A qualitative study to explore how patients identify and assess symptoms as adverse drug reactions

Purpose

To explore how Thai patients assess symptoms as adverse drug reactions (ADRs).

Methods

Out-patients at two hospitals in Thailand previously reporting suspected ADRs to statins were purposively selected to cover factors relevant to the accuracy of ADR reports. Semi-structured interviews explored the mechanisms participants used to work out whether their symptoms were related to their statin. All interviews were audio-recorded, transcribed and independently thematically analyzed by two researchers.

Results

One hundred interviews were suitable for analysis; 52 were male, age range was 36 to 77 years (mean?±?S.D.: 59.83?±?9.14) and most (92) were taking other medicines in addition to statins. Patient assessment of symptoms as ADRs fell into two major themes: medicine-related factors and external factors. Timing relationships were mentioned most frequently (74), followed by information received (55), seeing similar symptoms in others (7) and diagnosis through blood tests (4). Use of multiple medicines, consideration of the medicine versus diseases, symptoms occurring with more than one medicine or relieved through treatment reduced confidence in ADR attribution. Many participants proposed alternative explanations for symptoms, including old age. Lack of information and knowledge were obstacles to the assessment process.

Conclusions

Patients assessed possible ADRs most often by considering timing relationships. While they also used medicine information, Thai patients received inadequate information to help them assess their symptoms. Patients expressed uncertainty and difficulties in deciding attribution when concomitant medicines and diseases were involved. The findings could support the development of a patient-friendly systematic tool for identifying and assessing possible ADRs.     

Evaluating the efficiency of specimen pooling for PCR-based detection of COVID-19

In the age of a pandemic, such as the ongoing one caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the world faces a limited supply of tests, personal protective equipment, and factories and supply chains are struggling to meet the growing demands. This study aimed to evaluate the efficacy of specimen pooling for testing of SARS-CoV-2 virus, to determine whether costs and resource savings could be achieved without impacting the sensitivity of the testing. Ten previously tested nasopharyngeal and throat swab specimens by real-time polymerase chain reaction (PCR), were pooled for testing, containing either one or two known positive specimens of varying viral concentrations. Specimen pooling did not affect the sensitivity of detecting SARS-CoV-2 when the PCR cycle threshold (Ct) of original specimen was lower than 35. In specimens with low viral load (Ct > 35), 2 of 15 pools (13.3%) were false negative. Pooling specimens to test for Coronavirus Disease 2019 infection in low prevalence (≤1%) areas or in low risk populations can dramatically decrease the resource burden on laboratory operations by up to 80%. This paves the way for large-scale population screening, allowing for assured policy decisions by governmental bodies to ease lockdown restrictions in areas with a low incidence of infection, or with lower-risk populations.     

Reducing lower extremity amputations due to diabetes: the application of diabetic-foot protocol in Chiang Mai University Hospital

The aim of this study was to determine whether intensive treatment and education strategies for diabetic patients with ulcers help in preventing leg amputation. From August 2005 to March 2007, a diabetic-foot protocol using a multidisciplinary approach was applied at our hospital. All the subjects were educated regarding diabetic-foot disease and its complications and prevention. This report compares the amputation rate in patients receiving the protocol care from August 2005 to March 2007 with those who had standard care from August 2003 to July 2005. Seventy-three and 110 diabetic-foot ulcer patients received protocol and standard foot care, respectively. The incidence of major amputations in the protocol and standard care groups was 4.1% and 13.6%, respectively (P= .03). Our protocol was associated with improved diabetic-foot care outcomes. It can be used by any hospital to improve outcomes for patients with diabetes.     

Acute bacterial rhinosinusitis causes hyperresponsiveness to histamine challenge in mice

OBJECTIVES: To develop a physiologic test of nasal responsiveness in mice and to evaluate whether mice with acute bacterial sinusitis develop nasal hyperresponsiveness. DESIGN: Several experimental studies will be described. The first was a titration pilot study. The second was a randomized, placebo-controlled study. The remainder were before-and-after trials. SPECIES: BALB/c or C57BL/6 mice. INTERVENTIONS: For these experiments, we exposed mice to histamine intranasally, then counted the number of sneezes and nose rubs as the primary outcome measure of nasal responsiveness. First, we constructed a dose-response curve. Second, we treated the mice with desloratadine, a histamine 1 receptor antagonist, prior to histamine exposure. Third, we challenged, with intranasal histamine, mice made allergic using 2 techniques. Fourth, we infected mice with Streptococcus pneumoniae to determine whether acute sinusitis causes nasal hyperresponsiveness to histamine exposure. RESULTS: Nasal histamine challenge led to a reproducible, dose-dependent increase in sneezing and nose rubs. The response to histamine exposure was blocked by desloratadine (P < or = .05). Allergic mice had a significant increase in responsiveness (P < or = .05) over baseline after exposure to antigen. Mice with acute sinusitis had a sustained increase in responsiveness, although less severe than after allergy, compared with baseline values that lasted 12 days after infection (P < or = .05). CONCLUSIONS: Nasal challenge with histamine is a physiologic test of nasal responsiveness. The hyperresponsiveness of allergic mice to histamine exposure parallels the response to nonspecific stimuli during the human allergic reaction. In addition, we showed that acute bacterial sinusitis causes nasal hyperresponsiveness in mice.     

