The burden of dental care in Amelogenesis Imperfecta paediatric patients in the UK NHS: a retrospective, multi-centred analysis.

PURPOSE: The burden of dental care in Amelogenesis Imperfecta (AI) has not been well described. This condition results in weak, discoloured and often sensitive teeth. Specialist paediatric care is available for AI patients in the UK, but treatment protocols and care provided are inconsistent. The aim of this study was therefore to analyse the provision of treatment and burden of care for children and families with AI across four Paediatric Dentistry centres in the UK. METHODS: A retrospective evaluation of AI patient clinical records across four UK consultant-led Paediatric Dentistry centres was completed. Frequency and duration of care were recorded along with treatment and experience of inhalation sedation, local and general anaesthetic. RESULTS: In total, 138 records were available for analysis. The average patient age at first referral was 7.7 years (range 1-16 years) and families travelled an average 21.8 miles per appointment (range 0.2-286 miles). Patients attended on average 4.5 appointments per year for 5.8 years. In total, 65.2% had experience of local anaesthetic, 27.5% inhalation sedation and 31.9% general anaesthetic. Dental treatment including restorations and extractions were commonly required on multiple teeth per patient. CONCLUSION: AI carries a high burden of specialist dental care to patients and families. Specialist centres are required to provide longitudinal, comprehensive care.

Rapid molecular technique analysis of a KPC-3-producing Klebsiella pneumoniae outbreak in an Italian surgery unit.

The rapid emergence of KPC-producing Klebsiella pneumoniae has become a serious problem in health-care settings, increasing in frequency worldwide. These infections are worrisome, since the antimicrobial treatment options for infections due to multidrug-resistant strains are very limited, and outbreaks must be rapidly detected and controlled. A semi-automated, repetitive-sequence-based PCR (rep-PCR) instrument (DiversiLab system) was evaluated in comparison with the pulse-field gel electrophoresis (PFGE) and multilocus sequence typing to investigate the outbreak of KPC-producing K. pneumoniae in a surgery unit at the University Hospital of Verona, Italy, as a rapid method for outbreak investigations. A selection of seven epidemiologically related K. pneumoniae showing resistance to carbapenem and three epidemiologically unrelated K. pneumoniae isolates were collected from patient with hospital-acquired infection. Among the epidemiologically related isolates, PFGE and Rep-PCR identified a unique pattern with more than 90% of homology. The concordance between DiversiLab and PFGE results confirmed the usefulness of rapid molecular techniques to investigate outbreaks due to multidrug-resistant bacteria. Moreover, this result could meet the international need for a harmonised typing tool, allowing the implementation of strict control measures to prevent dissemination of these organisms in health-care settings.

Rhabdomyosarcoma of the mandible in a 6-year-old boy.

INTRODUCTION: Rhabdomyosarcoma is an aggressive malignant tumour composed of neoplastic mesenchymal cells that infiltrate surrounding tissue structures, making their precise site of origin unclear. Although rare, this is highly aggressive and the most common soft-tissue neoplasm of the head and neck in children. Regrettably by the time most cases are initially seen, the patients already have large tumours, due to rapid tumour growth and delayed medical consultation. CASE REPORT: This report describes a 6-year-old presenting with just such symptoms of facial swelling and pain but elicitation of further information and findings, including tooth mobility of 3 days duration, led to prompt referral and early treatment of an embryonal rhabdomyosarcoma. CONCLUSION: General dental practitioners are frequently presented with a child with a swollen face and pain. Experience would suggest a dental abscess to be the most likely cause with treatment as appropriate. However, all swellings in children, should be thoroughly investigated and reviewed as particularly in this age group, tumour growth is rapid while early diagnosis allows successful treatment with multimodality therapy.

T cell selection and differentiation in AIDS disease: the model of HIV-discordant monozygotic twins.

The model of monozygotic twins has been repeatedly studied to control the genetic and age-specific effects on HIV disease. Focusing on this natural model, the expression of CD27/CD45RA differentiation markers and the distribution of the Vbeta TCR repertoire was analyzed on CD4+ and CD8+ T cells. In our HIV-discordant monozygotic twins, a significant reduction of naive T cells and a parallel accumulation of effector/memory T cells was induced by HIV infection, as well as a skewing of T cell repertoire evidenced by VbetaTCR analysis. The block of HIV replication by highly active antiretroviral therapy (HAART) restored most of the T cell maturation and selection process, with some exception among CTL differentiation and repertoire. Altogether, the model of HIV-discordant monozygotic twins is a valuable tool showing that HAART is not able to completely restore the CTL profile.

