Errors in medication history at hospital admission: prevalence and predicting factors

Background

Data on adverse drug reactions (ADRs) related to antiretroviral (ARV) use in public health practice are few indicating the need for ART safety surveillance in clinical care.

Objectives

To evaluate the incidence, type and risk factors associated with adverse drug reactions (ADRs) among patients on antiretroviral drugs (ARV).

Methods

Patients initiated on ARVs between May 2006 and May 2009 were evaluated in a retrospective cohort analysis in three health facilities in Nigeria. Regimens prescribed include nucleoside backbone of zidovudine (AZT)/lamivudine (3TC), stavudine (d4T)/3TC, or tenofovir (TDF)/3TC in combination with either nevirapine (NVP) or efavirenz (EFV). Generalized Estimating Equation (GEE) model was used to identify risk factors associated with occurrence of ADR.

Results

2650 patients were followed-up for 2456 person-years and reported 114 ADRs (incidence rate = 4.6/100 person-years).There were more females 1706(64%) and 73(64%) of the ADRs were reported by women. Overall, 61(54%) of ADRs were reported by patients on AZT with 54(47%) of these occurring in patients on AZT/NVP. The commonest ADRs reported were pain 25(30%) and skinrash 10(18%). Most ADRs were grade 1(39%) with only 1% being life threatening (grade 4). Adjusted GEE analysis showed that ADR was less likely to occur in patients on longer duration of ART compared to the first six months on treatment; 6-12 months AOR 0.38(95% CI:0.16-0.91) and 12-24 months AOR 0.34(95% CI:0.16-0.73) respectively. Compared to patients on TDF, ADR was less likely to occur in patients on d4T and AZT AOR 0.18(95% CI 0.05-0.64) and AOR 0.24(95% CI:0.7-0.9) respectively. Age, gender and CD4 count were not significantly associated with ADRs.

Conclusion

ADRs are more likely to occur within the first six months on treatment. Close monitoring within this period is required to prevent occurrence of severe ADR and improve ART adherence. Further research on the tolerability of tenofovir in this environment is recommended.     

Strategy for antithyroid drug therapy in Graves' disease

A critical review of the literature concerning the treatment of patients with Graves' disease discusses the multitude of protocols used. Prospective studies of patients treated with carbimazole alone for a predetermined duration reveal that the remission rate after 6 years' follow-up is between 40 and 50%. The incidence of treatment duration on remission rates is discussed: the authors think that long-term treatments give better results than short-term treatments. Nevertheless, no standard duration for treatment can be indicated and the most appropriate attitude is an adaptation to each individual case. Various criteria which could modify the prognosis are discussed: small goiter size and normalization of early iodine uptake improve the prognosis. While better results were obtained after high doses of carbimazole in a preliminary work, further study is necessary to clarify this point.     

Proteomic analysis of the pathophysiological process involved in the antisnake venom effect of Mucuna pruriens extract

Previously, we reported the antisnake venom properties of a Mucuna pruriens seed extract (MPE) and tested its in vivo efficacy against Echis carinatus venom (EV) in short- (1 injection) and long-term (three weekly injections) treatments. The aim of the present study was to investigate plasma proteome changes associated with MPE treatments and identify proteins responsible for survival of envenomated mice (CHALLENGED mice). Six treatment groups were studied. Three control groups: one saline, one short-term and one long-term MPE treatment. One group received EV alone. Two test groups received EV with either a short-term or long-term MPE treatment (CHALLENGED mice). The plasma from each group was analysed by 2-DE/MALDI-TOF MS. The most significant changes with treatment were: albumin, haptoglobin, fibrinogen, serum amyloid A and serum amyloid P. Most of these changes were explained by EV effects on coagulation, inflammation and haemolysis. However, MPE treatments prevented the EV-induced elevation in HPT. Consequently, HPT levels were similar to controls in the plasma of CHALLENGED mice. The plasma of CHALLENGED mice showed substantial proteomic modifications. This suggests the mechanism of MPE protection involves the activation of counterbalancing processes to compensate for the imbalances caused by EV.     

