Barriers to school-based health programs implementation in basic schools in Ghana: education stakeholders' perspective.

School health has been identified as a neglected aspect of primary health care in Ghana, leading to compromised health, well-being and life satisfaction among students. To address this concern, this study identified the barriers hindering the implementation of school-based health programs in Ghana. It employed a qualitative approach, including 116 respondents who participated in interviews. The collected data were analyzed using thematic analysis with the aid of NVivo software. In line with the research objective, findings show that the implementation of school-based health programs faces several teething challenges that serve as barriers to the success and sustainability of the programs. These barriers included resource constraints; a lack of adequate parental and community participation and a lack of adequate collaboration between stakeholders' management and leadership issues, governance issues and political issues. The findings from the study have a relevant and innovative contribution to achieving good health and well-being and quality education as part of the 2030 Agenda for Sustainable Development Goals and shaping primary healthcare management in the context of a developing country. It recommends that policymakers and health practitioners pay special attention to school-based health programs as a key strategy for primary health care management in developing countries.

[Current status and influencing factors for physicians in different departments prescribing novel hypoglycemic agent with cardiovascular benefits].

Objective: To investigate the knowledge, use and barriers when prescribing GLP-1RA and SGLT2i among cardiologists, endocrinologists and general practitioners, and explore the influencing factors that hinder the use of these medications. Methods: A questionnaire was conducted among physicians in the above departments in Peking University Third Hospital and health service institutions at all levels in its medical consortium. A total of 342 physicians were involved. Among them, 40.6% (139) were cardiologists, 28.9% (99) were endocrinologists and 30.4% (104) were general practitioners; 66.7% (270) came from Beijing while 33.3% (72) from other provinces. The survey included clinicians' knowledge and current use of GLP-1RA and SGLT2i, and the possible reasons that influenced the prescription of these medications. Medical therapies of physicians were investigated by simulating different clinical scenarios. The difference of measures among physicians in different departments was compared. Results: A total of 342 physicians were involved, with the average age of 40 (35, 46) years old and the average working time of 13 (7, 20) years. Among them, 40.6% (139) were male. 77.5% (265) physicians had comprehensive knowledge of SGLT2i and prescribed it, which was higher than that for GLP-1RA (70.5%, 241) (P<0.001). 21.1% (72) physicians prescribed SGLT2i more than 20 times per month, which was higher than that for GLP-1RA (8.2%, 28) (P<0.001). Endocrinologists had more knowledge and prescribed more GLP-1RA and SGLT2i compared with other physicians (both P values<0.001). 38.1% (53) cardiologists, 22.2% (22) endocrinologists, and 30.8% (32) general practitioners believed patients needed an endocrinologist to evaluate and adjust GLP-1RA, which was the primary barrier for the use of medications (P=0.042). 27.4% (38) cardiologists, 14.1% (14) endocrinologists, and 30.8% (32) general practitioners believed patients needed an endocrinologist to evaluate and adjust SGLT2i, which was the primary barrier for the use of medications (P=0.018). 21.6% (30) cardiologists, 45.5% (45) endocrinologists, and 31.7% (33) general practitioners believed side effects of SGLT2i was the primary barrier for the use of medications (P<0.001). For patients with unqualified glycemic control and cardiovascular complications, 65.4% (75) cardiologists, 69.7% (69) endocrinologists, and 43.3% (45) general practitioners chose the above medications (P<0.001). For patients with qualified glycemic control, combined with cardiovascular complications and diabetic organ damage, 35.3% (49) cardiologists, 52.5% (52) endocrinologists, and 25.0% (26) general practitioners chose the above medications (P<0.001). Conclusions: Physicians had more knowledge and prescription of SGLT2i than that of GLP-1RA. Endocrinologists had more knowledge and prescription of the above medications than other physicians. The side effect of medications was potential primary barrier for the use of the novel hypoglycemic agent with cardiovascular benefits. In clinical practice, most of physicians considered that high-risk patients with cardiovascular comorbidities need to be referred to cardiologist or endocrinologist to adjust clinical therapies.

