Remdesivir use and risks of acute kidney injury and acute liver injury among patients hospitalised with COVID-19: a self-controlled case series study.

BACKGROUND AND AIM: To investigate and quantify the risks of AKI and ALI associated with remdesivir use, given the underlying diseases of SARS-CoV-2 infection. METHODS: This self-controlled case series (SCCS) study was conducted using electronic hospital records between 23 January 2020 and 31 January 2021 as retrieved from the Hong Kong Hospital Authority which manages all laboratory-confirmed COVID-19 cases in Hong Kong. Outcomes of AKI and ALI were defined using the KDIGO Guideline and Asia Pacific Association of Study of Liver consensus guidelines. Incidence rate ratios (IRR) for AKI and ALI following the administration of remdesivir (exposure) in comparison to a non-exposure period were estimated using the conditional Poisson regression models. RESULTS: Of 860 COVID-19 patients administered remdesivir during hospitalisation, 334 (38.8%) and 137 (15.9%) had incident ALI and AKI, respectively. Compared with the baseline period, both ALI and AKI risks were increased significantly during the pre-exposure period (ALI: IRR = 6.169, 95% CI = 4.549-8.365; AKI: IRR = 7.074, 95% CI = 3.763-13.298) and remained elevated during remdesivir treatment. Compared to the pre-exposure period, risks of ALI and AKI were not significantly higher in the first 2 days of remdesivir initiation (ALI: IRR = 1.261, 95% CI = 0.915-1.737; AKI: IRR = 1.261, 95% CI = 0.889-1.789) and between days 2 and 5 of remdesivir treatment (ALI: IRR = 1.087, 95% CI = 0.793-1.489; AKI: IRR = 1.152, 95% CI = 0.821-1.616). CONCLUSION: The increased risks of AKI and ALI associated with intravenous remdesivir treatment for COVID-19 may be due to the underlying SARS-CoV-2 infection. The risks of AKI and ALI were elevated in the pre-exposure period, yet no such increased risks were observed following remdesivir initiation when compared to the pre-exposure period.

Optimal Timing of Remdesivir Initiation in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Administered With Dexamethasone.

BACKGROUND: Evidence is lacking about any additional benefits of introducing remdesivir on top of dexamethasone, and the optimal timing of initiation. METHODS: In a territory-wide cohort of 10 445 coronavirus disease 2019 (COVID-19) patients from Hong Kong who were hospitalized between 21 January 2020 and 31 January 2021, 1544 had received dexamethasone during hospitalization. The exposure group consisted of patients who had initiated remdesivir prior to dexamethasone (n = 93) or co-initiated the 2 drugs simultaneously (n = 373), whereas the nonexposure group included patients who were given remdesivir after dexamethasone (n = 149) or those without remdesivir use (n = 929). Multiple imputation and inverse probability of treatment weighting for propensity score were applied and hazard ratios (HRs) of event outcomes were estimated using Cox regression models. RESULTS: Time to clinical improvement (HR = 1.23; 95% CI, 1.02-1.49; P = .032) and positive IgG antibody (HR = 1.22; 95% CI, 1.02-1.46; P = .029) were significantly shorter in the exposure group than that of nonexposure. The exposure group had a shorter hospital length of stay by 2.65 days among survivors, lower WHO clinical progression scale scores from 5 days of follow-up onwards, and lower risks of in-hospital death (HR = .59; 95% CI, .36-.98; P = .042) and composite outcomes; and without experiencing an increased risk of acute respiratory distress syndrome. Differences in the cumulative direct medical costs between groups were no longer significant from 17 days of follow-up onwards. CONCLUSIONS: Initiation of remdesivir prior to or simultaneously with dexamethasone was associated with significantly shorter time to clinical improvement and positive IgG antibody, lower risk of in-hospital death, in addition to shorter length of hospital stay in patients with moderate COVID-19.

Clinical Improvement, Outcomes, Antiviral Activity, and Costs Associated With Early Treatment With Remdesivir for Patients With Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Evidence remains inconclusive on any significant benefits of remdesivir in patients with mild-to-moderate COVID-19. This study explored the disease progression, various clinical outcomes, changes in viral load, and costs associated with early remdesivir treatment among COVID-19 patients. METHODS: A territory-wide retrospective cohort of 10 419 patients with COVID-19 hospitalized from 21 January 2020 to 31 January 2021 in Hong Kong was identified. Early remdesivir users were matched with controls using propensity-score matching in a ratio ≤1:4. Study outcomes were time to clinical improvement of at least 1 point on WHO clinical progression scale, hospital discharge, recovery, viral clearance, low viral load, positive IgG antibody, in-hospital death, and composite outcomes of in-hospital death requiring invasive ventilation or intensive care. RESULTS: After multiple imputation and propensity-score matching, median follow-up was 14 days for both remdesivir (n = 352) and control (n = 1347) groups. Time to clinical improvement was significantly shorter in the remdesivir group than that of control (HR: 1.14; 95% CI: 1.01-1.29; P = .038), as well as for achieving low viral load (1.51; 1.24-1.83; P < .001) and positive IgG antibody (1.50; 1.31-1.70; P < .001). Early remdesivir treatment was associated with lower risk of in-hospital death (HR: .58; 95% CI: .34-.99; P = .045), in addition to a significantly shorter length of hospital stay (difference: -2.56 days; 95% CI: -4.86 to -.26; P = .029), without increasing risks of composite outcomes for clinical deterioration. CONCLUSIONS: Early remdesivir treatment could be extended to hospitalized patients with moderate COVID-19 not requiring oxygen therapy on admission.

