Intradetrusor botox injection and augmentation cystoplasty trends among spina bifida patients at US freestanding children's hospitals.

INTRODUCTION: Intra-detrusor botulinum toxin (Botox) injection is a minimally invasive alternative to augmentation cystoplasty in patients with refractory neurogenic bladder. Botox was first used for neurogenic bladder children two decades ago. However, there are no existing guidelines on indications or use among patients with spina bifida. Furthermore, there are little data regarding its use relative to bladder augmentation and patient volume on a national scale. OBJECTIVE: We sought to investigate the contemporary trends of intra-detrusor Botox injection and augment cystoplasty in free-standing children's hospitals. STUDY DESIGN: We queried the Pediatric Health Information System database to identify spina bifida patients from 2016 to 2019 who underwent intra-detrusor Botox injection and augment cystoplasty based on CPT and ICD-10 codes. Total spina bifida population under care in the free-standing children's hospitals was estimated by all inpatient and ambulatory surgery encounters as denominators to calculate frequency by time for both intra-detrusor Botox injections and augmentation cystoplasty. RESULTS: In total, we included 1924 intra-detrusor Botox injections and 842 augmentation cystoplasties. 1413 (51.1%) patients were female. Median age at surgery was 10.0 (interquartile range 6.98-13.5) years. There was a significant increase in intra-detrusor Botox injection frequency (p < 0.001). While there was an overall decreasing, but not significant, trend for augmentation cystoplasty, there was a significant increase in this procedure during the summer months compared to the rest of the year (p < 0.001, Figure 1). Sensitivity analysis using only first intra-detrusor Botox injection per patient demonstrated similarly significant increasing trend. DISCUSSION: Use of intra-detrusor Botox injection for the management of neurogenic bladder has significantly increased among patients with spina bifida while augmentation cystoplasty has slightly decreased, but not significantly. CONCLUSIONS: Over time, practice patterns for the treatments of neurogenic bladder among spina bifida children have favored minimally invasive Botox injections while augmentation cystoplasty use has not significantly changed.

A comparison of conductive ink usage optimization techniques used in fabrication of epidermal UHF radio frequency identification tags for medical and sensing applications.

The aim of this work is to assess the performance of various inkjet printing techniques. These techniques are aimed at optimizing the volume of conductive ink used in the fabrication of inkjet printed Radio Frequency Identification tags. It is also possible that they can be used in fabricating other electronic and electromagnetic devices and structures. Three ink optimization approaches were examined viz. gridded (meshed) designs, conductive area trimming and selective ink deposition. The volume of conductive ink utilized in tag fabrication and the measured on-body (forearm) read range of the tag were used to develop a figure of merit which determined the best printing approach. Although the longest read range was obtained from the tag with 48% conductive area trimming (Trim 1), the best figure of merit, that is, the tag with the best balance between measured read range and utilized conductive ink, was obtained from the tag that had its surface area trimmed by 65% (Trim 2). It is however suggested that optimum use of conductive ink would be achieved with a combination of 65% surface area trimming and selective ink deposition technique.

Facilitators and challenges to transitioning to self-catheterization: Patient and caregiver perspectives.

INTRODUCTION: Clean intermittent catheterization (CIC) is a well-established method of managing lower urinary tract dysfunction. Depending on the age at introduction, caregivers might perform CIC initially but then transition responsibility to their children. Little is known about how to support families during this transition. Our aim is to learn the facilitators and challenges experienced when supporting the transition from caregiver-led CIC to patient self-CIC. MATERIALS AND METHODS: A phenomenological approach was used to gather information from caregivers and children >12 years through semistructured interviews. Thematic analysis was utilized to generate themes around experience with the transition from caregiver-led CIC to patient self-CIC. RESULTS: Of the 40 families interviewed, 25 families underwent successful transition to patient self-CIC. Analysis of excerpts identified a three-step process, including (1) desiring to learn self-CIC, (2) practical learning of CIC techniques, and (3) mastering of techniques leading to emotional and physical independence. Many families experienced challenges in transitioning to self-CIC, including patient or caregiver reluctance, improper equipment, past negative experiences, lack of knowledge about urinary tract anatomy and function, abnormal anatomy, and/or moderate to severe intellectual disability. DISCUSSION: Authors reviewed interventions to address challenges and provide clinical care recommendations to enhance success during the transition to patient self-CIC. CONCLUSION: No prior studies have identified this stepwise process that occurs in the transition from caregiver-led CIC to patient self-CIC. Healthcare providers and school officials (where indicated) can support families during this transition, with attention to facilitators and challenges identified in this study.