Theoretical and experimental study of peroxy and alkoxy radicals in the NO3-initiated oxidation of isoprene.

The initial stages of the nitrate radical (NO3) initiated oxidation of isoprene, in particular the fate of the peroxy (RO2) and alkoxy (RO) radicals, are examined by an extensive set of quantum chemical and theoretical kinetic calculations. It is shown that the oxidation mechanism is highly complex, and bears similarities to its OH-initiated oxidation mechanism as studied intensively over the last decade. The nascent nitrated RO2 radicals can interconvert by successive O2 addition/elimination reactions, and potentially have access to a wide range of unimolecular reactions with rate coefficients as high as 35 s-1; the contribution of this chemistry could not be ascertained experimentally. The chemistry of the alkoxy radicals derived from these peroxy radicals is affected by the nitrate moiety, and can lead to the formation of nitrated epoxy peroxy radicals in competition with isomerisation and decomposition channels that terminate the organic radical chain by NO2 elimination. The theoretical predictions are implemented in the FZJ-NO3-isoprene mechanism for NO3-initiated atmospheric oxidation of isoprene. The model predictions are compared against peroxy radical (RO2) and methyl vinyl ketone (MVK) measurements in a set of experiments on the isoprene + NO3 reaction system performed in the SAPHIR environmental chamber (IsopNO3 campaign). It is shown that the formation of NO2 from the peroxy radicals can prevent a large fraction of the peroxy radicals from being measured by the laser-induced fluorescence (ROxLIF) technique that relies on a quantitative conversion of peroxy radicals to hydroxyl radicals. Accounting for the relative conversion efficiency of RO2 species in the experiments, the agreement between observations and the theory-based FZJ-NO3-isoprene model predictions improves significantly. In addition, MVK formation in the NO3-initiated oxidation was found to be suppressed by the epoxidation of the unsaturated RO radical intermediates, allowing the model-predicted MVK concentrations to be in good agreement with the measurements. The FZJ-NO3-isoprene mechanism is compared against the MCM v3.3.1 and Wennberg et al. (2018) mechanisms.

[Experience and thinking on the normalization stage of prevention and control of COVID-19 in China].

COVID-19 is an important public health issue of great concern at home and abroad, and it is still in the state of global pandemic. During the normalization stage of prevention and control of the epidemic of COVID-19, China effectively controlled the outbreak and spread of the epidemic by adopting the strategy of "import of external prevention and rebound of internal prevention", and effectively reduced the occurrence of death cases. The social economy recovered quickly, and various measures were highly recognized by the public, and the positive trend of the epidemic continued to consolidate. At present, although the spread of the local epidemic has been basically stopped, the international epidemic continues to rise rapidly, and the pressure of "imported prevention and control" in China continues to increase. Considering the characteristics of the normalization of epidemic prevention and control and the particularity of the virus, the connotation of the normalization of epidemic prevention and control should be understood scientifically. The prevention and control goal of the epidemic in the normalization stage should be to maximize early detection, early treatment and early disposal, and resolutely prevent the continuous spread of the epidemic in communities, that is, to prevent the infection as much as possible, and resolutely prevent the rebound (sustained spread in communities), rather than "zero infection". The prevention and control policy of "timely detection, rapid disposal, precise management and control, and effective treatment" has been implemented in various localities, and a series of effective and regular experience in prevention and control has been formed in the practice of prevention and control. Winter and spring are the key periods for the prevention and control of the epidemic. We should continue to work together to prevent and control the epidemic, fulfill the responsibilities of all parties, and prevent and control the epidemic in a scientific and effective way.

[Application of "Internet +" technology in maternal and child health management and service of district at provincial level].

