PEPDar: A randomized prospective noninferiority study of ritonavir-boosted darunavir for HIV post-exposure prophylaxis.

OBJECTIVES: PEPDar compared the tolerability and safety of ritonavir-boosted darunavir (DRV/r)-based post-exposure prophylaxis (PEP) with the tolerability and safety of standard of care (SOC). The primary endpoint was the early discontinuation rate among the per-protocol population. METHODS: PEPDar was an open-label, randomized, multicentre, prospective, noninferiority safety study. Subjects were stratified by type of event (occupational vs. nonoccupational, i.e. sexual) and were randomized to receive DRV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) or SOC PEP. Twenty-two private or university HIV clinics in Germany participated. Subjects were ≥ 18 years old and had documented or potential HIV exposure and indication for HIV PEP. They initiated PEP not later than 72 h after the event and were HIV negative. RESULTS: A total of 324 subjects were screened, the per-protocol population was 305, and 273 subjects completed the study. One hundred and fifty-five subjects received DRV/r-based PEP and 150 subjects received ritonavir-boosted lopinavir (LPV/r)-based PEP for 28-30 days; 298 subjects also received tenofovir/emtricitabine. The early discontinuation rate in the DRV/r arm was 6.5% compared with 10.0% in the SOC arm (P = 0.243). Adverse drug reactions (ADRs) were reported in 68% of DRV/r subjects and 75% of SOC subjects (P = 0.169). Fewer DRV/r subjects (16.1%) had at least one grade 2 or 3 ADR compared with SOC subjects (29.3%) (P = 0.006). All grades of diarrhoea, nausea, and sleep disorders were significantly less frequent with DRV/r, while headache was significantly more frequent. No HIV seroconversion was reported during follow-up. CONCLUSIONS: Noninferiority of DRV/r to SOC was demonstrated. DRV/r should be included as a standard component of recommended regimens in PEP guidelines.

Avulsive axillary artery injury in reverse total shoulder arthroplasty.

In addition to neurologic injuries such as peripheral nerve palsy, axillary vessel injury should be recognized as a possible complication of reverse total shoulder arthroplasty. Limb lengthening associated with Grammont-type reverse total shoulder arthroplasty places tension across the brachial plexus and axillary vessels and may contribute to observed injuries. The Grammont-type reverse total shoulder arthroplasty prosthesis reverses the shoulder ball and socket, shifts the shoulder center of rotation distal and medial, and lengthens the arm. This alteration of native anatomy converts shearing to compressive glenohumeral joint forces while augmenting and tensioning the deltoid lever arm. Joint stability is enhanced; shoulder elevation is enabled in the rotator cuff­deficient shoulder. Arm lengthening associated with reverse total shoulder arthroplasty places a longitudinal strain on the brachial plexus and axillary vessels. Peripheral nerve palsies and other neurologic complications of reverse total shoulder arthroplasty have been documented. The authors describe a patient with rotator cuff tear arthropathy and a history of radioulnar synostosis who underwent reverse total shoulder arthroplasty complicated by intraoperative injury to the axillary artery and postoperative radial, ulnar, and musculocutaneous nerve palsies. Following a seemingly unremarkable placement of reverse shoulder components, brisk arterial bleeding was encountered while approximating the incised subscapularis tendon in preparation for wound closure. Further exploration revealed an avulsive-type injury of the axillary artery. After an unsuccessful attempt at primary repair, a synthetic arterial bypass graft was placed. Reperfusion of the right upper extremity was achieved and has been maintained to date. Postoperative clinical examination and electromyographic studies confirmed ongoing radial, ulnar, and musculocutaneous neuropathies.

[Papulovesicular exanthem after a safari in South Africa]. / Papulovesikuläres Exanthem nach einer Südafrika-Safari.

A 68-year-old man presented with a papulovesicular exanthem, fever and malaise after a safari in South Africa. Based on the history, the typical clinical picture with an exanthema and eschar as well as the detection of antibodies against rickettsioses of the spotted fever group, we diagnosed African tick-bite fever which is due to R. africae. During treatment with doxycycline 200 mg/d, all symptoms resolved completely within 11 days. Rickettsioses should always be considered in patients presenting with exanthema, fever and malaise. Particularly the presence of one or multiple eschars on the skin manifesting as erythematous plaques with central necrosis is a pathognomic sign. The serological detection of antibodies against rickettsia species of the spotted fever group is the established diagnostic standard. Due to extensive cross-reactions it is not possible to distinguish between the members of one rickettsial group. Furthermore antibody titers rise late in the disease, frequently 2 or 3 weeks after the onset of symptoms. This underscores the importance of the clinical diagnosis.

Improvement in the outcome of invasive fusariosis in the last decade.

