A Longitudinal Analysis of the Effect of Mass Drug Administration on Acute Inflammatory Episodes and Disease Progression in Lymphedema Patients in Léogane,Haiti

We conducted a longitudinal analysis of 117 lymphedema patients in a filariasis-endemic area of Haiti during 1995–2008. No difference in lymphedema progression between those who received or did not receive mass drug administration (MDA) was found on measures of foot (P = 0.24), ankle (P = 0.87), or leg (P = 0.46) circumference; leg volume displacement (P = 0.09), lymphedema stage (P = 0.93), or frequency of adenolymphangitis (ADL) episodes (P = 0.57). Rates of ADL per year were greater after initiation of MDA among both groups (P < 0.01). Nevertheless, patients who received MDA reported improvement in four areas of lymphedema-related quality of life (P ≤ 0.01). Decreases in foot and ankle circumference and ADL episodes were observed during the 1995-1998 lymphedema management study (P ≤ 0.01). This study represents the first longitudinal, quantitative, leg-specific analysis examining the clinical effect of diethylcarbamazine on lymphedema progression and ADL episodes.     

“Retirement Lost”—The New Role of the Elderly as Caretakers for Orphans in Western Kenya

A study on the new role of the elderly as caretakers of orphans was conducted in a rural part of Kenya applying a combination of qualitative and quantitative methods. One out of three children had lost at least one biological parent and one of nine had lost both. These figures are increasing exponentially. Most orphans were cared for by relatives, and about one out of five caretakers was 55 years of age or above. These elderly caretakers faced major difficulties in caring for the orphans in terms of schooling, food and medical care. There is a major difference between the present hardships of these caretakers and the traditional position of the elderly in the past. This dramatic deterioration in the situation of the elderly should be seen in the context of the rampant HIV/AIDS epidemic, population growth, changing socio-cultural values, and unfavourable macroeconomic trends.     

The Effect of Oral Administration of Silymarin on Serum Levels of Tumor Necrosis Factor-α and Interleukin-1ß in Patients with Rheumatoid Arthritis

Background: Rheumatoid Arthritis (RA) is a systemic chronic autoimmune disease. Several inflammatory agents play key roles in RA pathogenesis, among which tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL-1β) are of great importance. Silymarin is a potent anti-oxidant extracted from Silybummarianum L. seeds. Objective: To study the effect of silymarin on serum levels of TNF-α and IL-1β in patients with RA. Methods: Patients with stable RA received 140 mg of silymarin, 3 times a day, for 3 months. Serum samples were collected before and after the treatment. Both TNF-α and IL-1β serum levels were measured by ELISA. Results: 42 patients (14.3% male, and 85.7% female, with a mean age of 47.59±12.8 years old) completed the treatment course. There was no significant difference in the overall mean concentration of either TNF-α (p=0.14) or IL-1β (p=0.27) in all 42 patients after the treatment with silymarin. Conclusion: The addition of silymarin to the treatment regimen of patients with stable RA has no significant effect on the serum levels of TNF-α and IL-1β, however, this study needs further evaluation with a larger sample size.     

Effect of Eptifibatide for Acute Coronary Syndromes: Rapid Versus Late Administration—Therapeutic Yield on Platelets (The EARLY Platelet Substudy)

