Endocarditis and the impact of intravenous drug use: a cohort study.

OBJECTIVES: This cohort study is a comparison of infective endocarditis in intravenous drug users (IDUs) and non-IDUs within a single tertiary centre. We aim to quantify and describe the factors that influence prognosis and microbiological characteristics. METHOD: All consecutive admissions to a tertiary referral hospital in the north of England with a diagnosis of endocarditis from April 2013 to January 2020 were identified. Outcomes were all-cause mortality at 30 days, 12 months and 3 years, length of stay and progression to surgery. RESULTS: A total of 303 cases were identified via clinical coding of which 287 cases of endocarditis were confirmed. First episode endocarditis was then confirmed in 263 episodes, 44 in IDUs and 219 in non-IDUs. Methicillin sensitive Staphylococcus aureus (MSSA) was the most common organism seen overall, significantly more so in IDU than non-IDU cases (29/44 [65.9%] vs. 51/219 [23.3%], p < .001). Overall progression to valve surgery was similar between the two groups (92/219 [42.0%] vs. 19/44[43.2%], p = .886). In IDUs 30-d survival was 93% (80-98) and 3-year survival 47% (30-63%). In non-IDU 30-d survival was 88% (83-92%) and 60% (53-67%) at 3 years. Of the 19 IDUs who underwent valve surgery 7 (37%) survived to study completion without reinfection and 8 (42%) died following recurrent endocarditis. CONCLUSIONS: We demonstrate that prognosis in IDUs is worse than previously described, particularly in those undergoing valve surgery. This is despite comparable receipt of inpatient treatment to non-IDUs as demonstrated by equal length of stay and rates of surgery. Clinicians should consider the role of addictions services on discharge to break the cycle of reinfection.

The effect of scuba diving on airflow obstruction in divers with asthma.

BACKGROUND: People with asthma are an under-represented group amongst scuba divers. Many may avoid or are advised against diving due to the potential risks, including bronchoconstriction, pulmonary barotrauma and arterial gas embolism. The aim of this study was to establish whether divers with asthma were more likely to experience reversible airways obstruction following typical scuba diving than divers without asthma. METHOD: All divers with a history of asthma attending Operation Wallacea in Honduras were identified and peak expiratory flow rates (PEF) were measured pre and immediately post dive. All dives were boat dives in tropical sea water. Scuba dives were defined as those lasting between 40 and 55 minutes to a depth of between 10 and 18 metres. Of the 356 divers attending, 22 were identified as having asthma, of whom 19 were suitable for testing. They were classified by treatment regimen: five on no treatment, 11 on salbutamol only and three on regular preventative treatment. Twenty-four divers without a history of asthma acted as a control group. RESULTS: Open-water scuba diving caused a small decrease in PEF in all populations (median decrease 4.4%, P < 0.001). Percentage decrease in PEF was significantly more in divers with asthma on regular preventative medication than in the control group (mean 9.3%, median decrease 6% vs. mean 3.1%, median 4.3% P = 0.039). CONCLUSION: These findings support the view that asthmatics are more susceptible to airway changes following scuba diving. Differences to previous studies are likely due to environmental conditions, including dive depth.

Mutations in RAB39B cause X-linked intellectual disability and early-onset Parkinson disease with α-synuclein pathology.

Advances in understanding the etiology of Parkinson disease have been driven by the identification of causative mutations in families. Genetic analysis of an Australian family with three males displaying clinical features of early-onset parkinsonism and intellectual disability identified a ∼45 kb deletion resulting in the complete loss of RAB39B. We subsequently identified a missense mutation (c.503C>A [p.Thr168Lys]) in RAB39B in an unrelated Wisconsin kindred affected by a similar clinical phenotype. In silico and in vitro studies demonstrated that the mutation destabilized the protein, consistent with loss of function. In vitro small-hairpin-RNA-mediated knockdown of Rab39b resulted in a reduction in the density of α-synuclein immunoreactive puncta in dendritic processes of cultured neurons. In addition, in multiple cell models, we demonstrated that knockdown of Rab39b was associated with reduced steady-state levels of α-synuclein. Post mortem studies demonstrated that loss of RAB39B resulted in pathologically confirmed Parkinson disease. There was extensive dopaminergic neuron loss in the substantia nigra and widespread classic Lewy body pathology. Additional pathological features included cortical Lewy bodies, brain iron accumulation, tau immunoreactivity, and axonal spheroids. Overall, we have shown that loss-of-function mutations in RAB39B cause intellectual disability and pathologically confirmed early-onset Parkinson disease. The loss of RAB39B results in dysregulation of α-synuclein homeostasis and a spectrum of neuropathological features that implicate RAB39B in the pathogenesis of Parkinson disease and potentially other neurodegenerative disorders.

Accuracy of cause of death determination without forensic autopsy examination.

Medical examiners and coroners commonly determine cause and manner of death without an autopsy examination. Some death certificates generated in this way may not state the correct cause and manner of death. From the case files of the Department of Forensic Medicine in Sydney, Australia, the authors retrospectively reviewed investigative information of all cases in a 6-month period that were initially considered natural deaths (429). The authors, blinded to autopsy results, accepted 261 cases as appropriate for certification without autopsy and assigned a cause of death to each. Per standard local practice, all cases had been autopsied. The actual causes of death as determined by autopsy were then revealed and compared with the presumed causes of death. Most presumed and actual causes of death were cardiovascular (94% and 80%, respectively). The majority of presumed causes of death were listed as ASCVD as the cases lacked features of a more specific cardiovascular process. A large majority of cases had a presumed cause of death of ischemic heart disease based on individual case details. The actual causes of death demonstrated a large breadth of cardiovascular and noncardiovascular disease processes, even though ischemic heart disease accounted for 62% of deaths. The presumed cause of death was completely wrong in 28% of cases. A nonnatural manner of death was present in 3% of cases. This study demonstrates that experienced forensic pathologists may generate erroneous death certificates for cases that are not autopsied.