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At least 433 records · Page 24Linked to original sources
PubMed2006

Improved transgene expression fine-tuning in mammalian cells using a novel transcription-translation network.

Following the discovery of RNA interference (RNAi) and related phenomena, novel regulatory processes, attributable to small non-protein-coding RNAs, continue to emerge. Capitalizing on the ability of artificial short interfering RNAs (siRNAs) to trigger degradation of specific target transcripts, and thereby silence desired gene expression, we designed and characterized a generic transcription-translation network in which it is possible to fine-tune heterologous protein production by coordinated transcription and translation interventions using macrolide and tetracycline antibiotics. Integration of siRNA-specific target sequences (TAGs) into the 5' or 3' untranslated regions (5'UTR, 3'UTR) of a desired constitutive transcription unit rendered transgene-encoded protein (erythropoietin, EPO; human placental alkaline phosphatase, SEAP; human vascular endothelial growth factor 121, VEGF(121)) production in mammalian cells responsive to siRNA levels that can be fine-tuned by macrolide-adjustable RNA polymerase II- or III-dependent promoters. Coupling of such macrolide-responsive siRNA-triggered translation control with tetracycline-responsive transcription of tagged transgene mRNAs created an antibiotic-adjustable two-input transcription-translation network characterized by elimination of detectable leaky expression with no reduction in maximum protein production levels. This transcription-translation network revealed transgene mRNA depletion to be dependent on siRNA and mRNA levels and that translation control was able to eliminate basal expression inherent to current transcription control modalities. Coupled transcription-translation circuitries have the potential to lead the way towards composite artificial regulatory networks, to enable complex therapeutic interventions in future biopharmaceutical manufacturing, gene therapy and tissue engineering initiatives.

Alkaline Phosphatase↗
PubMed2005

Percutaneous access to upper pole renal stones: role of prone 3-dimensional computerized tomography in inspiratory and expiratory phases.

PURPOSE: We evaluated the role of noncontrast, prone position, inspiratory and expiratory 3-dimensional spiral computerized tomography (PIE-CT) for preoperative planning of percutaneous treatment in patients with complex upper pole renal calculi. MATERIALS AND METHODS: In this pilot study a total of 6 renal units in 4 women and 1 man with complex upper pole calculi who were candidates for percutaneous nephrolithotomy were evaluated with thin section PIE-CT. With the patient imaged in the prone position percutaneous access was simulated under 4 potential access conditions, including subcostal and intercostal, in inspiration and expiration. Each potential access was then deemed transpleural or extrapleural and minimally angulated or severely angulated cephalad. RESULTS: PIE-CT was performed uneventfully in all patients. Ideal nonangulated extrapleural percutaneous access was deemed possible in 5 of 6 renal units. However, inspiratory plus expiratory phases were necessary to identify the most suitable access site. In 2 renal units only 1 safe access site was identified. No pulmonary complications were noted in any of these patients. In 1 renal unit no suitable access could be identified and this patient was treated with laparoscopic caliceal diverticulectomy. CONCLUSIONS: Thin section PIE-CT offers 3-dimensionally rendered images that clearly demonstrate anatomical relationships among the kidney, calculi, pleura, diaphragm, ribs and surrounding organs. In this pilot study PIE-CT provided useful data for planning urological intervention for complex upper pole renal stones. This study also suggests that generalizations regarding the safety of upper pole access in the inspiratory or expiratory phase are not warranted.

Exhalation↗
PubMed2026

Process evaluation of a nurse-led transitional care model (Cardiolotse) within a randomized controlled trial aiming to improve care coordination for patients with cardiovascular diseases in Germany.

