Sexual and reproductive health services for people living with HIV/AIDS in Germany: are we up to the challenge?

PURPOSE: Germany is witnessing an increase in the number of new infections with human immunodeficiency virus (HIV). Enabling persons living with HIV (PLHIV) to adopt safer sex practices might contribute towards reducing the incidence of HIV infections. The aim of this study was to identify gaps in the sexual and reproductive health (SRH) services provided to PLHIV in Germany. METHODS: Within the framework of the European public health project Eurosupport 5, self-reported questionnaires were distributed to PLHIV and a survey of SRH-service providers was carried out. The completed questionnaires and survey results were analysed. RESULTS: Of the questionnaires distributed, 218 PLHIV (90 % men, 10 % women) returned a completed questionnaire. Of these, 74 % self-identified as men having sex with men (MSM) and 13 % as heterosexual men. MSM reported a median number of ten casual partners in the previous 6 months and unprotected sex in one-third of anal intercourses with casual partners, demonstrating that this group adopted more risky sexual behaviours than heterosexual PLHIV. Even though all PLHIV stated they would appreciate more support and service providers indicated that they provided a wide range of SRH services, SRH-relevant topics were rarely discussed between PLHIV and service providers. According to the patients' perception, shortage of time, lack of initiative by service providers and their own difficulty to address SRH-related topics were the most relevant obstacles to receiving satisfactory support. CONCLUSION: Many PLHIV consult their HIV-physician regularly for medical follow-up and also indicate that HIV-physicians should be the source of information concerning SRH counselling. HIV-physicians should take advantage of their key role in HIV care and strengthen their efforts to integrate SRH services in routine HIV care.

Cost impact of prospective HLA-B*5701-screening prior to abacavir/lamivudine fixed dose combination use in Germany.

OBJECTIVE: Avoiding abacavir in HIV-infected patients tested positive for HLA-B*5701 reduces the risk of abacavir hypersensitivity reaction (ABC-HSR). Our aim was to assess the costs of clinically suspected HSR and to estimate potential cost savings of implementing prospective HLA-B*5701-screening for HIV-infected patients initiating abacavir/lamivudine fixed-dose combination (ABC/3TC FDC) compared to initiating respective treatment without screening. METHODS: Employing a decision tree model the expected HSR-related costs of screening vs. no screening were estimated from the societal and healthcare payer perspective (reference year 2007). A retrospective standardized assessment of all clinically suspected ABC-HSR cases without screening at 5 German HIV-centres was performed to measure resource consumption. In- and outpatient care, discarded ABC/3TC FDC and concomitant medication were considered. Direct resource utilization was valued using German fees (EBM, G-DRGs). Indirect costs were measured with the human capital approach. Estimates for the HLA-B*5701-prevalence, HSR-incidence, and hospitalization rate were based on clinical trials and cohorts and it was assumed that screening reduces the incidence of clinically suspected ABC-HSR from 10% to 0.5%. RESULTS: Thirty-two ABC-HSR cases were identified from 1998 to 2007. Mean direct and total costs per clinically suspected HSR case were Euro 1,362 and Euro 2,235, respectively. Hospital costs contributed 63.3% to direct costs. Potential cost savings when implementing genetic screening were estimated at Euro 44 and Euro 127 per screened patient, from a healthcare payer or societal perspective. CONCLUSION: HLA-B*5701 screening prior to ABC/3TC FDC initiation prevents significant HSR-related costs per screened patient and is likely to lead to overall net savings.

Correction: Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Conservative treatment of partial gastrocnemius muscle avulsions in dogs using therapeutic ultrasound -- A force plate study.

OBJECTIVES: In this report two cases of partial gastrocnemius muscle avulsion treated with pulsed therapeutic ultrasound are described. METHODS: The outcome in these two dogs was evaluated using ultrasonographic imaging and the measurement of ground reaction forces with a force plate. RESULTS: Both dogs showed an amelioration of the clinical signs within one month after commencement of the ultrasound therapy. The follow-up time for these cases was one year and six months respectively. Both of the dogs were free of lameness and had returned to their normal amount of exercise. Palpation of the fabella associated with the muscle injury did not produce any signs of pain. Ultrasonographic imaging did not detect any signs of haemorrhage or oedema, although scarring of muscle fibres was present. The force-plate analyses revealed an improvement. CLINICAL SIGNIFICANCE: These results suggest that therapeutic ultrasound could be a beneficial treatment modality for this kind of muscle injury.

Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1.

Minimal residual disease (MRD) is a powerful prognostic factor in acute lymphoblastic leukemia (ALL) and is used for patient stratification and treatment decisions, but its precise role in Philadelphia chromosome positive ALL is less clear. This uncertainty results largely from methodological differences relating to the use of real-time quantitative PCR (qRT-PCR) to measure BCR-ABL1 transcript levels for MRD analysis. We here describe the first results by the EURO-MRD consortium on standardization of qRT-PCR for the e1a2 BCR-ABL1 transcript in Ph + ALL, designed to overcome the lack of standardisation of laboratory procedures and data interpretation. Standardised use of EAC primer/probe sets and of centrally prepared plasmid standards had the greatest impact on reducing interlaboratory variability. In QC1 the proportion of analyses with BCR-ABL1/ABL1 ratios within half a log difference were 40/67 (60%) and 52/67 (78%) at 10-3 and 36/67 (53%) and 53/67 (79%) at 10-4BCR-ABL1/ABL1. Standardized RNA extraction, cDNA synthesis and cycler platforms did not improve results further, whereas stringent application of technical criteria for assay quality and uniform criteria for data interpretation and reporting were essential. We provide detailed laboratory recommendations for the standardized MRD analysis in routine diagnostic settings and in multicenter clinical trials for Ph + ALL.

Treatment with CCR5 antagonists: which patient may have a benefit?

The concept of CCR5 antagonists introduces an additional molecular target. Maraviroc (MVR) is approved by the FDA for use in HIV-1 infected patients for combination antiretroviral treatment of adults infected with only CCR5-tropic HIV-1 who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents. Tropism and treatment history should guide the use of MVR. Data from clinical trials show significant efficacy of MVR for patients with pre-treatment and multiple class failure. Additional clinical data show a CD4 reconstitution that is more pronounced than with comparator in treatment naive and in late stage patients even without CCR5-tropic virus indicating patients in earlier stages and even patients without CCR5 testing will benefit from MVR. MVR is not licensed for treatment naive patients but it has a high potential for further development in this patient group. It shows better immunological reconstitution than efavirenz. Pooled safety data from all available trials shows good short term tolerability. Caution is needed in hepatitis co-infection with pre-existing liver damage and in patients with heart failure. Isolates from different geographic regions differ in coreceptor usage. Summarizing knowledge on HIV-1 subtypes and CCR5 tropism shows that in principle all subtypes are susceptible to MVR. However, in subtypes A and D dualtropic and alternative coreceptor use were found. Clinical efficacy in patients from regions with A and D predominance should be studied in future trials. In conclusion, MVR will be of benefit for patients in various treatment situations and regions.

Diagnosis of invasive fungal infections in haematological patients by combined use of galactomannan, 1,3-ß-D-glucan, Aspergillus PCR, multifungal DNA-microarray, and Aspergillus azole resistance PCRs in blood and bronchoalveolar lavage samples: results of a prospective multicentre study.

High mortality rates of invasive fungal disease (IFD), especially invasive aspergillosis (IA), in immunocompromised haematological patients and current diagnostic limitations require improvement of detection of fungal pathogens by defining the optimal use of biomarkers and clinical samples. Concurrent bronchoalveolar lavage (BAL) and peripheral blood samples of 99 haematological patients with suspected IFD were investigated within a multicentre prospective study. Diagnostic performance of a galactomannan (GM) enzyme immune assay (EIA), a 1,3-ß-D-glucan assay (BDG), an Aspergillus PCR, and a multifungal DNA-microarray (Chip) alone or in combination were calculated. IFD were classified as proven (n=3), probable (n=34), possible (n=33), and no IFD (n=29) according to EORTC/MSG criteria. GM, PCR, and Chip showed superior diagnostic performance in BAL than in blood, whereas specificity of BDG in BAL was poor (48% (14/29)). The combination of GM (BAL) with BDG (blood) showed sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and DOR (diagnostic odds ratio) of 92% (34/37), 93% (27/29), 94%, 90%, and 153.0, respectively. Combining GM (BAL) with PCR (BAL) showed convincing diagnostic potential for diagnosing IA with sensitivity, specificity, PPV, NPV, and DOR of 85% (17/20), 97% (28/29), 94%, 90%, and 158.7. Addition of the DNA-microarray resulted in further detection of two mucormycetes infections. In 1 out of 15 Aspergillus DNA-positive samples a triazole resistance-mediating Cyp51A mutation was found. Combination of biomarkers is superior to their sole use in diagnosing IFD, particularly IA. Integrating blood and BAL samples into a diagnostic algorithm is an advantageous approach.

