Medical complications of hemophilia

The modern, comprehensive care of patients with hemophilia requires an awareness that complications other than those caused by acute hemorrhage can occur. The use of newer, more potent plasma concentrates has been accompanied by an increased incidence of liver disease in transfusion-requiring hemophiliacs. The progression to chronic active hepatitis and cirrhosis are particularly ominous developments in these patients. There is also a high incidence of urinary tract abnormalities in hemophiliacs, though the long-term consequences of these abnormalities are unknown. Furthermore, it must be remembered that urinary tract disorders unrelated to hemorrhage, such as nephrolithiasis, tumors, and nephritis, can occur in patients with hemophilia and may be mistaken for hemorrhage. Finally, hypertension occurs more frequently in patients with hemophilia than in the general population and may in part contribute to the occurrence of bleeding within the central nervous system. Methods for evaluating and treating these various disorders are discussed. Greater awareness of these potentially treatable medical complications will improve further the quality of care in hemophilia.     

Water-bone transmission of influenza A viruses?

The isolation of influenza A viruses from unconcentrated lake water and from fecal samples on the shore of these lakes is reported for the first time. Influenza A viruses, representative of most of the major antigenic subtypes, co-circulate in ducks on the lakes.     

Utility of Autopsy among Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: One Last Chance to Learn?

Autopsy may confirm clinical diagnoses or identify conditions that were not suspected prior to a patient's death. Previous studies evaluating the utility of autopsy in hematopoietic stem cell transplant (HSCT) recipients yielded conflicting results.We conducted a retrospective cohort study of children (<18 years of age) undergoing allogeneic HSCT at Duke University who died of any cause between January 1, 1995, and December 31, 2016. We evaluated associations between patient characteristics and autopsy performance using chi-square or Fisher exact tests. We reviewed autopsy reports to determine the concordance between preautopsy causes of death and pathological diagnoses identified on autopsy. We classified unexpected diagnoses on autopsy using criteria developed by Goldman et al. We evaluated for temporal changes in the autopsy consent rate and the frequency of unexpected diagnoses on autopsy using Cochran-Armitage tests.During the 22-year study period, 475 patients died and had data available on autopsy performance, and 130 (27%) of these patients underwent autopsy. The autopsy consent rate declined over time (P < .0001), with autopsies being performed for 40% of deaths in 1995 to 1999 and 17% of deaths in 2009 to 2016. White patients were more likely to undergo autopsy than nonwhite patients (P?=?.03). There were no associations between autopsy performance and patient age, sex, HSCT indication, or HSCT donor. Unexpected diagnoses were identified in 31 (24%) autopsies. The proportion of autopsies with an unexpected diagnosis did not change during the study period (P?=?.45). However, infectious diagnoses that would have led to a change in management were more frequently identified on autopsies in 1995 to 2003 than in 2004 to 2016 (20% versus 0%; P?=?.001).The autopsy consent rate for pediatric HSCT recipients at our institution has declined substantially over the past several decades. The utility of autopsy in this patient population remains high despite a reduction in the identification of unexpected infections.     

Elevated skeletal muscle sodium-potassium-ATPase in human obesity

To determine whether muscle sodium-potassium-ATPase activity, an expression of energy turnover, is increased in obesity, we studied a group of nine non-obese and seven obese subjects undergoing elective cholecystectomy. The muscle ATPase activity was 87 per cent higher (p less than 0.001) in obese subjects compared with non-obese subjects. The increase in the ATPase activity positively correlated with both the body mass index (r = 0.81) and excess body weight (r = 0.75). No relationship was found between erythrocyte and muscle sodium-potassium-ATPase activities (r = 0.25). These findings demonstrate an increased ATPase activity in skeletal muscle obtained from obese subjects and that the erythrocyte is an inaccurate marker of this enzyme with respect to other body tissue.     

What are the costs to NHS Scotland of self-referral to physiotherapy? Results of a national trial

Background

Recent healthcare policies have encouraged increasing interest in the concept of patient self-referral, specifically with regard to physiotherapy. However, what has not been known until recently is the efficacy of this mode of access within the National Health Service (NHS), including the cost implications on which to reliably base the provision of future service models.

