Absence of chromosome heterogeneity between classical Fanconi's anemia and the Estren-Dameshek type

Chromosome investigations were carried out in 7 patients with Fanconi's anemia, type Estren-Dameshek. The frequency and types of chromosome instability found in cultured lymphocytes were in accord with those detected in individuals with classical Fanconi's anemia. The break-point distribution indicates a significant excess of breaks in chromosomes No. 1, 2, and 7 and a deficit in No. 18 and X and Y chromosomes. There was a clear clustering of breaks at certain locations in chromosomes No. 1, 2, 3, 7, 9, and 14. The location of the breaks with respect to the bands demonstrated an almost exclusive involvement of the lighter bands, regardless of the banding method used. These results suggest that most breaks take place in the interbands between the G and R bands. In all patients, chromosome instability was less frequent in direct bone marrow preparations than in lymphocyte cultures. However, cultured bone marrow cells showed a significant increase of chromosome aberrations. On the whole, the chromosome data derived from this series of patients are in agreement with those obtained in individuals with classical Fanconi's anemia and give no support to the idea of cytogenetic heterogeneity between subjects affected by these two forms of childhood aplastic anemia.     

Governing through problems: the formulation of policy on amphetamine-type stimulants (ATS) in Australia

Producing and implementing credible and effective policies on illicit drug use is generally seen as an important aspect of health governance in the West. Yet the controversy surrounding illicit drug use means this is no easy task. With public opinion perceived by policy makers to be set against illicit drug use, and understandings of its effects tending towards generalisation and pathologisation, the need for timely and rational responses is considered self evident. These responses are, however, regularly criticised as driven as much by electoral politics and expedience as by research findings or expert opinion. Destined to receive close critical scrutiny from all sides, these policies, and the processes undertaken to develop them, are obliged to negotiate a complex political domain. Despite this scrutiny, and the pressure it brings to bear on the policy-making process, little scholarly attention has been paid to the area to date. In this article, we examine in detail one important area of illicit drug policy - the use of amphetamine-type stimulants (ATS) in Australia. We draw on the international critical literature on the ATS problem to situate our analysis. We note that ideas of 'panic', including Cohen's notion of moral panic, have been used here to good effect, but, aiming to acknowledge the complexities of policy, we turn to poststructuralist methods of policy analysis to pursue a different approach. Following Bacchi's observation that 'we are governed through problematisations rather than policies' (2009, p. xi), we ask how the problem of ATS use has been formulated in policy. We examine key state and national policy documents, and two central themes found in them - causation and evidence - to identify the specific strategies used to authorise the recommendations and measures presented as following from the problem of ATS use. In doing so, we clarify important ways in which policy may at times work to obscure the limits of its legitimacy.     

Treatment of chronic pain with nerve blocks and stimulation

Nerve blocks and impulse augmentation represent two relatively noninvasive somatic procedures of use in the treatment of some chronic pain patients. In this paper the author outlines the clinical evidence for these procedures and the nature of the procedures. The author argues for their usefulness in modulating pain and their place within a more complete multi-disciplinary program.     

Comparison of Time to Next Treatment,Health Care Resource Utilization,and Costs in Patients with Chronic Lymphocytic Leukemia Initiated on Front-line Ibrutinib or Chemoimmunotherapy

BackgroundStudies assessing ibrutinib’s economic burden versus chemoimmunotherapy (CIT) focused on pharmacy costs but not medical costs. This study compared time to next treatment (TTNT), health care resource utilization (HRU), and total direct costs among patients with chronic lymphocytic leukemia (CLL) initiating front-line ibrutinib single agent (Ibr) or CIT.Materials and MethodsOptum Clinformatics Extended DataMart De-Identified Databases were used to identify adults with ≥ 2 claims with a CLL diagnosis initiating front-line Ibr or CIT from February 12, 2014 to June 30, 2017. Inverse probability of treatment weighting was used to control for potential differences in baseline characteristics between the Ibr and CIT cohorts. Two periods were considered: entire front-line therapy (until initiation of second-line therapy) and first 6 months of front-line therapy. Comparisons with a subgroup of CIT patients initiating bendamustine/rituximab (BR) were also conducted.ResultsTTNT was significantly longer for Ibr (N = 322) relative to CIT (N = 839; hazard ratio, 0.54; P = .0163; Kaplan-Meier rates [24 months]: Ibr = 88.6%, CIT = 75.9%) and the subset of CIT patients treated with BR (N = 455; hazard ratio, 0.54; P = .0208; Kaplan-Meier rates [24 months]: Ibr = 89.0%, BR = 79.0%). During the entire front-line therapy, Ibr patients had significantly fewer monthly days with outpatient visits (rate ratio = 0.75; P = .0200). Ibrutinib’s higher pharmacy costs (mean monthly cost difference [MMCD] = $6,849; P < .0001) were offset by lower medical costs (MMCD = ?$10,615; P < .0001), yielding net savings (MMCD = ?$3,766; P < .0001) versus CIT. Ibr was associated with net savings (MMCD = ?$5,569; P < .0001) versus BR. Cost savings and reductions in HRU were more pronounced during the first 6 months of front-line therapy.ConclusionDuring front-line CLL treatment, Ibr was associated with longer TTNT, fewer monthly days with outpatient visits, and net monthly total cost reduction versus CIT and BR.     