The art of introducing clean intermittent catheterization: How families respond and adapt: A qualitative study.

INTRODUCTION: Since its inception >50 years ago, clean intermittent catheterization (CIC) has become ubiquitous in managing lower urinary tract dysfunction in children. Emphasis has been on its impact on daily life, but little on its implementation and adjustment in families. The aim of the current study was to discover how families learned to implement and manage their child's CIC needs by interviewing caregivers, adolescents, and young adults about their experiences. Interviews were designed to uncover facilitators and barriers to beginning CIC to initiate potential improvements in a multidisciplinary approach. METHODS: A semi-structured interview guide was developed and piloted initially to 12 families for validation. Between August 2018 and October 2019, 40 families (52 interviews of caregivers and patients >12 years) were then interviewed with open-ended questions interspersed with more specific ones to generate discussion. Transcripts were coded using Dedoose software to create a base list with emergent codes. Inductive and deductive methods were employed to generate themes. Consensus was reached during successive team meetings. RESULTS: Five major and several subthemes emerged regarding implementation of CIC by caregivers and patients learning CIC for the first time. THEME 1: Parental reaction to CIC: Caregivers described benefits of an adjustment period on learning their child's need for CIC. Prenatal information to caregivers of spina bifida children gave them time to mentally process the need for CIC. THEME 2: Ease of learning CIC: impact of age and gender: caregivers identified advantages of initiating CIC in infancy. Caregivers speculated CIC was physically easier in boys than girls due to meatus location. Developmentally ready children expressed a desire for independence and privacy as they learned to initiate CIC. THEME 3: The impact of additional caregiver support in learning and performing CIC: presence of multiple caregivers optimized learning and implementation of CIC. Having secondary caregivers available provided peace of mind and more flexibility in maintaining reliable CIC care. Patients learning CIC found it helpful to have a parent present at the teaching session. Occasionally, female caregivers reported feelings of anger and frustration when male caregivers were reluctant to be involved in catheterization, irrespective of their child's gender. THEME 4: Satisfaction with healthcare team's approach: The healthcare team's responsiveness to their learning needs affected how they mastered CIC. The healthcare team's teaching and reassurance helped build caregiver confidence. Developmentally appropriate children were able to learn self-catheterization when supported by the healthcare team. Patients learning self-CIC articulated having a supportive healthcare team was helpful with implementation. THEME 5: Effect of CIC on employment status relative to job changes, insurance, and daycare: implementing and performing CIC presented a spectrum of issues related to employment. Educating employers regarding CIC facilitated a caregiver's ability to both remain at work and administer to their child. Caregivers underscored the importance of adequate insurance when considering employment choices. Concerns about daycare availability affected caregivers' work schedules. CONCLUSIONS: It is anticipated this information will aid healthcare personnel to more effectively teach and initiate CIC in families, and in individuals learning for the first time. The findings should serve as the basis for conducting future patient satisfaction studies, which would determine the effectiveness and reproducibility of these approaches.

Sumping's Up: A Multidisciplinary Educational Initiative on Gastric Drainage Tubes.

BACKGROUND: Nasogastric tube placement is widely taught, and tube maintenance relies on astute nursing care with adherence to both institutional and evidence-based recommendations. However, precise adherence to current recommendations relies on knowledge base regarding the identification of malfunctioning gastric drainage tubes. Troubleshooting skills are crucial in maintaining patient safety and recognizing malfunction. METHOD: Educational sessions on nasogastric and orogastric decompression tube management, led by a surgical intensive care fellow at a level 1 trauma center, were offered to critical care nurses. A presession and postsession survey evaluated the nurses' subjective and objective knowledge and comfort with naso/orogastric decompression tube management. RESULTS: Ninety-seven critical care RNs participated. For all questions, the proportion of correct answers significantly increased from presession survey to postsession survey (p < .001). Ninety-seven percent of all participants found the session to be very helpful. CONCLUSION: Physician-led educational sessions on naso/orogastric decompression tube management were well-received and improved subjective and objective measurements of nurses' knowledge and comfort level with gastric decompression tubes. [J Contin Educ Nurs. 2020;51(10):484-488.].