Aim

To establish the costs to National Health Service (NHS) Scotland of differing modes of access to physiotherapy in primary care.

Design

Cost-minimisation analysis, multi-centred national trial.

Setting

Twenty-six general practices throughout Scotland.

Participants

Three-thousand and ten patients.

Method

Self-referral was introduced in each site in parallel with referral by a general practitioner (GP). NHS-associated cost data were collated over a full year by referral type, i.e. self-referral, GP-suggested and GP-referral groups. A cost-minimisation analysis was performed and the main outcome measures were the number of GP and physiotherapy contacts, prescribing of non-steroidal anti-inflammatory drugs and analgesics, and referral for X-ray, magnetic resonance imaging and/or secondary care. Costs were established for 2004.

Results

The data from 3010 patients identified significant associations between referral group and prescribing, referral for X-ray and to secondary care, and GP and physiotherapy contacts (P < 0.001). The average cost of an episode of care was established as £66.31 for a self-referral, £79.50 for a GP-suggested referral and £88.99 for a GP referral. Extrapolated to identify national implications, the average cost benefit to NHS Scotland was identified as being approximately £2 million per annum.

Conclusion

There are significant positive implications associated with self-referral to physiotherapy that represent added value for NHS Scotland. These implications are also of relevance to the rest of the NHS in the UK.     

Amantadine-oseltamivir combination therapy for H5N1 influenza virus infection in mice

BACKGROUND: The clinical management of H5N1 influenza virus infection in humans remains unclear. Combination chemotherapy with drugs that target different viral proteins might be more effective than monotherapy. METHODS: BALB/c mice were treated by oral gavage for 5 days with amantadine (1.5, 15 or 30 mg/kg/day) and oseltamivir (1 or 10 mg/kg/day) separately or in combination. Mice were challenged 24 h after initiation of treatment with 10 mouse 50% lethal doses of either amantadine-sensitive (having S31 in the M2 protein) or amantadine-resistant (having N31 in the M2 protein) recombinant A/Vietnam/1203/04 (H5N1) virus. RESULTS: Combination treatment with amantadine (15 or 30 mg/kg/day) and oseltamivir (10 mg/kg/day) provided greater protection (60% and 90%, respectively) against lethal infection with amantadine-sensitive H5N1 virus than did monotherapy. Moreover, spread of the virus to the brain was prevented by both combination regimens. The efficacy of the drug combinations against amantadine-resistant H5N1 virus was comparable to that of oseltamivir alone. Oseltamivir produced a dose-dependent effect against both recombinant H5N1 viruses (P < 0.05) but did not provide complete protection against lethal infection. Importantly, no mutations in the HA, NA and M2 proteins were detected when the two drugs were used in combination. CONCLUSIONS: Combination chemotherapy provided a survival advantage over single-agent treatment of mice inoculated with neurotropic H5N1 influenza virus. This strategy might be an option for the control of pandemic influenza viruses that are sensitive to amantadine. Combinations that include other drugs should be explored.     

The cycle of uncertainty: parents’ experiences of childhood epilepsy

Uncertainty has been highlighted as an important aspect of experiences of chronic conditions generally and epilepsy in particular. However, there is little research exploring the extent to which uncertainty features in the experiences of family members or the form that this uncertainty may take. Drawing on in‐depth semi‐structured interviews with 27 parents who had a child with epilepsy, this article explores parents’ experiences of uncertainty and the way in which their views on childhood and epilepsy interacted and contributed to the uncertainties they experienced. It is argued that the occurrence of epilepsy during childhood shaped parents’ experiences as they used their ‘social clocks’ in order to interpret symptoms. Furthermore, parents described what has been termed a ‘cycle of uncertainty’. Indeed, the combination of epilepsy (a condition with various inherent forms of uncertainty) and childhood (a period in the life course that is seen as a time of development) meant that parents could not be sure which changes in their child were a result of the condition and which were a normal part of the ageing process. Overall, this article demonstrates that it is important to contextualise experiences of chronic conditions in relation to different stages in the life course.