A shortened course of Amoxicillin/Clavulanate is the preferred antibiotic treatment after surgery for perforated appendicitis in children.

BACKGROUND/PURPOSE: Despite evidence supporting short course outpatient antibiotic treatment following appendectomy for perforated appendicitis, evidence of real-world implementation and consensus for antibiotic choice is lacking. We therefore aimed to compare outpatient antibiotic treatment regimens in a national cohort. METHODS: We identified children who underwent surgery for perforated appendicitis between 2010 and 2018 using the PearlDiver database and compared 45-day disease-specific readmission between children who received shortened (5-8 days) versus prolonged (10-14 day) total antibiotic courses (inpatient intravenous and/or oral) completed with outpatient Amoxicillin/Clavulanate versus Ciprofloxacin/Metronidazole, and compared antibiotic type (5-14 days) to each other. RESULTS: 4916 children were identified, 2001 (90.0%) treated with Amoxicillin/Clavulanate (5-14 days), 381 (19.0%) with shortened (5-8 days), 1464 (73.2%) with prolonged (10-14 days) courses. 222 (10.0%) were treated with Ciprofloxacin/Metronidazole, 44 (19.8%) with shortened, 174 (78.4%) with prolonged courses. Freedom from readmission was not different between prolonged and shortened course whether they received Amoxicillin/Clavulanate (adjusted hazard ratio [AHR] 1.54, 95%CI 0.95-2.5) or Ciprofloxacin/Metronidazole (AHR 3.49, 95%CI 0.45-27.3). Antibiotic type did not affect readmission rate (Amoxicillin/Clavulanate versus Ciprofloxacin/Metronidazole, AHR 1.21, 95%CI 0.71-2.05). CONCLUSION: Prolonged antibiotic regimens are routinely prescribed despite evidence suggesting shorter courses and antibiotic choice are not associated with greater treatment failure. As it is better tolerated, we recommend a shortened course of Amoxicillin/Clavulanate for oral management of perforated appendicitis. STUDY DESIGN: Retrospective. LEVEL OF EVIDENCE: Level III.

Feasibility and acceptability of using a meditation app in adults with rheumatic disease.

OBJECTIVE: Meditation is a stress-reduction and contemplative technique that can improve emotional distress in people with chronic disease and may be especially beneficial for patients with rheumatic diseases. However, patient access to in-person programs is challenging. The goal of this pilot study was to evaluate the feasibility/acceptability associated with physician-directed use of a widely available smartphone application (app), Calm©. METHODS: In this single-arm, pre-post intervention study with recruitment over a 10-month period, adults with rheumatic disease were asked to use the app for ≥5 min/day for 30 days. Participants completed sociodemographic surveys and validated health related quality of life (HRQL) questionnaires from the Patient Reported Outcomes Information System (PROMIS) and NIH Toolbox at baseline and 30-days. RESULTS: Thirty-five participants who were mostly well-educated (66% ≥college degree) females (91%) with a mean age of 50 (SD 13) completed baseline questionnaires; 18 participants completed post-study questionnaires ("full completers"). Full completers had higher baseline stress, anxiety, pain, and patient global assessment scores (p's <0.05) compared to partial completers. Full completers who provided data used the app on average for 283 min/30 days (SD 257; n = 16) and showed significant improvements in fatigue (-7.6 T-Score units, p = 0.017), with trends for improvement in perceived stress, anxiety, sleep disturbance, self-efficacy for managing symptoms, and pain intensity (p's <0.15). CONCLUSIONS: A 30-day meditation, stress-reduction app used by patients with rheumatic disease revealed that this is a feasible non-pharmacologic modality to target HRQL and problematic symptoms like fatigue. More rigorous study on app use and potential effect is needed.

Real-Time Video Microscopy of In Vitro Demodex Death by Intense Pulsed Light.