Acoustic Poration and Dynamic Healing of Mammalian Cell Membranes during Inkjet Printing.

We have investigated the effect of piezoelectric actuating voltage on cell behavior after drop on demand inkjet printing using mouse 3T3 cells as a model cell line. Cell viability after printing was assessed using a live/dead assay, Alamar Blue as an assay for cell proliferation, and propidium iodide (PI) and Texas Red labeled dextran molecular probes to assess cell membrane integrity. No significant difference was found for the cell death rate compared between an unprinted control population and after printing at 80, 90, and 100 V, respectively. However, cell proliferation was lower than that of the control population at all time points postprinting. Cell membrane integrity was quantified using PI and dextran probes of mean molecular weight of 3, 10, 40, and 70 kDa. Total membrane damage (assessed by PI) increased with increasing piezoelectric actuator driving voltage, and this was always greater than the unprinted control cells. The uptake of the labeled dextran only occurs after inkjet printing and was never observed with the control cells. The largest dextran molecular probe of 70 kDa was only taken up by cells after printing using the lower printing voltages of 80 and 90 V and was absent after printing at 100 V. At the two lower printing voltages, the membrane damage is recovered, and no dextran molecule penetrated the cells 2 h after printing. However, printing at 100 V leads to an increased uptake of 3 and 10 kDa dextran molecules, the retention of membrane porosity, and continued uptake of these 3 and 10 kDa dextran for greater than 2 h postprinting. We hypothesize that the change in membrane porosity with increasing actuation voltage can be explained by distinct nucleation and growth stages for pore formation in response to printing stress.

Sigmoidectomy for Diverticulitis-A Propensity-Matched Comparison of Minimally Invasive Approaches.

BACKGROUND: As the availability and use of robotic surgery increases, current data suggest comparable outcomes to laparoscopic surgery but at an increased cost. Elective sigmoid resection for diverticular disease is the most common colorectal application of robotic surgery and there is limited comparative data specifically for this indication. METHODS: We identified all elective cases of laparoscopic- and robot-assisted surgery for diverticular disease among a practice of 7 colorectal surgeons within an established enhanced recovery protocol. We performed propensity matching based on surgical indications (recurrent disease, ongoing symptoms, or fistula), stoma creation, and body mass index to create a matched cohort. Our primary outcomes were return of bowel function, length of stay, opioid use, and pain scores during the first 72 h postoperatively. Secondary outcomes were operative room and hospital charges. RESULTS: From 2011 to 2016, 69 robotic cases were propensity matched from a group of 222 laparoscopic cases to create a 1:1 case ratio that was equivalent in terms of patient demographics and operative indications. Time to first bowel movement was slightly quicker in the robotic group (1 [1] versus 2 [1.5], P = 0.09), while length of stay (3.5 [1.6] versus 3.6 [1.4] d, P = 0.64) was equivalent. Pain scores were lower in the robotic group on day 0 (4.6 versus 6.1, P = 0.0001), but similar on day 1 and day 2 (4.3 versus 4.1, P = 0.62 and 3.8 versus 3.3, P = 0.19). There was no difference in postoperative 72-h opioid use between groups (110.8 MME [144.5] versus 97.4 MME [101.5], P = 0.70). In the robotic arm operating room charges were slightly more ($2835 ± $394 versus $2196 ± $359, P < 0.0001), but total hospital charges were over significantly increased ($41,159 [$7840] versus $25,761 [$11,689], P < 0.0001). CONCLUSIONS: Via a carefully matched cohort of elective sigmoid resection for diverticular disease at a single community institution, we have demonstrated that laparoscopic- and robotic-assisted surgery result in clinically equivalent return of bowel function, length of stay, postoperative pain, and opioid use.

The danger zone: Injuries and conditions associated with immediately fatal motorcycle crashes in the state of Michigan.

