Growth and Puberty in a 2-Year Open-Label Study of Lisdexamfetamine Dimesylate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

BACKGROUND: Stimulant medications for the treatment of attention-deficit/hyperactivity disorder have a history of safe and effective use; however, concerns exist that they may adversely affect growth trajectories in children and adolescents. OBJECTIVE: The objective of this study was to evaluate the longer-term effects of lisdexamfetamine dimesylate on weight, height, body mass index and pubertal development in children and adolescents with attention-deficit/hyperactivity disorder. METHODS: Children and adolescents aged 6-17 years with attention-deficit/hyperactivity disorder took open-label lisdexamfetamine dimesylate (30, 50 or 70 mg/day) in this open-label 2-year safety and efficacy study. Safety evaluations included treatment-emergent adverse events, measurement of weight, height and body mass index, and self-reported pubertal status using Tanner staging. RESULTS: The safety analysis population comprised all enrolled participants (N = 314) and 191 (60.8%) completed the study. Weight decrease was reported as a treatment-emergent adverse event in 63 participants (20.1%) and two participants (0.6%) discontinued the study as a result of treatment-emergent adverse events of weight decrease. Growth retardation of moderate intensity was reported as a treatment-emergent adverse event for two participants. From baseline to the last on-treatment assessment, there were increases in mean weight of 2.1 kg (standard deviation 5.83) and height of 6.1 cm (standard deviation 4.90), and a body mass index decrease of 0.5 kg/m2 (standard deviation 1.72). Mean weight, height and body mass index z-scores decreased over the first 36 weeks of the study and then stabilised. Changes from baseline to the last on-treatment assessment in mean z-scores for weight, height and body mass index were significantly less than zero (- 0.51, - 0.24 and - 0.59, respectively; nominal p < 0.0001). The proportion of participants with a z-score of < - 1 ranged from 5.1% (baseline) to 22.1% (week 84) for weight, 8.2% (baseline) to 12.6% (week 96) for height, and 8.3% (baseline) to 28.8% (week 96) for body mass index. Thirteen participants (4.1%) shifted to a weight below the fifth percentile at the last on-treatment assessment from a higher weight category at baseline. At the last on-treatment assessment, most participants remained at their baseline Tanner stage or had shifted higher. CONCLUSIONS: Findings from this comprehensive examination of growth outcomes associated with lisdexamfetamine dimesylate treatment over 2 years were consistent with previous studies of stimulant medications. Whilst mean weight and height increased over the course of the study, there was a small but transient reduction in mean weight, height and body mass index z-scores. A small increase in the proportion of participants in the lowest weight and body mass index categories highlights the importance of the regular monitoring of weight and height. There was no evidence of delayed onset of puberty. CLINICALTRIALS. GOV IDENTIFIER: NCT01328756

Safety Issues of Long-Term Glucose Load in Patients on Peritoneal Dialysis—A 7-Year Cohort Study

BACKGROUND: Effects of long-term glucose load on peritoneal dialysis (PD) patient safety and outcomes have seldom been reported. This study demonstrates the influence of long-term glucose load on patient and technique survival. METHODS: We surveyed 173 incident PD patients. Long-term glucose load was evaluated by calculating the average dialysate glucose concentration since initiation of PD. Risk factors were assessed by fitting Cox's models with repeatedly measured time-dependent covariates. RESULTS: We noted that older age, higher glucose concentration, and lower residual renal function (RRF) were significantly associated with a worse patient survival. We found that female gender, absence of diabetes, lower glucose concentration, use of icodextrin, higher serum high density lipoprotein cholesterol, and higher RRF were significantly associated with a better technique survival. CONCLUSIONS: Long-term glucose load predicted mortality and technique failure in chronic PD patients. These findings emphasize the importance of minimizing glucose load in PD patients

NOA1 Functions in a Temperature-Dependent Manner to Regulate Chlorophyll Biosynthesis and Rubisco Formation in Rice