Objective: To directly observe the in vitro real-time effects of intense pulsed light (IPL) on a Demodex mite extracted from an eyelash of a patient with ocular rosacea. Background: Demodex is a risk factor in the pathogenesis of oculofacial rosacea, meibomian gland dysfunction (MGD), and dry eye disease (DED). Recent studies suggested IPL to control or eradicate Demodex organisms in the periocular area. Despite encouraging reports, the direct effect of IPL on Demodex is not well understood. Methods: An eyelash infested with Demodex was epilated from a 62-year-old female patient with oculofacial rosacea. Following isolation and adherence of a mite onto a microscope slide, real-time video microscopy was used to capture live images of the organism before, during, and after administration of IPL pulses. IPL pulses were delivered with the M22 IPL (Lumenis), with IPL settings used for treatment of DED due to MGD (the "Toyos protocol"). A noncontact digital laser infrared thermometer was used to measure the temperature of the slide. Results: Before the IPL pulses, legs of the Demodex mite spontaneously moved in a repetitive and semicircular motion. During administration of IPL, spontaneous movements of the legs continued. Immediately after administration of five IPL pulses, the temperature of the slide increased from room temperature to 49°C. Immediately afterward, the Demodex mite became completely immobilized. The legs appeared retracted, smoother, less corrugated, bulkier, and less well-defined. Movement of the Demodex mite was not observed at the hourly inspections for 5 h and after 24 h following the application of IPL pulses. Conclusions: Our video directly demonstrates the effect of IPL on a live Demodex mite extracted from a freshly epilated eyelash. The results suggest that IPL application with settings identical to those used for treatment of DED due to MGD causes a complete destruction of the organism.

GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia.

We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P < .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P < .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors.

The Growing Role of CDK4/6 Inhibitors in Treating Hormone Receptor-Positive Advanced Breast Cancer.

OPINION STATEMENT: Single-agent endocrine therapy has been the standard therapeutic choice for the management of hormone receptor (HR)-positive, Her2-negative advanced breast cancer (ABC) for decades. However, the rapidly accumulating data regarding the biological role and safety of CDK4/6 inhibitors and the first-in-class approval of palbociclib have made these novel agents an essential component of treatment for HR-positive ABC. In the frontline setting, palbociclib in combination with endocrine therapy showed an improvement in progression-free survival (PFS) by 10 months to nearly 25 months when compared with endocrine therapy alone and a clinical benefit rate (CBR = stable disease >24 weeks + partial response + complete response) of 85%. Furthermore, clinically meaningful improvements in PFS were seen in combination with fulvestrant for patients with prior endocrine therapy, including premenopausal women. While neutropenia is experienced by most patients, it is typically uncomplicated and palbociclib is otherwise well tolerated. Recent analysis also demonstrated improved quality of life and reassuring evidence of no compromise in benefit from subsequent therapies after progression on palbociclib. Along with palbociclib, the CDK4/6 inhibitors ribociclib and abemaciclib are being evaluated in a variety of settings (metastatic, neoadjuvant, and adjuvant), alone and in combination with endocrine therapy, chemotherapy, and targeted therapies. Future research is needed to address challenges regarding the potential competition of these agents as the preferred partner in endocrine-sensitive disease, their use as single agents or in combination in the endocrine-refractory setting, and the clinical and molecular criteria for use as an alternative to chemotherapy. Unfortunately, despite efforts to determine predictive biomarkers for response, RB1 expression and HR-positive disease have been the only clear predictors of therapeutic benefit. Once more mature data become available, we hope to confirm a significant impact on long-term survival. Meanwhile, given the multiple therapies patients with ABC will receive, prolonged PFS with a well-tolerated oral regimen is a clinically meaningful endpoint. Palbociclib's impact on PFS, high CBR, and tolerability have made its use a preferred option for treating many HR-positive, Her2-negative ABC patients.

Unrelated donor hematopoietic stem cell transplantation for the treatment of non-malignant genetic diseases: An alemtuzumab based regimen is associated with cure of clinical disease; earlier clearance of alemtuzumab may be associated with graft rejection.