Background: Receptors other than GP IIb/IIIa may mediate leukocyte-platelet-endothelial interactions that obstruct the microvasculature in acute coronary syndromes (ACS) and cause microinfarcts. The effect of eptifibatide on these receptors was investigated in a substudy of the EARLY Trial. Methods: Patients received early (in the Emergency Department, n = 27) or late (12–24 h, n = 28) eptifibatide. Ten platelet receptors by flow cytometry and platelet aggregation (10 mol/L ADP) were measured serially at baseline, and at 3, 6, 12 and 24 h after randomization. Results: Platelet aggregation was rapidly inhibited by early eptifibatide therapy (baseline, 72 +/– 20%; 3 h post, 7 +/– 9%; p < 0.001). No significant differences were seen in either group for CD 31, CD 63, CD 107a, CD 107b, CD 41 (GPIIb/IIIa expression), or CD 62p. Leukocyte-platelet aggregate formation (mean fluorescense intensity) trended upward after presentation (early baseline, 43.1 +/– 26.0 versus 65.8 +/– 35.6, p = .09). PAC-1 (GP IIb/IIIa activity), CD 51/61 (vitronectin receptor) and CD 42b (GP Ib) were inhibited by eptifibatide (p < .05). Conclusions: In Emergency Department patients with unstable angina, early eptifibatide rapidly and profoundly inhibits platelet aggregation and reduces GP IIb/IIIa activity and the expression of CD51/61 and CD 42b; the latter two effects may also contribute to the drug's anti-thrombotic effect. However, platelet-leukocyte aggregate formation, a marker of platelet activity rises within 24 h after presentation despite eptifibatide therapy and is a potential mechanism for microvascular obstruction.     

The Effect of Nicorandil on Small Intestinal Ischemia–Reperfusion Injury in a Canine Model

Background  

It has been shown that nicorandil, which has both ATP-sensitive K⁺ (K_ATP) channel opener-like and nitrate-like properties, has an organ-protective effect in ischemia–reperfusion injury in several experimental animal models.     

Cost–Effectiveness of Different Strategies for Stroke Prevention in Patients with Atrial Fibrillation in a Health Resource-Limited Setting

Purpose

To compare the lifetime cost and effectiveness of five alternative chronic atrial fibrillation (AF) management strategies: rivaroxaban, warfarin, aspirin plus clopidogrel, aspirin and no prevention.

Methods

An individual-level state-transition model was developed to track the lifetime disease course associated with AF. The clinical and utility data were derived from published studies. The cost data were estimated based on local charges and current Chinese practices. Sensitivity analyses were used to explore the impact of uncertainty on the results.

Results

For base-case patients with a CHADS₂ score of 3, the cost per additional quality-adjusted life-years (QALYs) gained for rivaroxaban compared with no prevention, aspirin, aspirin plus clopidogrel and warfarin was $116,884, $153,944, $155,979 and $216,273, respectively. CHADS₂ score had a substantial impact on the model outcomes for different prevention strategies. The time distribution of warfarin international normalised ratio (INR), stroke and intracranial haemorrhage (ICH) risks, cost of rivaroxaban and utility of warfarin therapy had substantial impacts on the results. Based on a willingness-to-pay threshold of $16,350/QALY, no prevention strategy was the preferred therapy for a patient with a low risk for stroke and a high risk for ICH; aspirin was preferred for patients with a moderate risk for stroke and ICH; and warfarin was preferred for patients with a high risk for stroke and a low risk of ICH.

Conclusion

In the context of limited health resources, rivaroxaban is unlikely to be cost-effective, although it provided more health benefits comparing with other strategies. Additionally, warfarin with good INR control might be more suitable for AF patients in developing regions.     

The Effect of Measuring Ambulatory Blood Pressure on Nighttime Sleep and Daytime Activity—Implications for Dipping

