Circadian Rhythmicity as a Predictor of Quality of Life in Allogeneic Hematopoietic Cell Transplant Patients

Context

Quality of life (QoL) is increasingly recognized as an important outcome of cancer treatment. Previous studies have examined clinical predictors of QoL, but with the increasing prevalence of wearable sensors that monitor sleep and activity patterns, further investigation into whether these behaviors are predictive of post-treatment QoL is now feasible. Among patients receiving aggressive cancer treatment such as hematopoietic cell transplantation (HCT), analysis of circadian rhythms (24-hour patterns of sleep and activity) via wearable sensors is limited.

Minimally invasive mitral valve surgery

BACKGROUND: To reduce surgical trauma and the drawbacks associated with sternotomy, we performed robotically controlled, video-assisted mitral valve surgery, using either the port-access or the transthoracic clamp technique. METHODS AND RESULTS: Between September 1997 and September 2000, 221 patients (78 males, 143 females) underwent mitral valve surgery through a small right minithoracotomy using the port-access endovascular cardiopulmonary bypass system. Mitral valve exposure was facilitated with an endoscope attached to a voice-controlled robotic arm (AESOP 3000) allowing stabilization and voice-activated camera positioning. Twenty-six patients underwent mitral valve repair and 195 had valve replacement. In 197 patients, mitral valve surgery was the primary operation, while 24 were redo cases. Skin-to-skin mean operating time was 3.5 +/- 1.2 hours and aortic cross-clamp time was 58 +/- 16 min, mean intensive care unit stay was 22 +/- 7 hours and hospital stay 6.4 +/- 1.2 days. There was no re-exploration for bleeding. There was no late death or re-operation on mean follow-up of 16.4 +/- 12.2 months. Patients showed improvement in their NYHA functional class from 2.6 +/- 0.5 to 1.4 +/- 0.8 postoperatively. Outcomes were compared with those of our previous 220 patients who underwent mitral valve surgery with the median sternotomy approach. CONCLUSIONS: The use of video and robotic assistance in port-access mitral valve surgery not only minimizes the length of the incision, but also gives full visualization of the entire mitral valve apparatus. This approach provides comparable results with the sternotomy approach, as well as marked advantages of reduced intensive care unit stay. ,ower blood transfusion requirement, better cosmesis and earlier hospital discharge.     

Inclusion of supine period in short-duration pH monitoring is essential in diagnosis of gastroesophageal reflux disease

Prolonged esophageal pH monitoring is the most accurate method for detecting abnormal gastroesophageal reflux (GER) in patients with gastroesophageal reflux disease (GERD). However, some investigators have found that short-duration postprandial pH monitoring in the upright position is also useful, while others have failed to find such results. Therefore, we have compared a 6-hr period of pH monitoring (3-hr postprandial period after daytime meal and 3-hr supine period) with a total 24-hr period in detecting abnormal gastroesophageal reflux. Sixty-five patients (44 men, mean age 41.3 years) with GERD and 16 healthy volunteers (11 men, mean age 34.3 years) underwent 24-hr pH monitoring according to a standard protocol. Various reflux parameters during 24-hr pH monitoring were compared with reflux parameters during the 6-hr period. Abnormal GER was detected in 56 patients presenting with typical symptoms of GERD (sensitivity 86.2%). These patients could be further divided into upright (N=18), supine (N=15), and combined (N=23) refluxers, depending on the posture in which abnormal reflux occurred. Esophageal pH monitoring during the 3-hr postprandial upright period showed abnormal reflux in only 35 patients (sensitivity 53.8%;P<0.00005, compared with the 24-hr pH monitoring period). Abnormal GER was identified in 13 of 18 upright, 19 of 23 combined, and only one of 15 supine refluxers, as well as in two of nine patients with normal 24-hr pH-metry. However, inclusion of the 3-hr supine monitoring period in the 3-hr postprandial upright period improved detection of abnormal GER to 78.5% (51 patients;P=NS compared with 24-hr pH monitoring period). This was related mainly to improved detection of abnormal GER in supine refluxers (11 of 15; 73.3%). Esophageal acid exposure time correlated significantly with severity of esophagitis only during the total and supine periods of both the 24- and 6-hr periods and not during the upright period. Esophageal acid clearance correlated significantly with increasing grades of esophagitis for the supine and total periods only. We conclude that 3-hr postprandial pH monitoring, as has been conventionally practiced, is not appropriate in the detection of abnormal GER; inclusion of a supine period in the short-duration pH monitoring schedule increases the detection of pathological reflux. We therefore recommend that a supine period should be included in short-duration pH monitoring schedules. We also found that supine reflux was the most important factor in the development of esophagitis.     

