Lamivudine prophylaxis is effective in reducing hepatitis B reactivation and reactivation‐related mortality in chemotherapy patients: a meta‐analysis

Background: Hepatitis B viral (HBV) reactivation in patients undergoing chemotherapy is associated with significant morbidity and mortality. Lamivudine has been suggested to be useful as a prophylaxis for HBV reactivation; however, its impact on overall survival and HBV reactivation‐related liver disease survival is unclear. Objective: To determine the effect of lamivudine prophylaxis on the rate of HBV reactivation, overall survival and HBV reactivation‐related survival in patients with HBV undergoing chemotherapy. Methods: A comprehensive search of MEDLINE, Cochrane Collaboration Database, reference lists and abstracts from national meetings. Statistical analysis was performed using revman . Results: Eleven studies met the defined inclusion criteria and were included in the analysis. Two‐hundred and twenty patients received lamivudine prophylaxis and 400 did not receive prophylaxis. Patients given lamivudine prophylaxis had an 87% decrease in HBV reactivation [risk ratio (RR) 0.13, 95% confidence interval (CI), 0.07–0.24] than patients not given prophylaxis [absolute risk reduction (ARR) ?0.46, 95% CI, ?0.61 to ?0.31]. The number needed to treat to prevent one reactivation was 3. The Lamivudine prophylaxis group was also associated with a 70% reduction in reactivation‐related mortality (RR 0.30, 95% CI, 0.1–0.94) compared with controls (ARR ?0.03, 95% CI, 0.07–0.00). There was a reduction in treatment delays and premature termination of chemotherapy in the lamivudine prophylaxis arm (RR 0.41, 95% CI, 0.27–0.63; ARR ?0.33, 95% CI, ?0.33 to ?0.15). There was no significant heterogeneity in the comparisons. Conclusion: Lamivudine prophylaxis during chemotherapy is effective in reducing the rate of HBV reactivation, and reactivation‐related liver mortality. Patients with lamivudine prophylaxis had less chemotherapy treatment delays and premature termination of their chemotherapy. Few patients need to be treated to prevent reactivation. Patients with HBV undergoing chemotherapy should be started on lamivudine prophylaxis.     

The never‐ending story of CIED infection prevention: Shall we WRAP‐IT and go?

CIED infection is perceived as substantial, ranging from 1% to 4% in literature depending on different studies and on the population profile, and can appear either as surgical site or endovascular infection or both. Several factors have been found to be associated to CIED infection, that can be summarized as patient‐related (clinical profile, associated comorbidities, ongoing treatment as anticoagulants and immunosuppressants), Procedure‐related (complexity of CIED surgery, type of surgery, previous pocket exploration), and center‐/operator‐related (center/operator volume). Thus, it is difficult to disentangle the extent of benefit that any intervention may offer to decrease this threatened complication, owing to its multifaceted complexity. The recently completed PADIT and WRAP‐IT trials have significantly improved our knowledge in this field (nearly 20 000 patients enrolled), reporting an infection rate of 1% to 1.2% in control‐arm patients and a 20% to 67% infection decrease when incremental antibiotic prophylaxis is added on top of optimized preventative strategies. Observational registries highlighted that participation in a prospective survey of CIED infection dramatically decrease infection rate by optimization of antisepsis protocols and operator awareness, that explains the low event rate observed in PADIT and WRAP‐IT. While this consideration prompts each center to engage into a proactive infection prevention program, it makes a point in favor of antibiotic prophylaxis delivered locally in 7 days or more, as enabled by TYRX in the WRAP‐IT trial. However, care sustainability (the number needed to treat in the most favorable WRAP‐IT scenario is 100) suggests further analysis to understand the settings (patient‐ or procedure‐related) most likely to benefit by such an enhanced prevention strategy.     

Treatment for life for severe haemophilia A– A cost‐utility model for prophylaxis vs. on‐demand treatment

Prophylaxis has been established as the treatment of choice in children with haemophilia and its continuation into the adult years has been shown to decrease morbidity throughout life. The cost of factor therapy has made the option questionable in cost‐effectiveness studies. The role of prophylaxis in pharmacokinetic dosage and tolerization against inhibitor formation were used to model the cost utility of prophylaxis vs. on‐demand (OD) therapy over a lifetime horizon in severe haemophilia A. The model was applied to a single provider national health system exemplified by the United Kingdom's National Health Service and a third party provider in the United States. The incremental cost‐effectiveness ratio (ICER) was estimated and compared to threshold values used by payer agencies to guide reimbursement decisions. A cost per quality‐adjusted life year (QALY) was also estimated for Sweden. Prophylaxis was dominant over OD treatment in the UK. The model resulted in an ICER – $68 000 – within the range of treatments reimbursed in the USA. In Sweden, a cost/QALY of SEK 1.1 million was also within the range of reimbursed treatments in that country. Dosage‐ and treatment‐induced inhibitor incidence were the most important variables in the model. Subject to continuing clinical evidence of the effectiveness of pharmacokinetic dosage and the role of prophylaxis in decreasing inhibitor incidence, treatment for life with prophylaxis is a cost‐effective therapy, using current criteria for the reimbursement of health care technologies in a number of countries.     