Effect of platelet-rich-plasma on cranial distraction osteogenesis in sheep: preliminary clinical and radiographic results.

The purpose of this study was to investigate the effect of platelet-rich-plasma (PRP) on cranial distraction osteogenesis. Standardized calvaria critical size defects (6 cm x 5 cm) were created in 16 adult female sheep. Bifocal cranial transport distraction osteogenesis with autogenous free calvaria bone grafts (2 cm x 4 cm) was performed at a rate of 1mm once daily to a total of 30 mm. The 16 sheep involved in the experiment were randomly divided into four groups, four animals in each: Group 1 (no PRP, latency 5 days); Group 2 (no PRP, latency 0 day), Group 3 (PRP, latency 5 days) and Group 4 (PRP, latency 0 day). After a consolidation phase of 6 weeks, the animals were sacrificed and specimens harvested for conventional radiological and 3D quantitative computer tomographic (3D-QCT) assessment. New bone was generated in the distraction zone in all groups. There were significantly (P < 0.05) higher densities in the proximal region of the distraction regenerate in Group 4 (PRP, latency 0 day) compared to Group 2. However, no significant differences in mean density of the total distraction regenerate were found, neither in volume of the bony regenerate between the experimental groups. This study showed that PRP only had an effect on bone regeneration if active distraction was started immediately after application of PRP in the distraction gap.

The effects of insulin and growth hormone on the release of somatomedin by the isolated rat liver.

Livers from hypophysectomized (hypox) rats were perfused with oxygenated Waymouth's medium in a system which permitted continuous recirculation for separate 30 minute periods after which fresh medium was supplied. In most experiments 6 changes of medium were carried out over a 3 hour period. The somatomedin activity of each perfusate was determined by measuring its ability to stimulate sulfate uptake in hypox rat cartilage in vitro. For comparison between experiments the results are expressed as the per cent stimulation of sulfate uptake by the perfusate compared with the unperfused buffer. Without hormonal additions there was a progressive fall in the release of somatomedin activity during the 6 periods of study. When compared with the results without hormone, the addition of 1000 muU/ml of insulin per ml of medium during the 2nd to 6th period led to a significant increase in perfusate somatomedin activity at all periods. The addition of 100 muU/ml of insulin was without significant effect. The possible inter-relationship between insulin and growth hormone in the regulation of somatomedin release was studied with a dose of bGH of 250 ng/ml which had previously been shown to be insufficient by itsel to stimulate somatomedin release. When added to a medium containing 1000 muU/ml of insulin, this dose of bGH did not significantly stimulate somatomedin release beyond that obtained with insulin alone. However, when 250 ng/ml was added to a medium containing 100 muU/ml insulin, a significant stimulation of somatomedin release was observed while the addition of each hormone separately was without significant effect. These results support the hypothesis that insulin shares with GH the regulation of somatomedin release by the liver. Differences in insulin concentration may explain some clinical situations in which somatomedin concentrations cannot be correlated with GH levels.

Highlights of a ten-year experience with the Ross procedure.

BACKGROUND: A review of a 10-year experience with the Ross procedure as a root replacement by a single group of surgeons featuring specific highlights is presented. Highlights include our results from a subset of patients with endocarditis and their management and a comparison of outcomes in patients with aortic insufficiency based on technical changes made after 5 years' experience. METHODS: The total patient group was 191, with 148 male and 43 female participants with an age range from 1 day to 69 years. Five of the patients in the 0-to-20 age group were newborns. Fifty-three of the adults were operated on for infectious endocarditis. In the total patient group 43% had aortic insufficiency, 28% had aortic stenosis, and 29% had mixed disease. RESULTS: Operative mortality was 5.2% with a late mortality of 2.6%. The actuarial survival was 90.2% at 10 years. Freedom from autograft explantation was 93.2% and freedom from homograft replacement was 98.4%. The endocarditis patients had an operative mortality of 3.8% with 100% cure of the infection. Freedom from reinfection on the autograft was 98.1%, and freedom from infection of the pulmonary homograft was 98.1%. The actuarial survival was 86.3%. CONCLUSIONS: A specific review of the patients with aortic insufficiency resulted in a failure of the autograft in 7 patients among a cohort of 41 during the first 5 years of the study. After a change in technique in which the aortic annulus is narrowed and fixed to a measured size to match the body surface area, we have had no failures in the autograft. Although these results are early, we believe that these data support the use of the autograft as an excellent choice for replacement of the aortic valve in infective endocarditis. Finally, the use of the autograft for aortic insufficiency is reasonable with fixation of the aortic annulus so that subsequent dilation does not occur.

