Patient reported outcomes in gastroesophageal reflux disease: An overview of available measures

Gastroesophageal reflux disease (GERD) is a common, chronic disorder. The main symptom of GERD is heartburn, although a diverse range of symptoms can be associated with the disease including acid regurgitation and epigastric pain. GERD is also a risk factor for Barrett’s oesophagus and esophageal adenocarcinoma. The impact of GERD symptoms on patients’ lives can be profound and is unrelated to the presence or absence of esophagitis. The impact of GERD can be measured by assessing the patient perspective using Patient Reported Outcomes (PROs). There are two categories of questionnaires that can be used to measure the effect of GERD on health-related quality of life (HRQoL), namely generic and disease or treatment specific. The use of PRO instruments has become more accepted in the assessment of disease treatment. Well-designed instruments that assess physical, psychological and emotional factors can provide clinicians with the data that will promote effective management decisions for the treatment of GERD. The most frequently used instruments in GERD are reviewed here, in terms of their psychometric properties.     

Burden of illness in Polish patients with reflux disease

The clinical and socioeconomic burden of gastro-esophageal reflux disease (GERD) is considerable. The primary symptom of GERD is heartburn, but it may also be associated with extraesophageal manifestations, such as asthma, chest pain and otolaryngologic disorders. The objective of the study was to describe the impact of heartburn on patients' Health-Related Quality of Life (HRQL) in Poland, using validated generic and disease-specific instruments to measure patient-reported outcomes. Patients with symptoms of heartburn completed the Polish versions of the Gastrointestinal Symptom Rating Scale (GSRS), the Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD), the Short Form-36 (SF-36) and the Hospital Anxiety and Depression (HAD) scale. Frequency and severity of heartburn during the previous 7 days were also recorded. 135 patients completed the assessments (mean age of 44 years, SD = 15; 61% female). 55% of patients had moderate symptoms and nearly two thirds (64%) had symptoms on 5 or more days in the previous week. Patients were most bothered by symptoms of reflux (mean GSRS score of 4.1, on a scale of 1 [not bothered] to 7 [very bothered]), indigestion (3.5) and abdominal pain (3.2). As a result of their symptoms, patients experienced impaired vitality (mean QOLRAD score of 3.8, on a scale of 1 to 7, where 1 represents the most severe impact on daily functioning), problems with food and drink (3.9), emotional distress (4.1) and sleep disturbance (4.7). Using HAD, 32% of heartburn patients were anxious and 10% were depressed. In conclusion it should be stated that there is consistent evidence that GERD substantially impairs all aspects of health-related quality of life.     

Adapting the Jalowiec coping scale in Norwegian adult psoriasis patients

The aim of the present study was to adapt the Jalowiec Coping Scale (JCS) to accommodate adult patients with psoriasis. The sample comprised 334 patients who were treated consecutively at three dermatology departments in the eastern Norway. A total number of 273 hospitalised patients (20) and out-patients (80) completed the questionnaire, yielding a response rate of 82. The study assessed the reliability and the face, content and construct validity of the Norwegian version of the JCS. In addition, researchers investigated the most frequently used/effective coping strategies, the relationships between demographic/clinical variables, self-reported physical symptoms and the use of coping strategies. The results (correlational coefficients and interitem s) indicated that there was an overlap in substantive content among the original JCS' subscales, due either to measurement error (bias or response style) and/or because the patients in the present study were in a demanding situation in relation to their disease, which may have activated a variety of coping strategies. A factor analysis resulted in a three-factor solution (confrontive problem-solving, normalising/optimistic and combined emotive) with satisfactory internal consistency. This factor solution comprised 31 items with an explained variance of 37 of the total pool of items. The most frequently used and effective coping strategies could be labelled as emotion-focused (optimistic/maintain control). Significant correlations were found between age, hospital setting, self-reported physical symptoms and different coping subscales. However, further studies are needed to assess the validity and reliability of the JCS among different population groups in Norway.     