NITRIC OXIDE-ASSOCIATED1 (NOA1) encodes a circularly permuted GTPase (cGTPase) known to be essential for ribosome assembly in plants. While the reduced chlorophyll and Rubisco phenotypes were formerly noticed in both NOA1-supressed rice and Arabidopsis, a detailed insight is still necessary. In this study, by using RNAi transgenic rice, we further demonstrate that NOA1 functions in a temperature-dependent manner to regulate chlorophyll and Rubisco levels. When plants were grown at 30°C, the chlorophyll and Rubisco levels in OsNOA1-silenced plants were only slightly lower than those in WT. However, at 22°C, the silenced plants accumulated far less chlorophyll and Rubisco than WT. It was further revealed that the regulation of chlorophyll and Rubisco occurs at the anabolic level. Etiolated WT seedlings restored chlorophyll and Rubisco accumulations readily once returned to light, at either 30°C or 15°C. Etiolated OsNOA1-silenced plants accumulated chlorophyll and Rubisco to normal levels only at 30°C, and lost this ability at low temperature. On the other hand, de-etiolated OsNOA1-silenced seedlings maintained similar levels of chlorophyll and Rubisco as WT, even after being shifted to 15°C for various times. Further expression analyses identified several candidate genes, including OsPorA (NADPH: protochlorophyllide oxidoreductase A), OsrbcL (Rubisco large subunit), OsRALyase (Ribosomal RNA apurinic site specific lyase) and OsPuf4 (RNA-binding protein of the Puf family), which may be involved in OsNOA1-regulated chlorophyll biosynthesis and Rubisco formation. Overall, our results suggest OsNOA1 functions in a temperature-dependent manner to regulate chlorophyll biosynthesis, Rubisco formation and plastid development in rice

Changing Domesticity of Aedes aegypti in Northern Peninsular Malaysia: Reproductive Consequences and Potential Epidemiological Implications

BACKGROUND: The domestic dengue vector Aedes aegypti mosquitoes breed in indoor containers. However, in northern peninsular Malaysia, they show equal preference for breeding in both indoor and outdoor habitats. To evaluate the epidemiological implications of this peridomestic adaptation, we examined whether Ae. aegypti exhibits decreased survival, gonotrophic activity, and fecundity due to lack of host availability and the changing breeding behavior. METHODOLOGY/PRINCIPAL FINDINGS: This yearlong field surveillance identified Ae. aegypti breeding in outdoor containers on an enormous scale. Through a sequence of experiments incorporating outdoors and indoors adapting as well as adapted populations, we observed that indoors provided better environment for the survival of Ae. aegypti and the observed death patterns could be explained on the basis of a difference in body size. The duration of gonotrophic period was much shorter in large-bodied females. Fecundity tended to be greater in indoor acclimated females. We also found increased tendency to multiple feeding in outdoors adapted females, which were smaller in size compared to their outdoors breeding counterparts. CONCLUSION/SIGNIFICANCE: The data presented here suggest that acclimatization of Ae. aegypti to the outdoor environment may not decrease its lifespan or gonotrophic activity but rather increase breeding opportunities (increased number of discarded containers outdoors), the rate of larval development, but small body sizes at emergence. Size is likely to be correlated with disease transmission. In general, small size in Aedes females will favor increased blood-feeding frequency resulting in higher population sizes and disease occurrence

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Observational study of adult respiratory infections in primary care clinics in Myanmar: understanding the burden of melioidosis, tuberculosis and other infections not covered by empirical treatment regimes

Background Lower respiratory infections constitute a major disease burden worldwide. Treatment is usually empiric and targeted towards typical bacterial pathogens. Understanding the prevalence of pathogens not covered by empirical treatment is important to improve diagnostic and treatment algorithms. Methods A prospective observational study in peri-urban communities of Yangon, Myanmar was conducted between July 2018 and April 2019. Sputum specimens of 299 adults presenting with fever and productive cough were tested for Mycobacterium tuberculosis (microscopy and GeneXpert MTB/RIF [Mycobacterium tuberculosis/resistance to rifampicin]) and Burkholderia pseudomallei (Active Melioidosis Detect Lateral Flow Assay and culture). Nasopharyngeal swabs underwent respiratory virus (influenza A, B, respiratory syncytial virus) polymerase chain reaction testing. Results Among 299 patients, 32% (95% confidence interval [CI] 26 to 37) were diagnosed with tuberculosis (TB), including 9 rifampicin-resistant cases. TB patients presented with a longer duration of fever (median 14 d) and productive cough (median 30 d) than non-TB patients (median fever duration 6 d, cough 7 d). One case of melioidosis pneumonia was detected by rapid test and confirmed by culture. Respiratory viruses were detected in 16% (95% CI 12 to 21) of patients. Conclusions TB was very common in this population, suggesting that microscopy and GeneXpert MTB/RIF on all sputum samples should be routinely included in diagnostic algorithms for fever and cough. Melioidosis was uncommon in this population.</p