Adherence to fracture liaison service programs in patients over 70: the hidden part of the iceberg.

Significant dropout rates have been observed throughout Fracture Liaison Service (FLS) programs, especially for elderly patients. In an FLS program set up specifically for patients over 70, the non-initiation of osteoporosis treatment was the only factor associated with poor adherence to the program. Neither age nor frailty factors affected adherence. INTRODUCTION: FLS programs are considered the most effective interventions for secondary prevention of osteoporotic fractures. Our objective was to identify risk factors for non-adherence to an FLS program set up specifically for patients over 70. METHODS: Our multifaceted, intensive program included five appointments over a 2-year period. One hundred sixty-seven patients (mean age 83.5 years) who presented with a recent fragility fracture were enrolled. Multivariable analysis was conducted to determine whether the demographic, clinical, frailty, and osteoporotic risk factors of the patients influenced their adherence to the program. RESULTS: About half of the patients did not attend the follow-up visits. According to the regression analysis, non-initiation of osteoporosis treatment was associated with poor adherence to the program (aHR 3.66). Demographic, clinical, dwelling, frailty factors, osteoporotic risk factors, fracture type, or densitometric scores were not associated with adherence. The first self-reported reason for withdrawal was the difficulty of attending several follow-up visits, and the second was the feeling of not being concerned. CONCLUSION: We observed that non-initiation of osteoporosis treatment was the only factor correlated with non-adherence to an FLS program. Thus, neither age nor frailty factors should result in patients not being included in FLS. Beyond the necessity of the osteoporosis treatment, good patient understanding of the relevance of all the interventions included in the program is the key.

Impact of medication review via tele-expertise on unplanned hospitalizations at 3 months of nursing homes patients (TEM-EHPAD): study protocol for a randomized controlled trial.

BACKGROUND: Inappropriate drug prescribing causes preventable drug-related adverse events that result in increased morbidity and mortality, additional costs and diminished quality of life. Numerous initiatives have been launched to improve the quality of drug prescribing and safeguard the security of drug administration processes in nursing homes. Against the backdrop of implementation of telemedicine services, the focus of the present work is to evaluate the impact of a telemedication review carried out by a hospital physician and pharmacist as part of the telemedicine offer. METHODS: The present study is a randomized controlled clinical trial. A total of 364 patients will be randomized into two groups: (1) an experimental group (182 patients) benefiting from a telemedication review using tele-expertise and (2) a control group (182 patients) receiving standard care. The primary endpoint will be rate of all-cause unplanned hospital admissions occurring within 3 months of randomization. The secondary endpoints will be rate of unplanned admissions at 6 months, patient quality of life, incidence of behavioral disturbances, number of falls, number of residents prescribed at least one inappropriate medication, nursing staff satisfaction, proposed medication reviews and their acceptability rate, characteristics of patients whose general practitioners have taken account of tele-expertise, efficacy of tele-expertise as compared to standard prescription and acceptability and satisfaction surveys of participating caregivers. DISCUSSION: In the literature, various studies have investigated the utility of structured medication review processes, but outcome measures are heterogeneous, and results vary widely. Medication review can detect medication-related problems in many patients, but evidence of clinical impact is scant. Incremental cost-effectiveness ratios will be used to compare the cost and effectiveness of the experimental strategy and that of standard care. Our approach, involving the combination of an acceptability survey and a mixed-method (qualitative and quantitative) satisfaction survey, is particularly innovative. The results of this randomized trial are expected to confirm that medication review using tele-expertise has potential as a worthwhile care management strategy for nursing home residents. TRIAL REGISTRATION: Clinicaltrials.gov NCT03640845; registered August 21, 2018 (Clinicaltrials.gov NCT03640845).

Production of platelet-rich plasma gel from elderly patients under antithrombotic drugs: Perspectives in chronic wounds care.

