Drug dosage recommendations in patients with chronic liver disease

Chronic liver diseases (CLD) alter the kinetics of drugs. Despite dosage adjustment is based on Child-Pugh scores, there are no available recommendations and/or algorithms of reference to facilitate dosage regimens. A literature review about dose adjustment of the drugs from the hospital guide -which are included in the list of the WHO recommended drugs to be avoided or used with caution in patients with liver disease- was carried out. The therapeutic novelties from the last few years were also included. In order to do so, the summary of product characteristics (SPC), the database DrugDex-Micromedex, the WHO recommendations and the review articles from the last 10 years in Medline were reviewed. Moreover, the kinetic parameters of each drug were calculated with the aim of establishing a theoretical recommendation based on the proposal of Delcò and Huet. Recommendations for 186 drugs are presented according to the SPC (49.5%), DrugDex-Micromedex (26.3%) and WHO (18.8%) indications; six recommendations were based on specific publications; the theoretical recommendation based on pharmacokinetic parameters was proposed in four drugs. The final recommendations for clinical management were: dosage modification (26.9%), hepatic/analytical monitoring of the patient (8.6%), contraindication (18.8%), use with caution (19.3%) and no adjustment required (26.3%). In this review, specific recommendations for the practical management of patients with chronic liver disease are presented. It has been elaborated through a synthesis of the published bibliography and completed by following a theoretical methodology.     

High-Efficiency Postdilution Online Hemodiafiltration Reduces All-Cause Mortality in Hemodialysis Patients

Retrospective studies suggest that online hemodiafiltration (OL-HDF) may reduce the risk of mortality compared with standard hemodialysis in patients with ESRD. We conducted a multicenter, open-label, randomized controlled trial in which we assigned 906 chronic hemodialysis patients either to continue hemodialysis (n=450) or to switch to high-efficiency postdilution OL-HDF (n=456). The primary outcome was all-cause mortality, and secondary outcomes included cardiovascular mortality, all-cause hospitalization, treatment tolerability, and laboratory data. Compared with patients who continued on hemodialysis, those assigned to OL-HDF had a 30% lower risk of all-cause mortality (hazard ratio [HR], 0.70; 95% confidence interval [95% CI], 0.53–0.92; P=0.01), a 33% lower risk of cardiovascular mortality (HR, 0.67; 95% CI, 0.44–1.02; P=0.06), and a 55% lower risk of infection-related mortality (HR, 0.45; 95% CI, 0.21–0.96; P=0.03). The estimated number needed to treat suggested that switching eight patients from hemodialysis to OL-HDF may prevent one annual death. The incidence rates of dialysis sessions complicated by hypotension and of all-cause hospitalization were lower in patients assigned to OL-HDF. In conclusion, high-efficiency postdilution OL-HDF reduces all-cause mortality compared with conventional hemodialysis.In the last decades, renal replacement therapy with hemodialysis has become a standard of care for patients with ESRD. Despite continuous improvement, annual mortality among these patients ranges between 15% and 25%.^1,2 Hemodialysis techniques are based on the ability of molecules to diffuse across a semipermeable membrane, which allows adequate clearance of low molecular weight particles. To increase the clearance of middle-to-large molecules, synthetic membranes with high water permeability (high-flux membranes) were introduced years ago. The anticipated benefit of high-flux over low-flux hemodialysis on patient survival was not confirmed in the Hemodialysis (HEMO) study.³ However, the Membrane Permeability Outcome (MPO) study,⁴ as well as a post hoc analysis in diabetic patients, showed that high-flux hemodialysis improved long-term survival in patients with hypoalbuminemia.Clearance of middle-to-large molecules can be increased by combining diffusive and convective transport through hemodiafiltration. The introduction of online hemodiafiltration (OL-HDF) using ultrapure dialysate as the source of the replacement fluid has allowed the convective volume to be increased and has reduced the cost of the procedure.⁵ Randomized studies with limited sample sizes and nonrandomized studies have shown that OL-HDF improves hemodynamic stability and response to erythropoietic-stimulating agents (ESAs) and reduces the incidence of hemodialysis-associated amyloidosis and chronic inflammation.^6–11 The effect of OL-HDF on patient survival is derived from noncontrolled studies. The European Dialysis Outcomes and Practice Pattern Study was associated with a mortality risk reduction of 35% in patients treated with high-efficiency hemodiafiltration compared with those treated with conventional hemodialysis.¹² These results were confirmed in other noncontrolled studies conducted in several European countries,^13–15 although two recent, randomized studies failed to show differences in patient survival^16,17In 2007, the Catalonian Health Authorities approved a specific additional reimbursement for OL-HDF to dialysis care providers and the Catalonian Society of Nephrology promoted this randomized study (On-Line Hemodiafiltration Survival Study, or Estudio de Supervivencia de Hemodiafiltración On-Line [ESHOL]) to compare the effect of OL-HDF over hemodialysis on patient survival.¹⁸     

