cB)(rev) (more basic amines), and the change occurs at approximately the pK(a)'s (in ACN) of NPMS (17.94) and NPBS (17.68). The straight line Brønsted plot for NPMS with pyridines occurs because the later bases are not strong enough to substantially remove the substrate proton and initiate the mechanistic change observed in the reaction of NPMS with the strong alicyclic amines and quinuclidines. An entropy study supports the change from a bimolecular to a unimolecular mechanism. This is the first clear demonstration of this E1cB mechanistic changeover involving a nitrogen acid substrate.

Acetonitriles↗

Facial-selective allylation of methyl ketones for the asymmetric synthesis of alpha-substituted tertiary homoallylic ethers.

The asymmetric synthesis of enantiomerically pure a-substituted tertiary homoallylic ethers 4a, 11 and 12a-c by the allylation of ethyl methyl ketone (la) with gamma-substituted allylsilanes 9a-h is described. The allylsilanes were obtained by a nickel-catalysed Grignard cross-coupling reaction of (E)- and (Z)-(3-iodoallyl)trimethylsilane with various Grignard reagents. The reaction of the allylsilanes with la in the presence of the trimethylsilyl ether of N-trifluoroacetylnorpseudoephedrine (3), and catalytic amounts of a mixture of trimethylsilyl triflate and trifluoromethanesulfonic acid led to the homoallylic ethers 4a, 11 and 12a-c with two new stereogenic centres, with a selectivity of 1:9 to >20:1 for the homoallylic and of 1:99 to >60:1 for the allylic centre. The facial selectivity does not depend on the configuration of the allylsilane, and in all reactions the anti product is preferentially formed. Interestingly, a pronounced switch of facial selectivity takes place with increasing length of the alkyl group of the allylsilane.

Journal Article↗

Follow-up of patients with haematological malignancies and their families in regional, rural and remote Queensland: the GPs' perspective.

In rural areas of Australia the range of health services is limited and major inequities exist in health care provision. Consequently, general practitioners (GPs) are forced to play a pivotal role as key providers of health and medical services. Patients with a haematological malignancy returning home from the lengthy ordeal of high-tech specialist treatment in the metropolitan area will have a strong need for competent holistic support. For these patients and their families, establishing a positive relationship with the local GP will be an important factor in their post-treatment rehabilitation. The findings presented in this article are from recent Queensland research that looks at the support provided by GPs in regional, rural, and remote areas for patients with a haematological malignancy after they return home from specialist treatment in the metropolitan area. The findings indicate the need for support and education for GPs coping with such patients. Newsletters and telephone contact are recorded as the most popular means of support by the GPs surveyed.

Aftercare↗

Adherence to recommendations for clinical follow-up after benign breast biopsy.

PURPOSE: Women who undergo a benign breast biopsy are at elevated risk for the subsequent development of breast cancer (BC). Therefore, appropriate clinical follow-up of a benign breast biopsy is important. The present study examines the extent and correlates of nonadherence with follow-up recommendations after a benign breast biopsy. METHODS: Women (n = 114) who had undergone a benign breast biopsy completed an initial telephone interview within 50 days of their biopsy (mean = 21 days). Additional telephone interviews were completed at 4 and 8 months post-biopsy. Measures of BC risk perception, general and BC-specific distress, BC-related attitudes and beliefs, social support, optimism, and informational coping style were completed. Specific recommendations for clinical follow-up and evidence of actual follow-up were obtained from medical records. RESULTS: Of 103 women given a specific recommendation for clinical follow-up, 34% were classified as nonadherent with follow-up recommendations. Logistic regression analyses indicated that nonadherent women were characterized by younger age, recommendations for follow-up by clinical breast examination alone, greater confidence in their ability to perform breast self-examination properly, higher perceived personal risk for BC, and greater BC-specific distress. CONCLUSION: Despite the importance of appropriate clinical follow-up of a benign breast biopsy, about one-third of women did not adhere to recommended follow-up. Risk factors for nonadherence suggest potential avenues for interventions to enhance participation in appropriate clinical follow-up.

Adaptation, Psychological↗

'What is it?': findings on preschoolers' responses to play with medical equipment.

When young people enter a hospital they are exposed to a foreign world of unfamiliar people, medical equipment and language. Children diagnosed with leukaemia are particularly vulnerable to repeated exposure to these distressing hospital visits. Assessing a child's understanding of the stresses associated with treatment during hospitalization is now seen as a key element of caring for the paediatric patient. A population particularly vulnerable to the effects of the stress of intensive treatments during hospitalization are preschool children. In order to understand the impact on leukaemia preschool children of intensive hospital treatment it is necessary to have comparative information on healthy peers who have not been exposed to such treatment experiences. This article presents findings from recent qualitative research that explored the beliefs held by healthy preschoolers about what happens in hospital, what it means to be sick, their reactions to and knowledge of medical equipment and their level of knowledge regarding cancer and leukaemia. It is the hope and expectation that the findings will be used comparatively to contribute to a deeper understanding of the world of the child coping with leukaemia and related disorders.