Platelet-Rich Plasma (PRP) is an autologous biological therapy obtained by centrifuging the patient's own blood to concentrate platelets. The addition of autologous thrombin and calcium chloride to PRP allows the production of a semi-solid form called PRP gel. PRP gel is increasingly used in a variety of tissue defects and predominantly in the management of non-healing chronic wounds. The topical application of PRP gel seems promising due to the capability of platelets to store and secrete growth factors (GF), fibrin and cytokines, which are essentials for wound healing. Most patients who suffered from chronic wounds are elderly patients with co-morbidities and polypharmacy including antithrombotic drugs such as antiplatelet agents (AP) or anticoagulants (AC), which could hamper the feasibility of this autologous platelet-derived therapy. To date, no study has investigated PRP gel formation in patients with AP or AC. The aim of this study was to evaluate the influence of AP or AC drugs on the production of PRP gel formation from elderly patients. Different biological characteristics were determined to qualify the production of PRP gel from such patients (Interquartile range (IQR) = 75-92 years) compared to healthy volunteers (IQR = 23-37 years). No significant difference was observed in the volume, composition (quantity of platelets, leukocytes and red blood cells) and functionality of platelets from PRP except a higher ADP-induced P-selectin expression in healthy donors compared with elderly patients. Autologous thrombin characteristics were similar in the two groups. Gel time formation (IQR: 120-195 seconds for controls and 135-210 seconds for elderly patients) and final composition of PRP gel were not significantly modified. Concentrations of theoretical thrombin generated in the serum and in the gel were inversely correlated with the time of formation of PRP gel (r2 = 0.57, p = 0.012). Altogether these data indicate that PRP gel preparation is not impacted by the use of antithrombotic drugs. Such results support the feasibility of using this innovative autologous biotherapy in the management of elderly patients with non-healing chronic wounds.

[Medication reconciliation: Interests and limits]. / Conciliation médicamenteuse : intérêts et limites.

Admission to hospital is a critical transition point for the continuity of care in medication management. Medication reconciliation can identify and resolve errors due to inaccurate medication histories. The practice of medication reconciliation is securing for the patient because of the medication errors detected with significant clinical impact. Its implementation must comply with the recommendations of the French National Authority for Health (HAS) and its deployment is now integrated into the contract for improving the quality and efficiency of care (CAQES). However, although it allows to intercept medication errors, its impact on the length of hospitalization, the rate of readmission and/or death following discharge seems limited. Given the limited human resources to carry out this time-consuming activity, patient prioritization should be considered. Studies on the fate of patients and on the medico-economic issues are also necessary in order to make this activity sustainable.

The importance of lung recruitability: A novel ultrasound pattern to guide lung recruitment in neonates.

BACKGROUND: Lung Ultrasound (LUS)-guided Lung Recruitment Maneuver (LRM) has been shown to possibly reduce ventilator-induced lung injury in preterm infants. However, to avoid potential hemodynamic and pulmonary side effects, the indication to perform the maneuver needs to be supported by early signs of lung recruitability. Recently, a new LUS pattern (S-pattern), obtained during the reopening of collapsed parenchyma, has been described. This study aims to evaluate if this novel LUS pattern is associated with a higher clinical impact of the LUS-guided LRMs. METHODS: All the LUS-guided rescue LRMs performed on infants with oxygen saturation/fraction of inspired oxygen (S/F) ratio below 200, were included in this cohort study. The primary outcome was to determine if the presence of the S-pattern is associated with the success of LUS-guided recruitment, in terms of the difference between the final and initial S/F ratio (Delta S/F). RESULTS: We reported twenty-two LUS-guided recruitments, performed in nine patients with a median gestational age of 34 weeks, interquartile range (IQR) 28-35 weeks. The S-pattern could be obtained in 14 recruitments (64%) and appeared early during the procedure, after a median of 2 cmH2O (IQR 1-3) pressure increase. The presence of the S-pattern was significantly associated with the effectiveness of the maneuver as opposed to the cases in which the S-pattern could not be obtained (Delta S/F 110 +/- 47 vs 44 +/- 39, p = 0.01). CONCLUSIONS: Our results suggest that the presence of the S-pattern may be an early sign of lung recruitability, predicting LUS-guided recruitment appropriateness and efficacy.