BACKGROUND: Patients with higher age suffering from cardiovascular disease discharged from hospital are at greater risk of readmission within 30 days. We evaluated an innovative care program providing post-discharge support and helping patients to navigate through the healthcare system. This paper reports the findings of the process evaluation of the randomized controlled trial Cardiolotse, a nurse-led transitional care model improving care coordination for patients with cardiovascular diseases in Germany. METHODS: A process evaluation, following the guidelines of the Medical Research Council (MRC) Framework, was performed. Semi-structured interviews with all relevant target groups were conducted to gain more insight about implementation processes. Questionnaires and medical records were used to explore mechanisms of impact and understand how change was produced in the intervention. Qualitative data were analysed using content analysis with deductive and inductive categories. Descriptive statistics and subgroup analyses were utilized to explore quantitative data. RESULTS: Overall, the designed training programme was perceived positively by the study nurses, so called Cardiolotsen (CLs). Patients receiving support by the CLs reported positive satisfaction ratings. Interactions between CLs and patients were reported as trustworthy and reliable. A total of approximately 12,500 contacts were made over the course of the intervention. However, changes in satisfaction scores between intervention and control groups in terms of medical treatment or the interaction between medical health providers involved in the treatment could not be determined. Furthermore, data suggested reach issues with respect to office-based physicians, as regular CL contact could not be achieved with 90% of the participating general practitioners and cardiologists. CONCLUSIONS: The CLs served as an important source of support for the participating patients throughout the intervention. At regular intervals, they checked a patient's health status and their adherence to therapies after discharge. However, the process evaluation identified cross-sectoral communication and information exchange between CLs and office-based physicians as an implementation challenge. TRIAL REGISTRATION: The study was retrospectively registered at German Clinical Trial Register, http://www.drks.de/DRKS00020424 (Trial Registration Number DRKS00020424) on 18 June 2020.

Humans↗
PubMed2005

Retrofitting houses with insulation to reduce health inequalities: aims and methods of a clustered, randomised community-based trial.

This paper describes the purpose and methods of a single-blinded, clustered and randomised trial of the health impacts of insulating existing houses. The key research question was whether this intervention increased the indoor temperature and lowered the relative humidity, energy consumption and mould growth in the houses, as well as improved the health and well-being of the occupants and thereby lowered their utilisation of health care. Households in which at least one person had symptoms of respiratory disease were recruited from seven predominantly low-income communities in New Zealand. These households were then randomised within communities to receive retrofitted insulation either during or after the study. Measures at baseline (2001) and follow-up (2002) included subjective measures of health, comfort and well-being and objective measures of house condition, temperature, relative humidity, mould (speciation and mass), endotoxin, beta glucans, house dust mite allergens, general practitioner and hospital visits, and energy or fuel usage. All measurements referred to the three coldest winter months, June, July and August. From the 1352 households that were initially recruited, baseline information was obtained from 1310 households and 4413 people. At follow-up, 3312 people and 1110 households remained, an 84% household retention rate and a 75% individual retention rate. Final outcome results will be reported in a subsequent paper. The study showed that large trials of complex environmental interventions can be conducted in a robust manner with high participation rates. Critical success factors are effective community involvement and an intervention that is valued by the participants.

Adolescent↗
PubMed2005

A pilot, randomized, double-blinded, placebo-controlled trial of individualized homeopathy for symptoms of estrogen withdrawal in breast-cancer survivors.

OBJECTIVE: To pilot an investigation of individualized homeopathy for symptoms of estrogen withdrawal in breast cancer survivors. DESIGN: Randomized, double-blinded, placebo-controlled trial. SETTING: Outpatient department of a National Health Service (NHS) homeopathic hospital. PARTICIPANTS: Fifty-seven (57) women met inclusion criteria and 53 were randomized to the study. INTERVENTION: After 2 weeks of baseline assessment, all participants received a consultation plus either oral homeopathic medicine or placebo, assessed every 4 weeks for 16 weeks. OUTCOME MEASURES: The primary outcome measures were the activity score and profile score of the Measure Yourself Medical Outcome Profile (MYMOP). RESULTS: Eighty-five percent (85%) (45/53) of women completed the study. There was no evidence of a difference seen between groups for either activity (adjusted difference =-0.4, 95% confidence interval CI -1.0 to 0.2, p = 0.17) or profile scores (adjusted difference = -0.4, 95% CI -0.9 to 0.1, p = 0.13) using this trial design, although post hoc power calculations suggests that 65-175 would be needed per group to detect differences of this magnitude with sufficient precision. Clinically relevant improvements in symptoms and mood disturbance were seen for both groups over the study period. CONCLUSION: Improvements were seen for symptom scores over the study period. However, presuming these improvements were caused by the individualized homeopathic approach, the study failed to show clearly that the specific effect of the remedy added further to the nonspecific effects of the consultation. Future trial design must ensure adequate power to account for the nonspecific impact of such complex individualized interventions while pragmatic designs may more readily answer questions of clinical and cost effectiveness.

