Vascular-targeted photodynamic therapy with BF2-chelated Tetraaryl-Azadipyrromethene agents: a multi-modality molecular imaging approach to therapeutic assessment.

BACKGROUND: Photodynamic therapy (PDT) is a treatment modality for a range of diseases including cancer. The BF(2)-chelated tetraaryl-azadipyrromethenes (ADPMs) are an emerging class of non-porphyrin PDT agent, which have previously shown excellent photochemical and photophysical properties for therapeutic application. Herein, in vivo efficacy and mechanism of action studies have been completed for the lead agent, ADMP06. METHODS: A multi-modality imaging approach was employed to assess efficacy of treatment, as well as probe the mechanism of action of ADPM06-mediated PDT. RESULTS: Tumour ablation in 71% of animals bearing mammary tumours was achieved after delivery of 2 mg kg(-1) of ADPM06 followed immediately by light irradiation with 150 J cm(-2). The inherent fluorescence of ADPM06 was utilised to monitor organ biodistribution patterns, with fluorescence reaching baseline levels in all organs within 24 h. Mechanism of action studies were carried out using dynamic positron emission tomography and magnetic resonance imaging techniques, which, when taken together, indicated a decrease in tumour vascular perfusion and concomitant reduction in tumour metabolism over time after treatment. CONCLUSION: The encouraging treatment responses in vivo and vascular-targeting mechanism of action continue to indicate therapeutic benefit for this new class of photosensitiser.

Human papillomavirus (HPV) vaccines: a Canadian update.

A common sexually transmitted infection, human papillomavirus (HPV) has been linked to the development of cervical, anogenital, and head and neck cancers and genital warts. (2) Several randomized controlled trials have explored the efficacy and safety of two vaccines for primary prevention of infection by HPV types 16 and 18, those most commonly implicated in the development of cervical cancer. (3) An HPV vaccine, Gardasil, was approved in Canada in 2006, and a second vaccine, Cervarix, is undergoing Health Canada review. (4) Some unresolved questions about HPV vaccinations relate to the ideal age for immunization, duration of effect, immunization of women already infected, vaccination of males, implications for Papanicolaou (Pap) smear programs, barriers to uptake, need for monitoring and registries, cost effectiveness, and programs to ensure access for special populations.

Nicotine vaccines for smoking cessation.

(1) Cigarette smoking is the leading cause of preventable disease and death in the world. (2) Nicotine vaccines produce antibodies that bind nicotine, the chief addictive agent in cigarettes, and prevent it from entering the brain. (3) Early trials suggest nicotine vaccines are safe and well tolerated, but the duration of effect is unclear, and immunological response varies across recipients. (4) Nicotine vaccines have not yet been studied in phase 3 trials and the relative performance of different vaccines, alone or in combination with existing therapeutic options, is unknown.

Photoselective vaporization for benign prostatic hyperplasia.

(1) In photoselective vaporization of the prostate (PVP) for benign prostatic hyperplasia (BPH), laser energy is used to vaporize prostatic tissue rapidly and bloodlessly. (2) Studies suggest that PVP performs well in the short term. (3) Randomized controlled trials (RCTs) and longterm follow-up are required to determine PVP's place in the management of BPH.

Transient elastography (FibroScan) for non-invasive assessment of liver fibrosis.

(1) Liver fibrosis is associated with significant morbidity and mortality. The major cause is hepatitis C, which affects 240,000 Canadians. (2) Assessing the degree of liver fibrosis is critical to its management. Liver biopsy, an invasive procedure, is considered to be the diagnostic gold standard. (3) FibroScan is a rapid, non-invasive technology that uses low frequency vibration and ultrasound to assess the stiffness of liver tissue. (4) The diagnostic performance of FibroScan is good for identifying severe fibrosis or cirrhosis, but it is less accurate for milder presentations. (5) FibroScan is a promising technology, but large multi-centre trials comparing a range of emerging non-invasive fibrosis staging technologies are required.

A qualitative investigation into the levers and barriers to weight loss in children: opinions of obese children.

BACKGROUND: The alarming increase in the worldwide prevalence of childhood obesity is now recognised as a major public health concern. Failure to isolate and understand the external and internal factors contributing to successful weight loss may well be contributing to the ineffectiveness of current treatment interventions. AIM: To identify the physical and psychological levers and barriers to weight loss experienced by obese children using qualitative techniques. METHODS: 20 participants were randomly selected from a population of clinically obese children (7-15 years old) attending a weight-loss clinic for >3 months. The children expressed their opinions in a series of interviews and focus group sessions. Data were recorded, semitranscribed and analysed using the thematic framework analysis technique and behavioural-change models. RESULTS: Children described the humiliation of social torment and exclusion as the main reasons for wanting to lose weight, although initiation of behavioural change required the active intervention of a role model. The continuation of action was deemed improbable without continual emotional support offered at an individual level. Behavioural sacrifice, delayed parental recognition and previous negative experiences of weight loss were recognised as barriers to action. Participants identified shortcomings in their own physical abilities, the extended time period required to lose weight and external restrictions beyond their control as barriers to maintaining behavioural change. DISCUSSION: This study identifies the important levers and barriers experienced by obese children in their attempt to lose weight. Dealing with these levers and barriers while acknowledging the complex interplay of social and emotional factors unique to the individual may well promote successful weight control.