Invasive fusariosis (IF) has been associated with a poor prognosis. Although recent series have reported improved outcomes, the definition of optimal treatments remains controversial. The objective of this study was to evaluate changes in the outcome of IF. We retrospectively analysed 233 cases of IF from 11 countries, comparing demographics, clinical findings, treatment and outcome in two periods: 1985-2000 (period 1) and 2001-2011 (period 2). Most patients (92%) had haematological disease. Primary treatment with deoxycholate amphotericin B was more frequent in period 1 (63% vs. 30%, p <0.001), whereas voriconazole (32% vs. 2%, p <0.001) and combination therapies (18% vs. 1%, p <0.001) were more frequent in period 2. The 90-day probabilities of survival in periods 1 and 2 were 22% and 43%, respectively (p <0.001). In period 2, the 90-day probabilities of survival were 60% with voriconazole, 53% with a lipid formulation of amphotericin B, and 28% with deoxycholate amphotericin B (p 0.04). Variables associated with poor prognosis (death 90 days after the diagnosis of fusariosis) by multivariable analysis were: receipt of corticosteroids (hazard ratio (HR) 2.11, 95% CI 1.18-3.76, p 0.01), neutropenia at end of treatment (HR 2.70, 95% CI 1.57-4.65, p <0.001), and receipt of deoxycholate amphotericin B (HR 1.83, 95% CI 1.06-3.16, p 0.03). Treatment practices have changed over the last decade, with an increased use of voriconazole and combination therapies. There has been a 21% increase in survival rate in the last decade.

Therapy and prophylaxis of opportunistic infections in HIV-infected patients: a guideline by the German and Austrian AIDS societies (DAIG/ÖAG) (AWMF 055/066).

INTRODUCTION: There was a growing need for practical guidelines for the most common OIs in Germany and Austria under consideration of the local epidemiological conditions. MATERIALS AND METHODS: The German and Austrian AIDS societies developed these guidelines between March 2010 and November 2011. A structured Medline research was performed for 12 diseases, namely Immune reconstitution inflammatory syndrome, Pneumocystis jiroveci pneumonia, cerebral toxoplasmosis, cytomegalovirus manifestations, candidiasis, herpes simplex virus infections, varizella zoster virus infections, progressive multifocal leucencephalopathy, cryptosporidiosis, cryptococcosis, nontuberculosis mycobacteria infections and tuberculosis. Due to the lack of evidence by randomized controlled trials, part of the guidelines reflects expert opinions. The German version was accepted by the German and Austrian AIDS Societies and was previously published by the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF; German Association of the Scientific Medical Societies). CONCLUSION: The review presented here is a translation of a short version of the German-Austrian Guidelines of opportunistic infections in HIV patients. These guidelines are well-accepted in a clinical setting in both Germany and Austria. They lead to a similar treatment of a heterogeneous group of patients in these countries.

Reverse total shoulder arthroplasty in obese patients.

PURPOSE: To determine function and complications after reverse total shoulder arthroplasty (RTSA) in obese patients compared with a control group of nonobese patients. METHODS: Between 2005 and 2011, we performed 76 RTSAs in 17 obese, 36 overweight, and 23 normal weight patients, based on World Health Organization body mass index classification. We reviewed the charts for age, sex, body mass index, date of surgery, type of implant, type of incision, length of stay, comorbidities, surgical time, blood loss, American Society of Anesthesiologists score, shoulder motion, scapular notching, and postoperative complications. Complications and outcomes were analyzed and compared between groups. RESULTS: Reverse total shoulder arthroplasty in obese patients was associated with significant improvement in range of motion. Complication rate was significantly greater in the obese group (35%), compared with 4% in the normal weight group. We found no significant differences between scapular notching, surgical time, length of hospitalization, humeral component loosening, postoperative abduction, forward flexion, internal and external rotation, pain relief, or instability between groups. CONCLUSIONS: Our results show that obese patients have significant improvement in motion after RTSA but are at an increased risk for complication. Obesity is not a contraindication to RTSA, but obese patients need to understand fully the increased risk of complication with RTSA. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

[Interdisciplinary management of a large Legionella outbreak in Germany]. / Interdisziplinäres Management eines länderübergreifenden Legionellenausbruchs.

Between December 2009 and the end of January 2010, the largest hitherto known outbreak of Legionella in Germany took place in the cities of Ulm and Neu-Ulm. Of a total of 64 patients involved, 60 patients had to be hospitalized, and 5 patients died from the infection. This event was caused by a wet cooling tower of a large air conditioning system in the city center of Ulm. The search for the source of the Legionella emission was extremely difficult, since these plants are neither notifiable nor subject to authorization in Germany. We report about the search for the source and the measures to control the outbreak. We also discuss communication and coordination during these investigations. Regulatory measures as proposed by the World Health Organization (WHO) and the European Network for Legionellosis (EWGLI) and already implemented in numerous other European countries would be desirable to prevent such outbreaks in the future.

Preliminary report: outbreak of Legionnaires disease in the cities of Ulm and Neu-Ulm in Germany, December 2009 - January 2010.

Currently an investigation is ongoing to explore and control an outbreak of Legionnaires disease, affecting 65 people as of 22 January 2010, in the cities of Ulm and Neu-Ulm, south-west Germany. A hitherto unidentified wet cooling system in these twin cities is considered as the most likely source of infection.