A survey was conducted on the application status of "Internet plus" technology in maternal and child health management in 31 provincial maternal and child health care institutions through the national comprehensive information platform for maternal and child health. 19 provincial institutions had realized one or more maternal and child health management and service functions under their jurisdiction through the regional health information platform, accounting for 61%. Among thirteen functions of management and service achieved in the regional health information platform, the top four were maternal system management (39%), high-risk maternal management (29%), high-risk newborn management (26%) and children system management (26%). Most functions were better in the eastern regions than those in the central and western regions. 15 provinces had established maternal and child health information platforms. 52% of provincial maternal and child health institutions provided telemedicine services, which were mainly for remote consultation. The main cooperative institutions of telemedicine services were subordinate health care institutions (39%).

[Cause analysis and treatment strategies of "recurrence" with novel coronavirus pneumonia (COVID-19) patients after discharge from hospital].

With a large number of COVID-19 patients discharging from hospital, some had showed re-fever and positive nucleic acid test after discharge from hospital. This might be due to the biological characteristics of 2019-nCoV, and might also be related to the basic disease, clinical status, glucocorticoid using, sample sampling, processing and detecting of patients, and some even related to the re-infection or secondary bacterial virus infection. Therefore, we suggest that in view of this phenomenon, further stratified management of discharge from hospital should be carried out on the basis of guidelines, especially for patients with advanced age, underlying diseases or severe or critical pneumonia. For those patients who can't completely deoxygenate for a long time after hospitalization, individualized treatment methods and different discharge evaluation criteria should be adopted to ensure the complete cure of patients and prevent recurrencing after discharge from hospital.

[Clinical diagnosis and management of cervical spondylotic amyotrophy].

Objective: To investigate the clinical characteristics and surgical treatment of cervical spondylotic amyotrophy. Methods: Thirteen patients(13 man) with proximal (10) and distal(3) cervical spondylotic amyotrophy between November 2014 and September 2016 were included in this study. The average age of the patients was 55 (range, 47-66) years. The sex, age, clinical course, type of amyotrophy, lesion segment and postdecompression improvement in muscle power were reviewed. Results: Of 13 cervical spondylotic amyotrophy patients, 9 were performed on with cervical disectomy, 2 were performed on with cervical posterior operation, 2 remainding patients received nonoperative treatment. Cervical spondylotic amyotrophy patients were followed up 6-22 (average 10.6) months, muscle power of 4 patients (all proximal-type)were improved completely (the average recovery time were 4.4 months), muscle power of 6 patients were improved uncompletely, 1 patients failed to improve, the 2 remainding patients received nonoperative treatment had no change. Conclusion: Cervical spondylotic amyotrophy as a rare type of cervical spondylotic disorder, It should distinguish cervical spondylotic amyotrophy from amyotrophic lateral sclerosis, especially in the early stage of amyotrophic lateral sclerosis. A surgical treatment is recommended as the first line of proximal-type CSA, especially those with serious compression. It is important that clinicians should be aware that distal-type CSA had a poor results, resulting in a lower lower satisfaction, especially those with no, or insignificant, sensory disturbance.

[Experience of mesenteric sector fixation in mesenteric torsion treatment].

