Participation in research improves overall patient management: insights from the Global Rheumatic Heart Disease registry (REMEDY).

BACKGROUND: Rheumatic heart disease (RHD) is a major public health problem in low- and middle-income countries (LIMCs), with a paucity of high-quality trial data to improve patient outcomes. Investigators felt that involvement in a recent large, observational RHD study impacted positively on their practice, but this was poorly defined. AIM: The purpose of this study was to document the experience of investigators and research team members from LMICs who participated in a prospective, multi-centre study, the global Rheumatic Heart Disease Registry (REMEDY), conducted in 25 centres in 14 countries from 2010 to 2012. METHOD: We conducted an online survey of site personnel to identify and quantify their experiences. Telephone interviews were conducted with a subset of respondents to gather additional qualitative data. We asked about their experiences, positive and negative, and about any changes in RHD management practices resulting from their participation in REMEDY as a registry site. RESULTS: The majority of respondents in both the survey and telephone interviews indicated that participation as a registry site improved their management of RHD patients. Administrative changes included increased attention to follow-up appointments and details in patient records. Clinical changes included increased use of penicillin prophylaxis, and more frequent INR monitoring and contraceptive counselling. CONCLUSION: Our study demonstrates that participation in clinical research on RHD can have a positive impact on patient management. Furthermore, REMEDY has led to increased patient awareness and improved healthcare workers' knowledge and efficiency in caring for RHD patients.

A randomised controlled trial comparing a dietary antiplatelet, the water-soluble tomato extract Fruitflow, with 75 mg aspirin in healthy subjects.

BACKGROUND/OBJECTIVES: Increasing numbers of food ingredients are gaining acknowledgement, via regulated health claims, of benefits to human health. One such is a water-soluble tomato extract, Fruitflow (FF), a dietary antiplatelet. We examined relative platelet responses to FF and to 75 mg aspirin (ASA) in healthy subjects. SUBJECTS/METHODS: A total of 47 healthy subjects completed a double-blinded randomised controlled trial following a crossover design. Acute and 7-day treatments with 75 mg ASA were compared with control with and without concomitant FF, over a 5-h timecourse. Platelet aggregation response agonist, platelet thromboxane A2 release, plasma clotting times and time to form a primary haemostatic clot (PFA-100 closure time, TTC) were measured. RESULTS: Administration of all treatments lowered platelet function and thromboxane A2 generation, and extended the TTC, relative to baseline (P<0.001) and to control (P<0.001). Plasma clotting times were not affected. A single 75 mg dose of ASA showed approximately equal efficacy to a dose of FF, whereas daily 75 mg ASA was approximately three times as effective after 7 days (P=0.002). Platelet responses were heterogenous with distinct weak and strong responder groups. Weak ASA responders retained a functional platelet response to collagen agonist and were responsive to FF. Concomitant FF and ASA did not lead to significant additive effects. CONCLUSIONS: The suppression of platelet function observed after consuming FF is approximately one-third that of daily 75 mg ASA. The reversible action of FF renders it less likely to overextend the time to form a primary haemostatic clot than ASA, an important safety consideration for primary prevention.

Supra-treatment threshold neonatal jaundice: Incidence in HIV-exposed compared to non-exposed neonates at Queen Elizabeth Central Hospital in Blantyre, Malawi.

INTRODUCTION: Jaundice is the yellowish pigmentation of the skin, sclera, and mucous membranes resulting from bilirubin deposition. Children born to mothers with HIV are more likely to be born premature, with low birth weight, and to become septic-all risk factors for neonatal jaundice. Further, there has been a change in the prevention of mother-to-child transmission (PMTCT) of HIV guidelines from single-dose nevirapine to a six-week course, all of which theoretically put HIV-exposed newborns at greater risk of developing neonatal jaundice. AIM: We carried out a study to determine the incidence of severe and clinical neonatal jaundice in HIV-exposed neonates admitted to the Chatinkha Nursery (CN) neonatal unit at Queen Elizabeth Central Hospital (QECH) in Blantyre. METHODS: Over a period of four weeks, the incidence among non-exposed neonates was also determined for comparison between the two groups of infants. Clinical jaundice was defined as transcutaneous bilirubin levels greater than 5 mg/dL and severe jaundice as bilirubin levels above the age-specific treatment threshold according the QECH guidelines. Case notes of babies admitted were retrieved and information on birth date, gestational age, birth weight, HIV status of mother, type of feeding, mode of delivery, VDRL status of mother, serum bilirubin, duration of stay in CN, and outcome were extracted. RESULTS: Of the 149 neonates who were recruited, 17 (11.4%) were HIV-exposed. One (5.88%) of the 17 HIV-exposed and 19 (14.4%) of 132 HIV-non-exposed infants developed severe jaundice requiring therapeutic intervention (p = 0.378). Eight (47%) of the HIV-exposed and 107 (81%) of the non-exposed neonates had clinical jaundice of bilirubin levels greater than 5 mg/dL (p < 0.001). CONCLUSIONS: The study showed a significant difference in the incidence of clinical jaundice between the HIV-exposed and HIV-non-exposed neonates. Contrary to our hypothesis, however, the incidence was greater in HIV-non-exposed than in HIV-exposed infants.