Effects of Nonpharmaceutical COVID-19 Interventions on Pediatric Hospitalizations for Other Respiratory Virus Infections, Hong Kong.

To determine the effects of nonpharmaceutical interventions (NPIs) for coronavirus disease on pediatric hospitalizations for infection with respiratory viruses other than severe acute respiratory syndrome coronavirus 2, we analyzed hospital data for 2017-2021. Compared with 2017-2019, age-specific hospitalization rates associated with respiratory viruses greatly decreased in 2020, when NPIs were in place. Also when NPIs were in place, rates of hospitalization decreased among children of all ages for infection with influenza A and B viruses, respiratory syncytial virus, adenovirus, parainfluenza viruses, human metapneumovirus, and rhinovirus/enterovirus. Regression models adjusted for age and seasonality indicated that hospitalization rates for acute febrile illness/respiratory symptoms of any cause were reduced by 76% and by 85%-99% for hospitalization for infection with these viruses. NPIs in Hong Kong were clearly associated with reduced pediatric hospitalizations for respiratory viruses; implementing NPIs and reopening schools were associated with only a small increase in hospitalizations for rhinovirus/enterovirus infections.

An investigation of Human Clonorchiasis prevalence in an Endemic County in Guangxi Zhuang Autonomous Region, China, 2016.

To effectively promote the implementation of interventions, the identification of high-risk groups and the characteristics of Clonorchis sinensis infection in endemic regions are needed. In a clonorchiasis-endemic area, local residents were randomly enrolled for helminth egg examination in June 2016. The prevalence in subpopulations as well as the knowledge, attitudes, and behaviours and the factors influencing clonorchiasis in egg-positive populations were analysed. A total of 2282 local residents participated in the survey; the C. sinensis prevalence was 48.6% (1109 persons). A higher prevalence was found in males (62.6%) than in females (29.7%). People older than 30 years had the highest prevalence (52.7%-57.6%). Among the 888 persons who were infected with C. sinensis and participated the questionnaire investigation, 19.0% (169/888) knew that it could cause cancer. In addition, 60.6% of people reported that they intended to keep eating raw fish despite knowing the risk of infection. The two primary reasons for continuing to eat raw fish were the disease being regarded as not serious (38.3%) and the belief that anti-parasite medications are effective (39.6%). A total of 94.4% (797/844) of responders reported eating raw fish more frequently in the home than outside of the home. Our study revealed a notably high C. sinensis prevalence in the study area. Awareness of clonorchiasis disease severity should be increased among high-risk individuals and families in highly endemic areas.

Effect of Nonpharmaceutical Interventions on Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, South Korea, 2020.

We analyzed transmission of coronavirus disease outside of the Daegu-Gyeongsangbuk provincial region in South Korea. We estimated that nonpharmaceutical measures reduced transmissibility by a maximum of 34% without resorting to a strict lockdown strategy. To optimize epidemic control, continuous efforts to monitor the transmissibility are needed.

Antimetabolites as an adjunct to dacryocystorhinostomy for nasolacrimal duct obstruction.