Hematopoietic stem cell transplantation (HSCT) with matched unrelated donors (MUD), offers potentially curative therapy for patients with non-malignant genetic diseases. In this pilot study conducted from 2006 to 2014, we report the outcomes of 15 patients with non-malignant genetic diseases who received a myeloablative regimen with a reduced cyclophosphamide dose, adjunctive serotherapy and MUD HSCT [intravenous alemtuzumab (52 mg/m(2) ), busulfan (16 mg/kg), fludarabine (140mg/m(2) ), and cyclophosphamide (105 mg/kg)]. Graft-versus-host-disease (GVHD) prophylaxis consisted of tacrolimus/cyclosporine and methylprednisolone. Median (range) time to neutrophil engraftment (>500 cells/µL) and platelet engraftment (>20,000/mm(3) ) were 15 (12-28) and 25 (17-30) days, respectively. At a median follow-up of 2 (0.2-5.4) years, the overall survival (OS) was 93.3% (95% CI: 0.61-0.99) and disease-free survival (DFS) was 73.3% (95% CI: 0.44-0.89). Among this small sample, earlier alemtuzumab clearance was significantly associated with graft rejection (P = 0.047), earlier PHA response (P = 0.009) and a trend toward earlier recovery of recent thymic emigrants (RTE) (P = 0.06). This regimen was associated with durable donor engraftment and relatively low rates of regimen related toxicity (RRT); future alemtuzumab pharmacokinetic studies may improve outcomes, by allowing targeted alemtuzumab clearance to reduce graft rejection and promote more rapid immune reconstitution.

Post Splenectomy Outcome in ß-Thalassemia.

OBJECTIVES: To evaluate changes in annual blood transfusion requirements and complications after splenectomy in patients with ß-thalassemia. METHODS: Forty post-splenectomy ß-thalassemic patients aged 8-33 y, receiving regular blood transfusions and chelation therapy were included and non transfusion dependant patients were excluded from this retrospective cross-sectional study. Details about their surgery, transfusion requirements, and platelet levels were recorded on a standard proforma. All patients underwent a B-mode and color-coded duplex sonography of the hepatoportal system during the study period. RESULTS: The average ferritin level in the year prior to the study was 4432 mcg/L (range 480-12,200 mcg/L). The annual blood transfusion requirement in the first year and 5 y post splenectomy [mean ± SD (138.41 ± 90.38 ml/kg/y); (116 ± 41.44 ml/kg/y)] were significantly different from requirements before splenectomy [(mean ± SD) 294.85 ± 226 ml/kg/y; p value <0.001]. There was a significant rise in platelet counts within 24 h post splenectomy with a mean rise of 4,51,000/mm(3) (p value < 0.001). During the follow up period, infections were noted in 50 % of patients, with malaria (18.75 %) being the most common. Doppler study of the portal system in one case showed portal vein thrombosis. CONCLUSIONS: A significant sustained fall in annual blood transfusion requirement and a rise in platelet counts occurred post-splenectomy. Increase in annual blood transfusion requirement should be investigated to find the cause.

Oral and dental late effects in survivors of childhood cancer: a Children's Oncology Group report.

PURPOSE: Multi-modality therapy has resulted in improved survival for childhood malignancies. The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers provide practitioners with exposure- and risk-based recommendations for the surveillance and management of asymptomatic survivors who are at least 2 years from completion of therapy. This review outlines the pathophysiology and risks for oral and dental late effects in pediatric cancer survivors and the rationale for oral and dental screening recommended by the Children's Oncology Group. METHODS: An English literature search for oral and dental complications of childhood cancer treatment was undertaken via MEDLINE and encompassed January 1975 to January 2013. Proposed guideline content based on the literature review was approved by a multi-disciplinary panel of survivorship experts and scored according to a modified version of the National Comprehensive Cancer Network "Categories of Consensus" system. RESULTS: The Children's Oncology Group oral-dental panel selected 85 relevant citations. Childhood cancer therapy may impact tooth development, salivary function, craniofacial development, and temporomandibular joint function placing some childhood cancer survivors at an increased risk for poor oral and dental health. Additionally, head and neck radiation and hematopoietic stem cell transplantation increase the risk of subsequent malignant neoplasms in the oral cavity. Survivors require routine dental care to evaluate for potential side effects and initiate early treatment. CONCLUSIONS: Certain childhood cancer survivors are at an increased risk for poor oral and dental health. Early identification of oral and dental morbidity and early interventions can optimize health and quality of life.