复方丹参片中三七总皂苷的含量测定

目的:建立复方丹参片中三七皂苷R1、人参皂苷Rb1及人参皂苷Rg1含量测定方法。方法:采用HPLC法,用Diamonsil C18(250 mm×4.6 mm,5μm)色谱柱,乙腈-0.05%磷酸溶液为流动相。检测波长为203 nm,流速为1.0 mL/min,进样量为10μL。结果:三七皂苷R1线性回归方程Y=187.0X+16.16,r=0.9997,三七皂苷R1含量在0.366-3.206μg之间为良好线性关系。人参皂苷Rb1含量在0.911-9.241μg之间为良好线性关系。人参皂苷Rg1线性回归方程Y=403.6X+9.113,r=0.9994,人参皂苷Rg1含量在0.841-8.431μg之间为良好线性关系。结论:该法可以用于测定复方丹参片中三七皂苷R1、人参皂苷Rb1及人参皂苷Rg1含量,可以为药物的质量控制提供参考。     

Dual bronchodilatory and pulmonary anti-inflammatory activity of RO5024118, a novel agonist at vasoactive intestinal peptide VPAC2 receptors

BACKGROUND AND PURPOSE

Vasoactive intestinal peptide is expressed in the respiratory tract and induces its effects via its receptors, VPAC₁ and VPAC₂. RO5024118 is a selective VPAC₂ receptor agonist derived via chemical modification of an earlier VPAC₂ agonist, RO0251553. In the present studies, we characterized the pharmacological activity of RO5024118.

EXPERIMENTAL APPROACH

Stability of RO5024118 to human neutrophil elastase was assessed. Bronchodilatory activity of RO5024118 was investigated in guinea pig and human isolated airway smooth muscle preparations and in a guinea pig bronchoconstriction model. Pulmonary anti-inflammatory activity of RO5024118 was investigated in a lipopolysaccharide mouse model and in a porcine pancreatic elastase (PPE) rat model.

KEY RESULTS

RO5024118 demonstrated increased stability to neutrophil elastase compared with RO0251553. In human and guinea pig isolated airway preparations, RO5024118 induced bronchodilatory effects comparable with RO0251553 and the long-acting β-agonist salmeterol and was significantly more potent than native vasoactive intestinal peptide and the short-acting β-agonist salbutamol. In 5-HT-induced bronchoconstriction in guinea pigs, RO5024118 exhibited inhibitory activity with similar efficacy as, and longer duration than, RO0251553. In a lipopolysaccharide-mouse model, RO5024118 inhibited neutrophil and CD8⁺ cells and myeloperoxidase levels. In rats, intratracheal instillation of PPE induced airway neutrophilia that was resistant to dexamethasone. Pretreatment with RO5024118 significantly inhibited PPE-induced neutrophil accumulation.

CONCLUSIONS AND IMPLICATIONS

These results demonstrate that RO5024118 induces dual bronchodilatory and pulmonary anti-inflammatory activity and may be beneficial in treating airway obstructive and inflammatory diseases.     

Risk of cancer in pesticide applicators in Swedish agriculture.

The risk of cancer was analysed in a cohort of 20,245 licensed pesticide applicators in agriculture who had licences issued between 1965 and 1976. Most were men (99%) and about 50% had been born in 1935 or later. The cohort was followed up in the Swedish Cancer Register from date of licence until death or 31 December 1982. The mean follow up time was 12.2 years. Average time since first exposure was longer, however, since one fifth of the cohort was exposed in the 1950s. A total of 558 malignant tumours was found compared with 649.8 expected, which resulted in a statistically significantly decreased standardised incidence ratio (SIR) of 0.86 (95% confidence interval (CI): 0.79-0.93). Significantly decreased risks of cancer were also found for liver (SIR = 0.45, 95% CI: 0.18-0.93), pancreas (SIR = 0.50, 95% CI: 0.26-0.87), lung (SIR = 0.50, 95% CI: 0.35-0.68), and kidney (SIR = 0.53, 95% CI: 0.32-0.84). No statistically significantly increased risks or any time trends were observed. SIR for testicular cancer was increased (SIR = 1.55, 95% CI: 0.92-2.45) and increased with period since licence. Eighteen cases with testicular cancer were found. For those born in 1935 or later a non-significant increased overall risk of cancer was observed (SIR = 1.07, 95% CI: 0.82-1.37). Comparisons were made with agricultural workers in general since pesticide applicators are mainly farmers that use or have used pesticides to a greater extent. Higher risks for pesticide applicators were found for testicular cancer, tumours of the nervous system and endocrine glands, and Hodgkin's disease.     

Expression of cyclin A in soft tissue sarcomas correlates with tumor aggressiveness.