Low‐dose valganciclovir prophylaxis for cytomegalovirus in intermediate‐risk (R+) renal transplant recipients: Single‐center experience

Renal transplant recipients (RTR) who are seropositive for CMV (R+) are considered to be at intermediate risk for CMV disease. Current guidelines recommend high‐dose valganciclovir (VGCV) prophylaxis because of limited data on the efficacy of low‐dose VGCV. We describe our experience with using low‐dose VGCV in R+ RTR. We retrospectively reviewed a cohort of 316 R+ RTR at our institution between 2002 and 2006. The primary endpoint was CMV disease at 1 year post transplant. The incidence of CMV disease at 12 months after transplantation was only 3% (6/221) in the D+R+ and 4% (4/95) in the D?R+ RTR. Low‐dose VGCV was effective at preventing CMV disease in intermediate‐risk (R+) RTR.     

Short‐term low‐dose secondary prophylaxis for severe/moderate haemophilia A children is beneficial to reduce bleed and improve daily activity,but there are obstacle in its execution: a multi‐centre pilot study in China

We recently showed in a single centre trial that low‐dose secondary prophylaxis in severe/moderate haemophilia patients with arthropathy is feasible and beneficial. However, this regimen has not been validated in a multicentre setting and what obstacles are there to prophylaxis remain unclear. (i) Benefit study: to confirm the benefits of similar prophylaxis protocol in severe/moderate haemophilia A (HA) in a multicentre setting in China. (ii) Follow‐up obstacle study: to investigate obstacles in compliance to prophylaxis treatment. (i) Benefit study: severe/moderate HA children with arthropathy from 15 centres were enrolled to undergo an 8‐week on‐demand treatment, followed by 6 to 12‐week low‐dose secondary prophylaxis. Outcomes compared in the two periods include joint and severe bleeding, daily activities and factor consumption. (ii) Obstacle study: questionnaires to investigators to collect data on patient and centre factors contributing to inability to comply with prophylaxis. We enrolled 191 patients from 15 centres. Sixty‐six (34.6%) from three centres completed the prophylaxis protocol, and they had significantly decreased bleeding (78.8% haemarthrosis and 68.9% severe bleedings) and improved daily activities with no increase in factor consumption over that in the on‐demand therapy period. The remaining 125 patients from 12 centres were not compliant to the prophylaxis protocol; questionnaire data indicated that the major obstacles were inability of patients/parents to accept (41.7%) or to adhere (33.3%) to the prophylaxis protocol, mostly because of failure to understand the benefits and to accept the frequent injections. Non‐availability of a centre comprehensive care team was another important determinant. Short‐term low‐dose secondary prophylactic therapy is beneficial without increasing factors consumption for severe/moderate HA with arthropathy in a multi‐centre setting in China. Obstacles to overcome must include improvement in comprehensive care and in education to patient/parents and healthcare personnel.     

Post‐exposure prophylaxis in resource‐poor settings: review and recommendations for pre‐departure risk assessment and planning for expatriate healthcare workers

It is estimated that more than 3 million healthcare workers worldwide suffer needlestick and splash injuries whilst at work resulting in the potential transmission of blood‐borne pathogens via exposure to bodily fluids. Under‐reporting and the subsequent management of occupational injuries is a problem both in the United Kingdom and abroad. Many expatriate health care workers will work in low resource settings where the risk of transmission is greatest but in contrast to wealthier countries such as the United Kingdom, there is often a lack of effective systems for its safe management. This article provides important information about this risk and how to minimise it. The reasons for an increased risk in transmission, its subsequent management and pre‐departure planning are discussed, together with the evidence for initiation of post‐exposure prophylaxis; current National and International guidelines as well as the urgent need for International standardisation of these is also discussed.     

Failures of once‐a‐week trimethoprim‐sulfamethoxazole prophylaxis in children undergoing allogeneic hematopoietic stem cell transplant

Once‐a‐week cotrimoxazole is an effective prophylaxis for pneumocystosis during antineoplastic chemotherapy or autologous stem cell transplant. Following allogeneic stem cell transplant, this schedule is at risk of pneumocystosis or neurotoxoplasmosis, as demonstrated by these case reports. Therefore, a 3‐times‐a‐week schedule must be adopted in these patients.     

Nonoccupational HIV post‐exposure prophylaxis: a 10‐year retrospective analysis

Background

We conducted a retrospective analysis of administration of nonoccupational HIV post‐exposure prophylaxis (nPEP) in a single centre where tracing and testing of the source of exposure were carried out systematically over a 10‐year period.

Methods

Files of all nPEP requests between 1998 and 2007 were reviewed. Characteristics of the exposed and source patients, the type of exposure, and clinical and serological outcomes were analysed.

Results

nPEP requests increased by 850% over 10 years. Among 910 events, 58% were heterosexual exposures, 15% homosexual exposures, 6% sexual assaults and 20% nonsexual exposures. In 208 events (23%), the source was reported to be HIV positive. In the remaining cases, active source tracing enabled 298 HIV tests to be performed (42%) and identified 11 HIV infections (3.7%). nPEP was able to be avoided or interrupted in 31% of 910 events when the source tested negative. Of 710 patients who started nPEP, 396 (56%) reported side effects, among whom 39 (5%) had to interrupt treatment. There were two HIV seroconversions, and neither was attributed to nPEP failure.

Conclusions

nPEP requests increased over time. HIV testing of the source person avoided nPEP in 31% of events and was therefore paramount in the management of potential HIV exposures. Furthermore, it allowed active screening of populations potentially at risk for undiagnosed HIV infection, as shown by the increased HIV prevalence in these groups (3.7%) compared with a prevalence of 0.3% in Switzerland as a whole.