Benign nerve tumors of the hand and the forearm.

We used a hand surgeon's 1978-1994 pathology reports to retrospectively review the incidence, preoperative and postoperative diagnoses, and presenting signs and symptoms of benign nerve tumors. Twenty-four (11.5%) of our series of 208 soft-tissue tumors of the hand and the forearm were benign nerve tumors. Nerve tumors were the third most common tumor after giant cell tumors of tendon sheath and inclusion cysts. Correct preoperative diagnosis was made in only 1 (4.2%) of the 24 cases. Schwannomas and neurofibromas were equally distributed (12 each), and 2 cases of neurofibromatosis (8.3%) were documented. Two (16.7%) of the 12 patients with schwannomas and 4 (33.3%) of the 12 patients with neurofibromas had neurologic symptoms. Six (85.7%) of the 7 digital tumors were dorsally located. In the literature, incidence of benign nerve tumors is much lower (ie, 1%-5%), and preoperative diagnosis consistently incorrect in our study. Incidence of neurologic symptoms (numbness, paresthesia) as presenting symptoms was higher in our study than previously documented. Although benign nerve tumors are most often located on the volar surface of the hand, 25% of the lesions we found were on the dorsal surface of the fingers.

Expanded scoring criteria for the design fluency test: reliability and validity in neuropsychological and college samples.

In spite of sensitivity to right frontal lobe dysfunction, the Design Fluency Test (DFT) has been limited by one global score with little psychometric data. This study developed an expanded scoring system with standardized instructions for multiple dimensions of design performance and provided reliability and validity data in a college (n = 64) and diverse neuropsychological sample (n = 165). The scoring system allowed reliable scoring of number of novel designs, complexity of designs, variations in designs, and concrete, frankly perseverative, and scribbled responses. Performances for a college sample were relatively stable at 1-month retest, but showed practice effects for number of novel designs and complexity. Two principal components showed modest, expected relationships to other neuropsychological measures in the clinical sample. Clinical subjects with a history of closed-head injury or dementing disorder showed impaired DFT performances, with complexity the most sensitive indicator of impairment.

The limping child: a manifestation of acute leukemia.

Nine patients who presented to our institution with the chief complaint of a limp and no history of trauma were subsequently diagnosed with leukemia. A review of these patients identified clinical and laboratory findings that helped to establish the diagnosis. The presence of an antalgic gait with complaints of pain of variable intensity and duration, an irritable hip or knee, a mild to moderate elevation in body temperature, lymphadenopathy, hepatosplenomegaly, an increased erythrocyte sedimentation rate, thrombocytopenia, anemia, decreased neutrophils, increased lymphocytes, or blast cells on the peripheral blood smear should cause the physician to suspect leukemia in a limping child. Bone marrow biopsy confirms the diagnosis.

[The evaluation of dry chemical laboratory methods. Their value within the framework of step-by-step diagnosis in general medicine]. / Bewertung trockenchemischer Labormethoden. Stellenwert im Rahmen der Stufendiagnostik in der Allgemeinmedizin.

In a prospective study involving eleven general practices, dry-chemical laboratory methods were compared with wet-chemical methods in the establishment of the diagnosis. The study included 658 patients in whom defined liver disease, lipid metabolic disturbances, diabetes mellitus or hyperuricemia were clinically suspected. In the "dry chemistry" group, between 12 and 29% fewer basic examinations (ESR, Hb, erythrocytes, leukocytes) were performed than in the "wet chemistry" group. In addition the number of analyses per patient in the so-called search program and among the subsequently requested laboratory analyses were also lower by about 21% in the "dry chemistry" group. This indicates that through the use of "dry chemistry", laboratory examinations can be used with greater selectivity. A further advantage of "dry chemistry" is the appreciably shorter time required to establish and report the diagnosis.

[Programmed after care of breast cancer. Results of a follow-up model after 2 years later]. / Programmierte Nachsorge beim Mammakarzinom. Ergebnisse eines Nachsosgemodells nach zwei Jahren.

In two years 359 patients with breast cancer were evaluated in a cooperative follow-up programme in which the organisation and documentation were done in hospital, the medical care and investigations by the family doctor. 72% of 316 evaluable patients remained in regular control. 63% chose the family doctor for follow-up while the others preferred hospital. In the first year 71-80% attended their appointments, in the second year 60-74%. Statistically significant parameters for detection of metastases were the following: general condition, local signs, palpable lymph nodes, markedly increased ESR, alkaline phosphatase, chest radiograph, and bone scan. Cumulative freedom from recurrence in the whole group diminished from 1.0 to 0.631 in 25 months, cumulative survival from 1.0 to 0.876 in 20 months. In both groups there were significant differences between stages I, II and III. Forty patients (16%) out of 250 developed a recurrence within 2.25 years, in five (2%) a second carcinoma developed. There was a high proportion of local recurrences (20 out of 40) and these often led to generalised disease (11 out of 20).