BACKGROUND: Immediately fatal motorcycle crashes have not been well characterized. This study catalogues injuries sustained in fatal motorcycle crashes and assesses the impact of crash conditions on injury patterns. METHODS: Autopsy records from the office of the medical examiner of Kent County, MI and publicly available traffic reports were queried for information pertaining to motorcyclists declared dead on-scene between January 1, 2007, and December 31, 2016. RESULTS: A total of 71 autopsies of on-scene motorcycle crash fatalities were identified. The two most prevalent injuries were traumatic brain injury (TBI) (85%) and rib fractures (79%). The majority of fatalities occurred in daylight hours (54.3%) and in a 55 mph speed limit zone (63.8%). CONCLUSIONS: This study provides a catalogue of the injuries sustained in immediately fatal motorcycle crashes and the associated conditions. Advocacy efforts that highlight the risks associated with motorcycle riding and that promote safe riding practices are warranted.

An Exploration of Behind-the-Ear ECG Signals From a Single Ear Using Inkjet Printed Conformal Tattoo Electrodes.

Wearable sensors placed behind-the-ear are emerging as being very promising for unobtrusive long term monitoring. Factors such as gait, electroencephalography (EEG), and ballistocardiography (BCG) can all be measured from behind-the-ear in a socially acceptable hearing aid based form factor. Previous works have investigated the recording of electrocardiography (ECG) from the ear, but generally with one electrode placed some distance away from the ear itself. This paper uses recently introduced tattoo electrodes to investigate whether ECG components can indeed be measured from behind a single ear. Compared to a reference photophelsmography (PPG) device we show that the fundamental heart beat frequency is present in behind-the-ear ECG only in half of the cases considered. In contrast the second harmonic is present in all records and could allow the extraction of heart rate to within a few beats-per-minute accuracy. Further signal processing work is required to allow the automated extraction of this, particularly when working with short time windows of data, but our results characterize the signal and demonstrate the principle of behind-the-ear ECG collected from a single ear.

The impact of the repeal of Michigan's universal helmet law on traumatic brain injury: A statewide analysis.

BACKGROUND: In April of 2012, Michigan repealed its 35-year-old universal motorcycle helmet law in favor of a partial helmet law, which permits motorcyclists older than 21 years old with sufficient insurance and experience to drive un-helmeted. We evaluated the clinical impact of the repeal. METHODS: The Michigan Trauma Quality Improvement Program's trauma database was queried for motorcycle crash patients between 1/1/09-4/12/12 and between 4/13/12-12/31/14. RESULTS: There were 1970 patients in the pre-repeal analysis and 2673 patients in the post-repeal analysis. Following the repeal, patients were more likely to be un-helmeted (p < 0.001) and to have a traumatic brain injury (p < 0.001). Patients were also more likely to require neurosurgical interventions (relative risk 1.4, p = 0.011). CONCLUSION: Following the repeal of the universal helmet law, there has been a significant increase in traumatic brain injuries and neurosurgical interventions. This analysis highlights another detrimental impact of the repeal of the universal helmet law.

Deaths and parasuicides associated with mefloquine chemoprophylaxis: A systematic review.

BACKGROUND: Mefloquine is recommended in international health guidelines for preventing malaria in travellers. Reports of psychosis and suicide are often alluded to but are not clearly established. METHODS: We carried out a systematic review of the literature to identify and critically appraise any reported death or parasuicide associated with mefloquine prophylaxis. We developed a comprehensive search that included publications up to 11 July 2017. We included case studies but excluded newspaper reports. Two authors independently appraised each death or parasuicide against a standardised causality assessment tool. The protocol was registered on PROSPERO (CRD42016041988). RESULTS: We identified 527 articles that required full-text retrieval; of these 17 were unique publications that reported deaths or parasuicide. Eight unique publications had sufficient detail to be included in causality assessment. We identified 2 deaths with a probable association that appeared to be idiosyncratic drug reactions; we categorised the remaining 8 deaths as "unlikely" to be related to mefloquine, or "unclassifiable". There was one parasuicide with a possible causal association. There were 9 additional publications that searched spontaneous drug reporting databases; none provided sufficient detail to perform a causality assessment. CONCLUSIONS: Overall, the number of deaths that we could reliably attribute to the prophylactic use of mefloquine is very low.

Mefloquine for preventing malaria during travel to endemic areas.