BACKGROUND: Nasolacrimal duct obstruction (NLDO) is a condition that results in the overflow of tears (epiphora) or infection of the nasolacrimal sac (dacryocystitis). The etiology of acquired NLDO is multifactorial and is not fully understood. Dacryocystorhinostomy (DCR) is the surgical correction of NLDO, which aims to establish a new drainage pathway between the lacrimal sac and the nose. The success of DCR is variable; the most common cause of failure is fibrosis and stenosis of the surgical ostium. Antimetabolites such as mitomycin-C (MMC) and 5-fluorouracil (5-FU) have been shown to be safe and effective in reducing fibrosis and improving clinical outcomes in other ophthalmic surgery settings (e.g. glaucoma and cornea surgery). Application of antimetabolites at the time of DCR has been studied, but the utility of these treatments remains uncertain. OBJECTIVES: Primary objective: To determine if adjuvant treatment with antimetabolites improves functional success in the setting of DCR compared to DCR alone. Secondary objectives: To determine if anatomic success of DCR is increased with the use of antimetabolites, and if the surgical ostium is larger in participants treated with antimetabolites. SEARCH METHODS: We searched the Cochrane Register for Controlled Trials (CENTRAL) (which contains the Cochrane Eye and Vision Trials Register) (2019, Issue 9), Ovid MEDLINE, Embase.com, PubMed, LILACS (Latin American and Caribbean Health Sciences Literature database), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic searches. We last searched the electronic databases on 6 September 2019. SELECTION CRITERIA: We only included randomized controlled trials. Eligible studies were those that compared the administration of antimetabolites of any dose and concentration versus placebo or another active treatment in participants with NLDO undergoing primary DCR and reoperation. We only included studies that had enrolled adults 18 years or older. We also included studies that used silicone intubation as part of the DCR procedure. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently screened the search results, assessed risk of bias, and extracted data from the included studies using an electronic data collection form. MAIN RESULTS: We included 31 studies in the review, of which 23 (1309 participants) provided data relating to our primary and secondary outcomes. Many of the 23 studies evaluated functional success, while others also assessed our secondary outcomes of anatomic success or ostium size, or both. Study characteristics Participant characteristics varied across studies, with the age of participants ranging from 30 to 70 years. Participants were predominantly women. These demographics correspond to those most frequently affected by nasolacrimal duct obstruction. Almost all of the studies utilized MMC as the antimetabolite, with only one using 5-FU. We assessed most trials as at unclear risk of bias for most domains. Conflicts of interest were not frequently reported, although the antimetabolites used are generic medications, and studies were not likely to be conducted for financial interest. Findings Twenty studies provided data on the primary outcome of functional success, of which 7 (356 participants) provided data at 6 months and 14 (909 participants) provided data beyond 6 months. At six months, the results showed no evidence of effect of antimetabolite on functional success (risk ratio (RR) 1.12, 95% confidence interval (CI) 0.98 to 1.29; low-certainty evidence). Beyond six months, the results favored the antimetabolite group (RR 1.15, 95% CI 1.07 to 1.25; moderate-certainty evidence). Fourteen studies reported data on the secondary outcome of anatomic success, of which 4 (306 participants) reported data at 6 months and 12 (831 participants) provided data beyond 6 months. Results at six months showed no evidence of effect of antimetabolite on anatomic success (RR 1.02, 95% CI 0.95 to 1.11; low-certainty evidence). Beyond six months, participants in the antimetabolite group were more likely to achieve anatomic success than those receiving DCR alone (RR 1.09, 95% CI 1.04 to 1.15; moderate-certainty evidence). At six months and beyond six months follow-up, two studies reported mean change in ostium size. We did not conduct meta-analysis for the various follow-up periods due to clinical, methodological, and statistical heterogeneity. However, point estimates from these studies at six months consistently favored participants in the antimetabolite group (low-certainty evidence). Beyond six months, while point estimates from one study favored participants in the antimetabolite group, estimates from another study showed no evidence of a difference between the two groups. The certainty of evidence at both time points was low. Adverse events Adverse events were rare. One study reported that one participant in the MMC group experienced delayed wound healing. Other studies reported no significant adverse events related to the application of antimetabolites. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that application of antimetabolites at the time of DCR increases functional and anatomic success of DCR when patients are followed for more than six months after surgery, but no evidence of a difference at six months, low-certainty of evidence. There is low-certainty evidence that combining antimetabolite with DCR increases the size of the lacrimal ostium at six months. However, beyond six months, the evidence remain uncertain. Adverse effects of the application of antimetabolites were minimal.

Influenza vaccine effectiveness against influenza-associated hospitalization in 2015/16 season, Beijing, China.

BACKGROUND: Vaccination is recommended to prevent influenza virus infection and associated complications. This study aimed to estimate the influenza vaccine effectiveness (VE) against hospitalization in the 2015/16 season in Beijing. METHODS: Patients who were hospitalized in the 5 study hospitals between 1 Oct 2015 and 15 May 2016 were recruited. Influenza vaccination status was obtained for PCR-confirmed influenza patients and the selected controls who tested negative for the virus. Conditional logistic regression was used to estimate the influenza VE matching by calendar week, and adjusting for age, study sites, underlying medical conditions, smoking status, and hospital admissions over the past 12months. RESULTS: The overall VE was -37.9% (95% CI: -103.3, 6.5) against laboratory-confirmed influenza-associated hospitalization. The 2015-16 seasonal vaccine was had -61.9% (95% CI: -211.9, 15.9), -5.4% (95% CI: -108.1, 46.6) and -45.2% (95% CI: -152.6, 16.5) effectiveness to prevent infection from A(H1N1)pdm09, A(H3N2) and influenza B, respectively. CONCLUSIONS: Influenza vaccination did not show effective protection against hospitalization with influenza in 2015/16 season in Beijing.

Assessing perioperative body weight changes in patients thyroidectomized for a benign nontoxic nodular goitre.