European recommendations for the management of healthcare workers occupationally exposed to hepatitis B virus and hepatitis C virus.

Exposure prevention is the primary strategy to reduce the risk of occupational bloodborne pathogen infections in healthcare workers (HCW). HCWs should be made aware of the medicolegal and clinical relevance of reporting an exposure, and have ready access to expert consultants to receive appropriate counselling, treatment and follow-up. Vaccination against hepatitis B virus (HBV), and demonstration of immunisation before employment are strongly recommended. HCWs with postvaccinal anti-HBs levels, 1-2 months after vaccine completion, >or=10 mIU/mL are considered as responders. Responders are protected against HBV infection: booster doses of vaccine or periodic antibody concentration testing are not recommended. Alternative strategies to overcome non-response should be adopted. Isolated anti-HBc positive HCWs should be tested for anti-HBc IgM and HBV-DNA: if negative, anti-HBs response to vaccination can distinguish between infection (anti-HBs >or=50 mUI/ml 30 days after 1st vaccination: anamnestic response) and false positive results(anti-HBs >or=10 mUI/ml 30 days after 3rd vaccination: primary response); true positive subjects have resistance to re-infection. and do not need vaccination The management of an occupational exposure to HBV differs according to the susceptibility of the exposed HCW and the serostatus of the source. When indicated, post-exposure prophylaxis with HBV vaccine, hepatitis B immunoglobulin or both must be started as soon as possible (within 1-7 days). In the absence of prophylaxis against hepatitis C virus (HCV) infection, follow-up management of HCV exposures depends on whether antiviral treatment during the acute phase is chosen. Test the HCW for HCV-Ab at baseline and after 6 months; up to 12 for HIV-HCV co-infected sources. If treatment is recommended, perform ALT (amino alanine transferase) activity at baseline and monthly for 4 months after exposure, and qualitative HCV-RNA when an increase is detected.

Research reports on treatments for bipolar disorder: preliminary assessment of methodological quality.

OBJECTIVE: To assess frequencies of types of publications about bipolar disorder (BD) and evaluate methodological quality of treatment studies. METHOD: We classified 100 randomly selected articles (1998-2002) from five psychiatric journals with highest impact ratings, by topic areas, and assessed methods employed in treatment studies. RESULTS: Topics ranked: treatment (41%; 37% on pharmacotherapy) > biology (31%) > psychopathology (14%) = miscellaneous (14%). Of treatment studies, only 19% of original articles were randomized, 15% were relatively large (n > or = 50) but non-randomized, 65% were small non-randomized, case-series or -reports, and 53% relied on baseline-to-endpoint contrasts without a control group. Patient dropout rates were > or =40% in 43% of prospective studies. Only two reports provided confidence intervals; one included a power analysis, and 53% included no references on study design or statistical methods. CONCLUSION: Even in highly respected journals, the typical methodological quality of recent reports on therapeutics for BD was unexpectedly limited, and psychopathology and psychotherapies were little studied.

An investigation of the acceptability of undergraduate supervision by Senior House Officers and General Professional Trainees.

AIM: This study assessed whether Senior House Officers (SHO)/General Professional Trainees (GPT) are, or would be, comfortable supervising clinical undergraduates, whether they find this to be a valuable experience within their training programme, and whether undergraduates are or would be comfortable with SHO/GPTs supervising them. METHOD: Questionnaires were distributed to fourth and final year students at Glasgow and Dundee Dental Schools and fourth year students at Newcastle Dental School. Questionnaires were also distributed to SHO/GPTs at Glasgow Dental Hospital and School and Edinburgh Dental Institute. RESULTS: Seventy-nine per cent of respondent SHO/GPTs were currently not involved in the supervision of undergraduates within their present rotation, 65% of whom stated that they would value the experience of this within their training. Of those involved in supervision, 83% found the experience valuable. Forty-four per cent of students were unsure or not comfortable with SHO/GPTs supervising within an oral surgery department and approximately the same in other departments. Twenty-eight per cent of respondents felt that university lecturers should be the main trainer. CONCLUSION: SHO/GPTs value supervising undergraduates as part of their training experience. More than half of students are comfortable with SHO/GPTs supervising them. Both groups suggest that SHO/GPTs should receive some form of training in teaching prior to supervising undergraduates.

European recommendations for the management of healthcare workers occupationally exposed to hepatitis B virus and hepatitis C virus.