[Angiogenesis investigations in tissue engineering. The cylinder model on the chorioallantois membrane]. / Untersuchung der Angiogenese im Tissue Engineering. Das Zylindermodell auf der Chorioallantoismembran.

INTRODUCTION: Tissue engineering (TE) applications include the isolation, culture, and seeding of cells into a suitable matrix or scaffold prior to in vivo transplantation. After transplantation, vascularization of the scaffold is a principal factor limiting cell viability for the first 6-8 days post transplantation. A model has been developed for systematic analysis of this process. METHODS: Fertilized white Leghorn eggs were incubated and opened at day 3 of incubation. Preadipocyte-seeded fibrin constructs were implanted in a specially designed plastic cylinder and placed through the opening onto the surface of the chorioallantoic membrane (CAM) at day 8 of incubation. Vascularization of the constructs by chorioallantoic blood vessels was assessed for up to 8 days post transplantation. RESULTS: The survival rate for embryos receiving constructs was about 90%. Histology confirmed transplant cell viability at day 4 post transplantation, and vascularization of the constructs by avian endothelial cells progressively increased thereafter. CONCLUSION: A new in vivo model to study the effect of angiogenesis in TE constructs including assessments of viability, proliferation, and differentiation of transplanted cells and biomaterial properties is presented. Advantages include easy access to the CAM vascular network, lack of immunocompetence, low cost, and avoidance of animal experiments.

Nilotinib is active in chronic and accelerated phase chronic myeloid leukemia following failure of imatinib and dasatinib therapy.

Nilotinib is a highly selective Bcr-Abl inhibitor approved for imatinib-resistant chronic myeloid leukemia (CML). Nilotinib and dasatinib, a multi-targeted kinase inhibitor also approved for second-line therapy in CML, have different patterns of kinase selectivity, pharmacokinetics, and cell uptake and efflux properties, and thus patients may respond to one following failure of the other. An international phase II study of nilotinib was conducted in CML patients (39 chronic phase (CP), 21 accelerated phase (AP)) after failure of both imatinib and dasatinib. Median times from diagnosis of CP or AP to nilotinib therapy were 89 and 83 months, respectively. Complete hematological response and major cytogenetic response (MCyR) rates in CP were 79% and 43%, respectively. Of 17 evaluable patients with CML-AP, 5 (29%) had a confirmed hematological response and 2 (12%) a MCyR. The median time to progression has not yet been reached in CP patients. At 18 months 59% of patients were progression-free. Median overall survival for both populations has not been reached, and the estimated 18-month survival rate in CML-CP was 86% and that at 12 months for CML-AP was 80%. Nilotinib is an effective therapy in CML-CP and -AP following failure of both imatinib and dasatinib therapy.

Abdominal actinomycosis.

A 59-year-old, healthy Croatian presented with a slowly growing tumor in the left lower abdomen, which was slightly painful on compression. He complained of neither dyspepsia nor fever. There were no pathologic findings in laboratory analysis, particularly no elevation of leukocytes or C-reactive protein. MRI of the abdomen (T1w, fat saturated, and iv-contrast) shows a diffuse contrast enhancing mass of the left abdominal wall (Figure 1a, arrow) with infiltration of the peritoneal cavity (Figure 1b, arrow). Because a malignant process was suspected the patient underwent abdominal surgery and excision of the tumor. Histopathological examination showed chronic-fibrosing and granulocytic, abscess-forming inflammation with Gram- and PAS-positive bacteria, corresponding to the diagnosis of chronic actinomycosis (Figure 1c). Following surgery, the patient was treated 1 month with iv and 6 more months with oral penicillin. The patient remained well 1 year after surgery. Actinomycosis is a rare, chronic granulomatous disease, which affects most commonly the cervicofacial and abdominal area. Actinomycetes are filamentous, gram-positive, anaerobic bacteria and commensal inhabitants of the oral cavity and intestinal tract; however, they acquire pathogenicity through invasion of the breached tissue. Because of its rarity and non-specific symptoms, abdominal actinomycosis is usually diagnosed postoperatively since most patients undergo exploratory laparotomy for a suspected neoplasm.