Adult↗
PubMed2005

Rationale, design and conduct of a comprehensive evaluation of a school-based peer-led anti-smoking intervention in the UK: the ASSIST cluster randomised trial [ISRCTN55572965].

BACKGROUND: To date, no school-based intervention has been proven to be effective in preventing adolescent smoking, despite continuing concern about smoking levels amongst young people in the United Kingdom. Although formal teacher-led smoking prevention interventions are considered unlikely to be effective, peer-led approaches to reducing smoking have been proposed as potentially valuable. METHODS/DESIGN: ASSIST (A Stop Smoking in Schools Trial) is a comprehensive, large-scale evaluation to rigorously test whether peer supporters in Year 8 (age 11-12) can be recruited and trained to effect a reduction in smoking uptake among their fellow students. The evaluation is employing a cluster randomised controlled trial (RCT) design with secondary school as the unit of randomisation, and is being undertaken in 59 schools in South East Wales and the West of England. Embedded within the trial are an economic evaluation of the intervention costs, a process evaluation to provide detailed information on how the intervention was delivered and received, and an analysis of social networks to consider whether such a peer group intervention could work amongst schoolchildren in this age group. Schools were randomised to either continue with normal smoking education (n = 29 schools, 5562 students), or to do so and additionally receive the ASSIST intervention (n = 30 schools, 5481 students). No schools withdrew once the trial had started, and the intervention was successfully implemented in all 30 schools, with excellent participation rates from the peer supporters. The primary outcome is regular (weekly) smoking, validated by salivary cotinine, and this outcome has been obtained for 94.4%, 91.0% and 95.6% of eligible students at baseline, immediate post-intervention, and one-year follow-up respectively. DISCUSSION: Comprehensive evaluations of complex public health interventions of this scale and nature are rare in the United Kingdom. This paper demonstrates the feasibility of conducting cluster RCTs of complex public health interventions in schools, and how the rigour of such designs can be maximised both by thorough implementation of the protocol and by broadening the scope of questions addressed in the trial by including additional evaluative components.

Adolescent↗
PubMed2001

Composite effects of group drumming music therapy on modulation of neuroendocrine-immune parameters in normal subjects.

CONTEXT: Drum circles have been part of healing rituals in many cultures throughout the world since antiquity. Although drum circles are gaining increased interest as a complementary therapeutic strategy in the traditional medical arena, limited scientific data documenting biological benefits associated with percussion activities exist. OBJECTIVE: To determine the role of group-drumming music therapy as a composite activity with potential for alteration of stress-related hormones and enhancement of specific immunologic measures associated with natural killer cell activity and cell-mediated immunity. DESIGN: A single trial experimental intervention with control groups. SETTING: The Mind-Body Wellness Center, an outpatient medical facility in Meadville, Pa. PARTICIPANTS: A total of 111 age- and sex-matched volunteer subjects (55 men and 56 women, with a mean age of 30.4 years) were recruited. INTERVENTION: Six preliminary supervised groups were studied using various control and experimental paradigms designed to separate drumming components for the ultimate determination of a single experimental model, including 2 control groups (resting and listening) as well as 4 group-drumming experimental models (basic, impact, shamanic, and composite). The composite drumming group using a music therapy protocol was selected based on preliminary statistical analysis, which demonstrated immune modulation in a direction opposite to that expected with the classical stress response. The final experimental design included the original composite drumming group plus 50 additional age- and sex-matched volunteer subjects who were randomly assigned to participate in group drumming or control sessions. MAIN OUTCOME MEASURES: Pre- and postintervention measurements of plasma cortisol, plasma dehydroepiandrosterone, plasma dehydroepiandrosterone-to-cortisol ratio, natural killer cell activity, lymphokine-activated killer cell activity, plasma interleukin-2, plasma interferon-gamma, the Beck Anxiety Inventory, and the Beck Depression Inventory II. RESULTS: Group drumming resulted in increased dehydroepiandrosterone-to-cortisol ratios, increased natural killer cell activity, and increased lymphokine-activated killer cell activity without alteration in plasma interleukin 2 or interferon-gamma, or in the Beck Anxiety Inventory and the Beck Depression Inventory II. CONCLUSIONS: Drumming is a complex composite intervention with the potential to modulate specific neuroendocrine and neuroimmune parameters in a direction opposite to that expected with the classic stress response.