Redo mitral valve surgery using the port-access system

Redo mitral valve surgery is hazardous, hence we explored an alternative approach using a port-access system that avoids reentry. Between October 1997 and December 2000, 32 patients underwent mitral reoperation using the system. All patients had previous cardiac operations. This procedure consisted of a right anterolateral minithoracotomy and femorofemoral cannulation using special port-access instruments and endoaortic clamping in 24 patients or direct transthoracic sliding-rod aortic clamping in 8. The valve disease was of rheumatic etiology in 28 patients and degenerative in 4. The valve was replaced in 31 cases and a paravalvular leak after mitral valve replacement was closed in 1. In 2 cases, the tricuspid valve was repaired along with mitral valve replacement. Mean total operating time was 4.5 +/- 1.2 hours, cardiopulmonary bypass time 162 +/- 72 minutes, and aortic crossclamp time 62 +/- 21 minutes. There was no mortality, and mean stay in the intensive care unit was 22 +/- 7 hours and hospital stay 6.4 +/- 1.2 days. Postoperative blood transfusion was required in 12 patients. In view of the favorable results, we recommend using the port-access system as a standard approach for mitral reoperation.     

Zimbabwe's national AIDS levy: A case study

Background: We conducted a case study of the Zimbabwe National AIDS Trust Fund (‘AIDS Levy’) as an approach to domestic government financing of the response to HIV and AIDS.

Methods: Data came from three sources: a literature review, including a search for grey literature, review of government documents from the Zimbabwe National AIDS Council (NAC), and key informant interviews with representatives of the Zimbabwean government, civil society and international organizations.

Findings: The literature search yielded 139 sources, and 20 key informants were interviewed. Established by legislation in 1999, the AIDS Levy entails a 3% income tax for individuals and 3% tax on profits of employers and trusts (which excluded the mining industry until 2015). It is managed by the parastatal NAC through a decentralized structure of AIDS Action Committees. Revenues increased from inception to 2006 through 2008, a period of economic instability and hyperinflation. Following dollarization in 2009, annual revenues continued to increase, reaching US$38.6 million in 2014. By policy, at least 50% of funds are used for purchase of antiretroviral medications. Other spending includes administration and capital costs, HIV prevention, and monitoring and evaluation. Several financial controls and auditing systems are in place. Key informants perceived the AIDS Levy as a ‘homegrown’ solution that provided country ownership and reduced dependence on donor funding, but called for further increased transparency, accountability, and reduced administrative costs, as well as recommended changes to increase revenue.

Conclusions: The Zimbabwe AIDS Levy has generated substantial resources, recently over US$35 million per year, and signals an important commitment by Zimbabweans, which may have helped attract other donor resources. Many key informants considered the Zimbabwe AIDS Levy to be a best practice for other countries to follow.     

Morbidity compression or expansion? A temporal analysis of the age at onset of non-communicable diseases in India