My approach to the treatment of scleroderma.

Systemic sclerosis (scleroderma) is unique among the rheumatic diseases because it presents the challenge of managing a chronic multisystem autoimmune disease with a widespread obliterative vasculopathy of small arteries that is associated with varying degrees of tissue fibrosis. The hallmark of scleroderma is clinical heterogeneity with subsets that vary in the degree of disease expression, organ involvement, and ultimate prognosis. Thus, the term scleroderma is used to describe patients who have common manifestations that link them together, whereas a highly variable clinical course exists that spans from mild and subtle findings to aggressive, life-threatening multisystem disease. The physician needs to carefully characterize each patient to understand the specific manifestations and level of disease activity to decide appropriate treatment. This is particularly important in treating a patient with scleroderma because there is no treatment that has been proven to modify the overall disease course, although therapy that targets specific organ involvement early before irreversible damage occurs improves both quality of life and survival. This review describes our approach as defined by evidence, expert opinion, and our experience treating patients. Scleroderma is a multisystem disease with variable expression; thus, any treatment plan must be holistic, yet at the same time focus on the dominant organ disease. The goal of therapy is to improve quality of life by minimizing specific organ involvement and subsequent life-threatening disease. At the same time the many factors that alter daily function need to be addressed, including nutrition, pain, deconditioning, musculoskeletal disuse, comorbid conditions, and the emotional aspects of the disease, such as fear, depression, and the social withdrawal caused by disfigurement.

Sustainability of market-based community distribution of Sprinkles in western Kenya.

To evaluate the sustainability of market-based community distribution of micronutrient powders (Sprinkles(®), Hexagon Nutrition, Mumbai, India.) among pre-school children in Kenya, we conducted in August 2010 a follow-up survey, 18 months after study-related marketing and household monitoring ended. We surveyed 849 children aged 6-35 months randomly selected from 60 study villages. Nutritional biomarkers were measured by fingerstick; demographic characteristics, Sprinkles purchases and use were assessed through household questionnaires. We compared Sprinkles use, marketing efforts and biomarker levels with the data from surveys conducted in March 2007, March 2008 and March 2009. We used logistic regression to evaluate associations between marketing activities and Sprinkles use in the 2010 survey. At the 2010 follow-up, 21.9% of children used Sprinkles in the previous 7 days, compared with 64.9% in 2008 (P < 0.001). Average intake was 3.2 sachets week(-1) in 2008, 1.6 sachets week(-1) in 2009 and 1.1 sachets week(-1) in 2010 (P < 0.001). Factors associated with recent Sprinkles use in 2010 included young age [6-23 months vs. 24-35 months, adjusted odds ratio (aOR) = 1.5, P = 0.02], lowest 2 quintiles of socio-economic status (aOR = 1.7, P = 0.004), household attendance at trainings or launches (aOR = 2.8, P < 0.001) and ever receiving promotional items including free Sprinkles, calendars, cups and t-shirts (aOR = 1.7, P = 0.04). In 2010, there was increased prevalence of anaemia and malaria (P < 0.001), but not iron deficiency (P = 0.44), compared with that in 2008. Sprinkles use in 2010 was associated with decreased iron deficiency (P = 0.03). Sprinkles coverage reduced after stopping household monitoring and reducing marketing activities. Continued promotion and monitoring of Sprinkles usage may be important components to sustain the programme.

Phenothiazinium-fluoroquinolone drug conjugates.

Synthesis and antibacterial screening of a homologous series of 3-dialkylaminophenothiazinium-7-norfloxacin conjugates was carried out alongside a corresponding series of symmetrical methylene blue derivatives. The norfloxacin conjugates maintained typical methylene blue derivative photoproperties, such as long wavelength absorption, but produced no measurable singlet oxygen in the standard assay and provided no significant increase in the magnitude of photoantibacterial action, this being similar to the methylene blue homologues, although both the conjugates and homologues were considerably more active than methylene blue itself both against Staphylococcus aureus and Escherichia coli. DNA binding via intercalation was considerably greater for the series of norfloxacin conjugates than for the methylene blue homologues.