Background and objectives: Ambulatory blood pressure (BP) monitoring is commonly used to assess the circadian pattern of BP. Circadian BP pattern is influenced by physical activity and sleep cycle. The effect of BP monitoring itself on the level of physical activity and sleep remains unknown. If BP monitoring affects these parameters, then monitoring itself may influence the circadian BP pattern.Design, setting, participants, & measurements: To assess the effect of ambulatory BP monitoring on sleep duration, sleep efficiency, and daytime activity, we measured physical activity using wrist actigraphy in 103 veterans with chronic kidney disease. After 6 to 7 days of continuous activity monitoring, participants underwent ambulatory BP monitoring with simultaneous actigraphy. The above experiment was repeated after 1 mo.Results: Among the top tertile of patients (most sleep), when wearing ambulatory BP patients spent less time in bed at night (−92 min, P < 0.0001), were less asleep during those hours (−98 min, P < 0.0001), and had reduced sleep efficiency (82% versus 77%, −5% P = 0.02). On the day of ambulatory BP monitoring, patients were more sedentary during waking hours (+27 minutes, P = 0.002). During ambulatory BP monitoring, waking after sleep onset more than median was associated with greater odds for nondipping (odds ratio 10.5, P = 0.008).Conclusions: Ambulatory BP monitoring is associated with disturbed sleep and reduced physical activity, characteristics that influence dipping. Ambulatory BP monitoring may itself induce nondipping and may thus mitigate the prognostic significance of the dipping phenomenon.Blood pressure (BP) in healthy people follows a circadian pattern that is influenced by the level of activity during the day and depth of sleep at night (1). Sleeping systolic BP, which should at least be 10% lower than awake systolic BP, is often measured by 24-hour ambulatory BP monitoring. This fall in BP during sleep—dipping—is a determinant of prognosis (2). Nondipping occurs in a variety of conditions and diseases, such as in patients with chronic kidney disease (CKD), sleep apnea, volume overload, nocturia, and those with sympathetic activation (3); nondipping is associated with left ventricular hypertrophy (4) and increased cardiovascular risk (5).Davies et al. (6) have reported that sensory stimulation as may occur during cuff inflation may cause cortical arousal, disturb sleep, and raise BP—a phenomenon they characterized in the sleep laboratory among six normal volunteers. However, it remains unknown to what extent ambulatory BP recording can impair nighttime sleep and whether it can also affect daytime activity.The purpose of this study was to assess the effect of ambulatory BP monitoring on sleep duration, sleep efficiency, and daytime activity. We hypothesized that ambulatory BP monitoring will reduce sleep efficiency and reduce daytime activity. Further, we hypothesized that those patients who have the maximal sleep disturbance will have the least dipping at night. If so, it would suggest that ambulatory BP monitoring may induce nondipping per se. These findings would have implications for assessing the independent prognostic value of dipping.     

The Effect of Weight Loss on Clinical Outcomes in Patients Implanted With a Cardiac Resynchronization Therapy Device—A MADIT-CRT Substudy

BackgroundThere are no data regarding the effect of weight loss on clinical outcomes in patients undergoing cardiac resynchronization therapy. This study was designed to evaluate the effect of weight loss on clinical outcomes in patients implanted with a cardiac resynchronization therapy with defibrillator (CRT-D).Methods and ResultsThe risk of heart failure (HF) or death, and of death alone, was compared between patients with and without weight loss of ≥2 kg or more at 1 year in the CRT-D arm of the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT). Weight loss was observed in 170 of 994 patients (17%) implanted with a CRT-D. Multivariate analysis showed a significant increase in the risk of HF or death among patients with weight loss compared with those without weight loss (hazard ratio [HR] 1.82, 95% confidence interval [CI] 1.26–2.63; P = .001). Weight loss was associated with a 79% increase in the risk of all-cause mortality (HR 1.79, 95% CI 1.16–3.34; P = .01). When analyzed in a continuous fashion, each kg of weight loss was associated with a 4% increase in the risk of HF or death (P = .03). In left bundle branch block (LBBB) patients with a CRT-D, weight loss was associated with an especially high risk of HF or death (HR 2.23, 95% CI 1.36–3.65; P = .002) and of death alone (HR 2.33, 95% CI 1.07–5.06; P = .03; interaction P = .26).ConclusionsIn patients with mild symptoms of HF receiving CRT-D, weight loss observed at 1 year is associated with adverse clinical outcomes, especially in those with a LBBB electrocardiographic pattern.     