BACKGROUND: Following thyroidectomy, patients often complain of weight gain. Our study aimed to evaluate the extent of weight change in patients thyroidectomized for a nontoxic benign goitre after adjusting for patient demographics and pre-operative weight changes. METHODS: Three different patient groups were studied. The first comprised 898 patients who underwent thyroidectomy for benign nontoxic nodular goitre (group I). The second comprised 179 patients who had benign nontoxic goitre but did not undergo thyroidectomy (group II), and the third comprised 80 patients who underwent a simple excision of a parathyroid adenoma (group III). All patients were weighed 12 months preceding baseline, at baseline and 6 months after baseline. RESULTS: Baseline characteristics were comparable between groups. Patients in Group I who gained the least weight in the year leading to surgery gained the most weight 12 months after surgery (P = 0·030). After adjusting for demographics and pre-operative weight changes, Group I gained significantly more weight at post 6 and 12 months (0·71 (95% CI=0·46-0·95) kg and 1·21 (95% CI = 0·96-1·46) kg, respectively). Weight gain at post 12 months appeared similar between hemithyroidectomy and total thyroidectomy (1·32 vs 1·16 kg, P = 0·197). Younger age (ß coefficient -0·100, 95% CI = -0·030 to 0·003, P = 0·015) and higher baseline thyroid stimulating hormone (ß coefficient -0·315, 95% CI = -1·468 to 0·134, P = 0·020) were significant factors for weight gain at post 12 months. CONCLUSIONS: Compared to nonthyroidectomized patients, thyroidectomized patients experienced significant weight increases at post 6 and 12 months. The extent of thyroidectomy did not affect the extent of weight gain. Younger age and higher baseline thyroid stimulating hormone were significant factors of weight gain at post 12 months.

Towards informed decisions on breast cancer screening: Development and pilot testing of a decision aid for Chinese women.

OBJECTIVE: To pilot-test a novel, self-use breast cancer (BC) screening decision aid (DA) targeting Hong Kong (HK) Chinese women at average risk of BC. METHODS: Women were recruited through a population-based telephone survey using random digit dialling between October 2013 and January 2014. Eligible participants completed our baseline survey and then received the DA by post. Participants (n=90) completed follow-up telephone interviews one month later. RESULTS: Most participants thought that all/most DA content was presented clearly (86.7%), and was useful in helping women make screening-related decisions (88.9%). It also achieved its expected impact of improving informed decision-making and increasing shared-participation preference without increasing participants' anxiety levels. Participants showed a modest non-statistical increase in their screening knowledge scores. Older women rated the perceived severity of a BC diagnosis as significantly lower, and more educated women reported significantly lower perceived anxiety about the disease. CONCLUSION: Our DA appears acceptable and feasible for self-use by HK Chinese women who need to make an informed decision about BC screening without increasing overall anxiety levels. PRACTICE IMPLICATIONS: This study supports the potential of self-use DAs for cancer screening-related decision support in a Chinese population.

High False Positivity in Positron Emission Tomography is a Potential Diagnostic Pitfall in Patients with Suspected Adrenal Metastasis.

BACKGROUND: Although 18F-fluorodeoxyglucose (FDG) positron emission tomography combined with computed tomography (PET/CT) is a potentially powerful, non-invasive imaging tool in differentiating adrenal metastasis from benign disease, some adenomas also exhibit high FDG uptake, therefore mimicking metastasis (i.e., false positives). We aimed to evaluate the accuracy of FDG-PET/CT based exclusively on histology and to identify risk factors for adrenal metastasis. METHODS: Among the 289 consecutive patients who underwent adrenalectomy, 39 (78.0%) patients had suspected solitary adrenal metastasis and had a positive preoperative FDG-PET/CT. The FDG-PET/CT findings were correlated with the histology of the excised adrenal gland. To identify risk factors for adrenal metastasis, characteristics were compared between patients with histologically proven adrenal metastasis and those without. Youden's index was used to calculate the optimal cut-off value for predicting adrenal metastasis. RESULTS: Histology of the excised adrenal tumor confirmed adrenal metastasis in 28/39 (71.8%) patients while non-metastatic lesions comprised mostly benign adrenal cortical adenoma (n=10) and one non-functional pheochromocytoma. Therefore, the overall false-positive rate of FDG-PET/CT was 28.2%. History of primary lung malignancy [odds ratio (OR) (95% CI) 20.00 (1.01-333.3), p=0.049] and SUVmax>2.65 [OR (95% CI) 31.606 (2.46-405.71), p=0.008] were independent risk factors for adrenal metastasis. CONCLUSIONS: Single adrenal uptake on FDG-PET/CT in suspected solitary adrenal metastasis was associated with a high false-positive rate (28.2%). Risk factors associated with adrenal metastasis included a history of known primary lung malignancy and a SUVmax>2.65 at the adrenal lesion of interest on FDG-PET/CT. Based on these findings, a new algorithm was constructed.