[Minimal change nephropathy and IgA deposits associated with a Sezary syndrome]. / Néphropathie à IgA et LGM au cours d'un syndrome de Sézary.

INTRODUCTION: The Sézary syndrome (SS) is an aggressive form of cutaneous T-cell lymphoma (CTCL) requiring a rapid diagnosis due to its poor prognosis. CASE REPORT: We report the first case of an eighty-nine-year-old woman who presented with concomitant Sezary syndrome and anasarca, revealing a nephrotic syndrome caused by a minimal change nephropathy associated with immunoglobulin A (IgA) deposits. Scarce literature described rare cases associating these two entities (nephrotic syndrome and nephropathy). However, the nephrotic syndrome was delayed from disease onset, secondary to immunosuppressive treatment of SS, or due to the weaning of SS therapy. Thus, the direct link between the glomerular lesion and the cutaneous lymphoma was difficult to establish. However, the synchronous occurrence of both SS and glomerulopathy in our patient, along with Sezary cells in both urines (urinary cytology) and biopsy, and resolution of nephropathy after treatment of SS, support the likely attributability of SS in glomerulopathy. CONCLUSION: Practitioners must acknowledge the possible occurrence of glomerular involvement in SS.

Identification of Frailty in a Population of Former Immigrant Workers in the South of France.

BACKGROUND: Frailty is unevenly distributed across the world but also within different populations in the same country. OBJECTIVES: This study sought to identify frailty in former immigrant workers, known as Chibanis, living in an immigrant hostel in Marseille. The secondary objective was to describe health care access, as well as any chronic diseases reported. DESIGN, PARTICIPANTS AND SETTING: Our descriptive, observational, monocentric study conducted from January to April 2021 included 67 Chibanis, living in an immigrant hostel in Marseille. MEASUREMENTS AND RESULTS: Almost all this population (97%), with a median age of 77 years, presented at least one frailty criterion: 7.5% were malnourished, 55.2% had a grip strength of < 27 kg, and 41.8% were on multiple drugs. Majority of Chibanis (86.6%) had multimorbidity. CONCLUSION: Identifying frailty in this population of Chibanis must be proposed through a specific, adapted care pathway including referral to a specialist.

HoSAGE: Sarcopenia in Older Patients before and after Treatment with Androgen Deprivation Therapy and Radiotherapy for Prostate Cancer.

BACKGROUND: Sarcopenia is a muscle disease defined by a loss of muscle strength associated to a decrease in skeletal muscle mass. In addition to aging, many factors may contribute to sarcopenia as cancer and/or androgen deprivation therapy (ADT). OBJECTIVES: The aims of this study are to describe the prevalence of sarcopenia in older prostate cancer patients before initiation of treatment with ADT and radiotherapy, and to evaluate the impact of ADT on the occurrence or aggravation of sarcopenia in this population. DESIGN: longitudinal study. PARTICIPANTS AND SETTING: Sarcopenia was prospectively evaluated in 31 consecutive patients aged 70 to 88 years, referred in one hospital unit of south eastern France, for a comprehensive geriatric assessment (CGA) before cancer treatment initiation. MEASUREMENTS AND RESULTS: CGA, measures of muscle strength and physical performances were performed at baseline (T0) and at the end of cancer treatment (T1). Appendicular skeletal muscle mass was measured by Dual-energy X-ray absorptiometry (DXA) at the end of treatment. At T0, 8 patients (among 31) had a probable sarcopenia according to European consensus, and 18 had altered physical performance. At T1, 15 patients (among 19) had abnormal one leg balance test. Finally, only one patient had a sarcopenia confirmed by DXA. CONCLUSION: This preliminary study showed a high prevalence of muscle disorders before initiation of ADT in a population of elderly cancer prostate patients with intermediate frailty status, and an increased risk of falls at the end of ADT. This highlighted the importance of screening for sarcopenia before treatment initiation, to prevent the occurrence or aggravation of sarcopenia by possible adjustment of treatment, and implementation of appropriate exercise and nutrition interventions.

