OBJECTIVES: To assess the benefits and safety of growth hormone therapy in people with thalassaemia.
SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of latest search: 14 November 2019. We also searched the reference lists of relevant articles, reviews and clinical trial registries. Date of latest search: 06 January 2020.
SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing the use of growth hormone therapy to placebo or standard care in people with thalassaemia of any type or severity.
DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion. Data extraction and assessment of risk of bias were also conducted independently by two authors. The certainty of the evidence was assessed using GRADE criteria.
MAIN RESULTS: We included one parallel trial conducted in Turkey. The trial recruited 20 children with homozygous beta thalassaemia who had short stature; 10 children received growth hormone therapy administered subcutaneously on a daily basis at a dose of 0.7 IU/kg per week and 10 children received standard care. The overall risk of bias in this trial was low except for the selection criteria and attrition bias which were unclear. The certainty of the evidence for all major outcomes was moderate, the main concern was imprecision of the estimates due to the small sample size leading to wide confidence intervals. Final height (cm) (the review's pre-specified primary outcome) and change in height were not assessed in the included trial. The trial reported no clear difference between groups in height standard deviation (SD) score after one year, mean difference (MD) -0.09 (95% confidence interval (CI) -0.33 to 0.15 (moderate-certainty evidence). However, modest improvements appeared to be observed in the following key outcomes in children receiving growth hormone therapy compared to control (moderate-certainty evidence): change between baseline and final visit in height SD score, MD 0.26 (95% CI 0.13 to 0.39); height velocity, MD 2.28 cm/year (95% CI 1.76 to 2.80); height velocity SD score, MD 3.31 (95% CI 2.43 to 4.19); and change in height velocity SD score between baseline and final visit, MD 3.41 (95% CI 2.45 to 4.37). No adverse effects of treatment were reported in either group; however, while there was no clear difference between groups in the oral glucose tolerance test at one year, fasting blood glucose was significantly higher in the growth hormone therapy group compared to control, although both results were still within the normal range, MD 6.67 mg/dL (95% CI 2.66 to 10.68). There were no data beyond the one-year trial period.
AUTHORS' CONCLUSIONS: A small single trial contributed evidence of moderate certainty that the use of growth hormone for a year may improve height velocity of children with thalassaemia although height SD score in the treatment group was similar to the control group. There are no randomised controlled trials in adults or trials that address the use of growth hormone therapy over a longer period and assess its effect on final height and quality of life. The optimal dosage of growth hormone and the ideal time to start this therapy remain uncertain. Large well-designed randomised controlled trials over a longer period with sufficient duration of follow up are needed.
METHODS: A case-control study comprising 134 breast cancer patients and 265 cancer-free controls were conducted. Dietary intakes were assessed using a validated food frequency questionnaire (FFQ), from which the HEI-2015 score was calculated. Logistic regression was used to derive the odds ratios (ORs) for measuring the association between HEI-2015 scores and breast cancer risk.
RESULTS: Subjects in the top quartile of HEI-2015 had a 46% lower chance of breast cancer compared with subjects in the bottom quartile (OR 0.54; 95% CI 0.30, 0.98). After adjustment for potential confounders such as age, age at menarche, oral contraceptive drug use, menopausal status, marital status, body mass index, smoking and education level, the association between HEI-2015 score and a lower risk of breast cancer was enhanced (OR 0.32; 95% CI 0.16, 0.65).
CONCLUSION: We successfully demonstrated that a higher HEI-2015 score was associated with a reduced breast cancer risk.
AIM: To develop a neutron-activated, biodegradable and theranostics samarium-153 acetylacetonate (153SmAcAc)-poly-L-lactic acid (PLLA) microsphere for intraarterial radioembolization of hepatic tumors.
METHODS: Microspheres with different concentrations of 152SmAcAc (i.e., 100%, 150%, 175% and 200% w/w) were prepared by solvent evaporation method. The microspheres were then activated using a nuclear reactor in a neutron flux of 2 × 1012 n/cm2/s1, converting 152Sm to Samarium-153 (153Sm) via152Sm (n, γ) 153Sm reaction. The SmAcAc-PLLA microspheres before and after neutron activation were characterized using scanning electron microscope, energy dispersive X-ray spectroscopy, particle size analysis, Fourier transform infrared spectroscopy, thermo-gravimetric analysis and gamma spectroscopy. The in-vitro radiolabeling efficiency was also tested in both 0.9% sodium chloride solution and human blood plasma over a duration of 550 h.