Sustained benefits of a community dietetics intervention designed to improve oral nutritional supplement prescribing practices.

BACKGROUND: Healthcare professionals working in the community do not always prescribe oral nutritional supplements (ONS) according to best practice guidelines for the management of malnutrition. The present study aimed to determine the impact of a community dietetics intervention on ONS prescribing practices and expenditure 1 year later. METHODS: The intervention involved general practitioners (GPs), practice nurses, nurses in local nursing homes and community nurses. It comprised an education programme together with the provision of a new community dietetics service. Changes in health care professionals' nutrition care practices were determined by examining community dietetics records. ONS prescribing volume and expenditure on ONS were assessed using data from the Primary Care Reimbursement Service of the Irish Health Service Executive. RESULTS: Seven out of 10 principal GPs participated in the nutrition education programme. One year later, screening for malnutrition risk was better, dietary advice was provided more often, referral to the community dietetics service improved and ONS were prescribed for a greater proportion of patients at 'high risk' of malnutrition than before (88% versus 37%; P < 0.001). There was a trend towards fewer patients being prescribed ONS (18% reduction; P = 0.074) and there was no significant change in expenditure on ONS by participating GPs (3% reduction; P = 0.499), despite a 28% increase nationally by GPs on ONS. CONCLUSIONS: The community dietetics intervention improved ONS prescribing practices by GPs and nurses, in accordance with best practice guidelines, without increasing expenditure on ONS during the year after intervention.

The use of oral nutritional supplements in an Irish community setting.

BACKGROUND: The frequency of oral nutritional supplement (ONS) prescribing has been increasing steadily in the Republic of Ireland (ROI). Available evidence indicates that health professionals in the community setting in the ROI have a poor level of knowledge about ONS. The objectives of the present study were to investigate ONS prescribing practices and to identify the types of patient who were prescribed these products. METHODS: Ten of 17 eligible general practitioners were recruited and asked to refer all patients (aged > 16 years) who were prescribed ONS during a 3-month period. Patients were interviewed by a community dietitian, using a questionnaire incorporating the Malnutrition Universal Screening Tool (MUST). ONS prescriptions were judged either to fulfil or not to fulfil a set of criteria developed for ONS prescribing in the community. RESULTS: The majority of patients were female (62/78). Their mean (SD) age was 79 (10.5) years. According to MUST criteria, 31 of 78 patients were at 'low risk', 18 of 78 were at 'medium risk' and 29 of 78 were at 'high risk' of malnutrition. Less than half of the patients (36/78) had a body mass index of < 20 kg m(-2). Only 21 of 78 patients reported having received dietary advice in addition to their ONS prescription. Almost one-third (31%) of ONS prescriptions did not fulfil the criteria. Social factors, such as living alone, and difficulties with cooking and shopping, influenced the need for ONS in almost 70% of cases. CONCLUSIONS: ONS were prescribed in accordance with the prescribing criteria in the majority of cases; however, some patients who were prescribed ONS were not 'at risk' of malnutrition. Social circumstances played an important part in determining the need for ONS prescriptions.

Fluoroquinolones: a new treatment for tuberculosis?

The fluoroquinolones have secured an important place in the management of bacterial infection, they are well absorbed orally, are found in respiratory secretions in higher concentrations than in serum and are concentrated inside macrophages. The agents are well tolerated and have an excellent safety record in long-term therapy. No new antituberculosis agents have been developed since the introduction of rifampicin into clinical use, so fluoroquinolones have been investigated for potential efficacy in tuberculosis. In vitro studies have shown that they are active against Mycobacterium tuberculosis at achievable concentrations. Treatment studies in mice have demonstrated efficacy. Few clinical studies have been performed in humans, but ciprofloxacin has demonstrated significant early bactericidal activity. Regimens including a fluoroquinolone have been comparable to other standard regimens, although the outcome in human immunodeficiency virus (HIV) seropositive patients was significantly poorer. There is still insufficient clinical data to use fluoroquinolones in first-line treatment of tuberculosis, but they may find a role in the management of multidrug-resistant infections or in patients with adverse reactions to other agents.