Antithyroid drug therapy for Graves' hyperthyroidism: is long-term administration of a small maintenance dose necessary?

This retrospective study serves as an inquiry into the common practice of long-term administration of small maintenance doses of either methyl-mercaptoimidazole (MMI) or propylthiouracil (PTU) to Graves' hyperthyroid patients who became euthyroid with primary large doses of the same drugs. One hundred and two patients with Graves' hyperthyroidism treated with antithyroid drug (ATD) were studied. Sixty-one were treated with conventional long term therapy and 41 were treated with short-term therapy. Small maintenance doses of ATDs were not administered to the short-term therapy patients. The duration of long-term therapy was 28.6 +/- 20.2 months (from 12 to 48 months) and that of short-term therapy was 8.4 +/- 1.8 months (from 5 to 11). Post therapy and follow-up observation continued for 19.0 +/- 2.7 months (16-25 months) in both long-term and short-term patients. Of the 61 long-term therapy patients, 20 were relapsed and 41 (67.2%) continue to remain in remission. So too, of the 41 short-term therapy patients, 14 relapsed and 27 (65.9%) still remain in remission. There was no statistical difference between the long-term and short-term therapy group in age, sex, duration of symptoms before diagnosis, antithyroid antibodies, radioactive iodine uptake, free thyroid hormone levels or goiter size before treatment or in TBII levels at cessation of ATD. It is concluded that 'short-term ATD therapy' without a maintenance dose is sufficient and saves several months of the patient's and clinician's time.     

Obese patients in medical intensive care unit: influence of counseling on weight loss and cardiovascular parameters

A case series of 12 obese patients admitted to medical intensive care unit (ICU) due to life-threatening diseases and the influence of weight loss on cardiovascular parameters is presented. We assessed body weight, body mass index (BMI), blood pressure, pulse, and laboratory values on admission. At discharge from ICU patients were counseled on how to lose weight. They were examined one and six months later. Statistically significant (p < 0.05) decrease of body weight (median at the beginning of a treatment 134 kg, after six months 127.5 kg), BMI (median 41.5 kg/m2 at the beginning of a treatment; 38.9 kg/m2 after six months), systolic blood pressure (medians 145 mmHg and 130 mmHg), diastolic blood pressure (medians 95 mmHg and 85 mmHg) and pulse (medians 104 beats per minute, 78 beats per minute) was found. The reduction of the waist circumference was not significant. One patient died due to severe acute pancreatitis. Patients reported feeling much better after losing weight.     

Effect of long- and short-term intravaginal progestagen treatments on synchronization of oestrus and fertility in heifers.

A total of 273 Herford cross heifers were treated with intravaginal progestagen pessaries to determine some of the factors affecting oestrous response and fertility following long-term (20-day) and short-term (10-day) treatments. Oestrous response and degree of synchronization were high after treatment for 20 days, but the fertility rate was lower than that of control heifers. There was no difference in the fertility of heifers inseminated artificially and those mated naturally. When the treatment period was reduced to 10 days and 900 mg progesterone and 5 mg oestradiol valerate given intramuscularly at the start, a high oestrous response and a low degree of synchronization resulted, but the conception rate was similar to that of the control animals. Reducing the dose of progesterone to 250 mg resulted in a high oestrous response and a high degree of synchronization. The stage of the cycle at the start of the 10-day treatment did not affect the oestrous response. Retention of the progesterone pessary was low (79-9%) in heifers treated for 2- days, but was 100% in those treated for 10 days.     

Lithium action on adrenomedullary and adrenocortical functions and serum ionic balance in different age-groups of albino rats