Objective: The preliminary results was reported regarding the treatment of mesenteric torsion by mesenteric fixation in the last decade, especially preventing recurrence of mesenteric torsion by mesenteric fan-shaped fixation. Methods: We selected 12 patients who received emergency operation in Chongqing Hospital of the First Affiliated Hospital of Guangzhou University of Chinese Medicine from December 2010 to March 2022. All of them were made a definite diagnose of mesenteric torsion by the preoperative CT scan or exploratory laparotomy. The recurrence of mesenteric torsion will be prevented by taking the operation of mesenteric fan-shaped fixation. This technique is suitable for the patient who is suffering total mesenteric torsion, but enteric necrosis is excluded affirmatively. The operation is consists of the following progress: (1) Exploratory laparotomy to check for necrosis of the bowel and for lesions other than torsion. (2) Mesenteric torsion derotation.(3) Mesenteric linear fixation; the right posterior lower border of the small mesentery (terminal ileal mesentery) is intermittently sutured to the posterior peritoneum of the right lower quadrant to increase the width of the base of the small mesentery. (4) Mesenteric fan-shaped fixation, which is fan-shaped to the lower left and fixed in the posterior peritoneum, shortening the length of the mesentery and further increasing the width of the mesentery and posterior peritoneal fixation. Results: A total of 12 patients with mesenteric torsion were treated by operation for 15 times in all. Among them, 3 cases received resection of most small bowel were performed without recurrence; 3 patients received only derotation for a total of 4 times, 2 cases recurred, 1 of them recurred twice; 4 cases underwent derotation and mesenteric linear fixation,and 1 case recurred. Four patients with derotation and mesenteric fan-shaped fixation recovered well without recurrence. Conclusion: Mesenteric fan-shaped fixation may be an effective operative type to reduce or avoid postoperative recurrence of mesenteric torsion.

[Clinical effects of free pre-expanded internal thoracic artery perforator pedicled deltopectoral flap transfer in facial scar reconstruction].

Objective: To explore the clinical effects of free pre-expanded deltopectoral flap transfer in facial scar reconstruction by selecting appropriate internal thoracic artery perforator as the pedicle through preoperative color Doppler ultrasonic vascular assessment. Methods: A retrospective observational study was conducted. From September 2017 to March 2021, 11 patients with facial scar who met the inclusion criteria were admitted to the First Affiliated Hospital of Xi'an Jiaotong University, including 6 males and 5 females, aged 16-58 (31±12) years. The scar with area ranging from 7 cm×5 cm to 14 cm×9 cm was reconstructed by free pre-expanded internal thoracic artery perforator pedicled deltopectoral flap transfer. The operation was performed in 2 or 3 stages. Before operation, color Doppler ultrasonography was performed to evaluate the internal thoracic artery perforator. In the first stage, skin and soft tissue expander (hereinafter referred to as expander) implantation was performed, and a cylindrical expander with rated capacity of 400 to 600 mL was placed in the chest wall. The expansion time was 3 to 4 months, and the water injection volume reached 1.2-1.5 times of the rated capacity of expander. In the second stage, scar excision+free pre-expanded deltopectoral flap transfer was performed, with harvested flap area ranging from 9 cm×7 cm to 16 cm×10 cm. The vascular pedicle of flap (intercostal perforator of internal thoracic artery) was anastomosed end-to-end to the facial artery and vein or superficial temporal artery and vein. The wound in donor site was closed directly. Third stage operation thinning was performed at 3-6 months after the second stage operation in 5 patients because of bloated flap pedicle. At 6 months after the last operation, the flap survival and complications were recorded, the sensation of flap was evaluated by Semmes-Weinstein monofilament test, the color of flap was evaluated by color contrast of the flap to surrounding normal skin, and the curative effect satisfaction degree of patients was evaluated by 5-grade Likert scale. Results: At 6 months after the last operation, all the flaps of 11 patients survived well. One patient experienced venous congestion after flap transplantation, but the flap survived after re-anastomosis. One patient experienced hematoma after the first stage operation of expander implantation, but the rest treatment was not influenced after hematoma removal. No complications such as infection or expander exposure occurred in any patient. At 6 months after the last operation, the sensation of flap of patient was as follows: 9 cases recovered to protective sensation decrease or better, 1 case had protective sensation defect, and 1 case only had deep touch and pressure sensation; the color of flap of patient was as follows: 3 cases were very close to the color of surrounding normal skin, 6 cases were close to the color of surrounding normal skin, and 2 cases were different to the color of surrounding normal skin; the curative effect satisfaction degree of patients was as follows: 2 patients were very satisfied, 6 patients were satisfied, 2 patients were somewhat satisfied, and 1 patient was a little not satisfied. Conclusions: The large area facial scar can be treated safely and effectively by free pre-expanded deltopectoral flap with appropriate single internal thoracic artery perforator as vascular pedicle selected through vascular assessment by color Doppler ultrasonography before operation. After operation, the color of flap of patients is close to the surrounding normal skin and the sensation of flap can be partially recovered, with high curative effect satisfaction degree of patients.

