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Legalised non-consensual sterilisation - eugenics put into practice before 1945, and the aftermath. Part 2: Europe.

This article deals with the nine European nations which legalised non-consensual sterilisation during the interwar years, thus completing the review, the first part of which was published in an earlier issue of this Journal. Like we did for North America, Japan and Mexico, countries concerned are addressed in chronological order, as practices in one of these influenced policies in others, involved later. For each, we assess the continuum of events up to the present time. The Swiss canton of Vaud was the first political entity in Europe to introduce a law on compulsory sterilisation of people with intellectual disability, in 1928. Vaud's sterilisation Act aimed at safeguarding against the abusive performance of these procedures. The purpose of the laws enforced later in eight other European countries (all five Nordic countries; Germany and, after its annexation by the latter, Austria; Estonia) was, on the contrary, to effect the sterilisation of large numbers of people considered a burden to society. Between 1933 and 1939, from 36,000 to 400,000 residents (two-thirds of whom were women) were compulsorily sterilised in Nazi Germany. In Sweden, some 32,000 sterilisations carried out between 1935 and 1975 were involuntary. It might have been expected that after the Second World War ended and Nazi legislation was suspended in Germany and Austria, including that regulating coerced sterilisation, these inhuman practices would have been discontinued in all nations concerned; but this happened only decades later. More time still went by before the authorities in certain countries officially acknowledged the human rights violations committed, issued apologies and developed reparation schemes for the victims' benefit.

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Progressive multifocal leukoencephalopathy after fingolimod treatment.

We describe the characteristics of the 15 patients with fingolimod-associated progressive multifocal leukoencephalopathy (PML) identified from the Novartis data safety base and provide risk estimates for the disorder.

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Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia.

Donor availability and transplantation-related risks limit the broad use of allogeneic hematopoietic-cell transplantation in patients with transfusion-dependent β-thalassemia. After previously establishing that lentiviral transfer of a marked β-globin (β) gene could substitute for long-term red-cell transfusions in a patient with β-thalassemia, we wanted to evaluate the safety and efficacy of such gene therapy in patients with transfusion-dependent β-thalassemia.

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Discontinuation of antiviral prophylaxis increased the risk of hepatitis B virus reactivation in glomerulonephritis patients under immunotherapy: a real-life observation.

Antiviral prophylaxis is proved to be effective in reducing the risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-positive patients under immunotherapy. But outcomes referring to discontinuation of antiviral prophylaxis in these patients are lacking.

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Incidence, Predictors, and Outcomes Associated With Hypotensive Episodes Among Heart Failure Patients Receiving Sacubitril/Valsartan or Enalapril: The PARADIGM-HF Trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure).

In PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure), heart failure treatment with sacubitril/valsartan reduced the primary composite outcome of cardiovascular death or heart failure hospitalization compared with enalapril but resulted in more symptomatic hypotension. Concern on hypotension may be limiting use of sacubitril/valsartan in appropriate patients.

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In vitro cytotoxicity of galvanically coupled magnesium-titanium particles on human osteosarcoma SAOS2 cells: A potential cancer therapy.

Osteosarcoma is a malignant bone cancer that occurs mostly in children and young adults. This study investigated the cytotoxicity of Mg and Mg-Ti microparticles to human osteosarcoma cells. Osteosarcoma cells were killed in a dosage-dependent manner when cells, with a cell seeding density of 30,000 cells/cm , were cultured with 0 to 2500 µg/mL of Mg or Mg-Ti in cell culture media for 24-72 h. Mg-Ti killed cells more effectively, where 1250 µg/mL of Mg-Ti killed cells completely by 24 h, while 2500 µg/mL of Mg killed nearly all cells, but not all. Killing due to particle corrosion occurred mostly during the first 24 h, and so the percent cell viability between 24 and 72 h showed not much variability. However, the measurement of live and dead cell numbers, over the timeframe of 24-72 h, showed more insight, such as cell recovery. If particle concentrations were low, the number of live cells increased after 24 h, indicating cell proliferation. If particle concentrations were high, the number of live cells either remained steady or decreased, indicating cell quiescence or continued killing, respectively. Increase in the number of dead cells also indicated killing, while plateau meant discontinued killing. In addition, repeated killing of recovered cells exhibited the same dose-dependent killing profile as the initial experiment, implying little development of cell resistance to treatment. These results, together, show that osteosarcoma cells are susceptible to killing by way of exposure to corroding particles, showing highly effective killing using the galvanic couple of Mg-Ti. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018.