Randomized controlled trial of a drug regimen that includes ciprofloxacin for the treatment of pulmonary tuberculosis.

The fluoroquinolones are promising new antituberculous agents. A randomized controlled trial of 200 adult patients with sputum smear-positive pulmonary tuberculosis was conducted in Tanzania. Patients received either a trial regimen (HRC) consisting of isoniazid (300 mg), rifampin (600 mg), and ciprofloxacin (750 mg) or a control regimen (HRZE) consisting of isoniazid (300 mg), rifampin (600 mg), pyrazinamide (25 mg/kg), and ethambutol (15 mg/kg). The 168 evaluable patients all had negative smears and cultures by month 6, but the time to conversion to negativity was longer for the HRC group than for the HRZE group because of the poor response of patients infected with human immunodeficiency virus (HIV) to the HRC regimen. Relapse was more frequent in the HRC group. The sterilizing activity of ciprofloxacin does not appear to be equal to that of the combination of pyrazinamide and ethambutol, but the difference in outcome was significant only among HIV-infected patients.

Nutritional status and weight gain in patients with pulmonary tuberculosis in Tanzania.

We assessed nutritional status in 200 adult Tanzanian patients with smear-positive pulmonary tuberculosis before, during, and after 6 months of tuberculosis treatment; 148 patients (74%) were successfully followed for 12 months. Marked nutritional impairment was present on admission: 77% of males and 58% of females had a body mass index (BMI) below 18.5; approximately one-fifth had BMI < 16.0. The length of hospital stay and gender, rather than microbiological response, were the major determinants of weight gain during treatment. Patients infected with human immunodeficiency virus (HIV) gained more weight than uninfected patients. Most patients lost weight after completing treatment and returning home. At 12 months, 32% of male and 19% of female patients considered cured of tuberculosis had BMI < 18.5. It is concluded that patients with tuberculosis from this area of Tanzania frequently have evidence of malnutrition both before and after treatment for tuberculosis. Weight gain during therapy appeared to be an unreliable indicator of overall treatment response. However, the results also demonstrated that nutritional rehabilitation can be successfully achieved even in HIV-positive tuberculosis patients and in patients with a suboptimal response to therapy.

PIP: The authors assessed nutritional status in 200 adult Tanzanian patients with smear-positive pulmonary tuberculosis (TB) before, during, and after 6 months of TB treatment. 148 patients were successfully followed for 12 months. Upon admission, 77% of males and 58% of females had a body mass index (BMI) below 18.5, with about 20% having BMI less than 16.0. Most patients lost weight after completing treatment and returning home. At 12 months, 32% of male and 19% of female patients considered cured of TB had BMI less than 18.5. The length of hospital stay and gender, rather than microbiological response, were the major determinants of weight gain during treatment. Patients infected with HIV gained more weight than uninfected patients. The authors conclude that TB patients in Tanzania frequently have evidence of malnutrition both before and after treatment for TB. Weight gain during therapy appeared to be an unreliable indicator of overall treatment response. The study also demonstrated that nutritional rehabilitation can be successfully achieved even in HIV-positive TB patients and in patients with a suboptimal response to therapy.

Early bactericidal and sterilizing activities of ciprofloxacin in pulmonary tuberculosis.

The early bactericidal and sterilizing activities of ciprofloxacin were evaluated in the treatment of adult patients with smear positive pulmonary tuberculosis. Two randomized prospective studies were performed in Northern Tanzania. In study 1, ten patients received either 750 mg ciprofloxacin or 300 ng isoniazid daily for 7 days. Counts of colony-forming units (cfu) of Mycobacterium tuberculosis in early morning sputum were performed. In study 2, twenty patients received either a standard regimen of rifampin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E) (regimen HRZE) or a trial regimen of ciprofloxacin (C), isoniazid (H), and rifampin (R) (regimen HRC). Sputum colony counts were performed for 8 wk. Patients were tested for antibodies to human immunodeficiency virus (HIV)-1. The results demonstrate that ciprofloxacin alone has useful early bactericidal activity, resulting in a mean daily fall of 0.20 log10cfu/ml/day during 7 days compared with 0.25 log10cfu/ml/day for isoniazid. When HRZE and HRC regimens were compared, the HRC regimen appeared to be inferior in its sterilizing ability, with a culture conversion rate of 67% at 2 months compared with 100% for HRZE. The difference in outcome was most marked in HIV-1 positive patients. The role of ciprofloxacin in combination regimens may be as a bactericidal rather than a sterilizing agent.