[Schistosomiasis control in the evolution of China's international discourse power].

As a successful example of global public health, Chinese schistosomiasis control technology and experiences have been included in global public health governance. Chinese schistosomiasis control program progresses with China's international discourse power. During the period from the initial stage of the founding of the People's Republic of China to China's Reform and opening-up, the national schistosomiasis control program of China achieved great successes through mobilizing multi-sectorial resources under the policy of Independence and Self-reliance. Following China's Reform and opening-up, all advantageous opportunities were captured to solve problems pertaining to schistosomiasis control in the context of complex international situations. As a consequence, transmission control of schistosomiasis was achieved across China in 2015. Since the Eighteenth National Congress of the Communist Party of China, China has contributed the discourse system with distinct Chinese characteristics to the world, and has actively participated in health cooperation projects between China and other "Belt and Road" countries, which has contributed China's wisdom to global schistosomiasis control program and conveyed China's voice to the world.

[Current status of international discourse of China aid project of schistosomiasis control in Zanzibar].

Since the Eighteenth National Congress of the Communist Party of China, China has constantly innovated and developed its diplomatic concept, and proposed the important idea of the Community of Shared Future for Mankind (CSFM), which contributes a discourse system with Chinese characteristics to the world. It is indicated that discourse builds its subject and governs the subject's discourse practices, and the discourse subject strengthens and reiterates discourse rules in discourse practices. China aid project of schistosomiasis control in Zanzibar is a discourse subject of the CSFM discourse system. This paper analyzes the discourse status, discourse practices and the reiteration of discourse rules of China aid project of schistosomiasis control in Zanzibar.

[Analysis of correlation between plasma trough level and response of generic imatinib in the treatment of Chinese patients with chronic myeloid leukemia].

Objective: To analyze the correlation between plasma trough level of generic imatinib and its metabolism and clinical outcomes in Chinese patients with chronic myeloid leukemia in chronic phase (CML-CP) . Methods: The 21 patients with CML-CP who enrolled in a clinical trial YMTN 1.0 from Oct 11(th), 2012 to May 8(th), 2013 and received generic imatinib were as study subjects. The correlation between steady plasma trough levels of imatinib and its metabolism with clinical response, age, weight and body surface area (BSA) were evaluated. Results: ①The mean steady plasma trough level of generic imatinib and its metabolism was (1 185.07±417.91) µg/L and (251.53±76.50) µg/L, respectively. ②Age, weight and BSA has no significant effects on plasma trough level of generic imatinib and its metabolism (P>0.05) . ③Patients with steady plasma trough level of generic imatinib more than 1 000 µg/L are possible to have higher major molecular response (MMR) /complete molecular response (CMR) rate than those below 1 000 µg/L (42% vs 0, P<0.05) . Conclusion: Plasma trough levels of generic imatinib varied in CML patients. The steady plasma trough levels of generic imatinib is maybe related to molecular response in CML patients.

Chinese medicinal herbs for acute bronchitis.