The aim of the current study was to investigate lithium action on adrenomedullary and adrenocortical functions and on serum ionic balance in rats. Three age-groups of male rats (juvenile: 30 days, adult: 100 days and aged: 3 years) were used. Each age-group of animal was exposed to short- (10 days) and long-term (25 days) treatments with lithium. Each age-group of rat received lithium at a dose 2mEq/kg body weight daily for 10 and 25 days. Each daily dose (2mEq) was divided equally into half (1 mEq) and each half was injected intraperitoneally twice (at 9 am and 9 pm) for both the durations of experiments. Control animals received physiological saline for similar duration of experiments. Thirty animals were used for each age-group and they were divided equally into 6 groups with 5 each. After termination of all the experiments rats were sacrificed and, adrenal glands were quickly dissected out and processed for epinephrine, norepinephrine and corticosterone estimations and, 3 beta-hydroxysteroid dehydrogenase (3 beta-HSDH) activity of the adrenal gland. Blood was drawn from the heart of each rat and, serum was collected and stored at -20 degrees C until assayed for lithium, calcium, sodium, potassium and corticosterone concentrations. The findings revealed that lithium in both short- and long-term treatments was maintained well within the therapeutic range (0.3-0.8 mEq/l) in all the age-groups of rats. This alkali metal caused depletions of both epinephrine and norepinephrine concentrations from adrenal glands, and elevations of corticosterone in both adrenal and blood serum of each age-group of rat (juvenile, adult and aged). Additionally adrenal 3beta-HSDH activity was also increased in all the age-groups of rats irrespective of duration of the treatments. Short-term treatment of lithium elevated only serum K+ level in juvenile and adult rats and, Ca+ level only in adult animals. Significant elevations of serum K+ and Ca+ levels were observed following long-term treatments of lithium in all the age group of rats. No significant change in serum Na+ level was recorded after lithium treatment, irrespective of duration of treatments, in any age-group of rats. The findings suggest that lithium action, in respect of adrenomedullary and adrenocortical functions and, serum ionic balance, may not be largely related to the age-group of rats and that, lithium acts on adrenomedullary activity probably by stimulating the release mechanism of epinephrine and norepinephrine from the adrenal gland of rats, but stimulates adrenocortical activity by stimulating both synthesis (including 3 beta-HSDH activity) and release of corticorterone. Simultaneously, lithium disturbs normal ionic balance by elevating K+ and Ca+ levels in all the age-group of rats. Thus, the antimanic drug certainly disturbs both adrenomedullary and adrenocortical functions and, serum ionic balance in all the age-group of rats.     

Effect of estradiol supplementation on superovulation in Swamp buffalo

The effect of estradiol-17beta (E(2)) supplementation on superovulation with (PMSG) or (FSH) was investigated in Swamp buffalo. Sixty-eight buffalo were treated in seven groups. Group 1 served as control and was superovulated by standard PMSG or FSH treatment used in routine bovine embryo transfer protocols. Group 2 was superovulated by standard PMSG regimen plus two injections of E(2) at a 48 h interval beginning one day before the onset of gonadotropin treatment (short-term supplementation) for a total dosage of 2.5 mg E(2); Groups 3 and 4 received the same regimen as Group 2, but in doses of 5.0 and 7.5 mg E(2), respectively. Group 5 received the standard FSH regimen (40% LH). Group 6 received short-term E(2) (7.5 mg) supplementation of FSH-p. Group 7 was superovulated by standard FSH regimen (40% LH) plus three injections of E(2) at 48-72 h intervals beginning five days before the onset of gonadotropin treatment (long-term supplementation) for a total dosage of 7.5 mg E(2). The number of corpora lutea (CL) and follicles >/= 8 mm in diameter were recorded by palpation per rectum and after slaughter. The mean numbers of CL and follicles were 0.99, 5.8, 8.0, 10.6, 4.0, 3.9, 8.1 and 0.25, 6.8, 6.2, 6.2, 1.6, 0.0, 4.1 for Groups 1, 2, 3, 4, 5, 6, 7, respectively. In Group 7, the rates of nonsurgical and postmortem embryo recovery were 46 and 90.4%, respectively and 54.4% of the collected ova were fertilized. These results indicate the possibility of producing viable embryos in buffalo by using E(2) supplementation for the gonadotropin treatment.     