Oral valganciclovir treatment in newborns with symptomatic congenital cytomegalovirus infection.

This study was performed to assess oral valganciclovir V-GCV (GCV pro-drug), 15 mg/kg bid for 6 weeks to 13 neonates with symptomatic congenital cytomegalovirus (CMV). We monitored plasma levels of GCV within 30 days of therapy: C(trough), and C(2h) (before and the 2 hours after administration), we performed viral assessment in plasma and urine and tolerability at baseline, and every fortnight. Pharmacokinetics showed GCV stable and effective plasma concentrations: mean C(trough) = 0.51 +/- 0.3 and C(2h) : 3.81 +/- 1.37 microg/ml. No significant variability was seen neither intra-patient nor inter-patients. One newborn discontinued therapy because of thrombocytopenia, another finished with a neutrophils count of 1,000/microl. At the end of therapy 6 out of 12 and 8 out of 12 newborns were negative for CMV in urine and plasma. The 4 newborns positive for CMV DNA showed a 90% reduction of pre-therapy values. Clinically, the 4 patients reporting hepatic disease and the 3 with thrombocytopenia recovered after 6 weeks of therapy. Eight newborns suffered from SNHL; at the 6-month follow-up no patients had worsened, 2 had improved, and no deterioration was reported in 3 newborns with chorioretinitis scarring. The paucity of adverse events, and the effectiveness and stability of drug plasma concentrations are the important findings of our study.

[Amiodarone-induced optic neuropathy: A rare side effect]. / Un effet indésirable rare de l'amiodarone : la neuropathie optique.

INTRODUCTION: The diagnosis of bilateral papilledema implies emergency medical care to look for intracranial hypertension and arteritic ischemic neuropathy. However, other causes must also be mentioned, including drugs. Too often underrated because of their usual benignity, drug side ophthalmological effects can be severe and are typically bilateral. CASE REPORT: An 80-year-old woman was hospitalized for bilateral papilledema, predominantly in the left eye, with lowered visual acuity. After ruling out intracranial hypertension, arteritic ischemic optic neuropathy, non-arteritic, and inflammatory bilateral papilledema, the diagnosis was toxic optic neuropathy. CONCLUSION: Bilateral edematous optic neuropathy is a known side effect of amiodarone, uncommon but to be known because of the large number of patients benefiting from this treatment.

[Characteristics of giant cell arteritis patients under and over 75-years-old: A comparative study on 164 patients]. / Caractéristiques des patients de moins et de plus de 75 ans atteints d'artérite à cellules géantes : étude comparative de 164 patients.

PURPOSE: Giant cell arteritis (GCA) is the most common vasculitis of the elderly. In order to assess the impact of age at diagnosis, we compared the characteristics of patients of less than 75 years (<75 years), to those of the 75 years and over (≥75 years). PATIENTS AND METHODS: We conducted a retrospective study on 164 patients with GCA diagnosed from 2005 to 2017. All patients had at least 3/5 of the ACR criteria and had a CT-scan at diagnosis. The mean age was of 73±9.6 years. The age was<75 years for 84 patients (59 women) and≥75 years for 80 patients (53 women). RESULTS: Patients≥75 years had more cardiovascular underlying diseases (P=0.026), a higher rate of hypertension (P=0.005) and more ophthalmic complications (P=0.02). They had less large vessel involvement (P<0.001), showed lower biological inflammatory reaction and had a more frequently positive temporal artery histology (P=0.04). The oral initial dose of corticosteroids did not differ between the groups. Corticosteroids pulse therapy was more frequent in patients≥75 years (P=0.01). The frequency of anti-platelet agents use was similar in the two groups. Relapse rate, corticodependance and the rate of corticosteroids weaning were similar in both groups. CONCLUSION: Patients≥75 years at diagnosis of GCA were at lower risk of aortitis but were more likely to suffer from ophthalmic complications and to receive corticosteroid pulse therapy.

The ABC-Pyramid Atmospheric Research Observatory in Himalaya for aerosol, ozone and halocarbon measurements.