Is BRAFV600E mutation a marker for central nodal metastasis in small papillary thyroid carcinoma?

Utilizing BRAF(V600E) mutation as a marker may reduce unnecessary prophylactic central neck dissection (pCND) in clinically nodal negative (cN0) neck for small (≤2 cm) classical papillary thyroid carcinoma (PTC). We aimed to assess whether BRAF is a significant independent predictor of occult central nodal metastasis (CNM) and its contribution to the overall prediction after adjusting for other significant preoperative clinical factors in small PTC. Primary tumor tissue (paraffin-embedded) from 845 patients with small classical cN0 PTC who underwent pCND was tested for BRAF mutation. Clinicopathologic factors were compared between those with and without BRAF. BRAF was evaluated to see if it was an independent factor for CNM. Prediction scores were generated using logistic regression models and their predictability was measured by the area under the ROC curve (AUC). The prevalence of BRAF was 628/845 (74.3%) while the rate of CNM was 285/845 (33.7%). Male sex (odds ratio (OR): 2.68, 95% CI: 1.71-4.20), large tumor size (OR: 2.68, 95% CI: 1.80-4.00), multifocality (OR: 1.49, 95% CI: 1.07-2.09), lymphovascular permeation (OR: 10.40, 95% CI: 5.18-20.88), and BRAF (OR: 1.65, 95% CI: 1.10-2.46) were significant independent predictors of CNM, while coexisting Hashimoto's thyroiditis (OR: 0.56, 95% CI: 0.40-0.80) was an independent protective factor. The AUC for prediction score based on tumor size and male sex was similar to that of prediction score based on tumor size, male sex, and BRAF status (0.68 vs 0.69, P=0.60). Although BRAF was an independent predictor of CNM, knowing its status did not substantially improve the overall prediction. A simpler prediction score based on male sex and tumor size might be sufficient.

A systematic review and meta-analysis of prophylactic central neck dissection on short-term locoregional recurrence in papillary thyroid carcinoma after total thyroidectomy.

BACKGROUND: Prophylactic central neck dissection (pCND) at the time of total thyroidectomy (TT) remains controversial in clinically node-negative (cN0) papillary thyroid carcinoma (PTC). Despite occult central lymph node metastases being common, it is unclear if removing these metastases initially would reduce future locoregional recurrence (LRR). This systematic review and meta-analysis aimed at comparing the short-term LRR between patients who underwent TT with pCND and those who underwent TT alone. METHODS: A systematic review of the literature was performed to identify studies comparing LRR between patients with PTC who underwent TT + pCND (group A) and those who underwent TT alone (group B). Inclusion criteria were cN0 patients, with each comparative group containing > 10 patients, and with the number of LRR and mean follow-up duration available. The pooled incidence rate ratio (IRR) was used for calculating the LRR rate between the two groups. Other parameters evaluated included postoperative radioiodine (RAI) ablation, surgically related complications, and overall morbidity. Meta-analysis was performed using a fixed-effects model. RESULTS: Fourteen studies matched the selection criteria. Of the 3331 patients, 1592 (47.8%) belonged to group A, while 1739 (52.2%) belonged to group B. Relative to group B, group A was significantly more likely to have postoperative RAI ablation (71.7% vs. 53.1%; odds ratio [OR] = 2.60 [95% confidence interval (CI) = 2.12-3.18]), temporary hypocalcemia (26.0% vs. 10.8%; OR = 2.56 [CI = 2.04-3.21]), and overall morbidity (33.2% vs. 17.7%; OR = 2.12 [CI = 1.75-2.57]). When temporary hypocalcemia was excluded, overall morbidity was similar between the two groups (7.3% vs. 6.8%; OR = 1.07 [CI = 0.78-1.47]). Group A had a significantly lower risk of LRR than group B (4.7% vs. 8.6%; IRR = 0.65 [CI = 0.48-0.86]). CONCLUSIONS: Group A was more likely to have postoperative RAI ablation, temporary hypocalcemia, and overall morbidity than group B. Temporary hypocalcemia was the major surgical morbidity in pCND and, when excluded, the overall morbidity appeared similar between the two groups. Although our meta-analysis would suggest that those who undergo TT + pCND may have a 35% reduction in risk of LRR than those who undergo TT alone in the short term (< 5 years), it remains unclear how much of this risk reduction is related to increased use of RAI ablation and potential selection bias in some of the studies examined.

A systematic review and meta-analysis comparing the efficacy and surgical outcomes of total thyroidectomy between harmonic scalpel versus ligasure.