Complicating cure: How Australian criminal law shapes imagined post-hepatitis C futures

In recent years, highly tolerable and effective drugs have emerged promising a radical new ‘post-hepatitis C’ world. Optimism about medical cure potentially overlooks discrimination and stigma associated with hepatitis C and injecting drug use. Legal frameworks are especially relevant to hepatitis futures, since the law has the potential to reinforce or alleviate stigma and discrimination. This article explores how hepatitis C figures in Australian criminal law and with what potential effects. Drawing on Bruno Latour’s work on legal veridiction, Alison Kafer’s work on futurity and disability and case law data collected for a major study on hepatitis C and post-cure lives, we explore how the criminal law handles hepatitis C in the age of cure. We find that law complicates cure, constituting hepatitis C as disabling despite the advent of effective cures. The law steadfastly maintains its own approach to disease, disability and illness, untouched by medical and scientific developments, in ways that might complicate straightforwardly linear imaginaries of cure, transformation and progress of the kind that dominate biomedicine. We explore the implications of these tensions between law and medicine.     

Chikungunya Infection in Solid Organ Transplant Recipients

Background

Chikungunya virus (CHIKV) is an emerging mosquito-borne disease that causes acute febrile polyarthralgia and arthritis. CHIKV has spread rapidly to the Americas and, in Brazil, autochthonous cases are increasingly been reported. Solid organ transplant (SOT) recipients who travel to or live in CHIKV endemic areas are under high risk of acquiring the disease. Few data exist regarding the clinical characteristics of CHIKV infections in this population. We report the first case series of CHIKV infection in SOT recipients.

Gorham–Stout disease with involvement of the jaws: a systematic review

The purpose of this study was to systematically review all published cases of Gorham–Stout disease (GSD) involving the jaws and to identify the clinico-radiological and histopathological features associated with persistence of the lesions, as well as the best treatment options available. An electronic search was undertaken in November 2018. Eligibility criteria included publications with sufficient information to confirm the diagnosis. Eighty-six publications reporting 89 cases were included. Features observed included symptomatic disease (51.1%), swelling (34.1%), pathological fracture (31.8%), history of previous trauma (32.1%), high alkaline phosphatase levels (24.3%), and predominance of vascular tissue (72.4%). Nearly a quarter of the patients were only followed up, with no treatment implemented. Most treatments consisted of some type of surgery with/without additional therapies (42.0%), drugs (20.5%), and radiotherapy (14.8%). Half of the cases were found to persist after some treatment modality, and five patients died. Among the variables investigated, only a lesion crossing the midline showed an association with persistence of the disease. There remains much to understand about GSD, a rare condition with no clear consensus on the aetiopathology, an unpredictable clinical course, and no standard treatment. The high rate of persistence after treatment was found to be associated only with the lesion crossing the midline.     

Evidence-making controversies: the case of hepatitis C treatment and the promise of viral elimination

Contested science presents a problem for ‘evidence-based’ public health intervention. Taking a perspective that treats evidence as constituted through the practices which make it, we treat controversies in public health science as events of ‘evidence-making’ intervention. We look back on a recent controversy in evidence-making regarding the curative potential of new treatments for hepatitis C. The controversy concerned the publication of a systematic review conducted by the Cochrane Collaboration. We explore how published responses critical of the review enact their evidence-making. We do this to illuminate how moments of controversy offer useful sites of evidencing-making investigation for public health research. We identify four intersecting objects of evidence-making in the published responses: cure; expertise; hope; and morality. We reflect on how different experts perform evidence differently, how these evidence performances are in friction yet incorporate one another, and how such evidence-making practice fuses together different knowledge forms within and beyond science. Controversy makes visible the multiplicity and fluidity of evidence objects which might otherwise be constituted as singular and robust. A prime matter of concern in this exemplar is ‘cure’ and the protection of curative potential linked to new treatments in the presence of evidence uncertainty. We use our case study to argue for the benefits of an ‘evidence-making intervention’ approach to the study and use of evidence in critical public health research.