Adaptation, Psychological↗

Treatment for childhood acute lymphoblastic leukaemia: the fathers' perspective.

Research on parental adaptation to a child's chronic illness is still scant, and this is particularly so in relation to the experience of treatment for paediatric Acute Lymphoblastic Leukaemia (ALL). The work that does exist on parental reactions tends to conflate maternal responses with paternal responses, as fathers are usually seen as having a secondary role. Consequently, little is known about how fathers cope with treatment for childhood ALL. The present discussion seeks to make a contribution to this area by presenting findings on the paternal experience of treatment for paediatric ALL from a longitudinal study conducted at Royal Children's Hospital in Brisbane, Queensland. The findings from this research clearly indicate the emotional pain that fathers face in their struggle to accept the diagnosis of a serious, life-threatening illness such as ALL in their child. The findings challenge the notion of the make stereotype by showing that the shock of diagnosis, the emotional pain of coping with the illness, the expression of pain through tears, the desire to be with the child, the struggle to cope with the medical interventions, and concerns about other family members are not gender specific, but are rather issues common to both parents.

Adaptation, Psychological↗

Caregivers' insights on the dying trajectory in hematology oncology.

It is increasingly acknowledged in the research literature that palliative care is not offered to patients with a hematologic malignancy. The evidence indicates that patients are not dying at home or in the comfort of the hospice setting but are more likely to end up in the high-tech care of an intensive care unit. The holistic, compassionate care of the hospice/palliative care philosophy is not routinely made available to either these patients or the families who care for them. However, little is known about what the end-of-life experience is for such patients and their families and how they are managing to negotiate their dying experience in a system that is designed to cure not to palliate. In particular, there is a dearth of information on what happens to the caregivers during what is characteristically a prolonged and difficult period of sustained caring within the high-tech system. This discussion presents findings from recent research that is beginning to document the experience of the dying trajectory for patients from these diagnostic groups and their families. The hope and expectation from such research is that the information will make a contribution to building multidisciplinary plans of care for hematologic malignancies during the dying trajectory, to ensure that patients and their families are appropriately referred to the palliative system or, at least, are given sensitive palliative care within the curative system.

Adolescent↗

Returning home after specialist treatment for hematological malignancies: an Australian study.

The technologically advanced and specialist nature of the treatments for patients with hematological malignancies necessitate that they are carried out in major metropolitan treating hospitals. Consequently, patients from regional, rural, and remote areas in Queensland, Australia, must relocate, often for lengthy periods of time, for treatment. To date, there has been scant research carried out on what happens to these patients and their families when they return home after such intensive treatments in the metropolitan centers. This article documents recent, seminal work in this area. The findings indicate that these families have many emotional, medical, and practical needs. These needs change over time, depending on the trajectory of the illness.

Aftercare↗

Dying in the curative system: the haematology/oncology dilemma. Part 1.

Findings from qualitative research exploring the experience of a group of carers of patients with haematological malignancies in relation to end-of-life are presented as a contribution to documenting the emergent issues in this area. The findings are set in the context of parallel research on a group of carers who have experienced hospice care during the dying trajectory of their loved one. It is shown by comparison that the institutional deaths of this group of patients in haematology/oncology was far from the best practice end-of-life care that the hospice group received.

Adult↗

Prognostic significance of postchemoradiation stage following preoperative chemotherapy and radiation for advanced/recurrent rectal cancers.

PURPOSE: To evaluate the prognostic significance of postchemoradiation pathologic stage and implications for further therapy following preoperative chemoradiation and surgery for advanced/recurrent rectal cancer. METHODS AND MATERIALS: Seventy-seven patients with advanced (fixed or tethered T4) or recurrent rectal cancer were treated with preoperative chemoradation followed by surgical resection of disease. Chemotherapy consisted of either of bolus 5-FU 500 mg/m(2) per day or continuous venous infusion 225 mg/m(2) per day for the duration of radiation. Radiation therapy was planned to be delivered to the whole pelvis to a dose of 45 Gy followed by a boost to the area of the tumor of 5-15 Gy. Total radiation doses ranged from 40 to 63 Gy with a median of 55.8 Gy. Surgical resection was then carried out 6-10 weeks following the completion of treatment (median, 7 weeks). Twenty-eight patients underwent abdominoperineal resection and and 49 patients had sphincter-sparing surgical procedures. None of the patients received postoperative chemotherapy. Follow-up in these patients ranges from 1 year to 8 years with a median of 3 years. RESULTS: Significant downstaging of disease was observed with 12/77 (16%) having no residual disease(pT0) and 13% (10/77) found to have pT1-2, N0 disease, 31% (24/77) with pT3-4, N0 and 40% (31/77) for pT0-4, N1-2 cancers. Survival by pathologic stage was 100% for pT0-2, N0 cancers, 80% for pT3-4, N0 and 73% for pTx, N1-2. Local recurrence of disease was observed in 0% of patients with pT0-2, N0 as compared with 13% (3/24) in pT3-4, N0 and 16% (5/31) in pT0-4, N1-2 patients. CONCLUSION: Downstaging following preoperative chemoradiation is a significant prognostic factor. Patients with pT0, T1, or T2 disease have an excellent prognosis and are unlikely to fail locally or with systemic disease. However, patient with T3/T4 or N+ disease may benefit from further adjuvant chemotherapy.