BACKGROUND: Both ultrasonic coagulation (Harmonic Scalpel) (HS) and bipolar coagulation (Ligasure) (LS) are new energy devices commonly used in open thyroidectomy. This systematic review aimed at comparing the efficacy and surgical outcomes of total thyroidectomy (TT) between HS and. LS. METHODS: A systematic review of the literature was performed to identify studies comparing HS and LS. Intraoperative outcomes, surgically related complications, overall morbidity, and hospital stay were evaluated. Meta-analysis was performed using a fixed-effects model. RESULTS: There were 8 studies that matched the selection criteria. Of the 963 patients who underwent TT, 433 (45.0 %) used HS (HS group) while 530 (55.0 %) used LS (LS group). Compared with LS, the HS group had significantly less volume of blood loss by 2.22 ml (95 % CI = 0.26-4.23 ml) (standardized mean difference [SMD] = -0.2, 95 % CI = -0.38 to -0.02) and reduced total operating time by 3.32 minutes (95 % CI = 1.62-5.03 minutes) (SMD = -0.28, 95 % CI = -0.42 to -0.15). There was no significant difference in temporary postoperative hypocalcemia (OR = 1.29, 95 % CI = 0.88-1.90), permanent postoperative hypocalcemia (OR = 1.45, 95 % CI = 0.23-9.26), temporary recurrent laryngeal nerve (RLN) injury (OR = 1.34; 95 % CI = 0.66-2.71), permanent RLN injury (OR = 1.00; 95 % CI = 0.25-4.03), hematoma (OR = 1.00; 95 % CI = 0.3-3.31), overall morbidity (OR = 1.21, 95 % CI = 0.87-1.69), and hospital stay (SMD = -0.03; 95 % CI = -0.07 to 0.01). CONCLUSIONS: Compared with LS, using HS in TT significantly reduced the volume of blood loss and operating time. However, the clinical significance of these findings remained questionable because the overall mean difference appeared small. There was no significant difference in the rate of complications, overall morbidity, and hospital stay between the two devices.

Do low preoperative vitamin D levels reduce the accuracy of quick parathyroid hormone in predicting postthyroidectomy hypocalcemia?

BACKGROUND: Although some studies have suggested that low preoperative 25-hydroxyvitamin D (25-OHD) levels may increase the risk of hypocalcemia and decrease the accuracy of single quick parathyroid hormone in predicting hypocalcemia after total thyroidectomy, the literature remains scarce and inconsistent. Our study aimed to address these issues. METHODS: Of the 281 consecutive patients who underwent a total/completion total thyroidectomy, 244 (86.8%) did not require any oral calcium and/or calcitriol supplements (group 1), while 37 (13.2%) did (group 2) at hospital discharge. 25-OHD level was checked 1 day before surgery, and postoperative quick parathyroid hormone (PTH) was checked at skin closure (PTH-SC). Postoperative serum calcium was checked regularly. Hypocalcemia was defined by the presence of symptoms or adjusted calcium of <1.90 mmol/L. Significant factors for hypocalcemia were determined by univariate and multivariate analyses. The accuracy of PTH-SC in predicting hypocalcemia was measured by area under a receiver operating characteristic curve (AUC), and the AUC of PTH-SC was compared between patients with preoperative 25-OHD <15 and ≥15 ng/mL via bootstrapping. RESULTS: Preoperative 25-OHD level was not significantly different between groups 1 and 2 (13.1 vs. 12.5 ng/mL, p = 0.175). After adjusting for other significant factors, PTH-SC (odds ratio 2.49, 95% confidence interval 1.52-4.07, p < 0.001) and parathyroid autotransplantation (odds ratio 3.23, 95% confidence interval 1.22-8.60, p = 0.019) were the two independent factors for hypocalcemia. The AUC of PTH-SC was similar between those with 25-OHD <15 and ≥15 ng/mL (0.880 vs. 0.850, p = 0.61) CONCLUSIONS: Low 25-OHD was not a significant factor for hypocalcemia and did not lower the accuracy of quick PTH in predicting postthyroidectomy hypocalcemia.

Optimizing resource allocation for breast cancer prevention and care among Hong Kong Chinese women.

BACKGROUND: Recommendations about funding of interventions through the full spectrum of the disease often have been made in isolation. The authors of this report optimized budgetary allocations by comparing cost-effectiveness data for different preventive and management strategies throughout the disease course for breast cancer in Hong Kong (HK) Chinese women. METHODS: Nesting a state-transition Markov model within a generalized cost-effectiveness analytic framework, costs and quality-adjusted life-years (QALYs) were compared to estimate average cost-effectiveness ratios for the following interventions at the population level: biennial mass mammography (ages 40-69 years or ages 40-79 years), reduced waiting time for postoperative radiotherapy (by 15% or by 25%), adjuvant endocrine therapy (either upfront aromatase inhibitor [AI] therapy or sequentially with tamoxifen followed by AI) in postmenopausal women with estrogen receptor-positive disease, targeted immunotherapy in those with tumors that over express human epidermal growth factor receptor 2, and enhanced palliative services (either at home or as an inpatient). Usual care for eligible patients in the public sector was the comparator. RESULTS: In descending order, the optimal allocation of additional resources for breast cancer would be the following: a 25% reduction in waiting time for postoperative radiotherapy (in US dollars: $5000 per QALY); enhanced, home-based palliative care ($7105 per QALY); adjuvant, sequential endocrine therapy ($17,963 per QALY); targeted immunotherapy ($62,092 per QALY); and mass mammography screening of women ages 40 to 69 years ($72,576 per QALY). CONCLUSIONS: Given the lower disease risk and different age profiles of patients in HK Chinese, among other newly emergent and emerging economies with similar transitioning epidemiologic profiles, the current findings provided direct evidence to support policy decisions that may be dissimilar to current Western practice.