Free fatty acids reduce splanchnic and peripheral glucose uptake in patients with type 2 diabetes

Splanchnic glucose uptake (SGU) plays a major role in the disposal of an oral glucose load (OGL). To investigate the effect of an elevated plasma free fatty acid (FFA) concentration on SGU in patients with type 2 diabetes, we measured SGU in eight diabetic patients (mean age 51 +/- 4 years, BMI 29.3 +/- 1.4 kg/m(2), fasting plasma glucose 9.3 +/- 0.7 mmol/l) during an intravenous Intralipid/heparin infusion and 7-10 days later during a saline infusion. SGU was estimated by the OGL insulin clamp method: subjects received a 7-h euglycemic-hyperinsulinemic clamp (insulin infusion rate = 100 mU x m(-2) x min(-1)), and a 75-g OGL was ingested 3 h after starting the insulin clamp. After glucose ingestion, the steady-state glucose infusion rate during the insulin clamp was decreased appropriately to maintain euglycemia. SGU was calculated by subtracting the integrated decrease in glucose infusion rate during the 4-h period after glucose ingestion from the ingested glucose load (75 g). 3-[(3)H]glucose was infused during the 3-h insulin clamp before glucose ingestion to determine the rates of endogenous glucose production and glucose disappearance (R(d)). Intralipid/heparin or saline infusion was initiated 2 h before the start of the OGL clamp. Plasma FFA concentrations were significantly higher during the OGL clamp with the intralipid/heparin infusion than with the saline infusion (2.5 +/- 0.3 vs. 0.11 +/- 0.02 mmol/l, P < 0.001). During the 3-h insulin clamp period before glucose ingestion, Intralipid/heparin infusion reduced R(d) (4.4 +/- 0.3 vs. 5.3 +/- 0.3 mg x kg(-1) x min(-1), P < 0.01). During the 4-h period after glucose ingestion, SGU was significantly decreased during the intralipid/heparin versus saline infusion (30 +/- 2 vs. 37 +/- 2%, P < 0.01). In conclusion, an elevation in plasma FFA concentration impairs both peripheral and SGU in patients with type 2 diabetes.     

Dose-response effect of elevated plasma free fatty acid on insulin signaling

The dose-response relationship between elevated plasma free fatty acid (FFA) levels and impaired insulin-mediated glucose disposal and insulin signaling was examined in 21 lean, healthy, normal glucose-tolerant subjects. Following a 4-h saline or Liposyn infusion at 30 (n = 9), 60 (n = 6), and 90 (n = 6) ml/h, subjects received a 2-h euglycemic insulin (40 mU . m(-2) . min(-1)) clamp. Basal plasma FFA concentration ( approximately 440 micromol/l) was increased to 695, 1,251, and 1,688 micromol/l after 4 h of Liposyn infusion and resulted in a dose-dependent reduction in insulin-stimulated glucose disposal (R(d)) by 22, 30, and 34%, respectively (all P < 0.05 vs. saline control). At the lowest lipid infusion rate (30 ml/h), insulin receptor and insulin receptor substrate (IRS)-1 tyrosine phosphorylation, phosphatidylinositol (PI) 3-kinase activity associated with IRS-1, and Akt serine phosphorylation were all significantly impaired (P < 0.05-0.01). The highest lipid infusion rate (90 ml/h) caused a further significant reduction in all insulin signaling events compared with the low-dose lipid infusion (P < 0.05-0.01) whereas the 60-ml/h lipid infusion caused an intermediate reduction in insulin signaling. However, about two-thirds of the maximal inhibition of insulin-stimulated glucose disposal already occurred at the rather modest increase in plasma FFA induced by the low-dose (30-ml/h) lipid infusion. Insulin-stimulated glucose disposal was inversely correlated with both the plasma FFA concentration after 4 h of lipid infusion (r = -0.50, P = 0.001) and the plasma FFA level during the last 30 min of the insulin clamp (r = -0.54, P < 0.001). PI 3-kinase activity associated with IRS-1 correlated with insulin-stimulated glucose disposal (r = 0.45, P < 0.01) and inversely with both the plasma FFA concentration after 4 h of lipid infusion (r = -0.39, P = 0.01) and during the last 30 min of the insulin clamp (r = -0.43, P < 0.01). In summary, in skeletal muscle of lean, healthy subjects, a progressive increase in plasma FFA causes a dose-dependent inhibition of insulin-stimulated glucose disposal and insulin signaling. The inhibitory effect of plasma FFA was already significant following a rather modest increase in plasma FFA and develops at concentrations that are well within the physiological range (i.e., at plasma FFA levels observed in obesity and type 2 diabetes).     

Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes

The effect of pioglitazone on splanchnic glucose uptake (SGU), endogenous glucose production (EGP), and hepatic fat content was studied in 14 type 2 diabetic patients (age 50 +/- 2 years, BMI 29.4 +/- 1.1 kg/m(2), HbA(1c) 7.8 +/- 0.4%). Hepatic fat content (magnetic resonance spectroscopy) and SGU (oral glucose load- insulin clamp technique) were quantitated before and after pioglitazone (45 mg/day) therapy for 16 weeks. Subjects received a 7-h euglycemic insulin (100 mU. m(-2). min(-1)) clamp, and a 75-g oral glucose load was ingested 3 h after starting the insulin clamp. Following glucose ingestion, the steady-state glucose infusion rate during the insulin clamp was decreased appropriately to maintain euglycemia. SGU was calculated by subtracting the integrated decrease in glucose infusion rate during the 4 h after glucose ingestion from the ingested glucose load. 3-[(3)H]glucose was infused during the initial 3 h of the insulin clamp to determine rates of EGP and glucose disappearance (R(d)). Pioglitazone reduced fasting plasma glucose (10.0 +/- 0.7 to 7.5 +/- 0.6 mmol/l, P < 0.001) and HbA(1c) (7.8 +/- 0.4 to 6.7 +/- 0.3%, P < 0.001) despite increased body weight (83 +/- 3 to 86 +/- 3 kg, P < 0.001). During the 3-h insulin clamp period before glucose ingestion, pioglitazone improved R(d) (6.9 +/- 0.5 vs. 5.2 +/- 0.5 mg. kg(-1). min(- 1), P < 0.001) and insulin-mediated suppression of EGP (0.21 +/- 0.04 to 0.06 +/- 0.02 mg. kg(-1). min(-1), P < 0.01). Following pioglitazone treatment, hepatic fat content decreased from 19.6 +/- 3.6 to 10.4 +/- 2.1%, (P < 0.005), and SGU increased from 33.0 +/- 2.8 to 46.2 +/- 5.1% (P < 0.005). Pioglitazone treatment in type 2 diabetes 1) decreases hepatic fat content and improves insulin-mediated suppression of EGP and 2) augments splanchnic and peripheral tissue glucose uptake. Improved splanchnic/peripheral glucose uptake and enhanced suppression of EGP contribute to the improvement in glycemic control in patients with type 2 diabetes.     

Normalization of plasma glucose concentration by insulin therapy improves insulin-stimulated glycogen synthesis in type 2 diabetes.

Considerable evidence suggests that skeletal muscle insulin resistance is an inherent feature of type 2 diabetes and contributes to the pathogenesis of the disease. In patients with poorly controlled diabetes, hyperglycemia is thought to produce additional insulin resistance in muscle. The magnitude and nature of hyperglycemia-induced insulin resistance is not known. The purpose of the present study was to determine the biochemical mechanisms responsible for increased insulin-stimulated glucose disposal after the achievement of tight glycemic control with a mixed-split regimen. We performed hyperinsulinemic-euglycemic clamps with indirect calorimetry and vastus lateralis muscle biopsies in eight type 2 diabetic patients who had poor glycemic control (HbA(1c) 10.1%) and again after 3 months of intensive insulin therapy designed to produce near-normoglycemia (HbA(1c) 6.6%). Improved glycemic control increased insulin-stimulated glucose disposal (5.16 +/- 0.32 vs. 3.69 +/- 0.33 mg x kg(-1) x min(-1); P < 0.01); nonoxidative glucose disposal, which primarily reflects glycogen synthesis (2.11 +/- 0.26 vs. 0.90 +/- 0.16 mg x kg(-1) x min(-1); P < 0.01); and glycogen synthase fractional velocity (0.094 +/- 0.017 vs. 0.045 +/- 0.007; P < 0.05). There was no improvement in insulin-stimulated glucose oxidation (3.05 +/- 0.25 vs. 2.79 +/- 0.20 mg x kg(-1) x min(-1)), hexokinase II mRNA expression (increase over basal values), or hexokinase II enzymatic activity (0.51 +/- 0.16 vs. 0.42 +/- 0.18 pmol x min(-1) x microg(-1) protein). All of the increase in insulin-stimulated glucose disposal could be accounted for by increased glycogen synthesis, which is likely attributable to increased activation of glycogen synthase by insulin.     

Anti-inflammatory activity of lansais from endophytic Streptomyces sp. SUC1 in LPS-induced RAW 264.7 cells

This research was undertaken to find the in vitro inflammatory action of lansai A–D produced by Streptomyces sp. SUC1. We investigated the effects of lansai C not only on the formation of nitric oxide (NO), prostaglandin E₂ (PGE₂), tumour necrosis factor (TNF-α), interleukin (IL)-1α, IL-6 and IL-10, but also on inducible NO synthase and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells. The data obtained were consistent with the modulation of inducible nitric oxide synthase enzyme expression. A similar fashion was also observed when LPS-induced PGE₂ release and COX-2 expression were tested. The significant inhibitory effects were shown in concentration-dependent manners. In addition, lansai C also mildly but significantly reduced the formation of TNF-α. These findings support the application of lansai C as anti-inflammatory agent.