While there is evidence of morbidity compression in many countries, temporal patterns of non-communicable diseases (NCDs) in developing countries, such as India, are less clear. Age at onset of disease offers insights to understanding epidemiologic trends and is a key input for public health programs. Changes in age at onset and duration of major NCDs were estimated for 2004 (n = 38,044) and 2018 (n = 43,239) using health surveys from the India National Sample Survey (NSS). Survival regression models were used to compare trends by sociodemographic characteristics. Comparing 2004 to 2018, there were reductions in age at onset and increases in duration for overall and cause-specific NCDs. Median age at onset decreased for NCDs overall (57 to 53 years) and for diabetes, hypertension, heart disease, asthma, mental diseases, eye disease, and bone disease in the range of 2–7 years and increased for cancer, neurological disorders, some genitourinary disorders, and injuries/accidents in the range of 2–14 years. Hazards of NCDs were higher among females for cancers (HR 1.51, 95% CI 1.19–1.90) and neurological disorders (HR 1.18, 95% CI 1.06–1.32) but lower for heart diseases (HR 0.88, 95% CI 0.79–0.97) and injuries/accidents (HR 0.87, 95% CI 0.77–0.99). Hazards were greater among those with lower educational attainment at younger ages and higher educational attainment later in life. Unlike many countries, chronic disease morbidity may be expanding in India for many chronic diseases, indicating excess strain on the health system. Public health programs should focus on early diagnosis and prevention of NCDs.

     

Evaluation of formalin preserved allogeneic bone graft as a grafting material

Formalin preserved allogeneic (FPA) bone graft was used in 18 patients with benign bone cavities, nine patients with malignant bone cavities, 12 patients with atrophic nonunion of fractures, seven with gap nonunion and 18 with comminuted fractures. The benign bone cavities were obliterated in 20 weeks and malignant cavities in 24 weeks. Union was obtained in atrophic ununited fractures in 29 weeks, in gap nonunion in 40 weeks and in comminuted fractures in 27 weeks. FPA is a simple, inexpensive and easily available alternative to autologous bone and to deep frozen bone in filling bone defects and enhancing fracture union.     

The role of endoscopic ultrasound in biliary strictures

The role of endoscopic ultrasound (EUS) in the diagnosis of biliary strictures is well established, and emerging evidence suggests it may also play a therapeutic role. Differentiating between benign and malignant causes of biliary strictures can be challenging, but EUS can aid in their diagnosis and may predict resectability. The diagnostic yield of EUS combined with fine-needle aspiration (FNA) is excellent, especially in distal bile duct strictures, and far surpasses endoscopic retrograde cholangiopancreatography (ERCP) with brushings. Intraductal ultrasound may add to the diagnostic sensitivity of ERCP with brushings when no mass is seen on cross-sectional imaging or EUS, or when EUS with FNA is negative and suspicion of cancer persists. EUS-guided cholangiography is an emerging technique that may aid biliary decompression when ERCP has failed or is not possible; however, new therapeutic echoendoscopes or accessories are needed before the use of this technique can become more widespread.     

Peyer's patch eosinophils: identification, characterization, and regulation by mucosal allergen exposure, interleukin-5, and eotaxin

The gastrointestinal immune system is traditionally thought to be composed of lymphocytes located within Peyer's patches and the lamina propria. We have recently reported that eosinophils also reside in the gastrointestinal tract during healthy states, in particular, within the lamina propria, and that these cells substantially increase after oral allergen exposure. We now demonstrate the presence of eosinophils in Peyer's patches and characterize the signals that regulate the accumulation of eosinophils in Peyer's patches. In contrast to the lamina propria, intestinal Peyer's patches have very low levels of eosinophils under healthy states. However, elevated levels of interleukin-5 (IL-5), generated by transgenic or pharmacologic approaches, result in a dramatic increase in eosinophil levels in Peyer's patches. Most eosinophils are located in the outer cortex and interfollicular regions of the Peyer's patches. To dissect the mechanism of eosinophil trafficking to Peyer's patches, the role of eotaxin was examined. Mice transgenic for IL-5 and genetically deficient in eotaxin were found to have reduced levels of eosinophils in Peyer's patches compared with IL-5-transgenic mice. To prove that eosinophils also traffic to Peyer's patches in wild-type mice, allergic hypersensitivity was induced and Peyer's patches were examined. Exposure to mucosal allergen promoted marked accumulation of eosinophils in Peyer's patches and this process was attenuated in eotaxin-deficient mice. In summary, these data demonstrate that elevated levels of IL-5 and mucosal allergen exposure promote eotaxin-dependent eosinophil trafficking to Peyer's patches. These studies suggest that eosinophils may cooperate with lymphocytes in the development of mucosal immune responses in the gastrointestinal tract. (Blood. 2000;96:1538-1544)