BACKGROUND: Mefloquine is one of four antimalarial agents commonly recommended for preventing malaria in travellers to malaria-endemic areas. Despite its high efficacy, there is controversy about its psychological side effects. OBJECTIVES: To summarize the efficacy and safety of mefloquine used as prophylaxis for malaria in travellers. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published on the Cochrane Library; MEDLINE; Embase (OVID); TOXLINE (https://toxnet.nlm.nih.gov/newtoxnet/toxline.htm); and LILACS. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; http://www.who.int/ictrp/en/) and ClinicalTrials.gov (https://clinicaltrials.gov/ct2/home) for trials in progress, using 'mefloquine', 'Lariam', and 'malaria' as search terms. The search date was 22 June 2017. SELECTION CRITERIA: We included randomized controlled trials (for efficacy and safety) and non-randomized cohort studies (for safety). We compared prophylactic mefloquine with placebo, no treatment, or an alternative recommended antimalarial agent. Our study populations included all adults and children, including pregnant women. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility and risk of bias of trials, extracted and analysed data. We compared dichotomous outcomes using risk ratios (RR) with 95% confidence intervals (CI). Prespecified adverse outcomes are included in 'Summary of findings' tables, with the best available estimate of the absolute frequency of each outcome in short-term international travellers. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 20 RCTs (11,470 participants); 35 cohort studies (198,493 participants); and four large retrospective analyses of health records (800,652 participants). Nine RCTs explicitly excluded participants with a psychiatric history, and 25 cohort studies stated that the choice of antimalarial agent was based on medical history and personal preference. Most RCTs and cohort studies collected data on self-reported or clinician-assessed symptoms, rather than formal medical diagnoses. Mefloquine efficacyOf 12 trials comparing mefloquine and placebo, none were performed in short-term international travellers, and most populations had a degree of immunity to malaria. The percentage of people developing a malaria episode in the control arm varied from 1% to 82% (median 22%) and 0% to 13% in the mefloquine group (median 1%).In four RCTs that directly compared mefloquine, atovaquone-proguanil and doxycycline in non-immune, short-term international travellers, only one clinical case of malaria occurred (4 trials, 1822 participants). Mefloquine safety versus atovaquone-proguanil Participants receiving mefloquine were more likely to discontinue their medication due to adverse effects than atovaquone-proguanil users (RR 2.86, 95% CI 1.53 to 5.31; 3 RCTs, 1438 participants; high-certainty evidence). There were few serious adverse effects reported with mefloquine (15/2651 travellers) and none with atovaquone-proguanil (940 travellers).One RCT and six cohort studies reported on our prespecified adverse effects. In the RCT with short-term travellers, mefloquine users were more likely to report abnormal dreams (RR 2.04, 95% CI 1.37 to 3.04, moderate-certainty evidence), insomnia (RR 4.42, 95% CI 2.56 to 7.64, moderate-certainty evidence), anxiety (RR 6.12, 95% CI 1.82 to 20.66, moderate-certainty evidence), and depressed mood during travel (RR 5.78, 95% CI 1.71 to 19.61, moderate-certainty evidence). The cohort studies in longer-term travellers were consistent with this finding but most had larger effect sizes. Mefloquine users were also more likely to report nausea (high-certainty evidence) and dizziness (high-certainty evidence).Based on the available evidence, our best estimates of absolute effect sizes for mefloquine versus atovaquone-proguanil are 6% versus 2% for discontinuation of the drug, 13% versus 3% for insomnia, 14% versus 7% for abnormal dreams, 6% versus 1% for anxiety, and 6% versus 1% for depressed mood. Mefloquine safety versus doxycyclineNo difference was found in numbers of serious adverse effects with mefloquine and doxycycline (low-certainty evidence) or numbers of discontinuations due to adverse effects (RR 1.08, 95% CI 0.41 to 2.87; 4 RCTs, 763 participants; low-certainty evidence).Six cohort studies in longer-term occupational travellers reported our prespecified adverse effects; one RCT in military personnel and one cohort study in short-term travellers reported adverse events. Mefloquine users were more likely to report abnormal dreams (RR 10.49, 95% CI 3.79 to 29.10; 4 cohort studies, 2588 participants, very low-certainty evidence), insomnia (RR 4.14, 95% CI 1.19 to 14.44; 4 cohort studies, 3212 participants, very low-certainty evidence), anxiety (RR 18.04, 95% CI 9.32 to 34.93; 3 cohort studies, 2559 participants, very low-certainty evidence), and depressed mood (RR 11.43, 95% CI 5.21 to 25.07; 2 cohort studies, 2445 participants, very low-certainty evidence). The findings of the single cohort study reporting adverse events in short-term international travellers were consistent with this finding but the single RCT in military personnel did not demonstrate a difference between groups in frequencies of abnormal dreams or insomnia.Mefloquine users were less likely to report dyspepsia (RR 0.26, 95% CI 0.09 to 0.74; 5 cohort studies, 5104 participants, low certainty-evidence), photosensitivity (RR 0.08, 95% CI 0.05 to 0.11; 2 cohort studies, 1875 participants, very low-certainty evidence), vomiting (RR 0.18, 95% CI 0.12 to 0.27; 4 cohort studies, 5071 participants, very low-certainty evidence), and vaginal thrush (RR 0.10, 95% CI 0.06 to 0.16; 1 cohort study, 1761 participants, very low-certainty evidence).Based on the available evidence, our best estimates of absolute effect for mefloquine versus doxycyline were: 2% versus 2% for discontinuation, 12% versus 3% for insomnia, 31% versus 3% for abnormal dreams, 18% versus 1% for anxiety, 11% versus 1% for depressed mood, 4% versus 14% for dyspepsia, 2% versus 19% for photosensitivity, 1% versus 5% for vomiting, and 2% versus 16% for vaginal thrush.Additional analyses, including comparisons of mefloquine with chloroquine, added no new information. Subgroup analysis by study design, duration of travel, and military versus non-military participants, provided no conclusive findings. AUTHORS' CONCLUSIONS: The absolute risk of malaria during short-term travel appears low with all three established antimalarial agents (mefloquine, doxycycline, and atovaquone-proguanil).The choice of antimalarial agent depends on how individual travellers assess the importance of specific adverse effects, pill burden, and cost. Some travellers will prefer mefloquine for its once-weekly regimen, but this should be balanced against the increased frequency of abnormal dreams, anxiety, insomnia, and depressed mood.