Adult↗
PubMed2005

Comparison of 6 and 7 French guiding catheters for percutaneous coronary intervention: results of a randomised trial with a vascular ultrasound endpoint.

OBJECTIVE: To perform a randomized, ultrasound controlled trial to define the procedural and clinical advantages and limitations of 6 French (Fr) compared with 7 Fr transfemoral coronary intervention in the stenting era. BACKGROUND: The use of 7 Fr guiding catheters may facilitate Percutaneous Coronary Intervention (PCI), but may be associated with increased vascular complications when compared with 6 Fr catheters. METHODS: Patients undergoing PCI considered suitable for either a 6 or 7 Fr sheath and guiding catheter system were included. All vascular sheaths were removed with assisted manual compression. Femoral vascular ultrasounds were performed prior to hospital discharge and interpreted by a vascular surgeon blinded to treatment assignment. The primary endpoint was a composite of significant vascular complications including major haematoma, retroperitoneal haematoma, pseudoaneurysm, arterio-venous fistula, or femoral venous or arterial thrombosis. RESULTS: During the study, 414 patients (mean age 61+/-11 years, 27% females) were randomly assigned to 6 Fr or 7 Fr sheath groups. The incidence of major vascular complications was 5.7% in the 6 Fr group and 3.9% in the 7 Fr group (P=0.383). There was no significant difference in procedural or angiographic success between the groups. The use of contrast volume was higher in the 7 Fr group (157+/-58 ml vs. 144+/-58 ml; P=0.029). There was a trend toward better operator satisfaction with the 7 Fr guide (P=0.08). CONCLUSIONS: This prospective, randomized trial indicates no reduction in major peripheral vascular complications with the use of smaller guiding catheters in PCI. There was less contrast used in the 6 Fr group, which may benefit some patient subsets, however operators tended to prefer the larger 7 Fr system. The target coronary anatomy and need for complex device intervention should mandate the choice of guiding catheter size, not a perceived impact on vascular complications.

Angioplasty, Balloon, Coronary↗
PubMed2001

Reduction in periprocedural enzyme elevation by abciximab after rotational atherectomy of type B2 lesions: Results of the Rota ReoPro randomized trial.

BACKGROUND: Abciximab has been shown to reduce ischemic complications and creatine kinase-myocardial band (CK-MB) elevation of both simple and complex coronary interventions. In addition to the procedural complications, one of the important mechanisms for CK-MB elevation after rotational atherectomy is an interaction between platelets and the atheromatous debris. METHODS: This study was conducted to determine whether abciximab would limit the extent of periprocedural CK-MB release after rotational atherectomy of American Heart Association/American College of Cardiology type B(2) lesions in a double-blind, randomized, placebo-controlled manner. A total of 100 lesions in 100 patients were randomized with the primary end point being a CK-MB elevation of >16 U/L. RESULTS: Procedural success was achieved in 100% in the abciximab arm compared with 98% in the placebo group with any CK-MB elevation >16 U/L of 8% in the abciximab versus 22% in the placebo group (P =.04). The peak creatine phosphokinase level (units per liter) was 102 +/- 14 versus 153 +/- 22 (P =.05) and the peak CK-MB level was 12.8 +/- 1.8 versus 24.6 +/- 3.5 (P =.06) between the abciximab and placebo groups, respectively. Slow-flow or postprocedure chest pain occurred in 14% in the abciximab group versus 30% in the placebo group (P =.04). There was 1 Q-wave myocardial infarction in the placebo arm and 1 nonhemorrhagic stroke in the abciximab group. CONCLUSIONS: Therefore the Rota ReoPro randomized trial revealed the benefit of abciximab during rotational atherectomy in reducing procedural morbidity and CK-MB elevation, and its routine use can be justified even in moderately complex lesions undergoing rotational atherectomy.

