Malignant mesothelioma: A histomorphological and immunohistochemical study of 24 cases from a tertiary care hospital in Southern India

Monalisa Hui, Shantveer Gurulingappa Uppin, Kakarla Bhaskar, Narahari Narendra Kumar, Gongati Kruparao Paramjyothi

Indian Journal of Cancer 2018 55(2):190-195

BACKGROUND: Malignant mesotheliomas are histologically heterogeneous neoplasms. Definite diagnosis requires a varied panel of immunohistochemical (IHC) markers to differentiate these from histological mimics. Only a few case series have been reported in the Indian literature where mesotheliomas have been analyzed on routine histology and IHC. AIM: To evaluate the histological features of malignant mesothelioma and to elucidate the best possible immunomarker combination useful in different scenarios. MATERIALS AND METHODS: A total of 24 cases of malignant mesotheliomas of different sites encountered over a 6-year period were retrospectively analyzed with regard to their histomorphology and IHC findings. RESULTS: The pleura was the most common site of involvement (16 cases) followed by peritoneum (5 cases) and pericardium (3 cases). Epithelioid mesothelioma was the most common histological type (15 cases, 62.5%) followed by sarcomatoid (5 cases, 20.84%), deciduoid (2 cases, 8.34%), and 1 case each of desmoplastic and biphasic mesothelioma. Among the mesothelial markers, WT1 was positive in 17 of 20 (85%) cases and calretinin was positive in 20 of 21 (95.23%) cases. D2-40 and CK5/6 were positive in all cases where they were studied. Adenocarcinoma markers TTF-1, napsin A, and CEA had very high negative predictive value in ruling out mesothelioma. CONCLUSION: The differential diagnosis of mesotheliomas varies with histological type and tumor location. Judicious use of various combinations of IHC markers in different situation has been highlighted in this article.

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Stereotactic body radiotherapy for lung tumors: Dosimetric analysis and clinical outcome

Kaustav Talapatra, Dipanjan Majumder, Pranav Chadha, P Shaju, Sandeep Goyle, BK Smruti, Rajesh Mistry

Indian Journal of Cancer 2018 55(2):170-175

INTRODUCTION: Stereotactic body radiotherapy (SBRT) has emerged as an important modality in malignant lung tumor treatment both in early localized primary and oligometastatic setting. This study aims to present the results of lung SBRT both in terms of dosimetry and clinical outcome. MATERIALS AND METHODS: Twenty-seven patients were assessed from 2012 to 2016. Both the primary and oligometastatic lung tumors were evaluated. Respiratory motion management was done employing ANZAI (Siemens, Germany) based four-dimensional computed tomography (CT). Commonly used fractionations were 60 Gy/5 fractions for peripheral tumors and 48 Gy/6 fractions for central tumors. Radiation Therapy Oncology Group toxicity criteria were used for toxicity and whole-body positron emission tomography-CT scan was done at follow-up for response evaluation. RESULTS: Twenty-seven patients were evaluated, 18 (66.7%) patients had a primary, and 9 (33.3%) patients had metastatic lung tumors. The male-to-female ratio for the entire cohort was 2:1. The median age at diagnosis was 65.8 years. Mean planning target volume (PTV) D2cc was 54.9 ± 9.04 Gy and mean internal target volume diameter was 3.0 ± 1.07 cm. Mean V20 Gy, V10 Gy, and V5 Gy of (lungs total-PTV) and (Lung ipsilateral - PTV) were 5.4 ± 4% and 10.9 ± 7.9%, 11.7 ± 5.8% and 24.2 ± 14.0%, and 22.05 ± 12.4% and 33.2 ± 15.3%, respectively. In total 21 (84%) patients and 4 patients (16%) showed a complete and partial response, respectively. One (3%) patient developed Gr 3 radiation pneumonitis. One year local control was in 18 (81%) patients whereas 4 (14%) patients progressed and three patients did not report. A higher prescribed dose significantly correlated with 1 year tumor control (P = 0.036). CONCLUSION: This study infers the feasibility and a favorable outcome for lung cancer amenable to SBRT in addition to being one of the largest clinical experiences for lung stereotactic treatment in our country.

