Sustained, retransplantable, multilineage engraftment of highly purified adult human bone marrow stem cells in vivo

Data from many laboratory and clinical investigations indicate that CD34+ cells comprise approximately 1% of human bone marrow (BM) mononuclear cells, including the progenitor cells of all the lymphohematopoietic lineages and lymphohematopoietic stem cells (stem cells). Because stem cells are an important but rare cell type in the CD34+ cell population, investigators have subdivided the CD34+ cell population to further enrich stem cells. The CD34+/CD38- cell subset comprises less than 10% of human CD34+ adult BM cells (equivalent to < 0.1% of marrow mononuclear cells), lacks lineage (lin) antigens, contains cells with in vitro replating capacity, and is predicted to be highly enriched for stem cells. The present investigation tested whether the CD34+/CD38- subset of adult human marrow generates human hematopoiesis after transfer to preimmune fetal sheep. CD34+/ CD38- cells purified from marrow using immunomagnetic microspheres or fluorescence-activated cell sorting generated easily detectable, long- term, multilineage human hematopoiesis in the human-fetal sheep in vivo model. In contrast, transfer of CD34+/CD38+ cells to preimmune fetal sheep generated only short-term human hematopoiesis, possibly suggesting that the CD34+/CD38+ cell population contains relatively early multipotent hematopoletic progenitor cells, but not stem cells. This work extends the prior in vitro evidence that the earliest cells in fetal and adult human marrow lack CD38 expression. In summary, the CD34+/ CD38- cell population has a high capacity for long-term multilineage hematopoietic engraftment, suggesting the presence of stem cells in this minor adult human marrow cell subset.     

Improving pediatric emergency department physicians’ adherence to clinical practice guidelines on the diagnosis and management of group A beta-hemolytic streptococcal pharyngitis—a cross-sectional study

Introduction

Pharyngitis is one of the major and commonly seen presentations in pediatric emergency departments. While it could be caused by both bacterial and viral pathogens, antibiotics are improperly prescribed regardless of the pathogen. Inappropriate usage of antibiotics has risen the concern of microbial resistance and the need for stricter guidelines. Many guidelines have been validated for this reason, and the Centor score (Modified/McIsaac) is most commonly implemented. This study aims to assess the adherence and enumerate the reasons behind the suboptimal adherence to guidelines (Centor/McIsaac score) of pediatric emergency department physicians in the diagnosis and management of GABHS pharyngitis to lay the groundwork for future actions and to employ educational programs and implement local guidelines for the prevention of the development of multi-drug resistant microorganisms.

Methodology

We surveyed pediatric emergency department physicians of ten teaching hospitals of Riyadh, Saudi Arabia. We used convenient sampling and estimated a sample size of 170 physicians, and interns and medical centers without pediatric emergency department were excluded from the study. Elements of the Centor score (Modified/McIsaac) were used as a part of the assessment of physicians’ knowledge of the guidelines. Adherence was assessed by requiring the participants to answer questions regarding their usage of diagnostic means when they suspect a bacterial cause of pharyngitis, as recommended by the guidelines.

Results

A total of 243 physicians answered the questionnaire, 43 consultants (17.6%) and 200 non-consultants (82.4%). On the knowledge score, 9.1% scored 0, and the majority of both groups, 46.5%, earned a score of 1. The remainder 44.4%, earned a score of 2. Adherence to guidelines was defined as when diagnostic tests (throat culture or rapid antigen detection test) were always requested prior to prescribing antibiotics when acute bacterial pharyngitis was suspected. Only 27.3% (n?=?67) of our sample are adherent to guidelines, whereas the majority, 72.7% (n?=?175), are non-adherent. Several factors were assessed as reasons for lack of adherence.

Conclusion

Lack of knowledge and adherence to guidelines is prevalent in our setting, with awareness, knowledge, and behavior of physicians playing as major factors behind this low adherence. Studies should aim towards the assessment of adherence towards locally developed guidelines.