Predictors of response to combined wake and light therapy in treatment-resistant inpatients with depression

ABSTRACT

There is growing evidence for combined chronotherapeutic interventions as adjunctive treatments for major depression. However, as the treatments can be demanding, we need to identify predictors of response. This study aimed to describe predictors of response, remission and deterioration in the short-term phase, as well as predictors of long-term response. The predictors investigated were gender, type of depression, severity of depression, treatment resistance, quetiapine use, general self-efficacy, educational level and positive diurnal variation. Follow-up data from 27 inpatients with moderate-to-severe depression participating in a chronotherapeutic intervention were analysed. As a supplement to standard treatment, they completed 3 wake therapy sessions in the first week, 30 min daily light treatment and sleep-time stabilisation in the entire 9-week study period. Patients had a significant decrease of depressive symptoms during the first 6 days measured by HAM-D6. At Day 6, 41% of the patients responded to the treatment and 19% fulfilled the criteria of remission. Deterioration by the end of wake therapy sessions was however not uncommon. In the short-term phase, mild degree of treatment resistance was associated with remission and low educational level associated with deterioration. Positive diurnal variation (mood best in the evening) was a predictor of both short-term and long-term response to combined wake and light therapy. Furthermore, patients with evening chronotypes (measured with morningness-eveningness score) were more responsive. Our results suggest that targeting the combined chronotherapeutic intervention at patients with positive diurnal variation and evening types is a viable option.     

Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions

We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2–10 months for known ADRs and 19–44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0–122.5 days and 185.5–306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release.     

Integration of HBV-DNA into liver and hepatocellular carcinoma cells during persistent HBV infection

The hepatitis B virus carrier state (persistent HBV infection) is characterized by the presence of viral surface antigen (HBsAg) and virion particles (Dane particles) in the blood. From 1% to 10% of carriers develop chronic liver disease and/or hepatocellular carcinoma. Recent studies have demonstrated integrated HBV-DNA in hepatocellular carcinomas and in several human hepatoma cell lines. In hepatoma patients, integrated HBV-DNA has been found in all HBsAg carriers. Nontumorous liver also revealed integrated HBV-DNA with the same or a different hybridization pattern from that observed in the tumor. To explore when integration occurs, carriers of short-term (less than 2 years) or long-term (greater than 8-10 years) were evaluated. DNA extracts from percutaneous (needle) liver biopsies showed free viral DNA with no specific integration bands in short-term carriers. In long-term carriers, HBV-DNA was integrated into the host genome with either a diffuse or a unique hybridization pattern. HBV-DNA integration correlated with the duration of the carrier state and absence of virions in the serum but did not correlate with histologic evidence of chronic hepatitis. These studies suggest that integration of HBV-DNA occurs during persistent HBV infection irrespective of liver disease and precedes development of hepatocellular carcinoma.     

Rituximab in patients with rheumatoid arthritis in routine practice (GERINIS): six-year results from a prospective,multicentre, non-interventional study in 2,484 patients

Introduction

The aim of this study was to evaluate the safety and efficacy of rituximab (RTX) in a large cohort of patients with rheumatoid arthritis in routine care, and to monitor changes in daily practice since the introduction of RTX therapy.

Methods

This was a multicentre, prospective, non-interventional study conducted under routine practice conditions in Germany. Efficacy was evaluated using Disease Activity Score in 28 joints (DAS28) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Safety was assessed by recording adverse drug reactions (ADRs). Physician and patient global efficacy and tolerability assessments were also evaluated.

Results

Overall, 2,484 patients (76.7% female, mean age 56.4 years, mean disease duration 11.7 years) received RTX treatment (22.7% monotherapy). The total observation period was approximately six-years (median follow-up 14.7 months). RTX treatment led to improvements in DAS28 and HAQ-DI that were sustained over multiple courses. DAS28 improvements positively correlated with higher rheumatoid factor levels up to 50 IU/ml. Response and tolerability were rated good/very good by the majority of physicians and patients. Mean treatment intervals were 10.5 and 6.8 months for the first and last 400 enrolled patients, respectively. Infections were the most frequently reported ADRs (9.1%; 11.39/100 patient-years); approximately 1% of patients per course discontinued therapy due to ADRs.

Conclusions

Prolonged RTX treatment in routine care is associated with good efficacy and tolerability, as measured by conventional parameters and by physicians’ and patients’ global assessments. Rheumatoid factor status served as a distinct and quantitative biomarker of RTX responsiveness. With growing experience, physicians repeated treatments earlier in patients with less severe disease activity.     