MAASH Technique for Total Hip Arthroplasty: A Capsular Work

Background

Dislocation and leg length discrepancy are major complications following total hip arthroplasty (THA). Many surgical approaches for THA have been described, but none suggest a capsular incision that assures good exposure while maintaining adequate capsule integrity in closure.

Purposes

Modified anterolateral approach for stable hip (MAASH) is a modification of the classical Hardinge approach, but specifically preserves the anterior iliofemoral lateral ligament and pubofemoral ligament excising the “weak area” of the capsule, in the so called “internervous safe zone” and introducing the “box concept” for the anterior approach to the hip. This is the main difference of the MAASH approach. This technique can be used as a standard for all THA standard models, but we introduce new devices to make it easier.

Methods

From November 2007 to May 2012, data were collected for this observational retrospective consecutive case study. We report the results of 100 THA cases corresponding to the development curve of this new concept in THA technique.

Results

MAASH technique offers to hip surgeons, a reliable and reproducible THA anterolateral technique assuring accurate reconstruction of leg length and a low rate of dislocation. Only one dislocation and six major complications are reported, but most of them occurred at the early stages of technique development.

Conclusion

MAASH technique proposes a novel concept on working with the anterior capsule of the hip for the anterolateral approach in total hip arthroplasty, as well as for hemiarthroplasty in the elderly population with high dislocation risk factors. MAASH offers maximal stability and the ability to restore leg length accurately.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-013-9332-1) contains supplementary material, which is available to authorized users.     

Use of proton pump inhibitors and risk of fragility hip fracture in a Mediterranean region

ObjectiveTo determine whether there is an increased risk of hip fracture associated with the use of proton pump inhibitors in a Mediterranean area after adjusting for other potential risk factors.MethodsRetrospective multicenter case–control study carried out in 6 primary health care centers in Catalonia, Spain. Cases were patients aged 50 years and over with a fragility hip fracture registered between January 2007 and December 2010, matched with 2 controls by sex and age. Data collected: use of proton pump inhibitors (type, dosage) in the 5 years previous to the hip fracture, socio-demographic data, body mass index, alcohol and tobacco consumption as well as health conditions and drugs associated with an increase risk of fragility hip fracture.Results358 cases were matched with 698 controls. The mean age was 82 years old in both groups. Women represented 77.1% in the case group and 76.9% in the control group. Crude association between proton pump inhibitors and hip fracture was 1.44 (95% CI, 1.09–1.89) and adjusted OR was 1.24 (95% CI, 0.93–1.65). No association was found with the continuous or discontinuous use of proton pump inhibitors, OR 1.17 (95% CI, 0.77–1.79), and OR of 1.16 (95% CI, 0.85–1.60) respectively. No association was found when restricting the analysis by sex, OR of 1.19 (95% CI, 0.27–5.14) or by age, younger or older than 80 years, OR of 0.72 (95% CI, 0.24–2.15).ConclusionThe use of proton pump inhibitors was not associated with an increased risk of hip fracture after adjusting for other risk factors in a Mediterranean area. This result suggests the existence of protective environmental factors linked to this southern area of Europe that eventually could compensate for the potential harm produced by proton pump inhibitors.     