Hepatosplenic Candidiasis,its Treatment and Effect on Remission Status in Patients with Acute Leukaemia—a Report of Five Cases

Hepatosplenic candidiasis is an increasingly encountered complication of treatment of patients with acute leukaemia [[1] Clin. Infect. Dis. 24 (1997) 375]. Management is difficult as delay in further chemotherapy may allow relapse of the leukaemia while the infection may progress if chemotherapy is continued [[2] Anticancer Res. 19 (1999) 757]. We report five cases of suspected hepatosplenic candidiasis in a single haematology unit over a 30-month period. All patients were treated with oral fluconazole following intravenous amphotericin or liposomal amphotericin B lipid complex. Chemotherapy was withheld during treatment of infection. Two patients remain in haematological remission despite suboptimal therapy for their leukaemia. One patient died from progressive fungal infection, 1 patient of cardiac disease and 1 patient has had recent relapse of their leukaemia. We demonstrate that hepatosplenic candidiasis may be treated with oral fluconazole while chemotherapy is discontinued and also suggest that this infection or its treatment may have had a beneficial immunomodulatory affect on the leukaemic process in the surviving patients.     

An Analysis of “No Effect of Insulin Pen with Memory Function on Glycemic Control in a Patient Cohort with Poorly Controlled Type 1 Diabetes: A Randomized Open-Label Study”

Missing meal bolus and nonadherence is an important barrier to achieving glycemic goals in type 1 diabetes (T1DM). In this issue of Journal of Diabetes Science and Technology, Danne and coauthors reported the results of a 24-week randomized-controlled study designed to evaluate if using an insulin pen with memory function, the HumaPen® Memoir™, might improve injection compliance and, therefore, overall glycemic control in T1DM. Patients treated with the pen device with memory function improved, albeit nonsignificantly, their mean HbA1c by 0.43%. Among the reasons to justify why this study was not positive, the most important is the high proportion of adult patients included in the study (87.9%)—children and adolescents being under-represented. I am convinced that pen devices with memory function might be helpful for forgetful patients (children, adolescents), as suggested in another recent study.     

Suppressive Effect of Antiulcer Agents on Granulocytes—A Role for Granulocytes in Gastric Ulcer Formation

Many clinicians have believed that H₂-blockers and proton pump inhibitors ameliorate gastric ulcers via their antacid function. We examined the effects of these antacids on granulocytes. Gastric ulcer patients were administered an H₂-blocker or proton pump inhibitor for a week and the number of granulocytes and the superoxide production were examined. To determine the trafficking of granulocytes, mice were exposed to restraint stress for 24 hr. The H₂-blocker decreased the number of granulocytes, while the proton pump inhibitor suppressed their superoxide production in humans and mice. The major function of H₂-blockers and proton pump inhibitors in curing gastric ulcers seems to be their suppressive effects on granulocytes. In this case, stress accelerates the trafficking of granulocytes from the bone marrow to the gastric mucosa. If we demonstrate a role for granulocytes in gastric ulcer formation, an gap in the acid–pepsin theory and the Helicobacter pylori theory is filled in.     

The questioning for routine monthly monitoring of proteinuria in patients with β-thalassemia on deferasirox chelation

Background: Iron chelation therapy is one of the mainstays of the management of the patients with β-thalassemia (BT) major. Deferasirox is an oral active iron chelating agent. Proteinuria is one of the potential renal adverse effects of deferasirox, and monthly follow-up for proteinuria is suggested by Food and Drug Administration and European Medicine Agency.

Methods: We aimed to investigate the necessity for monthly monitoring for proteinuria among patients with BT on deferasirox. A retrospective laboratory and clinic data review was performed for patients with BT major or intermedia who were treated with deferasirox chelation therapy. All patients were monitored for proteinuria for every 3 or 4 weeks after the initiation of deferasirox with serum creatinine and spot urine protein/creatinine ratios.

Results: The median follow-up time of the 37 (36 BT major and one BT intermedia) patients was 44 months. Seven patients (18.9%) developed significant proteinuria (ratio ≥0.8). Of the 1490 measurements, 12 tests (0.8%) were proteinuric. Urine proteinuria resolved in all of the patients during the follow-up. The risk of proteinuria was higher at ages below a cut-off point of 23 years (p?=?0.019). Patients, who were on deferasirox at doses above a cut-off dose of 29?mg/kg/day, were found to have higher risk of proteinuria development (p?=?0.004).

