Morphology and genetics reveal an intriguing pattern of differentiation at a very small geographic scale in a bird species, the forest thrush Turdus lherminieri.

Mobile organisms are expected to show population differentiation only over fairly large geographical distances. However, there is growing evidence of discrepancy between dispersal potential and realized gene flow. Here we report an intriguing pattern of differentiation at a very small spatial scale in the forest thrush (Turdus lherminieri), a bird species endemic to the Lesser Antilles. Analysis of 331 individuals from 17 sampling sites distributed over three islands revealed a clear morphological and genetic differentiation between these islands isolated by 40-50 km. More surprisingly, we found that the phenotypic divergence between the two geographic zones of the island of Guadeloupe was associated with a very strong genetic differentiation (Fst from 0.073-0.153), making this pattern a remarkable case in birds given the very small spatial scale considered. Molecular data (mitochondrial control region sequences and microsatellite genotypes) suggest that this strong differentiation could have occurred in situ, although alternative hypotheses cannot be fully discarded. This study suggests that the ongoing habitat fragmentation, especially in tropical forests, may have a deeper impact than previously thought on avian populations.

Isolation rooms for highly infectious diseases: an inventory of capabilities in European countries.

Isolation of patients with highly infectious diseases (HIDs) in hospital rooms with adequate technical facilities is essential to reduce the risk of spreading disease. The European Network for Infectious Diseases (EUNID), a project co-funded by European Commission and involving 16 European Union member states, performed an inventory of high level isolation rooms (HIRs, hospital rooms with negative pressure and anteroom). In participating countries, HIRs are available in at least 211 hospitals, with at least 1789 hospital beds. The adequacy of this number is not known and will depend on prevailing circumstances. Sporadic HID cases can be managed in the available HIRs. HIRs could also have a role in the initial phases of an influenza pandemic. However, large outbreaks due to natural or to bioterrorist events will need management strategies involving healthcare facilities other than HIRs.

Loss to follow-up in an international, multicentre observational study.

OBJECTIVE: The aim of this work was to assess loss to follow-up (LTFU) in EuroSIDA, an international multicentre observational cohort study. METHODS: LTFU was defined as no follow-up visit, CD4 cell count measurement or viral load measurement after 1 January 2006. Poisson regression was used to describe factors related to LTFU. RESULTS: The incidence of LTFU in 12 304 patients was 3.72 per 100 person-years of follow-up [95% confidence interval (CI) 3.58-3.86; 2712 LTFU] and varied among countries from 0.67 to 13.35. After adjustment, older patients, those with higher CD4 cell counts, and those who had started combination antiretroviral therapy all had lower incidences of LTFU, while injecting drug users had a higher incidence of LTFU. Compared with patients from Southern Europe and Argentina, patients from Eastern Europe had over a twofold increased incidence of LTFU after adjustment (incidence rate ratio 2.16; 95% CI 1.84-2.53; P<0.0001). A total of 2743 patients had a period of >1 year with no CD4 cell count or viral load measured during the year; 743 (27.1%) subsequently returned to follow-up. CONCLUSIONS: Some patients thought to be LTFU may have died, and efforts should be made to ascertain vital status wherever possible. A significant proportion of patients who have a year with no follow-up visit, CD4 cell count measurement or viral load measurement subsequently return to follow-up.

A curriculum for training healthcare workers in the management of highly infectious diseases.

The SARS epidemic, the threat of bioterrorism, and recent examples of imported highly infectious diseases (HID) in Europe have all highlighted the importance of competent clinical and public health management of infectious disease emergencies. Although the European Union of Medical Specialists in Europe and the Infectious Diseases Society of America have developed curricula for training in infectious disease medicine, neither of those mentions training in the management of HIDs. The European Network for Infectious Diseases (EUNID, http://www.eunid.com) is a European Commission co-funded network of experts in HID management, created to help improve the preparedness for HID emergencies within Europe. One of EUNID's agreed tasks is the development of a curriculum for such a training. Between April 2005 and September 2006, EUNID developed a curriculum and accompanying training course on the basis of a questionnaire that was sent to all country representatives and discussion, followed by amendment of drafts shared through the project website, and a final consensus meeting. The resulting curriculum consists of a two-module course covering the core knowledge and skills that healthcare workers need to safely treat a patient who has, or who may have, an HID. The first module introduces theoretical aspects of HID management, including disease-specific knowledge, infection control, and the public health response, through didactic teaching and class-based discussion. The second module involves a "skill station" and a clinical scenario, and equips trainees with relevant practical skills, including the use of specialised equipment and teamwork practice in patient management. Together, the curriculum and course contribute to the creation of a common framework for training healthcare professionals in Europe, and although they are designed primarily for clinicians that are directly involved in patient care, they are relevant also to public health professionals and others who may be involved in HID management and emergency response.