Abciximab↗
PubMed2006

Pediatric renal transplantation in a South African teaching hospital: a 20-year perspective.

INTRODUCTION: Renal transplantation is established as the standard of care for end-stage renal failure (ESRF) in the developed world. In emerging nations, the appropriateness of such costly interventions has been questioned. We undertook an analysis of all renal transplants undertaken under the care of the pediatric nephrology service at the Johannesburg Hospital, South Africa, in order to establish the outcomes of a transplantation service in a resource-constrained environment in a developing country. METHODS: This was a retrospective review of renal transplantation undertaken at a single teaching hospital in Johannesburg, part of the University of the Witwatersrand. Two hundred and eighty-two transplants were performed between 1984 and 2003. Demographic characteristics of the transplanted population, diagnosis, morbidity, graft survival, and mortality were recorded. RESULTS: Overall 1-, 5-, and 10-yr graft survival was 82, 44, and 23%. Overall 1-, 5-, and 10-yr patient survival was 97, 84, and 68%. The median graft survival for all transplantation episodes was 4.38 yr; 70% of patients survive 10 yr and 54% survive 20 yr or more. Although early graft survival was good, there was a more rapid rate of graft loss than when compared to results from developed centers with much poorer results at 5 and 10 yr. Causes of ESRF show marked variation between the races, and black patients have significantly worse outcomes than others. Compared with white patients, black recipients received fewer living donor kidneys (26 vs. 10%, p = 0.0019), a greater proportion of totally mismatched organs (56 vs. 36%, p = 0.015), less pre-emptive transplantation (7 vs. 35%, p = 0.0001) and experienced a higher rate of primary non-function (13 vs. 3%, p = 0.004). Surgical complications of transplantation occurred in 9% of recipients, but rarely led to graft loss. CONCLUSION: Pediatric renal transplantation in Johannesburg can be accomplished with low complication rates, but medium and long-term graft survival is poor when compared with contemporary results achieved in developed countries. The difficulties of undertaking such complex, multidisciplinary interventions in a developing nation are daunting, but we believe that renal transplantation should still be the treatment of choice for all children with ESRF. The poorer outcomes in black recipients can be addressed by increasing education in our communities and expanding the pool of appropriate donors. Better institutional support would allow for improved long-term patient care.

Actuarial Analysis↗
PubMed2004

Change in visual function after macular translocation with 360 degrees retinectomy for neovascular age-related macular degeneration.