Radiofrequency neurotomy for lumbar pain.

(1) Chronic lumbar (lower back) pain, which affects many Canadians, imposes a large economic burden. (2) Symptoms may occur in the vertebral facet joints of 15% to 40% of patients with lower back pain. (3) Medial branch radiofrequency neurotomy is a minimally invasive outpatient procedure that reduces pain by interrupting the nerve supply to painful facet joints. (4) Four systematic reviews of this procedure offer disparate conclusions. (5) One small well designed observational study has shown positive results, but no equally rigorous randomized controlled trial has been conducted.

Ventrogluteal area--a suitable site for intramuscular vaccination of infants and toddlers.

Buttock vaccination has lower reactogenicity and similar immunogenicity to the two other recommended paediatric vaccination sites (deltoid and anterolateral thigh). Safety concerns about buttock injection derived from injections with neurotoxic agents, like penicillin but not vaccines, have become entrenched. However, the ventrogluteal area is considered safe for intramuscular injection. This study outlines the development of the ventrogluteal area as a suitable site for intramuscular vaccination of infants and toddlers. Measurement was made in 642 children, aged 2-18 months and age-specific templates were prepared. These were used in an untrasonographic study of 57 children aged 2-18 months to determine the tissue composition of the ventrogluteal area compared with the recommended anterolateral thigh vaccination site. The ventrogluteal area was found to be clearly defined by the template and suitable for intramuscular injection. Subsequent vaccination studies with the area showed that it was:

Achievements and challenges on policies for allied health professionals who use telehealth in the Canadian Arctic.

We formulated policies and procedures for allied health professionals (AHPs) who provide services using telehealth in Nunavut, Canada's newest Arctic territory. These are a supplement to the clinical policies and procedures already established for Nunavut physicians and nurses. The services were in the areas of audiology, dietetics/nutrition, midwifery, occupational therapy, ophthalmic services, pharmacy, physiotherapy, psychology, respiratory therapy, social work and speech therapy. Documents specific to each of the services were developed, drawing on information from Government of Nunavut data, Nunavut healthcare providers and links made through the Internet. Topics included the scope and limitations of telehealth services, staff responsibilities, training and reporting, professional standards and cultural considerations. We also considered generic policies covering common issues such as jurisdiction, licensing and liability. The policies and procedures for AHPs will enhance and expand the successes already achieved with telehealth in Nunavut. The challenges are to balance the preferred approaches to service provision with the realities of health care and communications in an Arctic setting.

Vaccines for prevention of human papillomavirus infection.

(1) High risk types of human papillomavirus (HPV) are the causal agents of cervical cancer. The prevention of HPV infection can reduce the incidence of this cancer. (2) Five phase II clinical trials have been published, and several large phase III trials are underway. (3) Trials have shown marked reductions in HPV infection. Most studies did not evaluate the effect of the vaccines on cancer because of lengthy time spans between HPV infection and the development of cancer. (4) Injection site pain, headache, and fatigue are the most common adverse events reported. (5) Important considerations include vaccine efficacy; acceptability; integration into existing vaccine schedules; cost; role of cervical screening programs; and access, particularly for people in the developing world.

Reduction in hospitalization rates following cardiac resynchronisation therapy in cardiac failure: experience from a single centre.

AIMS: Frequent, lengthy hospital admissions for congestive cardiac failure (CCF) result in excessive health care costs. Cardiac resynchronisation therapy (CRT) is a novel treatment option for patients with CCF and associated cardiac conduction defects. We investigated whether CRT resulted in significant improvements in New York Heart Association (NYHA) symptom class, exercise tolerance, and hospitalization rates in such patients. METHODS: Twenty-seven patients who underwent CRT in a single centre were studied, with NYHA symptom class, exercise tolerance and hospitalization rates noted in the 12 months prior to and following CRT. RESULTS: Following 12 months of CRT, NYHA symptom class improved from 3.3 +/- 0.5 to 2.1 +/- 0.4 (P < 0.05). Exercise tolerance, assessed by 6 min hall walk test increased by 64% from 195 +/- 114 m to 320 +/- 85 m (P = 0.007). Days in hospital for stabilisation of cardiac failure decreased by 98% from 472 to 9 days (P < 0.001). Significant hospitalization cost savings of 201,684 euros were calculated, with an overall saving of 12,420 euros. CONCLUSIONS: These data demonstrate that CRT results in significant improvement in clinical parameters, and considerable reductions in hospital admissions, and costs in patients with CCF.