Cyclins and cyclin-dependent kinases regulate the cell cycle. Cyclin A has a dual role in cell proliferation. It is essential in the S phase for DNA replication, and it is also involved in G2-M-phase transition, signifying actively dividing cells. The expression of cyclin A was determined by immunohistochemistry in paraffin sections of 126 soft tissue sarcomas. The median cyclin A score was 10.8% (range, 1-54%). Cyclin A expression correlated with the S-phase fraction, Ki-67 score, G2-M phase, and grade. It did not correlate with the size of the tumor. A high cyclin A score predicted a poor metastasis-free survival (P < 0.01) and a poor disease-specific overall survival (P = 0.01). We concluded that the expression of cyclin A is a powerful prognostic factor in soft tissue sarcoma. Moreover, the cyclin A score determines the fraction of tumor cells in the S phase and the G2 phase, which are the most sensitive cell cycle phases for current modalities of cancer treatment.     

Development and validation of a disease-specific treatment satisfaction questionnaire for gastro-oesophageal reflux disease

BACKGROUND: Currently, no disease-specific, patient-based, treatment satisfaction instruments related to gastro-oesophageal reflux disease exist. AIM: To develop and validate a treatment satisfaction questionnaire for gastro-oesophageal reflux disease (TSQ-G). METHODS: A new questionnaire was developed from patient focus groups, clinician input and literature review. A validation study was conducted in treated gastro-oesophageal reflux disease patients. Ancillary measures included the Medical Outcomes Study Short Form-36, Quality of Life in Reflux and Dyspepsia, Gastrointestinal Symptom Rating Scale, Socially Desirable Response Scale, Patient Satisfaction Questionnaire-18 and physician and patient measures of symptoms and satisfaction. Statistical analyses included exploratory factor analysis, Cronbach's alpha, intra-class correlations, analyses of variance and t-tests. RESULTS: A total of 198 gastro-oesophageal reflux disease patients participated in the study, with a mean age of 50.7 years, 68% female and 84% Caucasian. The physician-rated severity of gastro-oesophageal reflux disease was mild (32%), moderate (50%) and severe (18%); 83% were on proton pump inhibitors. The final TSQ-G consisted of 28 items with seven sub-scales; Cronbach's alpha ranged from 0.58 to 0.94. Correlations with the expected sub-scales of the ancillary measures were moderate to strong. The TSQ-G sub-scales discriminated significantly between levels of physician-rated disease severity, symptom days and patient and physician ratings of satisfaction. CONCLUSIONS: The TSQ-G has excellent reliability and construct validity and appears to be a useful tool for the evaluation of treatment satisfaction in gastro-oesophageal reflux disease patients.     

A new self-assessment questionnaire to measure well-being in children,particularly those of short stature

The impact of short stature on children is commonly assessed in terms of psychosocial consequences. Proxy respondents and formal behavioural performance tests constitute standard methods in the evaluation of growth hormone therapy in children of short stature. Therefore, a self-administered, short and simple adjective check-list was developed and tested on 342 children of both sexes, aged 9–13 years. Six dimensions covering alertness, self-esteem, mood, elation, stability and vitality were derived after factor analysis. High internal consistency reliability was found for all dimensions. Modest correlations with height, reaching statistical significance for alertness, mood and vitality, were observed. Girls described themselves as having lower self-esteem and vitality than boys, while boys had lower scores for elation. It was concluded that the measure was relevant and potentially useful in children with short stature.     

Cancer among farmers. A review

During the performance of routine tasks farmers may come in contact with a variety of substances, including pesticides, solvents, oils and fuels, dusts, paints, welding fumes, zoonotic viruses, microbes, and fungi. Because some of these substances are known or suspected carcinogens, the epidemiologic literature regarding cancer risks concerning farmers has been reviewed. Farmers had consistent deficits for cancers of the colon, rectum, liver, and nose. The deficits for cancer of the lung and bladder were particularly striking, presumably due to less frequent use of tobacco among farmers than among people in many other occupational groups. Malignancies frequently showing excesses among farmers included Hodgkin's disease, leukemia, non-Hodgkin's lymphoma, multiple myeloma, and cancers of the lip, stomach, prostate, skin (nonmelanotic), brain, and connective tissues. The etiologic factors that may contribute to these excesses in the agricultural environment have not been identified. Detailed, analytic epidemiologic studies that incorporate environmental and biochemical monitoring are needed to clarify these associations.