Risk of second primary malignancy in differentiated thyroid carcinoma treated with radioactive iodine therapy.

BACKGROUND: Differentiated thyroid cancer survivors are at increased risk of nonsynchronous second primary malignancy, but the cause remains unclear. This study aimed to evaluate the association between radioiodine therapy and risk of nonsynchronous second primary malignancy and to examine whether the risk of nonsynchronous second primary malignancy in differentiated thyroid cancer survivors treated with radioiodine therapy is increased relative to the general population. METHODS: Among 895 radiation-naïve patients with differentiated thyroid cancer, 643 (71.8%) received ≥1 course of radioiodine therapy (radioiodine therapy-positive group) and 252 (28.2%) received no radioiodine therapy (radioiodine therapy-negative group). After a median follow-up of 93.5 months (range, 23.4-570.8), 64 (7.2%) patients developed ≥1 nonsynchronous second primary malignancy. Potential risk factors for nonsynchronous second primary malignancy were entered into a multivariable regression model and cancer incidence in the radioiodine therapy-positive and -negative groups were compared to that of the general population by estimating the standardized incidence ratios. RESULTS: The 20-year cumulative nonsynchronous second primary malignancy risk in radioiodine therapy-positive group was significantly higher than radioiodine therapy-negative group (13.5% vs 3.1%; P = .015). Cumulative radioiodine therapy activity of 3.0 to 8.9 GBq (relative risk, 2.77; 95% CI, 1.079-7.154; P = .034) was the only independent risk factor for nonsynchronous second primary malignancy after adjusting for age, sex, period of differentiated thyroid cancer diagnosis, and stage of differentiated thyroid cancer. For females, the standardized incidence ratio in the radioiodine therapy-positive group was 1.54 (95% CI, 1.11-2.08) and in the radioiodine therapy-negative group it was 0.92 (95% CI, 0.37-1.90). CONCLUSION: Differentiated thyroid cancer female survivors treated by radioiodine therapy appeared to be at elevated risk of nonsynchronous second primary malignancy when compared to the general population and this risk was not apparent in those not previously treated by radioiodine therapy.

Impact of the 1990 Hong Kong legislation for restriction on sulfur content in fuel.