OBJECTIVE: To measure the change in vision and visual outcomes at 12 months after macular translocation with 360 degrees retinectomy (MT360) and silicone oil tamponade in patients with bilateral vision loss resulting from subfoveal choroidal neovascular membranes in age-related macular degeneration (AMD). DESIGN: A prospective, interventional, consecutive, noncomparative case series. PARTICIPANTS: Sixty-four patients with bilateral vision loss resulting from neovascular AMD. METHODS: Eligible patients had AMD with subfoveal choroidal neovascularization in the operative eye and a maximum of 6 months of central vision loss. Preoperative and 12-month postoperative evaluations included standardized testing of near and distance acuity and reading speed. Patients underwent MT360 with silicone oil tamponade, followed 2 months later by extraocular muscle surgery and silicone oil removal. MAIN OUTCOME MEASURES: Change in distance acuity, near acuity, and reading speed at 12 months after MT360 compared with those values before surgery. RESULTS: Sixty-one patients were followed up for 12 months. All eyes were translocated successfully. Median distance acuity letter score improved from 62 letters (Snellen equivalent of approximately 20/125) before surgery to 69 letters (approximately 20/80) by 12 months after surgery (P = 0.03). Median near acuity improved from 0.70 logarithm of the minimum angle of resolution (logMAR) units (approximately 20/100) before surgery to 0.44 logMAR units (approximately 20/55) at 12 months (P<0.001). Median reading speed improved from 71 words per minute (wpm) before surgery to 105 wpm at 12 months after surgery (P<0.001). At 12 months, distance acuity improved by 1 or more lines in 32 patients (52%). In patients with either preoperative distance or near acuity of 20/80 or better, 74% and 95% of patients, respectively, remained in this range of acuity. In patients with either preoperative distance or near acuity of worse than 20/80, 40% and 48% of patients, respectively, improved to 20/80 or better. Postoperative retinal detachment developed in 5 patients (8%), with the macula involved in 2 patients, and all retinas were reattached successfully. CONCLUSIONS: Macular translocation with 360 degrees retinectomy with silicone oil tamponade is effective in significantly improving visual function in patients with neovascular AMD, as demonstrated by the improvement in distance and near acuity and reading speed at 12 months after surgery in these patients. Although this is a complex surgical intervention, patients with preoperative visual acuity of 20/80 or better at near or distance are highly likely to retain the 20/80 or better acuity at 12 months after surgery. Macular translocation with 360 degrees retinectomy is an effective treatment option for patients with vision loss in their second eye resulting from neovascular AMD.

Aged↗
PubMed1999

Radiation exposure to children during coil occlusion of the patent ductus arteriosus.

The risks of excessive exposure to ionizing radiation are well described and measures are routinely taken to limit such exposure to both patient and personnel in the catheterization laboratory. Coll occlusion of the patent ductus arteriosus (PDA) as well as other more complex pediatric interventions has raised concern regarding radiation exposure, particularly as minimally invasive surgical techniques are being developed which lack such exposure risk. In eight consecutive patients, aged 0.7-7 years (median, 2.3 years), coil occlusion of a PDA was performed and surface entrance radiation dose determined by thermoluminescent dosimetry (TD). Total cumulative doses (PA + lateral dose) were also calculated for each patient. Entrance and cumulative dose was likewise measured in 12 patients undergoing standard diagnostic catheterization (DC) and in 5 consecutive patients undergoing pulmonary balloon valvuloplasty (PBV). The groups were comparable in age, weight, and body surface area (BSA). Total cumulative dose in the PDA patients was 97 +/- 25 mGy (mean +/- SE). There was no significant difference between the three groups in entrance dose absorbed at each location or in total cumulative dose. The mean total fluoroscopy time in the PDA occlusion group was significantly less than that of the PBV group (10.1 +/- 1.81 min vs. 19.3 +/- 2.29 min, P < 0.05) but was comparable to the DC group (13.2 +/- 1.5 min, P = NS). When the subjects were analyzed collectively, no correlation between fluoroscopy time and measured entrance dose was observed. The strongest correlates of total cumulative dose were patient weight (r = 0.67, P < 0.001) and BSA (r = 0.62, P = 0.001). Patients undergoing coil occlusion of a PDA are not exposed to increased radiation entrance dose compared to those undergoing standard DC and PBV. Furthermore, surface entrance radiation dose as determined by TD varies according to patient size for a given fluoroscopy time.

Body Height↗
PubMed2000

On-site mental health workers in primary care: effects on professional practice.