RESULTS: The SmAcAc-PLLA microspheres with different SmAcAc contents remained spherical before and after neutron activation. The mean diameter of the microspheres was about 35 µm. Specific activity achieved for 153SmAcAc-PLLA microspheres with 100%, 150%, 175% and 200% (w/w) SmAcAc after 3 h neutron activation were 1.7 ± 0.05, 2.5 ± 0.05, 2.7 ± 0.07, and 2.8 ± 0.09 GBq/g, respectively. The activity of per microspheres were determined as 48.36 ± 1.33, 74.10 ± 1.65, 97.87 ± 2.48, and 109.83 ± 3.71 Bq for 153SmAcAc-PLLA microspheres with 100%, 150%, 175% and 200% (w/w) SmAcAc. The energy dispersive X-ray and gamma spectrometry showed that no elemental and radioactive impurities present in the microspheres after neutron activation. Retention efficiency of 153Sm in the SmAcAc-PLLA microspheres was excellent (approximately 99%) in both 0.9% sodium chloride solution and human blood plasma over a duration of 550 h.
CONCLUSION: The 153SmAcAc-PLLA microsphere is potentially useful for hepatic radioembolization due to their biodegradability, favorable physicochemical characteristics and excellent radiolabeling efficiency. The synthesis of the formulation does not involve ionizing radiation and hence reducing the complication and cost of production.
OBJECTIVES: To assess the effect of oral galactagogues for increasing milk production in non-hospitalised breastfeeding mother-term infant pairs.
SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Health Research and Development Network - Phillippines (HERDIN), Natural Products Alert (Napralert), the personal reference collection of author LM, and reference lists of retrieved studies (4 November 2019).
SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs (including published abstracts) comparing oral galactagogues with placebo, no treatment, or another oral galactagogue in mothers breastfeeding healthy term infants. We also included cluster-randomised trials but excluded cross-over trials.
DATA COLLECTION AND ANALYSIS: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two to four review authors independently selected the studies, assessed the risk of bias, extracted data for analysis and checked accuracy. Where necessary, we contacted the study authors for clarification.
MAIN RESULTS: Forty-one RCTs involving 3005 mothers and 3006 infants from at least 17 countries met the inclusion criteria. Studies were conducted either in hospitals immediately postpartum or in the community. There was considerable variation in mothers, particularly in parity and whether or not they had lactation insufficiency. Infants' ages at commencement of the studies ranged from newborn to 6 months. The overall certainty of evidence was low to very low because of high risk of biases (mainly due to lack of blinding), substantial clinical and statistical heterogeneity, and imprecision of measurements. Pharmacological galactagogues Nine studies compared a pharmacological galactagogue (domperidone, metoclopramide, sulpiride, thyrotropin-releasing hormone) with placebo or no treatment. The primary outcome of proportion of mothers who continued breastfeeding at 3, 4 and 6 months was not reported. Only one study (metoclopramide) reported on the outcome of infant weight, finding little or no difference (mean difference (MD) 23.0 grams, 95% confidence interval (CI) -47.71 to 93.71; 1 study, 20 participants; low-certainty evidence). Three studies (metoclopramide, domperidone, sulpiride) reported on milk volume, finding pharmacological galactagogues may increase milk volume (MD 63.82 mL, 95% CI 25.91 to 101.72; I² = 34%; 3 studies, 151 participants; low-certainty evidence). Subgroup analysis indicates there may be increased milk volume with each drug, but with varying CIs. There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints, such as tiredness, nausea, headache and dry mouth (very low-certainty evidence). No adverse effects were reported for infants. Natural galactagogues Twenty-seven studies compared natural oral galactagogues (banana flower, fennel, fenugreek, ginger, ixbut, levant cotton, moringa, palm dates, pork knuckle, shatavari, silymarin, torbangun leaves or other natural mixtures) with placebo or no treatment. One study (Mother's Milk Tea) reported breastfeeding rates at six months with a concluding statement of "no significant difference" (no data and no measure of significance provided, 60 participants, very low-certainty evidence). Three studies (fennel, fenugreek, moringa, mixed botanical tea) reported infant weight but could not be meta-analysed due to substantial clinical and statistical heterogeneity (I2 = 60%, 275 participants, very low-certainty evidence). Subgroup analysis shows we are very uncertain whether fennel or fenugreek improves infant weight, whereas moringa and mixed botanical tea may increase infant weight compared to placebo. Thirteen studies (Bu Xue Sheng Ru, Chanbao, Cui Ru, banana flower, fenugreek, ginger, moringa, fenugreek, ginger and turmeric mix, ixbut, mixed botanical tea, Sheng Ru He Ji, silymarin, Xian Tong Ru, palm dates; 962 participants) reported on milk volume, but meta-analysis was not possible due to substantial heterogeneity (I2 = 99%). The subgroup analysis for each intervention suggested either benefit or little or no difference (very low-certainty evidence). There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints such as mothers with urine that smelled like maple syrup and urticaria in infants (very low-certainty evidence). Galactagogue versus galactagogue Eight studies (Chanbao; Bue Xue Sheng Ru, domperidone, moringa, fenugreek, palm dates, torbangun, moloco, Mu Er Wu You, Kun Yuan Tong Ru) compared one oral galactagogue with another. We were unable to perform meta-analysis because there was only one small study for each match-up, so we do not know if one galactagogue is better than another for any outcome.