BACKGROUND: Acute bronchitis is one of the most common diagnoses made by primary-care physicians. It is traditionally treated with antibiotics (although the evidence for their effectiveness is weak and modest at best), and other even less effective treatments. Chinese medicinal herbs have also been used as a treatment. OBJECTIVES: This review aimed to summarise the existing evidence on the comparative effectiveness and safety of Chinese medicinal herbs for treating uncomplicated acute bronchitis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2007, Issue 1), which includes the Cochrane Acute Respiratory Infections Group's specialised register; MEDLINE (1966 to March Week 1, 2007); EMBASE (1988 to January 2007); The Chinese Cochrane Centre's Controlled Trials Register (up to January 2007); and the Chinese Biomedical Database (CBM) (1980 to January 2007). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing Chinese medicinal herbs with placebo, antibiotics or other Western medicines for the treatment of uncomplicated acute bronchitis. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data and assessed trial quality. MAIN RESULTS: No studies met the inclusion criteria for this review. One study with 300 participants but uncertain randomisation was analysed . The study showed that treatment with the Chinese medicinal herb Huoke granules leads to a shorter duration of cough, fever and sputum compared to using penicillin and Xiaoer Shangfeng Zhike tangjiang syrup. However, the study also lacked allocation concealment and blinding. There was a high possibility of conflict of interest as the Huoke granules were made by the trial author's hospital. AUTHORS' CONCLUSIONS: There is insufficient quality data to recommend the routine use of Chinese herbs for acute bronchitis. Study-design limitations of the individual studies meant that no conclusion about the benefits of Chinese herbs could be taken. In addition, the safety of Chinese herbs is unknown due to the lack of toxicological evidence on these Chinese herbs, though adverse events were reported in some case reports.

[A review on the preparedness plans on influenza pandemics, by WHO and China: the current status and development].

Every influenza pandemic in history would end up with disastrous outcomes on mankind, of which the most notorious one was the "Spanish flu" pandemic in 1918. In the past century, with advanced knowledge on influenza viruses, laboratory technologies and surveillance methods, human beings were not as helpless when facing the influenza pandemic. In order to control the outbreaks and reducing the negative impacts, programs as: setting up and improving the influenza pandemic preparedness and response plan were recognized as important issues on early detection or prompt warning of any influenza virus strain that might lead to potential pandemics. The scheduled and planned control measures towards the pandemic preparedness and response plan had been considered of key importance in mitigating the peak of pandemic or controlling the transmission of virus. Since the "1918 influenza pandemic" , we had reviewed the evolution and development of plans regarding the preparedness and response on influenza pandemic issued by both WHO and China. We also emphasized on the variety of strategies which were linked to the preparedness and response at different historical stages, to provide reference for the pandemic preparedness of the disease, in the future.

TC > 0.05 as a Pharmacokinetic Parameter of Paclitaxel for Therapeutic Efficacy and Toxicity in Cancer Patients.

BACKGROUND: Paclitaxel (PTX) has remarkable anti-tumor activity, but it causes severe toxicities. There is an urgent need to seek an appropriate pharmacokinetic parameter of PTX to improve treatment efficacy and reduce adverse effects. OBJECTIVE: To evaluate the association of pharmacokinetic parameter TC > 0.05 of paclitaxel (PTX) and its therapeutic efficacy and toxicity in patients with solid tumors. METHODS: A total of 295 patients with ovarian cancer, esophageal cancer, breast cancer, and non-small cell lung cancer (NSCLC), who were admitted to the Tumor Hospital of Shantou University Medical College, China, were recruited for this study. Patients received 3 weeks of PTX chemotherapy. The plasma concentrations of PTX were examined using the MyPaclitaxel™ kit. The patients' PTX TC > 0.05 (the time during which PTX plasma concentration exceed 0.05µmol/L) were calculated based on pharmacokinetic analysis. RESULTS: The results showed that: (1) the concentrations of PTX in these 295 patients ranged from 0.0358-0.127 µmol/L; (2) the PTX TC > 0.05 ranged from 14 to 38h with a median time of 27h; (3) among all treatment cycles, there was a statistically significant difference in the PTX TC > 0.05 between CR+PR and SD+PD; (4) with the increasing value of TC > 0.05, level of leukopenia and leukopenic fever increased; (5) high PTX TC > 0.05 led to the occurrence of neutropenia, neutropenic fever, severe anemia, and severe peripheral neurotoxicity. Taken together, our results indicated that the pharmacokinetic parameter PTX TC > 0.05 was an effective measure of treatment efficacy and toxicity in patients with solid tumors. Maintaining PTX TC > 0.05 at 26 to 30h could improve its efficacy and reduce the incidence of leukopenia, neutropenia, anemia, and peripheral neurotoxicity in these patients. CONCLUSION: PTX TC > 0.05 is a key pharmacokinetic parameter of PTX which should be monitored to optimize individual treatment in patients with solid tumors.