Exposure prevention is the primary strategy to reduce the risk of occupational bloodborne pathogen infections in healthcare workers (HCW). HCWs should be made aware of the medicolegal and clinical relevance of reporting an exposure, and have ready access to expert consultants to receive appropriate counselling, treatment and follow-up. Vaccination against hepatitis B virus (HBV), and demonstration of immunisation before employment are strongly recommended. HCWs with postvaccinal anti-HBs levels, 1-2 months after vaccine completion, >10 mIU/mL are considered as responders. Responders are protected against HBV infection: booster doses of vaccine or periodic antibody concentration testing are not recommended. Alternative strategies to overcome non-response should be adopted. Isolated anti-HBc positive HCWs should be tested for anti-HBc IgM and HBV-DNA: if negative, anti-HBs response to vaccination can distinguish between infection (anti-HBs >50 mUI/ml 30 days after 1st vaccination: anamnestic response) and false positive results(anti-HBs >10 mUI/ml 30 days after 3rd vaccination: primary response); true positive subjects have resistance to re-infection. and do not need vaccination The management of an occupational exposure to HBV differs according to the susceptibility of the exposed HCW and the serostatus of the source. When indicated, post-exposure prophylaxis with HBV vaccine, hepatitis B immunoglobulin or both must be started as soon as possible (within 1-7 days). In the absence of prophylaxis against hepatitis C virus (HCV) infection, follow-up management of HCV exposures depends on whether antiviral treatment during the acute phase is chosen. Test the HCW for HCV-Ab at baseline and after 6 months; up to 12 for HIV-HCV co-infected sources. If treatment is recommended, perform ALT (amino alanine transferase) activity at baseline and monthly for 4 months after exposure, and qualitative HCV-RNA when an increase is detected.

Towards a standard HIV post exposure prophylaxis for healthcare workers in Europe.

Antiretroviral prophylaxis (PEP) after occupational exposure to HIV in healthcare workers (HCWs) is used across Europe, but not in a consistent manner. A panel of experts, funded by the European Commission, formulated a set of recommendations. When it has been decided that the characteristics of the exposure indicate the initiation of PEP, PEP should be started as soon as possible; initiation is discouraged after 72 hours. PEP should be initiated routinely with any triple combination of antiretrovirals approved for the treatment of HIV-infected patients; a two class regimen is to be preferred. The source patient's treatment history should be sought. Counselling, psychological support, HIV testing and clinical evaluation should be performed at baseline, at 6-8 weeks, and at least 6 months post exposure. Additional clinical and laboratory monitoring at one and two weeks should be considered, as adherence with and tolerance of the regimen can highlight adverse reactions and potential toxicity. Routine HIV resistance tests in the source patient, and direct virus assays in the exposed HCW are not recommended.

Towards a standard HIV post exposure prophylaxis for healthcare workers in Europe.

Antiretroviral prophylaxis (PEP) after occupational exposure to HIV in healthcare workers (HCWs) is used across Europe, but not in a consistent manner. A panel of experts, funded by the European Commission, formulated a set of recommendations. When it has been decided that the characteristics of the exposure indicate the initiation of PEP, PEP should be started as soon as possible; initiation is discouraged after 72 hours. PEP should be initiated routinely with any triple combination of antiretrovirals approved for the treatment of HIV-infected patients; a two class regimen is to be preferred. The source patient's treatment history should be sought. Counselling, psychological support, HIV testing and clinical evaluation should be performed at baseline, at 6-8 weeks, and at least 6 months post exposure. Additional clinical and laboratory monitoring at one and two weeks should be considered, as adherence with and tolerance of the regimen can highlight adverse reactions and potential toxicity. Routine HIV resistance tests in the source patient, and direct virus assays in the exposed HCW are not recommended.

Factors related to virologic failure among HIV-positive injecting drug users treated with combination antiretroviral therapy including two nucleoside reverse transcriptase inhibitors and nevirapine.

Treatment strategies in human immunodeficiency virus (HIV)-positive active injecting drug users (IDUs) must take into account their lifestyles, that often result in low adherence to therapy. The nonnucleoside reverse transcriptase inhibitors (NNRTI) offer simpler treatment regimens, but the appearance of drug resistance during treatment failure may cause high levels of cross-resistance to all NNRTIs. We adopted a combination therapy of two NRTIs and nevirapine (NVP) for treatment of IDU patients to evaluate its feasibility in such patients. From October 1998 to December 1999, demographic, clinical, and laboratory data from 80 IDUs on this regimen were collected. Fisher's exact test, Kaplan Meier method, and Cox model were used for statistical analysis. Overall, 20 IDUs discontinued the treatment because of side effects and 20 IDUs experienced treatment failure. Considering the treatment failure as an end point, 55.6% (95% confidence interval [CI]: 37.9%-72.6%) of patients was still undergoing treatment after 12 months compared to 44.6% (31.8%-58.6%) when discontinuation was also taken into account. An increasing trend over time was observed in the CD4+ lymphocyte count, among failing and nonfailing IDUs. By multivariate analysis, baseline HIV-RNA, treatment breaks and low adherence and active injecting drug use turned out to be significantly associated with treatment failure. Our results show that continuing injecting drug use and treatment breaks are the main factors that can lead to treatment failure in IDUs and easily to NNRTI class resistance.