Safety of primaquine given to people with G6PD deficiency: systematic review of prospective studies.

BACKGROUND: Haemolysis risk with single dose or short course primaquine was evaluated in glucose-6-phosphate dehydrogenase (G6PD) deficient people. METHODS: Major electronic databases (to August 2016) were searched for single or short course 8-aminoquinolines (8-AQ) in (1) randomized comparisons against placebo in G6PD deficient people; and (2) observational comparisons in G6PD deficient compared to replete people. Two authors independently assessed eligibility, risk-of-bias, and extracted data. RESULTS: Five randomized controlled trials and four controlled observational cohorts were included. In G6PD deficient individuals, high-dose (0.75 mg/kg) PQ resulted in lower average haemoglobin levels at 7 days (mean difference [MD] -1.45 g/dl, 95% CI -2.17 to -0.74, 2 trials) and larger percentage fall from baseline to day 7 (MD -10.31%, 95% CI -17.69 to -2.92, 3 trials) compared to placebo. In G6PD deficient compared to replete people, average haemoglobin was lower at 7 days (MD -1.19 g/dl, 95% CI -1.94 to -0.44, 2 trials) and haemoglobin change from baseline to day 7 was greater (MD -9.10%, 95% CI -12.55 to -5.65, 5 trials). One small trial evaluated mid-range PQ dose (0.4-0.5 mg/kg) in G6PD deficient people, with no difference detected in average haemoglobin at day 7 compared to placebo. In one cohort comparing G6PD deficient and replete people there was a greater fall with G6PD deficiency (MD -4.99%, 95% CI -9.96 to -0.02). For low-dose PQ (0.1-0.25 mg/kg) in G6PD deficient people, haemoglobin change from baseline was similar to the placebo group (MD 1.72%, 95% CI -1.89 to 5.34, 2 trials). Comparing low dose PQ in G6PD deficient with replete people, the average haemoglobin was lower in the G6PD deficient group at 7 days (-0.57 g (95% CI -0.97 to -0.17, 1 trial)); although change from baseline was similar (MD -1.45%, 95% CI -5.69 to 2.78, 3 trials). CONCLUSIONS: Falls in average haemoglobin are less marked with the 0.1 to 0.25 mg/kg PQ than with the 0.75 mg/kg dose, and severe haemolytic events are not common. However, data were limited and the evidence GRADE was low or very low certainty.

High throughput cryopreservation of cells by rapid freezing of sub-µl drops using inkjet printing--cryoprinting.