In this work we present the new ABC-Pyramid Atmospheric Research Observatory (Nepal, 27.95 N, 86.82 E) located in the Himalayas, specifically in the Khumbu valley at 5079 m a.s.l. This measurement station has been set-up with the aim of investigating natural and human-induced environmental changes at different scales (local, regional and global). After an accurate instrumental set-up at ISAC-CNR in Bologna (Italy) in autumn 2005, the ABC-Pyramid Observatory for aerosol (physical, chemical and optical properties) and trace gas measurements (ozone and climate altering halocarbons) was installed in the high Khumbu valley in February 2006. Since March 2006, continuous measurements of aerosol particles (optical and physical properties), ozone (O3) and meteorological parameters as well as weekly samplings of particulate matter (for chemical analyses) and grab air samples for the determination of 27 halocarbons, have been carried out. These measurements provide data on the typical atmospheric composition of the Himalayan area between India and China and make investigations of the principal differences and similarities between the monsoon and pre-monsoon seasons possible. The study is carried out within the framework of the Ev-K2-CNR "SHARE-Asia" (Stations at High Altitude for Research on the Environment in Asia) and UNEP-"ABC" (Atmospheric Brown Clouds) projects. With the name of "Nepal Climate Observatory-Pyramid" the station is now part of the Observatory program of the ABC project.

[Impact of an evaluation of the professional practices on the relevance of proton pump inhibitors prescriptions pertinence at the hospital]. / Impact d'une évaluation des pratiques professionnelles sur la pertinence des prescriptions d'inhibiteurs de la pompe à protons à l'hôpital.

INTRODUCTION: Proton pump inhibitors (PPI) are widely prescribed for unrecognized indications, at high a dose and for a long duration, in spite of side effects and numerous drug interactions. In 2009, the HAS (French Health Authority) published recommendations of good prescription but the latter are poorly respected. In this context of over prescription and additional cost for the society, we performed a professional practice evaluation of on the model of the Deming wheel. The objective of this work was to optimize the relevance of the prescriptions of the IPP in two services of internal medicine and geriatrics through an evaluation of the professional practices. All PPI prescriptions introduced in outpatient visits or during hospitalization were analyzed. PATIENTS AND METHODS: Data collection was prospective, over two periods of 2 months and included 163 (first phase), then 139 patients (second phase). An assessment grid of PPI prescriptions was completed by physicians regarding the active substance, the dose, the duration and the indication of the prescription. The relevance of the prescription corresponded to PPI with a conformed indication and duration and to the prescriptions no recommended stopped. Following the first period of data collection, information was given to medical students and physicians on the relevance of their prescriptions with regard to the current recommendations and informative flyers were offered with the aim of improving the practices before the second period of evaluation (second phase). RESULTS: During the first phase, only 25% of the pre-hospital prescriptions and 33% of the hospital prescriptions respected the HAS recommendations. The main indication of the PPI was the prevention of peptic ulcers in a context of associated drug estimated at risk. An improvement of the global relevance of prescription was observed after awareness of the physicians: 26% relevance during the first phase and 60% in the second one (P<0.012). During the second phase, the part of PPI prescriptions introduced at hospital decreased from 33 to 17% and the discontinuation of the not corresponding prescriptions increased from 6 to 33%, with an additional information given to the general practitioner (P<0.001). However, during the second phase, 33% of the prescriptions introduced in hospitalization were always not corresponding and 61% of the not corresponding prescriptions begun in outpatient visits were always pursued on discharge, probably due to the lack of sufficient information to stop the prescription. CONCLUSION: Our study underlines the frequent disrespect of the indications in the prescription of PPI. Interestingly, a professional practices evaluation improved the relevance of the prescriptions with a more frequent withdrawal of the not corresponding exposure and a decrease in global not corresponding prescriptions. Our study suggests that it is crucial to regularly inform physicians on the good prescription of PPI. Patient information focused on the indications and the limited duration of PPI prescription, potentially severe side effects of chronic exposure and on the risk of drug interactions also remains necessary in order to facilitate the stop of the exposure and restrict self-medication.