Short- and long-term cognitive effects of chronic cannabinoids administration in late-adolescence rats

The use of cannabis can impair cognitive function, especially short-term memory. A controversial question is whether long-term cannabis use during the late-adolescence period can cause irreversible deficits in higher brain function that persist after drug use stops. In order to examine the short- and long-term effects of chronic exposure to cannabinoids, rats were administered chronic i.p. treatment with the CB1/CB2 receptor agonist WIN55,212-2 (WIN; 1.2 mg/kg) for two weeks during the late adolescence period (post-natal days 45-60) and tested for behavioral and electrophysiological measures of cognitive performance 24 hrs, 10 and 30 days after the last drug injection. The impairing effects of chronic WIN on short-term memory in the water maze and the object recognition tasks as well as long-term potentiation (LTP) in the ventral subiculum (vSub)-nucleus accumbens (NAc) pathway were temporary as they lasted only 24 h or 10 d after withdrawal. However, chronic WIN significantly impaired hippocampal dependent short-term memory measured in the object location task 24 hrs, 10, 30, and 75 days after the last drug injection. Our findings suggest that some forms of hippocampal-dependent short-term memory are sensitive to chronic cannabinoid administration but other cognitive impairments are temporary and probably result from a residue of cannabinoids in the brain or acute withdrawal effects from cannabinoids. Understanding the effects of cannabinoids on cognitive function may provide us with tools to overcome these impairments and for cannabinoids to be more favorably considered for clinical use.     

Response of Winter Wheat Seedlings Respiration to Long-Term Cold Exposure and Short-Term Daily Temperature Drops

Russian Journal of Plant Physiology - The effects of a long-term (6-day) exposure to low positive temperature (4°С, LT treatment) and short-term (3 h per a day for 6 days) daily...     

Autoimmune progesterone dermatitis in a patient with endometriosis: case report and review of the literature

Autoimmune progesterone dermatitis (APD) is a condition in which the menstrual cycle is associated with a number of skin findings such as urticaria, eczema, angioedema, and others. In affected women, it occurs 3-10 days prior to the onset of menstrual flow, and resolves 2 days into menses. Women with irregular menses may not have this clear correlation, and therefore may be missed. We present a case of APD in a woman with irregular menses and urticaria/angioedema for over 20 years, who had not been diagnosed or correctly treated due to the variable timing of skin manifestations and menses. In addition, we review the medical literature in regards to clinical features, pathogenesis, diagnosis, and treatment options.     

Short-term and long-term effects of mowing on the vegetation of two calcareous fens

Abstract. Short-term field experiments are often used to predict and evaluate long-term management effects. Based on a mowing experiment in two calcareous fens near Lake Neuchâtel, Switzerland, we investigated whether short-term treatment effects (i.e. during the first four years) were confirmed by long-term results (13 - 14 yr). Plots were mown in summer or in winter or left unmown. The main long-term trends in overall species composition (based on percentage cover estimates) were already observable in the first four years: mown and unmown plots diverged, whereas summer-cut and winter-cut plots remained similar. At the individual species level, however, short-term and long-term treatment effects differed considerably: many species whose abundance seemed affected by treatments during the first four years showed no response in the long term, and vice versa. These discrepancies were similar when based on cover estimates or on counts of shoots. Species responses did actually depend on the time scale considered. Short-term and long-term treatment effects on species richness were similar (i.e. a decrease in unmown plots), although only long-term effects were significant. Treatment effects on the above-ground biomass varied considerably, and short-term trends (lower biomass in unmown plots) differed from long-term trends (higher biomass in unmown plots). Our sites showed little overall change in species composition during the period investigated, and treatment effects were low compared with other similar experiments. If study sites are less stable or treatment effects more drastic, a short-term evaluation is expected to be even less reliable. Knowledge on species dynamics at a site may help to choose the adequate spatial and temporal scale of investigation, and thus increase the efficiency of management experiments.     

Improved combination chemotherapy in advanced gastric cancer.