     

Recognition and management of idiopathic systemic capillary leak syndrome: an evidence-based review

Introduction: Idiopathic systemic capillary leak syndrome (SCLS) is a unique disorder characterized by episodes of massive systemic leak of intravascular fluid leading to volume depletion and shock. A typical attack of SCLS consists of prodromal, leak and post-leak phases. Complications, such as compartment syndrome and pulmonary edema, usually develop during the leak and post-leak phases respectively. Judicious intravenous hydration and early use of vasopressors is the cornerstone of management in such cases.

Areas covered: The purpose of the present review is to provide an up-to-date, evidence-based review of our understanding of SCLS and its management in the light of currently available evidence.

Commentary: Idiopathic SCLS was first described in 1960 and, since then, more than 250 cases have been reported. A large number of cases have been reported over the past one decade, most likely due to improved recognition. In the acute care setting, most patients with SCLS are managed as per the Surviving Sepsis guidelines and receive aggressive volume resuscitation – which is not the optimal management strategy for such patients. There is a need to raise awareness amongst physicians and clinicians in order to improve recognition of this disorder and ensure its appropriate management.     

Complex Regional Pain Syndrome,Current Concepts and Treatment Options

Purpose of Review

Complex regional pain syndrome (CRPS) refers to a chronic pain condition that is characterized by progressively worsening spontaneous regional pain without dermatomal distribution. The symptomatology includes pain out of proportion in time and severity to the inciting event. The purpose of this review is to present the most current information concerning epidemiology, diagnosis, pathophysiology, and therapy for CRPS.

Recent Findings

In recent years, discovery of pathophysiologic mechanisms of CRPS has led to significant strides in the understanding of the disease process.

Summary

Continued elucidation of the underlying pathophysiological mechanisms will allow for the development of more targeted and effective evidence-based therapy protocols. Further large clinical trials are needed to investigate mechanisms and treatment of the disorder.

     

Novel Interventional Nonopioid Therapies in Headache Management

Purpose of Review

Headaches encompass a broad-based category of a symptom of pain in the region of the head or neck. For those patients who unfortunately do not obtain relief from conservative treatment, interventional techniques have been developed and are continuing to be refined in an attempt to treat this subset of patients with the goal of return of daily activities. This investigation reviews various categories of headaches, their pathophysiology, and types of interventional treatments currently available.

Recent Findings

Injection of botulinum toxin has been shown to increase the number of headache free days for patients suffering from chronic tension-type headaches. Suboccipital steroid injection has been demonstrated as a successful treatment option for patients suffering from cluster headache. Occipital nerve stimulation (ONS) has been described as a treatment for all types of trigeminal autonomic cephalgias. Percutaneous ONS is a minimally invasive and reversible approach to manage occipital neuralgia performed utilizing subcutaneous electrodes placed superficial to the cervical muscular fascia in the suboccipital area. Radiofrequency lesioning is another commonly used treatment in the management of chronic pain syndromes of the head and neck. If a diagnostic sphenopalatine ganglion block successfully resolves the patient’s symptoms, neurolysis can be employed as a more permanent solution.

Summary

Although many patients who suffer from headaches can be treated with conservative, less-invasive treatments, there still remains at present an ever-increasing need for those patients who are refractory to conservative measures and thus require interventional treatments. These procedures are continually evolving to become safer, more precise, and more readily available for clinicians to provide to their patients.

     

The Impact of Local Immigration Enforcement Policies on the Health of Immigrant Hispanics/Latinos in the United States