REM sleep behavior disorder and narcoleptic features in anti-Ma2-associated encephalitis

A 69-year-old man with anti-Ma2 paraneoplastic encephalitis presented with subacute onset of severe hypersomnia, memory loss, parkinsonism, and gaze palsy. A brain magnetic resonance imaging study showed bilateral damage in the dorsolateral midbrain, amygdala, and paramedian thalami. Videopolysomnography disclosed rapid eye movement (REM) sleep behavior disorder, and a Multiple Sleep Latency Test showed a mean sleep latency of 7 minutes and 4 sleep-onset REM periods. The level of hypocretin-1 in the cerebrospinal fluid was low (49 pg/mL). This observation illustrates that REM sleep behavior disorder and narcoleptic features are 2 REM-sleep abnormalities that (1) may share the same autoimmune-mediated origin affecting the brainstem, limbic, and diencephalic structures and (2) may occur in the setting of the paraneoplastic anti-Ma2-associated encephalitis.     

Genetic analyses of celiac disease in a Spanish population confirm association with CELIAC3 but not with CELIAC4

Genetic predisposition to celiac disease (CD) is determined primarily by the human leukocyte antigen (HLA) genes (CELIAC1 region; 6p21), although many loci are involved in disease susceptibility. First, we have analysed a large series of CD patients from the Spanish Mediterranean region who had previously been characterised for the HLA complex. We have investigated how relevant regions contribute to CD susceptibility: CELIAC3 (CD28/CTLA4/ICOS region on 2q33) and CELIAC4 (19p13) as well as the tumour necrosis factor alpha (TNF-alpha) and the linfotoxin loci by case-control and association analyses. We highlight the association with the +49*A allele of cytotoxic T-lymphocyte-associated antigen 4 locus (P = 0.01), and the -308*A of TNF-alpha locus (P = 0.0008) in DQ2 individuals, although an independent role for TNF-alpha as risk factor has not been proven. Moreover, we do not confirm the association with the CELIAC4 region polymorphisms described in other populations.     

Evolución del cierre de ileostomía en una unidad de cirugía colorrectal. Análisis comparativo según la técnica

Introduction

The objective of this study is to assess whether the results of loop ileostomy closure in terms of morbidity and hospital stay are influenced by the type of anastomosis and suture used.

Method

All patients who underwent loop ileostomy closure were reviewed. A retrospective cohort study comparing morbidity and hospital stay according to the type of anastomosis (TT/LL) and the type of suture (hand sewn/mechanical) was performed.

Results

From January 2003 to November 2011 a total of 167 loop ileostomy closures were analized. The groups were: type of anastomosis (TT 95/LL 72) and type of suture (manual 105/stapled 62). In 76% of the observed population the underlying disease was cancer. Mortality occurred in one case. The stratified morbidity analysis by type of complications showed no significant differences between the groups in terms of local (7.4% TT, LL 8.3%, 6.7% hand sewn, stapled 9.7%), general (TT 9.5%, 16.7% LL, hand sewn 6.7%, 6.5% stapled) and surgical (TT 15.8%, 19.4% LL, hand sewn 17.1%, 17.7% stapled) complications, nor in the rate of reoperations (TT 6.3%, 6.9% LL, hand sewn 6.7%, 6.5% stapled) and hospital stay in days (TT 7.8, 8 LL, hand sewn 8.6, stapled 6.7)

Conclusions

Closure of loop ileostomy can be performed regardless of the type of suture or anastomosis used, with the same rate of morbidity and hospital stay.