Comparative reactogenicity and parental acceptability of pertussis vaccines administered into the ventrogluteal area and anterolateral thigh in children aged 2, 4, 6 and 18 months.

The importance of site of injection of combined pertussis/diphtheria/tetanus vaccines was investigated in two single blind studies. In the pilot study, in which the research instrument was trialed, 283 children aged 2-18 months received whole cell pertussis vaccine (DTPw) by the intramuscular route either into the anterolateral thigh or the ventrogluteal site. In the larger randomised study, 566 children aged 2-18 months were similarly injected with acellular pertussis vaccine (DTPa). Adverse reactions monitored after 24h showed the same lower rates for both vaccines with ventrogluteal injection compared with anterolateral thigh injection for systemic reactions (irritability (P<0.0001), perceived fever (P<0.0001), persistent crying/screaming (P<0.0001) and local reactions (bruising (P<0.0001) and redness/swelling (P<0.0001)). The Haemophilus influenzae type b vaccine (HibTITER) given concurrently in the contralateral site to the pertussis vaccine showed the same lower rates in both studies for ventrogluteal injection compared with anterolateral thigh injection for local reactions (redness/swelling both studies (P<0.0001) and bruising DTPw study (P<0.0001) and DTPa study (P<0.0004)).Parental acceptability was greater (P<0.0001) in both studies for ventrogluteal injection compared with anterolateral thigh injection.

Comparative immunogenicity of hepatitis B vaccine administered into the ventrogluteal area and anterolateral thigh in infants.

OBJECTIVE: To compare the immunological response of hepatitis B vaccine given by intramuscular injection into the anterolateral thigh and ventrogluteal site of infants up to 10 months old at initiation of vaccination. METHODS: An open, randomized study of 200 healthy infants recruited from a single practice in a small regional town in New South Wales was carried out. Infants were vaccinated with hepatitis B vaccine (Engerix-B 10 microg) using a 0 months, 1 month, 6 months regimen, with venous blood being collected from children 4-6 weeks after the last dose of vaccine for quantitative determination of hepatitis B surface antibody (anti-HBs) titre. Infants with anti-HBs titre > or = 100 m IU/mL were considered to be 'good' responders and were unlikely to acquire clinically significant hepatitis B infection. Infants with anti-HBs titre < 100 m IU/mL were considered to be 'poor' responders and were given a booster dose of Engerix-B 20 micro g; serology was repeated for anti-HBs titre 2-3 months after this injection. RESULTS: Quantitative anti-HBs titre was obtained from 177 infants: 171 4-6 weeks after the last dose of vaccine; 87 at the ventrogluteal site (46 boys, 41 girls); and 84 at the anterolateral thigh site (38 boys, 46 girls). Good antibody response (anti-HBs titre > or = 100 m IU/mL) was not significantly different for the two sites (ventrogluteal 96.6%, anterolateral thigh 93.2%), and antibody geometric mean titres (GMT) for anti-HBs were comparable for the two sites (ventrogluteal 2071.2 +/- 5.8m IU/mL, anterolateral thigh 2073.2 +/- 5.2m IU/mL). CONCLUSION: The ventrogluteal and anterolateral thigh vaccination sites in infants are immunologically comparable for hepatitis B vaccine. Presumably the variance of this study with studies of adults reflected the uniform injection of vaccine antigen into muscle tissue in infants.

The patient perspective survey. Can consultations for complex health problems be enhanced?

BACKGROUND: Patients with complex health problems pose particular difficulties due to the interaction between psychosocial factors and physical disease. The aim of this study is to investigate the usefulness of a paper based instrument (the Patient Perspective Survey, or PPS) to enhance general practitioner-patient communication and patients' self reported coping skills. METHODS: A previously validated questionnaire was modified and distributed to a self selected group of 21 GPs. They recruited 77 patients with complex health problems and asked them to complete a PPS questionnaire. The patients then returned for an extended consultation to discuss the results of the questionnaire with the GP. Patients and GPs subsequently completed PPS evaluation forms. RESULTS: The PPS was useful for patients with chronic conditions with mixed physical and psychological components. It appeared to enhance the GP-patient relationship and gave patients a better understanding of their coping skills. DISCUSSION: Patients with complex health problems can use paper based questionnaires to improve the quality of communication between themselves and their GPs.

Renal colic and recurrent urinary calculi. Management and prevention.

BACKGROUND: Urinary calculi are a relatively common problem and up to 80% of patients with calculi who are untreated will experience one or more recurrences within five years. OBJECTIVE: This paper outlines the causes of urinary calculi and presents evidence for the less conventional treatment of renal colic with NSAIDs such as intramuscular diclofenac in preference to traditional pethidine injections. The paper also deals with ways to prevent recurrence of stone formation. DISCUSSION: Effective treatment requires a clear understanding of the cause, and investigations need to be directed toward establishing this. Prevention is the cornerstone of management and requires patients to have a clear understanding of the problem. Follow up of these patients is essential.