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Twelve-month clinical outcomes of 206 patients with chronic pulmonary aspergillosis.

There is a paucity of evidence surrounding the optimal antifungal therapy for use in chronic pulmonary aspergillosis (CPA) and the duration of therapy remains unclear. We retrospectively evaluated treatment outcomes, including change in quality of life scores (St George's Respiratory Questionnaire (QoL)), weight and Aspergillus IgG at 6 and 12 months following initiation of therapy in a cohort of 206 CPA patients referred to the UK National Aspergillosis Centre (NAC), Manchester between April 2013 and March 2015. One hundred and forty-two patients (69%) were azole naïve at presentation and 105 (74%) (Group A) were commenced on itraconazole, 27 (19%) on voriconazole, and 10 (7%) were not treated medically. The remainder (64 patients, 31%) had previously trialled, or remained on, azole therapy at inclusion (Group B) of whom 46 (72%) received itraconazole, 16 (25%) voriconazole, and 2 (3%) posaconazole. Initial therapy was continued for 12 months in 78 patients (48%) of those treated; the azole was changed in 62 (32%) patients and discontinued in 56 (29%) patients for adverse reactions (32, 57%), azole resistance (11, 20%), clinical failure (8, 14%) or clinical stability (5, 9%). Azole discontinuation rates were higher in Group B than in Group A (42% vs. 22%, p = 0.003). For all patients who survived, weight increased (median of 62.2Kg at baseline, to 64.8 at 12 months), mean Aspergillus IgG declined from 260 (baseline) to 154 (12 months) and QoL improved from 62.2/100 (baseline) to 57.2/100 (12 months). At 12 months, there was no difference in median survival between Groups A and B (95% vs. 91%, p = 0.173). The rate of emergence of resistance during therapy was 13% for itraconazole compared to 5% for voriconazole. Bronchial artery embolization was done in 9 (4.4%) patients and lobectomy in 7 (3.2%). The optimal duration of azole therapy in CPA is undetermined due to the absence of evidenced based endpoints allowing clinical trials to be undertaken. However we have demonstrated itraconazole and voriconazole are modestly effective for CPA, especially if given for 12 months, but fewer than 50% of patients manage this duration. This suggests extended therapy may be required for demonstrable clinical improvement.

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Overview of Systemic Candida Infections in Hospital Settings and Report of Candida After DMEK Successfully Treated With Antifungals and Partial Graft Excision.

To report novel surgical and medical management of intraocular and corneal infection with Candida glabrata that manifested 3 months after Descemet membrane endothelial keratoplasty (DMEK) and to review demographic reasons for increasing fungal contamination of donor tissue.

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Cefazolin-Related Acute Interstitial Nephritis with Associated Nephrotic-Range Proteinuria: A Case Report.

A 67-year-old male with history of well controlled type 2 diabetes mellitus and hypertension developed acute interstitial nephritis (AIN) with nephrotic-range proteinuria during treatment with cefazolin for methicillin-sensitive Staphylococcus aureus and Group B Streptococcus (GBS) bacteremia. The patient received intravenous cefazolin 2 g every 8 h for 4 weeks prior to presentation to the emergency department with abdominal distension, nausea, and vomiting. Investigations revealed a serum ascites albumin gradient of 1.0 with total protein of 1.8 g/dL suggestive of nephrotic syndrome, which was confirmed with a spot urine protein/creatinine ratio that estimated 7.95 g of protein per day. Serum creatinine was elevated compared with baseline. Urine studies showed sterile pyuria with 3+ protein and eosinophiluria. The patient was diagnosed with AIN with nephrotic-range proteinuria associated with cefazolin use. Cefazolin was discontinued and, within a couple of days, the patient's creatinine stabilized. He was discharged with prednisone 60 mg once a day for 10 days with a taper over 2 weeks for his AIN. The patient's creatinine and proteinuria slowly decreased over the next couple of weeks, however, did not recover to baseline. A Naranjo assessment score of 6 was obtained, indicating a probable relationship between the patient's AIN with nephrotic-range proteinuria and his use of cefazolin.

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Preventable statin adverse reactions and therapy discontinuation. What can we learn from the spontaneous reporting system?

Statin treatment is often associated with poor adherence, which may be due to the onset of adverse drug reactions (ADRs). We investigated on potential risk factors related to preventable cases of statin-induced ADRs and to the discontinuation of statin therapy.

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