BACKGROUND: Mental health problems are common in primary care and mental health workers (MHWs) are increasingly working in this setting. In addition to treating patients, the introduction of on-site MHWs may lead to changes in the clinical behaviour of primary care providers (PCPs). OBJECTIVES: To assess the effects of on-site MHWs in primary care on the clinical behaviour of primary care providers (PCPs). SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register (18-22 June 1998), the Cochrane Controlled Trials Register (18-22 June 1998), MEDLINE (1966 to 1998), EMBASE (1980 to 1998), PsychInfo (1984 to 1998), CounselLit (18-22 June 1998), NPCRDC skill-mix in primary care bibliography, and reference lists of articles. SELECTION CRITERIA: Randomised trials, controlled before and after studies and interrupted time series analyses of MHWs either replacing PCPs as providers of mental health care ('replacement' models) or providing collaborative care/support to PCPs in managing patients' mental health problems ('consultation-liaison' models). The participants were primary care providers. The outcomes included objective PCP behaviours such as diagnosis, prescribing and referral. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Thirty-eight studies were included involving more than 460 PCPs and more than 3880 patients. There was some evidence that 'replacement' model MHWs achieved significant short-term reductions in PCP psychotropic prescribing and mental health referral, but the effects were not reliable. Consultation rates were also reduced, but with even less evidence of a consistent effect. There were no indirect effects in prescribing behaviour on the wider population and no consistent pattern to the impact on referrals. 'Indirect' effects on PCP consultation rates were not assessed. There was some evidence that 'consultation-liaison' model MHWs had a direct effect on PCP prescribing behaviour when used as part of complex, multifaceted interventions. Few studies examined the 'indirect' effects of such interventions, and those that did failed to provide evidence that 'direct' effects were generalisable to the wider population or endured once the 'consultation-liaison' intervention was removed. REVIEWER'S CONCLUSIONS: This review does not support the hypothesis that adding MHWs to primary care provider organisations in 'replacement' models causes a significant or enduring change in PCP behaviour. 'Consultation-liaison' interventions may cause changes in psychotropic prescribing, but these seem short-term and limited to patients under the direct care of the MHW. Longer-term studies are needed to assess the degree to which demonstrated effects endure over time.

Humans↗
PubMed2006

Strategies for integrating primary health services in middle- and low-income countries at the point of delivery.

BACKGROUND: Strategies to integrate primary health care aim to bring together inputs, organisation, management and delivery of particular service functions to make them more efficient, and accessible to the service user. In some middle and low income countries, services have been fragmented by separate vertical programmes established to ensure delivery of particular technologies. We examined the effectiveness of integration strategies at the point of delivery. OBJECTIVES: To assess the effects of strategies to integrate primary health care services on producing a more coherent product and improving health care delivery and health status. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register (August 2005), MEDLINE (1966 to September 2005), EMBASE (1988 to 2005), Socio Files (1974 to September 2005), Popline (1970 to September 2005), HealthStar (1975 to September 2005), Cinahl (1982 to September 2005); Cab Health (1972 to 1999), International Bibliography of the Social Sciences (1970 to 1999), and reference lists of articles. We also searched the Internet and World Health Organization (WHO) library database, hand searched relevant WHO publications and contacted experts in the field. SELECTION CRITERIA: Randomised trials, controlled before and after studies, and interrupted time series analyses of integration strategies in primary health care services. Health services in high-income countries were excluded. The primary outcomes were indicators of health care delivery, user views on any measure of service coherence, and health status. We also sought information on comparative costs. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed study quality. MAIN RESULTS: Three cluster randomised trials and two controlled before and after studies were included, with three types of comparison: integration by adding on an additional component to an existing service (family planning); integrated services versus single special services (for sex workers); integrated delivery systems versus a vertical service (for family planning); and packages of enhanced primary child care services (integrated management of childhood illnesses) vs. routine child care. Interventions were complex and in some studies inputs varied substantially between comparison arms. Overall, no consistent pattern emerged. Only one study attempted to assess the user's view of the service provided. AUTHORS' CONCLUSIONS: Few studies of good quality, large and with rigorous study design have been carried out to investigate strategies to promote service integration in low and middle income countries. All describe the service supply side, and none examine or measure aspects of the demand side. Future studies must also assess the client's view, as this will influence uptake of integration strategies and their effectiveness on community health.

Child↗
PubMed2003

Artificial regulatory networks and cascades for discrete multilevel transgene control in mammalian cells.