Adaptation to a marginal intake of energy in young children.

Six male children, aged 8-28 months, were studied for three consecutive periods of 1 week each. They were given diets that provided 1.7 g protein/kg per d and supplements of minerals and vitamins, with a metabolizable energy intake during the 1st, 2nd and 3rd week of 419, 293 and 335 kJ (100, 70 and 80 kcal)/kg per d, diets 1, 2 and 3 respectively. All the food offered was consumed. Each child was weighed at the same time each day on an electronic balance. On the 6th and 7th day of each study period urine and stool were collected for 24 h to assess nitrogen balance. Using linear regression analysis it was shown that all children gained weight on diet 1, 2.3 (SD 1.3) g/kg per d, and five of six children gained weight on diet 3, the mean for the whole group being 2.7 (SD 2.3) g/kg per d, not significantly different. On diet 2 all children lost weight, -5.4 (SD 1.3) g/kg per d, highly significantly different from each of the other dietary periods. Using asymptotic regression analysis it could be shown that the rate of weight loss during the first part of the week on diet 2, -11 g/kg per d, was greater than at the end of the week, -2 g/kg per d, with a tendency towards a steady weight by day 7. Apparent N retention (mg/kg per d) was positive at the end of each of the three dietary periods: diet 1, 112 (SD 25); diet 2, 54 (SD 34); diet 3, 82 (SD 20). In five of the six children there was a marked reduction in stool frequency on diet 2 compared with diet 1, that was maintained to the period on diet 3. The findings suggest that during the period on diet 2 there was a saving of energy of the order of 105 kJ (25 kcal)/kg per d, which lasted through into the period on diet 3.

Total and peripheral bone mass in patients with psoriatic arthritis and rheumatoid arthritis.

Psoriatic arthritis is thought to be associated with periarticular osteoporosis while rheumatoid arthritis may be associated with generalised as well as periarticular bone loss. To assess the extent of total and peripheral bone loss in these two diseases, total body calcium was measured by in vivo neutron activation analysis and peripheral bone mass was assessed by metacarpal indices in age-matched patients with psoriatic arthritis and rheumatoid arthritis treated with nonsteroidal anti-inflammatory drugs alone. In comparison with age and sex-matched normal controls, total and peripheral bone mass was normal in psoriatic arthritis. There were significant reductions in total (6.2% in men; 7.9% in women) and peripheral (10.9% in men; 12.8% in women) bone mass in patients with rheumatoid arthritis compared with controls. Peripheral bone mass was significantly correlated with the degree of radiographic damage in male and female patients with rheumatoid arthritis. The mean annual loss of total body calcium was insignificant in psoriatic arthritis (0.6% in men; 1.9% in women) but markedly greater in rheumatoid arthritis (4.4% in men; 2.7% in women). The data suggested that total and peripheral bone loss is greater in rheumatoid arthritis than psoriatic arthritis. Substantial reductions in peripheral bone mass in patients with rheumatoid arthritis not receiving corticosteroids may account in part for the small reductions in total bone mass.

Bone loss in rheumatoid arthritis and primary generalized osteoarthrosis: effects of corticosteroids, suppressive antirheumatic drugs and calcium supplements.

The annual rate of bone loss in rheumatoid arthritis (RA) and primary generalized osteoarthrosis (PGOA) was determined by measurement of total body calcium (TBCa). The mean annual rate of bone loss in 24 patients with RA treated with nonsteroidal anti-inflammatory drugs (NSAIDs) alone was 3.4%. This rate of bone loss was not reduced in ten RA patients responding to suppressive antirheumatic drugs (4.3%) or seven patients receiving oral calcium supplements (4.5%). The mean annual rate of loss of TBCa in 19 patients with PGOA was 1.6%, a figure which probably represents age-associated bone loss. The rate of bone loss in PGOA was significantly less than that in RA patients not receiving corticosteroids. The mean annual rate of change of TBCa in 30 RA patients receiving corticosteroids (+0.7%) was significantly less than that in any of the other RA groups despite an initial normalized bone mass which was significantly less than in those RA patients receiving NSAIDs alone. The data supported the hypothesis that bone loss occurred early in the course of corticosteroid therapy and thereafter the drugs might have a protective effect on the loss of bone in RA.