INTRODUCTION: After the implementation of a regulation restricting sulfur to 0.5% by weight in fuel on July 1, 1990, in Hong Kong, sulfur dioxide (SO2*) levels fell by 45% on average and as much as 80% in the most polluted districts (Hedley et al. 2002). In addition, a reduction of respiratory symptoms and an improvement in bronchial hyperresponsiveness in children were observed (Peters et al. 1996; Wong et al. 1998). A recent time-series study (Hedley et al. 2002) found an immediate reduction in mortality during the cool season at six months after the intervention, followed by an increase in cool-season mortality in the second and third years, suggesting that the reduction in pollution was associated with a delay in mortality. Proportional changes in mortality trends between the 5-year periods before and after the intervention were measured as relative risks and used to assess gains in life expectancy using the life table method (Hedley et al. 2002). To further explore the relation between changes in pollution-related mortality before and after the intervention, our study had three objectives: (1) to evaluate the short-term effects on mortality of changes in the pollutant mix after the Hong Kong sulfur intervention, particularly with changes in the particulate matter (PM) chemical species; (2) to improve the methodology for assessment of the health impact in terms of changes in life expectancy using linear regression models; and (3) to develop an approach for analyzing changes in life expectancy from Poisson regression models. A fourth overarching objective was to determine the relation between short- and long-term benefits due to an improvement in air quality. METHODS: For an assessment of the short-term effects on mortality due to changes in the pollutant mix, we developed Poisson regression Core Models with natural spline smoothers to control for long-term and seasonal confounding variations in the mortality counts and with covariates to adjust for temperature (T) and relative humidity (RH). We assessed the adequacy of the Core Models by evaluating the results against the Akaike Information Criterion, which stipulates that, at a minimum, partial autocorrelation plots should be between -0.1 and 0.1, and by examining the residual plots to make sure they were free from patterns. We assessed the effects for gaseous pollutants (NO2, SO2, and O3), PM with an aerodynamic diameter < or = 10 microm (PM10), and its chemical species (aluminum [Al], iron [Fe], manganese [Mn], nickel [Ni], vanadium [V], lead [Pb], and zinc [Zn]) using the Core Models, which were developed for the periods 5 years (or 2 years in the case of the sensitivity analysis) before and 5 years after the intervention, as well as in the10-year (or 7-year in the case of the sensitivity analysis) period pre- and post-intervention. We also included an indicator to separate the pre- and post-intervention periods, as well as the product of the indicator with an air pollution concentration variable. The health outcomes were mortality for all natural causes and for cardiovascular and respiratory causes, at all ages and in the 65 years or older age group. To assess the short- and long-term effects, we developed two methods: one using linear regression models reflecting the age-standardized mortality rate D(j) at day j, divided by a reference D(ref); and the other using Poisson regression models with daily mortality counts as the outcome variables. We also used both models to evaluate the relation between outcome variables and daily air pollution concentrations in the current day up to all previous days in the past 3 to 4 years. In the linear regression approach, we adjusted the data for temperature and relative humidity. We then removed season as a potential confounder, or deseasonalized them, by calculating a standard seasonal mortality rate profile, normalized to an annual average of unity, and dividing the mortality rates by this profile. Finally, to correct for long-term trends, we calculated a reference mortality rate D(ref)(j) as a moving average of the corrected and deseasonalized D(j) over the observation window. Then we regressed the outcome variable D(j)/D(ref) on an entire exposure sequence {c(i)} with lags up to 4 years in order to obtain impact coefficient f(i) from the regression model shown below: deltaD(j)/D (ref) = i(max)sigma f(i) c(j - i)(i = 0). The change in life expectancy (LE) for a change of units (deltac) in the concentration of pollutants on T(day)--representing the short interval (i.e., a day)--was calculated from the following equation (deltaL(pop) = average loss in life expectancy of an entire population): deltaL(pop) = -deltac T(day) infinity sigma (j = 0) infinity sigma f(i) (i = 0). In the Poisson regression approach, we fitted a distributed-lag model for exposure to previous days of up to 4 years in order to obtain the cumulative lag effect sigma beta(i). We fit the linear regression model of log(LE*/LE) = gamma(SMR - 1) + alpha to estimate the parameter gamma by gamma, where LE* and LE are life expectancy for an exposed and an unexposed population, respectively, and SMR represents the standardized mortality ratio. The life expectancy change per Ac increase in concentration is LE {exp[gamma delta c(sigma beta(i))]-1}. RESULTS: In our assessment of the changes in pollutant levels, the mean levels of SO2, Ni, and V showed a statistically significant decline, particularly in industrial areas. Ni and V showed the greatest impact on mortality, especially for respiratory diseases in the 5-year pre-intervention period for both the all-ages and 65+ groups among all chemical species. There were decreases in excess risks associated with Ni and V after the intervention, but they were nonsignificant. Using the linear regression approach, with a window of 1095 days (3 years), the losses in life expectancy with a 10-microg/m3 increase in concentrations, using two methods of estimation (one with adjustment for temperature and RH before the regression against pollutants, the other with adjustment for temperature and RH within the regression against pollutants), were 19.2 days (95% CI, 12.5 to 25.9) and 31.4 days (95% CI, 25.6 to 37.2) for PM10; and 19.7 days (95% CI, 15.2 to 24.2) and 12.8 days (95% CI, 8.9 to 16.8) for SO2. The losses in life expectancy in the current study were smaller than the ones implied by Elliott and colleagues (2007) and Pope and colleagues (2002) as expected since the observation window in our study was only 3 years whereas these other studies had windows of 16 years. In particular, the coefficients used by Elliott and colleagues (2007) for windows of 12 and 16 years were non-zero, which suggests that our window of at most 3 years cannot capture the full life expectancy loss and the effects were most likely underestimated. Using the Poisson regression approach, with a window of 1461 days (4 years), we found that a 10-microg/m3 increase in concentration of PM10 was associated with a change in life expectancy of -69 days (95% CI, -140 to 1) and a change of -133 days (95% CI, -172 to -94) for the same increase in SO2. The effect estimates varied as expected according to most variations in the sensitivity analysis model, specifically in terms of the Core Model definition, exposure windows, constraint of the lag effect pattern, and adjustment for smoking prevalence or socioeconomic status. CONCLUSIONS: Our results on the excess risks of mortality showed exposure to chemical species to be a health hazard. However, the statistical power was not sufficient to detect the differences between the pre- and post-intervention periods in Hong Kong due to the data limitations (specifically, the chemical species data were available only once every 6 days, and data were not available from some monitoring stations). Further work is needed to develop methods for maximizing the information from the data in order to assess any changes in effects due to the intervention. With complete daily air pollution and mortality data over a long period, time-series analysis methods can be applied to assess the short- and long-term effects of air pollution, in terms of changes in life expectancy. Further work is warranted to assess the duration and pattern of the health effects from an air pollution pulse (i.e., an episode of a rapid rise in air pollution) so as to determine an appropriate length and constraint on the distributed-lag assessment model.