Prototype drug-adjustable heterologous transcription control systems designed for gene therapy applications typically show sigmoid dose-response characteristics and enable fine-tuning of therapeutic transgenes only within a narrow inducer concentration range of a few nanograms. However, the design of clinical dosing regimes which achieve tissue-specific concentrations with nanogram precision is yet a "mission impossible." Therefore, most of today's transcription control systems operate as ON/OFF switches and not in a true adjustable mode. The availability of robust transcription control configurations which lock expression of a single therapeutic transgene at desired levels in response to fixed clinical doses of different inducers rather than minute concentration changes of a single inducer would be highly desirable. Based on in silico predictions, we have constructed a variety of mammalian artificial regulatory networks by interconnecting the tetracycline- (TET(OFF)), streptogramin- (PIP(OFF)), and macrolide- (E(OFF)) repressible gene regulation systems as linear (auto)regulatory cascades. These networks enable multilevel expression control of several transgenes in response to different antibiotics or allow titration of a single transgene to four discrete expression levels by clinical dosing of a single antibiotic: 1) high expression in the absence of any antibiotic (+++), 2) medium level expression following addition of tetracycline (++), 3) low level expression in response to the macrolide erythromycin (+), and 4) complete repression by streptogramins such as pristinamycin (-). The first-generation artificial regulatory networks exemplify modular interconnections of different heterologous gene regulations systems to achieve multigene expression, fine-tuning, or to design novel control networks with unprecedented transgene regulation properties. Such higher-level transcription control modalities will lead the way towards composite artificial regulatory networks able to effect complex therapeutic interventions in future gene therapy and tissue engineering scenarios.

Alkaline Phosphatase↗
PubMed2004

Initial clinical experience with intracardiac echocardiography in guiding balloon mitral valvuloplasty: technique, safety, utility, and limitations.

The objective of this study was to examine the feasibility and technique of intracardiac echocardiography during percutaneous balloon mitral valvuloplasty. Echocardiographic imaging is commonly used during mitral valvuloplasty. Intracardiac echocardiography is a newer technology that may provide superior imaging during complex valvular interventions. Intracardiac echocardiography and transthoracic echocardiography were performed in 19 patients undergoing percutaneous balloon mitral valvuloplasty. Intracardiac ultrasound images were obtained via the femoral vein in all patients. Imaging projections and catheter locations that were useful for the performance of mitral valvuloplasty were defined. Intracardiac echocardiography guided transseptal puncture, augmented the assessment of valve apparatus deformity, facilitated balloon positioning across the mitral valve, and permitted postprocedural valvular assessment including identification of mitral regurgitation with color Doppler. Intracardiac echocardiography provided essential imaging guidance and procedural monitoring during percutaneous mitral valvuloplasty.

Adult↗
PubMed2004

Internal mandibular distraction to relieve airway obstruction in infants and young children with micrognathia.

Micrognathia may cause upper airway obstruction requiring complex medical interventions and sometimes tracheostomy. The role of distraction techniques to lengthen the mandible is yet to be clarified. The aim of this paper is to present a series of five cases in which mandibular lengthening by osteotomy and internal distraction was used to relieve airway obstruction. Five patients whose ages ranged from 4-39 months (mean, 15 months) were managed at our center with internal distraction osteogenesis to relieve airway obstruction. Three patients had a tracheostomy, and two patients had refractory airway obstruction prior to distraction. Following osteotomy and insertion of internal distraction devices, the mandible was distracted a mean of 17 mm (range, 15-25 mm). The distraction devices were removed at the end of a consolidation period ranging from 3-10 weeks. Two of 3 patients with a tracheostomy were decannulated, while the third patient with tracheostomy is awaiting choanal atresia repair before being decannulated. The two patients who were not managed with a tracheostomy but who had persistent upper airway obstruction have not required further airway intervention after mandibular distraction. In conclusion, mandibular lengthening by distraction osteogenesis can relieve airway obstruction in infants and small children. This is a promising new technique that may avoid the need for tracheostomy in some infants with micrognathia, and facilitate early decannulation in those who have a tracheostomy.

Airway Obstruction↗