Meta-analysis of major bleeding events on aspirin versus vitamin K antagonists in randomized trials.

BACKGROUND AND OBJECTIVES: The relative bleeding risk of aspirin versus vitamin K antagonists (VKA) is unclear. Most of previous meta-analyses included trials with target INR for VKA therapy far beyond usually recommended range (2-3). The aim of this study was to compare the bleeding risk of aspirin and VKA, as indicated by the aggregate body of clinical evidence including data from the recently published WARCEF trial. METHODS: In this meta-analysis we included randomized controlled trials that compared aspirin to VKA (1.4

Antiplatelet therapy for primary prevention in diabetes.

Aspirin is currently recommended by ADA (American Diabetes Association) for the diabetic patients over 40 years of age and without cardiovascular disease. This recommendation is at odds with drug approval for aspirin. The main explanation is the absence of appropriate trials assessing the usefulness of aspirin in such patients. Two assumptions, central to these guidelines are that diabetes is a coronary risk equivalent, and that aspirin benefit/risk ratio is similar in diabetic patients than in coronary disease patients. Unfortunately, vascular risk level is variable in diabetic patients. Patients with new onset diabetes have lower cardiovascular risk than patients with established cardiovascular disease. Smoking habits markedly increase the risk. Benefits may be lower in diabetic patients since aspirin resistance is common in these patients. Haemorrhagic risk may be higher since diabetes is a risk factor for haemorrhagic stroke. Awaiting trial evidence, aspirin therapy should be considered in diabetic patients with a very high risk, such as smokers, patients with long diabetes duration, or atherosclerotic plaques at echography.

935 MHz cellular phone radiation. An in vitro study of genotoxicity in human lymphocytes.

PURPOSE: The possibility of genotoxicity of radiofrequency radiation (RFR) applied alone or in combination with x-rays was investigated in vitro using several assays on human lymphocytes. The chosen specific absorption rate (SAR) values are near the upper limit of actual energy absorption in localized tissue when persons use some cellular telephones. The purpose of the combined exposures was to examine whether RFR might act epigenetically by reducing the fidelity of repair of DNA damage caused by a well-characterized and established mutagen. METHODS: Blood specimens from 14 donors were exposed continuously for 24 h to a Global System for Mobile Communications (GSM) basic 935 MHz signal. The signal was applied at two SAR; 1 and 2 W/Kg, alone or combined with a 1-min exposure to 1.0 Gy of 250 kVp x-rays given immediately before or after the RFR. The assays employed were the alkaline comet technique to detect DNA strand breakage, metaphase analyses to detect unstable chromosomal aberrations and sister chromatid exchanges, micronuclei in cytokinesis-blocked binucleate lymphocytes and the nuclear division index to detect alterations in the speed of in vitro cell cycling. RESULTS: By comparison with appropriate sham-exposed and control samples, no effect of RFR alone could be found for any of the assay endpoints. In addition RFR did not modify any measured effects of the x-radiation. CONCLUSIONS: This study has used several standard in vitro tests for chromosomal and DNA damage in Go human lymphocytes exposed in vitro to a combination of x-rays and RFR. It has comprehensively examined whether a 24-h continuous exposure to a 935 MHz GSM basic signal delivering SAR of 1 or 2 W/Kg is genotoxic per se or whether, it can influence the genotoxicity of the well-established clastogenic agent; x-radiation. Within the experimental parameters of the study in all instances no effect from the RFR signal was observed.

Antinociceptive activity of eel calcitonin, injected into the inflamed paw in rats.