Conclusion: Proteinuria resolves without any complication or major intervention according to our results. Potentially more risky groups (age below 23 years old and receivers above a dose of 29?mg/kg/day) might be suggested to be followed monthly, besides monitoring all of the patients.     

The influence of position-dependency on surgical success in sleep apnea surgery — a systematic review

Sleep and Breathing - To evaluate the influence of position-dependency on surgical success of upper airway (UA) surgery in obstructive sleep apnea (OSA) patients. Systematic review. Two prospective...     

The effect of interleukin-1 blockade on fatigue in rheumatoid arthritis—a pilot study

Fatigue occurs in many patients with rheumatoid arthritis (RA) and other chronic inflammatory diseases and may be defined as an overwhelming sense of tiredness, lack of energy, and feeling of exhaustion. It can be restrictive and severely disabling. We recently found more than 3/4 of systemic lupus erythematosus patients to be significantly affected by this phenomenon. We hypothesized that fatigue in patients with RA might be comparable to sickness behavior in animals possibly caused by disturbances in interleukin-1 beta signaling pathways and thus accessible to blockade by biologic agents. This study compared measures of disease behavior and fatigue symptoms in eight RA patients before and at three time points during treatment with daily administration of anakinra.     

The impact of pretreatment assessment of oropharynx on interstitial soft palate radiofrequency surgery outcome—a multi-center study in patients with habitual snoring

Purpose  

Interstitial radiofrequency (RF) surgery of the soft palate (SP) is an established option in the treatment of habitual snoring. The decision-making process in the management of habitual snoring would benefit from diagnostic guidelines for oropharyngeal findings. Our aim was to investigate the correlation of systematic clinical pretreatment oropharyngeal examination scores with the efficacy of interstitial RF surgery of SP in a multi-center study.     

Exercise therapy in patients with hip osteoarthritis: Effect on hip muscle strength and safety aspects of exercise—results of a randomized controlled trial

Purpose: To evaluate the effect of an exercise therapy concept (the Tübingen exercise therapy approach THüKo) for increasing hip muscle strength (HMS) in patients with hip osteoarthritis (OA), and to investigate whether patients do adhere to the intervention and if there are any adverse events related to the intervention.

Methods: A total of 210 hip OA patients (89 females, 121 males) were randomized into a 12-week exercise intervention (THüKo) including group sessions (1/week) and home exercising (2/week), a placebo ultrasound group (1/week) or a control group (no treatment). HMS was measured as isometric peak torque of hip abduction, adduction, flexion, and extension. Adherence to exercise and safety aspects were monitored as additional outcomes.

Results: Baseline adjusted post intervention HMS of the THüKo group were higher compared to the control group (differences of 0.11–0.27?Nm/kg, p?p?Conclusions: The Tübingen exercise therapy approach has shown to have a significant positive effect on HMS. Its implementation has shown to be feasible and safe according to the percentage of exercise participation and the absence of sustainable adverse events.     

The Effect of Somatostatin Analogue SMS 201—995 on Serotonin Levels in the Medium of Primary Carcinoid Cell Cultures

Carcinoid cell cultures were established from primary tumours and liver and mesenteric metastases. The cells continued to produce serotonin for up to 6 months. Cells from different tumours showed different properties. In most wells carcinoid cells grew on a layer of fibroblasts. The tendency to co-culture seemed to be less marked in cells from liver biopsy specimens. The amount of serotonin decreased to 63% 300 min after addition of the somatostatin analogue SMS 201–995 (SMS) to the culture, compared with controls (p < 0.05; n = 10). This decrease was observed up until 12 days, when SMS was added at each change of medium (p < 0.005; n = 8). In the first 10 min, however, SMS induced an increase in serotonin concentration (p < 0.005; n = 11). This effect may be related to other, immediate stimulatory effects of SMS seen in other cell lines originating from neural ridge-derived tissue. We believe it is important to elucidate the properties of individual tumours, as choice of therapy may vary between patients with the same diagnosis. We have described a method to obtain such information within a couple of days, before a definite treatment is selected.