Decompressive craniectomy for massive cerebral infarction with enlarged cruciate duraplasty.

The use of decompressive craniectomy for massive cerebral infarction is attracting renewed interest because conventional medical treatment is associated with high mortality. The technique of duraplasty may be important. We have developed a 4 step volume-enlarged cruciate duraplasty and report its use in 12 patients with massive cerebral infarction. None of the patients needed an additional anterior temporal lobectomy to reduce intraoperative intracranial pressure and none suffered epilepsy after the operation. This initial experience suggests that the use of a stepwise cruciate duraplasty during a decompression may promote clinical outcomes and further evaluation is merited.

Integration of Physiologically-Based Pharmacokinetic Modeling into Early Clinical Development: An Investigation of the Pharmacokinetic Nonlinearity.

BMS-911543, a promising anticancer agent, exhibited time-dependent and dose-dependent nonlinear pharmacokinetics (PKs) in its first-in-human (FIH) study. Initial physiologically based pharmacokinetic (PBPK) modeling efforts using CYP1A2-mediated clearance kinetics were unsuccessful; however, further model analysis revealed that CYP1A2 time-dependent inhibition (TDI) and perhaps other factors could be keys to the nonlinearity. Subsequent experiments in human liver microsomes showed that the compound was a time-dependent inhibitor of CYP1A2 and were used to determine the enzyme inactivation parameter values. In addition, a rat tissue distribution study was conducted and human plasma samples were profiled to support the refinement of the PBPK model. It was concluded that the interplay between four BMS-911543 properties, namely, low solubility, saturation of the metabolizing enzyme CYP1A2, CYP1A2 TDI, and CYP1A2 induction likely resulted in the time-dependent and dose-dependent nonlinear PKs. The methodology of PBPK model-guided unmasking of compound properties can serve as a general practice for mechanistic understanding of a new compound's disposition.

Supplementary iodine fails to reverse hypothyroidism in adolescents and adults with endemic cretinism.

The efficacy of supplemental iodine in correcting hypothyroidism in adults and older children with endemic myxedematous cretinism is not known. To investigate this issue we administered im iodized oil (1.5 mL) to 28 hypothyroid endemic cretins (TSH, greater than 5 mIU/L) from western China, aged 14-52 yr (mean = 29 SD = 11 yr). Clinical examination, intelligence testing (Hiskey Nebraska Test of Learning Aptitude and the Griffiths Mental Development Scales), and thyroid function tests were performed before and 6 months after iodine supplementation. We found that signs of thyroid hormone deficiency, dwarfism, and delayed sexual maturity persisted after iodine supplementation. Further, mental disability and other clinical features of neurological damage were not altered by treatment. The mean serum concentration of total T4 before treatment was 75 nmol/L (SD = 40) and fell after iodized oil administration to 56 nmol/L (SD = 29; P less than 0.001). Mean serum levels of TSH before and after iodine showed a paradoxical fall [85 mIU/L (SD = 102) and 46 mIU/L (SD = 46), respectively]. Serum TSH levels decreased into the normal range (less than 5 mIU/L) in only 1 of 28 patients (4%). We conclude that iodine supplementation does not reverse thyroid hormone deficiency or its sequelae in adolescents and adults with endemic myxedematous cretinism. Iodized oil in this age group of patients with endemic cretinism does not appear to be beneficial and should be used with caution.