We have successfully used inkjet printing to cryopreserve 3T3 mouse fibroblast cells and human neuroprogenitor cells (NPCs) derived from human embryonic stem cells (hESCs). Sessile drops of volume 114 nl were formed by printing cell suspensions containing dimethyl sulphoxide (DMSO) as a cryoprotection agent (CPA) at rates in the region 100 Hz-20 kHz, from individual droplets of 380 pl. After printing and a freeze/thaw cycle (with a minimum 24 hours hold period at liquid N2 temperature), 3T3 cells showed an average viability of >90% with CPA concentration <0.8 M at all drop deposition rates. This is a significantly lower CPA concentration than normally used with conventional cryopreservation methods. Cell viability shows a small variation with the polymer substrates used, with the best results obtained using a polyimide substrate. The viability of 3T3 cells after 2 months storage at liquid nitrogen temperature was slightly reduced compared to the cells held for 24 hours but there was no significant further deterioration after 4 or 6 months storage. The viability of NPCs after an identical freeze/thaw cycle were only 55% but this is comparable with conventional cryopreservation methods that use much higher CPA concentrations. A parallel series of experiments printing cells onto substrates held at 195 K or directly into liquid N2 showed considerable variation in cell survival rate with drop deposition rate. Cell suspensions required higher levels of CPA than when printing followed by freezing. At low deposition rates a combination of DMSO and polyethylene glycol (PEG) was needed to allow cell viability after freezing. These results show that inkjet printing provides a practical high throughput method for the cryopreservation of cells with lower CPA concentrations than are required for current low volume cryopreservation methods.

Cytokine Kinetics in the First Week of Tuberculosis Therapy as a Tool to Confirm a Clinical Diagnosis and Guide Therapy.

BACKGROUND: Many patients treated for tuberculosis (TB) in low and middle income countries are treated based on clinical suspicion without bacteriological confirmation. This is often due to lack of rapid simple accurate diagnostics and low healthcare provider confidence in the predictive value of current tests. We previously reported in an animal TB model that levels of host markers rapidly change in response to treatment initiation. METHODS: We assessed the potential of host biomarker kinetics of TB patients during the first two weeks of therapy to identify patients responding to treatment. Adult patients clinically diagnosed with and treated for TB, 29 in Nigeria and 24 in Nepal, were analyzed. RESULTS: Changes in concentrations of non-specific host biomarkers, particularly IP-10, in response to the first week of anti-TB therapy were strongly associated with bacteriological confirmation of TB. A decrease in IP-10 level of >300pg/ml between 0 and 7 days of treatment identified 75% of both smear-positive and smear-negative culture positive patients and correctly excluded TB in all nine culture negative patients. CONCLUSIONS: Monitoring of early IP-10 responses to treatment could form the basis of a simplified assay and could help identify patients who were erroneously clinically diagnosed with TB or those infected with drug resistant strains on inappropriate treatment. We believe this approach may be particularly appropriate for difficult to diagnose patients, e.g. smear-negative HIV-positive, or those with extra-pulmonary TB, often treated without bacterial confirmation.

Safety of 8-aminoquinolines given to people with G6PD deficiency: protocol for systematic review of prospective studies.

INTRODUCTION: A single dose or short course of primaquine given to people infected with malaria may reduce transmission of Plasmodium falciparum through its effects on gametocytes. Primaquine is also known to cause haemolysis in people with variants of glucose-6-phosphate dehydrogenase (G6PD) deficiency. The objective of this systematic review was to assess the risk of adverse effects in people with G6PD deficiency given primaquine or other 8-aminoquinoline (8AQ) as a single dose or short course (less than 7 days). METHODS AND ANALYSIS: We will search the following databases: Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS. Prospective cohort studies, randomised and quasi-randomised trials that evaluated 8AQs for whatever reason in adults or children with a known G6PD deficiency will be included. Two authors will independently assess each study for eligibility, risk of bias and extract data. ETHICS AND DISSEMINATION: This systematic review will be published in a peer-reviewed journal. Brief reports of the review findings will be disseminated directly to the appropriate audiences and the WHO Technical Expert Group in Malaria Chemotherapy. As no primary data collection will be undertaken, no additional formal ethical assessment and informed consent are required. PROTOCOL REGISTRATION IN PROSPERO: The protocol is registered with PROSPERO, registration number CRD42013006518.