AUTHORS' CONCLUSIONS: Due to extremely limited, very low certainty evidence, we do not know whether galactagogues have any effect on proportion of mothers who continued breastfeeding at 3, 4 and 6 months. There is low-certainty evidence that pharmacological galactagogues may increase milk volume. There is some evidence from subgroup analyses that natural galactagogues may benefit infant weight and milk volume in mothers with healthy, term infants, but due to substantial heterogeneity of the studies, imprecision of measurements and incomplete reporting, we are very uncertain about the magnitude of the effect. We are also uncertain if one galactagogue performs better than another. With limited data on adverse effects, we are uncertain if there are any concerning adverse effects with any particular galactagogue; those reported were minor complaints. High-quality RCTs on the efficacy and safety of galactagogues are urgently needed. A set of core outcomes to standardise infant weight and milk volume measurement is also needed, as well as a strong basis for the dose and dosage form used.
METHOD: We conducted in-depth interviews with stakeholders in Malaysia (N = 44) and Thailand (N = 50), alongside policy document review in both countries. Data were analysed thematically. Results informed development of Systems Thinking diagrams hypothesizing potential intervention points to improve cultural competency, namely via addressing language barriers.
RESULTS: Language ability was a core tenet of cultural competency as described by participants in both countries. Malay was perceived to be an easy language that migrants could learn quickly, with perceived proficiency differing by source country and length of stay in Malaysia. Language barriers were a source of frustration for both migrants and health workers, which compounded communication of complex conditions including mental health as well as obtaining informed consent from migrant patients. Health workers in Malaysia used strategies including google translate and hand gestures to communicate, while migrant patients were encouraged to bring friends to act as informal interpreters during consultations. Current health services are not migrant friendly, which deters use. Concerns around overuse of services by non-citizens among the domestic population may partly explain the lack of policy support for cultural competency in Malaysia. Service provision for migrants in Thailand was more culturally sensitive as formal interpreters, known as Migrant Health Workers (MHW), could be hired in public facilities, as well as Migrant Health Volunteers (MHV) who provide basic health education in communities.
CONCLUSION: Perceptions of overuse by migrants in a health system acts as a barrier against system or institutional level improvements for cultural competency, in an already stretched health system. At the micro-level, language interventions with migrant workers appear to be the most feasible leverage point but raises the question of who should bear responsibility for cost and provision-employers, the government, or migrants themselves.
DESIGN: This pilot study over April 2016 to September 2019 adopts a before-and-after comparison design of a lung-protective mechanical ventilation protocol. All admissions to the PICU were screened daily for fulfillment of the Pediatric Acute Lung Injury Consensus Conference criteria and included.
SETTING: Multidisciplinary PICU.
PATIENTS: Patients with pediatric acute respiratory distress syndrome.
INTERVENTIONS: Lung-protective mechanical ventilation protocol with elements on peak pressures, tidal volumes, end-expiratory pressure to FIO2 combinations, permissive hypercapnia, and permissive hypoxemia.
MEASUREMENTS AND MAIN RESULTS: Ventilator and blood gas data were collected for the first 7 days of pediatric acute respiratory distress syndrome and compared between the protocol (n = 63) and nonprotocol groups (n = 69). After implementation of the protocol, median tidal volume (6.4 mL/kg [5.4-7.8 mL/kg] vs 6.0 mL/kg [4.8-7.3 mL/kg]; p = 0.005), PaO2 (78.1 mm Hg [67.0-94.6 mm Hg] vs 74.5 mm Hg [59.2-91.1 mm Hg]; p = 0.001), and oxygen saturation (97% [95-99%] vs 96% [94-98%]; p = 0.007) were lower, and end-expiratory pressure (8 cm H2O [7-9 cm H2O] vs 8 cm H2O [8-10 cm H2O]; p = 0.002] and PaCO2 (44.9 mm Hg [38.8-53.1 mm Hg] vs 46.4 mm Hg [39.4-56.7 mm Hg]; p = 0.033) were higher, in keeping with lung protective measures. There was no difference in mortality (10/63 [15.9%] vs 18/69 [26.1%]; p = 0.152), ventilator-free days (16.0 [2.0-23.0] vs 19.0 [0.0-23.0]; p = 0.697), and PICU-free days (13.0 [0.0-21.0] vs 16.0 [0.0-22.0]; p = 0.233) between the protocol and nonprotocol groups. After adjusting for severity of illness, organ dysfunction and oxygenation index, the lung-protective mechanical ventilation protocol was associated with decreased mortality (adjusted hazard ratio, 0.37; 95% CI, 0.16-0.88).
CONCLUSIONS: In pediatric acute respiratory distress syndrome, a lung-protective mechanical ventilation protocol improved adherence to lung-protective mechanical ventilation strategies and potentially mortality.