Thirty-five patients with advanced-stage metastatic or unresectable gastric adenocarcinoma were given combination chemotherapy consisting of fluorouracil, doxorubicin, and 1,3-bis (2-chlorbethyl)-1-nitrosourea. Two patients achieved complete remission and 16 partial remission to give an overall response rate of 52%. Six further patients (17%) had stable disease, while in 11 (31%) the disease showed clear-cut progression despite treatment. The only pretreatment factors that suggested poor prognosis were poor initial patient performance and the stomach as the predominant site of disease. Patients responding to treatment had a significantly longer time to relapse (median 48 weeks) than patients with stable disease (median 16 weeks) and a significantly improved survival time (medians, 52 weeks with 30% of patients'' living at 88 weeks and 32 weeks with all dead at 64 weeks respectively). Comparing these results with those in other reports indicated that the three-drug combination chemotherapy consisting of fluorouracil, doxorubicin, and either a nitrosourea or mitomycin was superior to single and two-drug regimens and currently represents the optimum treatment for advanced-stage gastric cancer. Gastric adenocarcinoma should now be considered to be a gastrointestinal malignancy that is relatively susceptible to chemotherapy, and studies of these improved chemotherapeutic regimens as post-surgical adjuvants may lead to further improvements in prognosis.     

Successful simplification of HAART in patients with acute primary HIV infection

Aggressive treatment has been advocated for the management of primary HIV infection (PHI), but the composition and the optimal duration of therapy are still to be determined. In addition, time to undetectable viral load (VL), rate and duration of VL suppression as well as subsequent therapeutic choices remain issues widely debated. We evaluated the rate and duration of VL suppression in 12 consecutive patients with PHI given triple-drug treatment with zidovudine, lamivudine and indinavir (highly active antiretroviral therapy, HAART) at onset of the acute illness and subsequently switched to a simplified 2-NRTI-based regimen once VL suppression was maintained for at least 6 months. Throughout the study, no patient discontinued treatment because of symptoms attributed to the study medications. In the study population, undetectable VL was achieved after a median of 84 days (range: 67-135) on HAART and was maintained for a median of 194 days (range: 179-205) before simplification. After switching to simplified maintenace, undetectable VL was maintained in all patients for at least 6 months. Only one patient experienced virological failure, plasma HIV-RNA remaining suppressed for a median foliow-up of 33 months (15-54) and T-CD4+ being steadily higher than 500/mL in the remaining patients. Our results suggest that simplification of HAART in patients promptly treated during PHI and maintaining undetectable VL for at least 6 months before simplification may be a valid option capable of controlling viral replication and maintaining an optimal immunological profile for a prolonged time.     

CO2浓度升高和不同氮源对紫茎泽兰生长及光合特性的影响

大气CO2浓度升高和植物入侵是全世界面临的两大重要问题。CO2浓度升高促进植物的光合作用,但在某些植物中,这种促进作用出现在短期高浓度CO2下,而在长期高浓度CO2处理下消失（称为CO2驯化）,被认为源于高浓度CO2对光呼吸和NO-3同化的抑制。通过比较研究不同形式氮源（全氮、硝态氮）和短期（8 days）、长期（40 days）CO2浓度升高处理对入侵植物紫茎泽兰生理特征的影响,结果表明在全氮供应下,短期和长期CO2浓度升高均促进了紫茎泽兰的光合;氨态氮缺失情况下,长期CO2浓度升高促进紫茎泽兰的光合,而短期CO2浓度升高对紫茎泽兰的光合没有促进作用;缺NH＋4下,短期高浓度CO2提高了叶片叶绿素含量,长期CO2升高又使其回复到正常CO2下的较低水平。这些结果表明紫茎泽兰并不会对长期的CO2升高产生驯化,即长期CO2升高会促进紫茎泽兰的光合作用,而且这一促进作用不受土壤中缺NH＋4的影响。鉴于培养介质中缺NH＋4会导致一些植物产生“CO2驯化”,未来CO2浓度升高情况下,在缺NH＋4的土壤中,紫茎泽兰的竞争力可能会更强。