Epidemiology and prognosis of AIDS-associated progressive multifocal leukoencephalopathy in the HAART era.

Whereas most AIDS-related neurologic disorders have reduced incidence since HAART therapy was introduced, we find that the incidence of progressive multifocal leukoencephalopathy (PML) did not significantly differ between the pre-HAART and the HAART period (OR 0.78; 95% CI 0.41-1.50). These findings were confirmed by the preliminary results of the Italian Register Investigative Neuro AIDS (IRINA) Study, a prospective multicenter study started in January 2000, which showed that PML was the second most frequently diagnosed neurologic disorder after TE. A similar proportion of cases were found in HAART-naïve and HAART-experienced patients in our experience. PML was more common in the presence of HIV RNA > 500 copies/ml. Most of the cases occurring in HAART-exposed patients developed within the first 6 months of therapy. As others have reported, we find a prolonged survival in PML subjects prescribed HAART (245 days in the group treated with HAART versus 66 days in the group not treated with HAART; P at log rank = 0.001). However despite the survival benefit, AIDS-associated PML still has a serious prognosis. In fact, PML had the lowest 1-year survival probability of any cerebral disorder in our study (P = 0.0005). Our findings also confirm that CSF JCV DNA burden at baseline is a useful prognostic indicator with a threshold of 4.7 log(10) JCV copies/ml (P at log rank = 0.01) in our experience. CSF JCV DNA load at 4 weeks of follow-up and clearance of JCV-DNA from CSF are associated with a better neurologic outcome and a longer survival.

Cardiomyopathy and encephalopathy in AIDS.

HIV encephalopathy has been in the past years the most typical CNS disorder in patients with AIDS. Histologic abnormalities consist in astrocytosis, myelin pallor, infiltration by infected macrophages, resident microglia and multinucleated giant cells, generally in absence of direct infection of neurons. Mononuclear phagocytes in the brain are the main target of HIV-1 infection and the site of productive viral replication, and viral stimulation leads to the release of neurotoxic products causing neurologic damage. Subclinical cardiac abnormalities are common in HIV+ patients and several studies suggested a role for cytokines and other inflammatory products as mediators of cardiac abnormalities. The common pathway for neurologic and cardiac manifestations supports the relationship between neurologic disease and cardiac dysfunction in HIV infection. Clinical observations suggest that cardiomyopathy could be associated with encephalopathy in HIV+ patients and that it may affect survival. Antiretroviral therapy may reduce impact of neurologic and cardiac abnormalities by suppressing plasma HIV-1 viral load.

Nosocomial candidemia in non-neutropenic patients at an Italian tertiary care hospital.

In a retrospective study conducted in an Italian tertiary care hospital, the incidence of nosocomial candidemia was evaluated together with causative pathogens, treatment, and risk factors for death. Over a 6-year period (1992-1997), a total of 189 episodes of candidemia occurred in 189 patients (mean age 58+/-19 years), accounting for an average incidence of 1.14 episodes per 10,000 patient-days per year. The most common reasons for hospitalization were solid neoplasia (21%), trauma (17%), abdominal diseases requiring surgery (13%), and cardiovascular diseases (13%). No patient was neutropenic within 3 weeks prior to the onset of candidemia. One hundred thirty patients were hospitalized in intensive care units, 47 patients in surgical wards, and 12 patients in medical wards. Candida albicans was the most frequently isolated pathogen, accounting for 54% of fungal isolates, followed by Candida parapsilosis (23%), Candida glabrata (7%), Candida tropicalis (5%), Candida pelliculosa (4%), Candida lusitaniae (1%), Candida humicula (1%), and other non-albicans Candida spp. (5%). Seventy-six (41%) patients received adequate antifungal therapy. Seventy-one (58%) of the 123 evaluable patients with central venous catheters underwent line removal; 51 of them had catheter-related candidemia. The 30-day crude mortality rate was 45%. Older age, hospitalization in an intensive care unit, a longer duration of candidemia, retention of central lines, and inadequate antifungal therapy were significantly associated with poor outcome. In the present study, nosocomial candidemia was a frequent and relatively underestimated illness. Adequate antifungal therapy and central line removal independently reduced the high mortality of the disease.