Objectives. We sought to understand how local immigration enforcement policies affect the utilization of health services among immigrant Hispanics/Latinos in North Carolina.Methods. In 2012, we analyzed vital records data to determine whether local implementation of section 287(g) of the Immigration and Nationality Act and the Secure Communities program, which authorizes local law enforcement agencies to enforce federal immigration laws, affected the prenatal care utilization of Hispanics/Latinas. We also conducted 6 focus groups and 17 interviews with Hispanic/Latino persons across North Carolina to explore the impact of immigration policies on their utilization of health services.Results. We found no significant differences in utilization of prenatal care before and after implementation of section 287(g), but we did find that, in individual-level analysis, Hispanic/Latina mothers sought prenatal care later and had inadequate care when compared with non-Hispanic/Latina mothers. Participants reported profound mistrust of health services, avoiding health services, and sacrificing their health and the health of their family members.Conclusions. Fear of immigration enforcement policies is generalized across counties. Interventions are needed to increase immigrant Hispanics/Latinos’ understanding of their rights and eligibility to utilize health services. Policy-level initiatives are also needed (e.g., driver’s licenses) to help undocumented persons access and utilize these services.Federal immigration enforcement policies have been increasingly delegated to state and local jurisdictions, leading to increased enforcement activities by local police. This shift has resulted largely from the implementation of 2 federal initiatives: section 287(g) of the Immigration and Nationality Act and the Secure Communities program. Section 287(g) authorizes Immigration and Custom Enforcement to enter into agreements with state and local law enforcement agencies to enforce federal immigration law during their regular, daily law enforcement activities. The original intention was to “target and remove undocumented immigrants convicted of violent crimes, human smuggling, gang/organized crime activity, sexual-related offenses, narcotics smuggling and money laundering.”1 Added to the Immigration and Nationality Act in 1996, section 287(g) was not widely used in its first decade, but its use accelerated in the mid- to late 2000s.2,3The Secure Communities program differs from section 287(g) in that it does not authorize local enforcement bodies to arrest individuals for federal immigration violations. Instead, when individuals are arrested for nonimmigration matters, the Secure Communities program facilitates the sharing of local arrestees’ fingerprints and information with Immigration and Custom Enforcement and the Federal Bureau of Investigation, which checks them against immigration databases. If these checks reveal that an individual is unlawfully present in the United States or otherwise removable because of a criminal conviction, Immigration and Custom Enforcement takes enforcement action.4Some evidence suggests that both section 287(g) and the Secure Communities program contribute to Hispanic/Latino immigrants’ general mistrust of local law enforcement and fear of utilizing a variety of public services, such as police protection and emergency services.2,5–7 Although many immigrant Hispanics/Latinos in the United States experience barriers to care because of a lack of bilingual and bicultural services, low health literacy, insufficient public transportation, and limited knowledge of available health services,8–12 studies have suggested that individuals lacking legal status may have more difficulty obtaining health services and may experience worse health outcomes than do individuals with legal status.13–18 Among immigrant Hispanics/Latinos, the fear of deportation, a lack of required forms of documentation, interaction with law enforcement personnel, and racial profiling are factors also associated with reduced utilization of health services and worse health.6,19–22 Such fears lead to incomplete sequences of care,19,20,23,24 promote the use of nonstandard and unsafe contingencies for care,16,25–27 and contribute to public health hazards, as immigrants delay preventive care or treatment.13,22,28 These fears further affect long-term health outcomes as immigrant Hispanics/Latinos alter their physical activity, food purchasing behaviors, and food consumption because of concerns about being in public.29 They may withhold information from health care providers19 and experience high levels of stress, leading to compromised mental health.20,30,31The Patient Protection and Affordable Care Act bars undocumented or recent legal immigrants from receiving financial assistance for health insurance32; thus, many will continue to remain uninsured and dependent on public health services and free clinics for a significant portion of their care. Because these services are associated with government authority, there is the potential that increasing immigration enforcement policies will deter noncitizens from seeking needed care, not only to their detriment but also to the detriment of public health.Currently there is little research examining the impact of recent immigration enforcement policies on the access to and utilization of health care, and there has been a call to better understand the public health impact of current immigration policies and their enforcement.29 Through mixed methods, we explored the effect of local immigration enforcement policies on access to and utilization of health services among immigrant Hispanics/Latinos in North Carolina. We analyzed vital records data to determine whether there were differences in utilization of prenatal services by Hispanic/Latina mothers pre- and postimplementation of section 287(g), and we conducted focus groups and in-depth interviews with Hispanics/Latinos living in counties that had implemented section 287(g) and in “sanctuary” counties, counties in which leaders, including politicians and clergy, have spoken out against the program.     