Adjustable maintenance dosing with budesonide/formoterol or budesonide: double-blind study.

Adjustable maintenance dosing with either budesonide/formoterol or budesonide was compared in asthma patients. This double-blind trial randomized 133 patients (mean forced expiratory volume in 1s 66% predicted) to receive 2 inhalations twice daily of budesonide/formoterol 160/4.5 microg (640/18 microg/day) or budesonide 320 microg (1280 microg/day) for 4 weeks. The study drug was adjusted in both groups according to symptoms to 2-4 inhalations daily during Weeks 5-8 and 1-4 inhalations daily during Weeks 9-20. Asthma was well controlled in both groups, with minimal levels of treatment failure (5 budesonide/formoterol vs. 2 budesonide patients; P=NS) and minimal use of reliever therapy. Clinically important improvements in health-related quality of life (HRQL) occurred in the physical functioning and emotional role functioning domains (both P<0.05) for the budesonide/formoterol group compared with budesonide. Physician and patient treatment satisfaction favored budesonide/formoterol (both P<0.05). Budesonide/formoterol patients used fewer daily inhalations of study drug (P=0.024). The median average daily inhaled corticosteroid dose during the study was 448 microg with budesonide/formoterol and 1152 microg with budesonide. Adjustable maintenance dosing with budesonide/formoterol and budesonide resulted in high levels of asthma control. Adjustable budesonide/formoterol treatment achieved greater HRQL benefits and patient satisfaction, with lower overall drug use.

Hitting them where it hurts? Low dose nalbuphine therapy.

OBJECTIVE: To determine if low dose nalbuphine provides an adequate reduction in pain with minimal side effects. METHODS: Prospective cohort of 115 patients given nalbuphine by paramedics in Wales and the English borders. OUTCOME MEASURES: (1) Mean total dose of nalbuphine administered, change in pain score, time to adequate pain relief (score below four), and change in respiratory rate and systolic blood pressure; (2) proportion of patients continuing to suffer moderate to severe pain on arrival at hospital; (3) incidence of adverse events. RESULTS: Full data were obtained for all patients. The mean total dose of nalbuphine administered was 6.09 mg (range 2.5 to 12.5 mg). This was significantly higher in trauma than ischaemic chest pain patients (7.03 versus 5.13 mg). The mean reduction in pain score was -3.97 (95% CI -4.38 to -3.57, p<0.001). The mean time to adequate pain relief (where this was achieved) was 15.7 minutes (95% CI 13.4 to 17.9 minutes). On arrival at hospital 60% of patients (n=69, 95% CI 50.9 to 68.5%) still met ambulance criteria for analgesia (70.7% of trauma patients and 49.1% with ischaemic chest pain). Systolic blood pressure fell by a mean of -3.67 (95% CI -6.76 to -0.58, p=0.02) and respiratory rate increased by a mean of 1.63 (95% CI 1.08 to 2.17, p<0.001). Two patients complained of nausea (1.74%, 95% CI 0.5 to 6.0%). No other adverse events were reported. CONCLUSION: Low dose nalbuphine results in few adverse events, but offers poor pain control for a high proportion of patients.

Genetic polymorphisms of CYP1A1 and GSTM1 and lung cancer risk.

Susceptibility to lung cancer may, in part, be determined by interindividual differences in the cytochrome P450-catalysed bioactivation and the glutathione S-transferase-catalysed detoxification of procarcinogens. Therefore a lung cancer case-control study was set up to investigate the association of three polymorphisms of the CYP1A1 gene (CYP1A1*2A, CYP1A1*2B, CYP1A1*4) and GSTM1*0 genotype with lung cancer risk in Austrian Caucasians. Genomic DNA was isolated from the peripheral blood lymphocytes of 134 male lung cancer patients and 134 age-matched controls with nonmalignant conditions and PCR-based analyses were performed. There was no significant difference in risk between cases and controls, either for the CYP1A1*2A (OR=1.09, 95%CI=0.46-2.58), CYP1A1*2B (OR=1.09, 95%CL=0.46-2.58) or for the CYP1A1*4 polymorphism (OR=0.49, 95%CL=0.20-1.16). The prevalence of the GSTM1*0 genotype in the lung cancer group (47.8%) was comparable to that found in the control group (49.3%) and also had no effect on lung cancer risk (OR=0.94, 95%CL=0.54-1.57). Further, in a subgroup of male ever-smokers (n=126), no significant influence on the relative risk was found for these polymorphisms. Our results suggest that these investigated polymorphisms can not be considered as genetic susceptibility markers for lung cancer within the Austrian Caucasian population.

Hearing aid possession in the population: lessons from a small country.