Antimetabolites, Antineoplastic↗

Taking control: findings of a prospective study of an educational course for patients with leukaemia.

The challenge of coping with a chronic and life-threatening diagnosis such as a haematological malignancy, with the associated repeated, lengthy, and often invasive treatment interventions, can have a profound effect on all aspects of life. Patients and their families not only need information to help them understand the cancer experience, but also need support to generate coping strategies as the demands of the illness and its treatment exceed the individual's resources. Structured psycho-educational interventions, based on a strong informational component that aim to improve participants' adaptation to the disease and cancer situation, are one approach to providing such support. This article presents the findings from a recent prospective evaluation of the Leukaemia Foundation of Queensland's educational support course, Taking Control, which is designed for patients with a haematological malignancy and their families. The aim of this study was to record the participants' understanding of the positive and negative aspects and outcomes of course attendance. This is a prospective study of participants' perceptions of their experience with the 'Taking Control' course during the first half of 1999 (n =35; response rate 74.3%), using an author-designed, self-report questionnaire. The findings indicate that participants experience a high level of satisfaction, gain substantially in terms of knowledge, coping skills, and a positive framework within which to view their illness. Many obtain great value from the opportunity to meet and talk with others in similar situations. This study, which builds on previous retrospective research, affirms that this course has much to offer those who are confronted with the life-altering diagnosis of a haematological malignancy. However, the work also points to the need for special consideration to be given to a consistent minority of participants who will find socialising with their peers difficult whilst they are feeling so vulnerable and who have styles of processing information that can easily lead to 'information overload'. It is anticipated that the discussion of these findings will go some way to providing sufficient information and insight for similar courses to be duplicated, with confidence, elsewhere.

Adaptation, Psychological↗

The feasibility of dose escalation using concurrent radiation and 5-fluorouracil therapy following pancreaticoduodenectomy for pancreatic carcinoma.

We evaluated the feasibility of dose escalation using external beam radiation therapy (RT) and 5-fluorouracil (5-FU) following pancreaticoduodenectomy for pancreatic carcinoma. Fourteen patients who underwent pancreaticoduodenectomy for stage I-III adenocarcinoma of the pancreas received postoperative high-dose chemoradiation. RT was given at 1.8-Gy daily fractions to total doses of 54 Gy for patients with negative surgical margins (n = 12), and 64.8 Gy for those with gross residual disease (n = 2). Concurrent 5-FU was given as a continuous infusion (CI) at 225 mg/m2 per day (n = 9) beginning or day 1 and continuing until the completion of RT, or by bolus injection at 500 mg/m2 per day (n = 5) during weeks 1 and 4 of RT. Follow-up ranged from 32 to 36 months (median, 35 months). All patients were able to complete the planned high-dose postoperative chemoradiation and none required a treatment break. No grade 4 acute toxicity was observed. Grade 3 acute toxicity was limited to 2 patients. Two patients developed grade 3 (n = 1) or 4 (n = 1) subacute toxicity, all gastrointestinal-related. There have been no fatal toxicities and no grade 3 or 4 late toxicity has been observed. The 3-year survival is 21%. Dose escalation of postoperative 5-FU chemoradiation following pancreaticoduodenectomy for pancreatic carcinoma is well tolerated. Further dose-intensification of postoperative adjuvant therapy in these patients appears feasible and is being evaluated in a recently activated national trial.

Adenocarcinoma↗

The patient transit assistance scheme: a consumer's perspective.

This article presents findings from State-wide research in Queensland on experiences with the Patient Transit Assistance Scheme (PTAS) from the point of view of patients with a haematological malignancy who travelled for specialist treatment. The findings indicate that the PTAS is of crucial importance to patients and their families and goes some way to buffering the financial hardship incurred from relocation. However, there are also strong indications that there is insufficient community awareness of the scheme, with the consequence that it is not appropriately accessed by those in need. The results confirm previous research that points to the hardship, both financial and emotional, associated with the experience of relocation for specialist treatment.

Health Knowledge, Attitudes, Practice↗

"It's horrendous--but really, what can you do?" Preliminary findings on financial impact of relocation for specialist treatment.

There has been little analysis of the process of relocation for specialist treatment for patients with haematological malignancies. Existing work does not cover the financial impact on families of such an experience. This paper describes seminal work in this area by presenting findings from research based on interviews with patients and families affected by relocation. The two-fold intent informing this discussion is to provide data to initiate research in the area, whilst fostering a consideration of epistemological issues at the interface of qualitative and quantitative research. The results show that there are very significant financial problems. In planning psychosocial support for such families, serious consideration must be given to both their short and long-term economic plight.

Adolescent↗