This study examined the possible peripheral activity of eel calcitonin in the modulation of the response to noxious pressure on inflamed paws in rats (Randall and Selitto test). The intraplantar injection of eel calcitonin (20-200 ng/rat) but not the subcutaneous administration (200 ng and 2 micrograms/rat, s.c.), was able to significantly inhibit hyperalgesia induced by intraplantar injection of carrageenin. The development of oedema on the other hand was not inhibited. The intraplantar administration of eel calcitonin (200 ng/rat) in a non-inflamed paw did not modify paw pressure thresholds. Eel calcitonin (200 ng/rat, intraplantar, i.pl.) was also able to elicit an antinociceptive effect on formalin-induced hyperalgesia, both when the peptide was injected before or after (60 min) formalin. This effect, at difference with morphine (80 micrograms/rat, i.pl.), was not blocked by naloxone (10 micrograms/rat, i.pl.). These results demonstrate the local antinociceptive effect of eel calcitonin in inflammatory pain and might indicate a new way of using calcitonin in the control of pain.

Evidence for an inhibitory role of central histamine on carrageenin-induced hyperalgesia.

The effects of intracerebroventricular (i.c.v.) injection of histamine, the H1 agonist 2-methyl-histamine and the H2 agonist dimaprit were tested on carrageenin induced hyperalgesia by the Randall-Selitto paw pressure test in the rat. Treatment with histamine (0.1, 0.2, 0.4 mumol/rat, i.c.v.) 150 min after intraplantar carrageenin (0.1 ml of 1% solution) caused a significant increase of paw pressure thresholds in inflamed (but not in non-inflamed) paws. The magnitude and the duration of the antinociceptive effects of histamine were dose-dependent. Administration of 2-methyl-histamine (0.2, 0.4, 0.8, 1.0 mumol/rat, i.c.v.) and dimaprit (0.1, 0.2, 0.4, 0.8 mumol/rat, i.c.v.) also displayed dose-dependent blockade of carrageenin-induced hyperalgesia. Antinociceptive ED50 values calculated 30 min after drug treatments were: histamine 0.18 mumol/rat; 2-methyl-histamine 0.65 mumol/rat; dimaprit 0.33 mumol/rat. These data indicate that histamine through central H1 and H2 receptors exerts an inhibitory role in the control of nociception in pain resulting from inflammation.

Comparison of the plasma pharmacokinetics of lamivudine during twice and once daily administration in patients with HIV.

OBJECTIVE: To compare the plasma pharmacokinetics of lamivudine 150mg twice daily and 300mg once daily in patients with HIV-1 infection. DESIGN: Nonblind, sequential, pharmacokinetic study. PARTICIPANTS: 13 patients with HIV-1 infection (median age 36 years). METHODS: Patients were tested during twice daily and then once daily regimens of lamivudine. In both regimens, the total daily dose of lamivudine was identical (300 mg/day). Blood samples for pharmacokinetic analysis were taken over a 12-hour period after > or =7 days of twice daily administration, and again over a 24-hour period after 7 days of once daily administration,. RESULTS: 12 patients completed the study. Lamivudine pharmacokinetic parameters (mean +/- SD) after administration of 150mg twice daily were: peak plasma concentration (Cmax) 2077+/-816 microg/L; trough plasma concentration (Cmin) 332+/-219 microg/L; elimination half-life (t 1/2beta) 6.1+/-1.9h; time to Cmax (t(max)) 1.6+/-0.7h; average concentration over the dosage interval (Cav) 711+/-269 microg/L; and area under the concentration-time curve (AUC) over 2 dosage intervals (24h) 17085+/-6464 microg x h/L. Corresponding values after administration of 300mg once daily were: Cmax 3461+/-854 microg/L; Cmin 146+/-87 microg/L; t1/2 7.9+/-3.4h; t(max) 2.2+/-1.3h; Cav 705+/-177 microg/L; and AUC over 1 dosage interval (24h) 16644+/-4150 microg x h/L. Statistical analysis showed a significant difference (p < 0.05) between the 2 schedules for Cmax and Cmin values, whereas no significant differences emerged for the other parameters. CONCLUSIONS: Once daily lamivudine leads to a similar exposure in plasma as twice daily administration of the same total daily dose. Since once daily administration may result in improved compliance, these results provide the pharmacokinetic basis for using lamivudine in a once daily regimen. Randomised clinical studies are needed to confirm this pharmacokinetic finding.