Factors Associated With Attrition in a Multicenter Longitudinal Observational Study of Patients With Advanced Cancer

Context

Attrition is common in longitudinal observational studies in palliative care. Few studies have examined predictors of attrition.

The yield of stool testing in hospital-onset diarrhea: Has evidence changed practice?

Introduction: Aside from examination for Clostridium difficile, the yield of stool testing in hospital-onset diarrhea is poor. Clinical practice guidelines discourage overzealous stool testing in patients with diarrhea that develops after the third hospital day. However, the adoption of this recommendation into clinical practice is limited. Furthermore, the effect of microbiology laboratory improvements on hospital-onset diarrhea testing is largely unknown. Methods: A retrospective cohort study was conducted in a university-affiliated community-hospital and included all adult inpatients who developed diarrhea after hospitalization. Results: 132 adult patients (53% female) developed diarrhea after hospitalization in 2013. The cohort’s mean age was 55.6 years. 46.2% of patients developed diarrhea in the first 3 days of hospitalization. Testing for parasites was negative in all examined 67 samples. Testing for C. difficile was positive in 13 cases (10.8%) out of 120 tested samples. Testing for other pathogens was positive in 1 sample (Campylobacter) out of 129 samples. Stool samples tested in the first 3 days of hospitalization were more likely to be positive (64.3 vs 35.7%, p = 0.1). Change in management was reported in 9 out of 14 patients (64.3%) with positive stool testing compared with 31 out of 118 patients (26.3%) with negative stool testing, p = 0.01. Conclusion: Despite improvements in stool samples’ testing, the yield continues to be low, especially in hospital-onset diarrhea past the third hospital day. Physicians’ embracement of the ‘3-day rule’ continues to be poor.     

Continuation rates and reasons for discontinuation of intra-uterine device in three provinces of Pakistan: results of a 24-month prospective client follow-up

Background

Long-acting reversible contraceptives, such as the intrauterine device (IUD), remain underutilised in Pakistan with high discontinuation rates. Based on a 24-month prospective client follow-up (nested within a larger quasi-experimental study), this paper presents the comparison of two intervention models, one using private mid-level providers branded as “Suraj” and the other using community midwives (CMWs) of Maternal Newborn and Child Health Programme, for method continuation among IUD users. Moreover, determinants of IUD continuation and the reasons for discontinuation, and switching behaviour were studied within each arm.

Methods

A total of 1,163 IUD users, 824 from Suraj and 339 from the CMW model, were enrolled in this 24-month prospective client follow-up. Participants were followed-up by female community mobilisers physically every second month to ascertain continued IUD usage and to collect information on associated factors, switching behaviour, reasons for discontinuation, and pregnancy occurrence. The probabilities of IUD continuation and the risk factors for discontinuation were estimated by life table analysis and Cox proportional-hazard techniques, respectively.

Results

The cumulative probabilities of IUD continuation at 24 months in Suraj and CMW models were 82% and 80%, respectively. The difference between the two intervention areas was not significant. The probability distributions of IUD continuation were also similar in both interventions (Log rank test: χ² = 0.06, df = 1, P = 0.81; Breslow test: χ² = 0.6, df = 1, P = 0.44). Health concerns (Suraj = 57.1%, CMW = 38.7%) and pregnancy desire (Suraj = 29.3%, CMW = 40.3%) were reported as the most prominent reasons for IUD discontinuation in both intervention arms. IUD discontinuation was significantly associated with place of residence in Suraj and with age (15–25 years) in the CMW model.

Conclusion

CMWs and private providers are equally capable of providing quality IUD services and ensuring higher method continuation. Pakistan’s National Maternal Newborn and Child Health programme should consider training CMWs and providing IUDs through them. Moreover, private sector mid-level providers could be engaged in promoting the use of IUDs.