The results of several studies on hearing aid use in the Welsh population were considered to investigate some general principles on determinants of such use within the general populations of developed countries. Overall hearing aid possession and use were not found to have changed significantly over the past 18 years, remaining at 4 per cent having obtained hearing aids and 3 per cent using them. The possession figures were consistent across all methodologies used. Higher hearing aid use in the post-industrial valleys (in which the traditional industries of coal mining and steel production had disappeared) was explained entirely by a higher level of reported hearing difficulties there. In all populations, less than 20 per cent of those reporting difficulties possessed hearing aids. Whether a hearing aid had been obtained free of charge from the National Health Service or purchased privately did not influence whether it was still used. It was concluded that an effort to improve the acceptability of hearing aids and reduce their stigma is required.

Comparison of sequence analysis and the INNO-LiPA HBV DR line probe assay for detection of lamivudine-resistant hepatitis B virus strains in patients under various clinical conditions.

A line probe assay (INNO-LiPA HBV DR) detecting drug-resistant hepatitis B virus (HBV) strains was evaluated. Results concordant with sequence analysis were obtained with 48 of 56 serum samples from HBV-infected patients undergoing lamivudine therapy. In eight cases, additional minor subpopulations could be identified by the line probe assay.

Influence of age on CD4 cell recovery in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy: evidence from the EuroSIDA study.

Influence of age on the CD4 cell response to highly active antiretroviral therapy (HAART) was examined in 1956 patients (median age, 37.2 years) in the EuroSIDA study. Median initial CD4 cell count was 192x106 cells/L, follow-up was 31 months, and time to maximum CD4 cell response was 20 months. Age groups were not different for baseline CD4 cell count, baseline human immunodeficiency virus RNA load, or treatment history. CD4 cell increase, stratified by age quartiles, differed during months 3-36 of HAART (P=.023). Maximum CD4 cell increase from start of HAART differed by age group (P=.0003), as did maximum CD4 cell count (P<10-4). Multivariate analysis confirmed the inverse relationship between age and maximum CD4 cell response (P=.023). Time to a CD4 increase of >200x106 cells/L was shorter for patients in the younger age groups (P=.0026), as confirmed by multivariate analysis (P<10-4). Younger age may favor CD4 cell restoration because of preserved thymic function.

Delavirdine in combination with zidovudine in treatment of human immunodeficiency virus type 1-infected patients: evaluation of efficacy and emergence of viral resistance in a randomized, comparative phase III trial. The M/3331/0013B Study Group.

We compared the activity of delavirdine (DLV) plus zidovudine (AZT) (n = 300) with that of AZT (n = 297) against human immunodeficiency virus type 1 in a randomized, double-blind, placebo-controlled trial. DLV exerted a transient antiviral effect, and mutations for resistance to DLV were found in more than 90% of subjects at week 12. The K103N mutation, which confers nonnucleoside reverse transcriptase inhibitor cross-resistance, was found in 85% of the patients.

[HIV/AIDS in gynecology. On the treatment readiness of established gynecologists for HIV positive women]. / HIV/AIDS in der Gynäkologie. Zur Behandlungsbereitschaft niedergelassener Gynäkologen und Gynäkologinnen für HIV-positive Frauen.

BACKGROUND: Decreasing vertical transmission rates of HIV due to highly active antiretroviral therapy regimens faciliate the choice for childbearing in HIV positive women. Recent trends in epidemiology of HIV show increasing incidence of HIV-related gynecologic diseases. These facts implicate the question about the role of gynecologists in primary care of HIV-infected women and furthermore about the use of health services by HIV-infected women. MATERIALS AND METHODS: 143 of the total of 298 office-based gynecologists practicing in Vienna (41%) completed a questionnaire to assess their knowledge, attitudes, and practice with respect to HIV-infection and AIDS. In addition, personal interviews with 30 HIV-positive women were conducted. RESULTS: Although about 75% of the gynecologists are willing to care for HIV-positive women in their private practice, only about a third of them already care and 17.9% refuse to care for these patients. More than two thirds of the gynecologists refuse to care for intravenous drug users and patients with manifestations of AIDS. Barriers to care are the fear to be confronted with the psychosocial problems of patients, the fear to need more time to care for these patients and the fear of a lack in knowledge about HIV/AIDS. HIV-positive women are highly satisfied with care, although the majority of the women reported about a lack of confidentiality and therefore did not inform their gynecologist about their HIV-infection. CONCLUSIONS: The physician-patient relationship of gynecologists and HIV-positive women is characterized by gynecologist's barriers to care on the one hand, on the other hand HIV-positive women report about a lack of confidentiality, which often is associated with a delay in seeking medical care. DISCUSSION: A strategy to overcome gynecologist's barriers in care for HIV-positive women is medical education. The improvement of the physician-patient relationship will enhance the effects of HIV/STD risk assessment as well as the quality of care.