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Radical radiotherapy or chemoradiotherapy for inoperable, locally advanced, non-small cell lung cancer: Analysis of patient profile, treatment approaches, and outcomes for 213 patients at a tertiary cancer center

Raj Kumar Shrimali, Chandran Nallathambi, Animesh Saha, Avipsa Das, Sriram Prasath, Anurupa Mahata, B Arun, Indranil Mallick, Rimpa Achari, Deepak Dabkara, Robin Thambudorai, Sanjoy Chatterjee

Indian Journal of Cancer 2018 55(2):125-133

INTRODUCTION: Radical radiotherapy (RT) with curative intent, with or without chemotherapy, is the standard treatment for inoperable, locally advanced nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively reviewed the data for all 288 patients who presented with inoperable, locally advanced NSCLC at our institution, between May 2011 and December 2016. RESULTS: RT alone or sequential chemoradiotherapy (SCRT) or concurrent chemoradiotherapy (CCRT) was used for 213 patients. Median age was 64 years (range: 27–88 years). Stage-III was the biggest stage group with 189 (88.7%) patients. Most patients with performance status (PS) 0 or 1 received CCRT, whereas most patients with PS 2 received RT alone (P < 0.001). CCRT, SCRT, and RT alone were used for 120 (56.3%), 24 (11.3%), and 69 (32.4%) patients, respectively. A third of all patients (32.4%) required either volumetric-modulated arc radiotherapy (VMAT) or tomotherapy. Median follow-up was 16 months. The median progression-free survival and median overall survival (OS) were 11 and 20 months, respectively. One-year OS and 2-year OS were 67.9% and 40.7%, respectively. Patients treated using CCRT lived significantly longer with a median survival of 28 months, compared with 13 months using SCRT and RT alone (P < 0.001). On multivariate analysis, OS was significantly affected by age, stage group, treatment approach, and response to treatment. CONCLUSION: RT including CCRT is feasible, safe, and well tolerated in our patient population and results in survival benefits comparable with published literature. CCRT should be considered for all patients with inoperable, locally advanced NSCLC, who are fit and have good PS.

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Carcinoma cervix – No role for surgery in stages IB2-IIB?

Prasanth Ganesan

Indian Journal of Cancer 2018 55(2):123-124



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Primary cutaneous B-cell lymphoma: A single-center 5-year experience

Linu Abraham Jacob, Vikas Asati, KC Lakshmaiah, Babu K Govind, Dasappa Lokanatha, Suresh MC Babu, KN Lokesh, AH Rudresh, LK Rajeev, Nikita J Mulchandani, Abhishek Anand, Deepak Koppaka, Suma Narayana Mysore

Indian Journal of Cancer 2018 55(2):134-137

BACKGROUND: Skin is the second most common site for extranodal non-Hodgkin's lymphoma (NHL). Most primary cutaneous NHLs are of T-cell origin (70%). Primary cutaneous B-cell lymphoma (PCBCL) is a rare entity. MATERIALS AND METHODS: Patients diagnosed with PCBCL between January 2012 and July 2017 at our center were retrospectively analyzed. RESULTS: Eight patients of PCBCL were diagnosed. Three patients (37.5%) were males while 5 patients (62.5%) were females. The median age at diagnosis was 45 years (range, 18–60 years). Scalp was the most common site of involvement (50% of the patients). Diffuse large B-cell lymphoma (DLBCL) was the most common histology (63%), with leg-type DLBCL diagnosed in 1 patient. Two patients had primary cutaneous follicle center lymphoma, whereas the remaining 1 patient had precursor B-lymphoblastic lymphoma. All 5 DLBCL cases were treated with CHOP chemotherapy, and rituximab was given to 3 patients. Of the primary cutaneous follicle center lymphomas, 1 patient with stage II disease was treated with CHOP and is alive without recurrence for the past 5 years, whereas the other patient is on observation alone. The patient with precursor B-lymphoblastic lymphoma was started on MCP-841 protocol; however, the patient did not complete the treatment and died after 11 months. CONCLUSIONS: PCBCL is a heterogeneous group of diseases and dividing them into subtypes, based on morphology and immunophenotype, has therapeutic implications.

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Impact of gene polymorphism of TNF-α rs 1800629 and TNF-β rs 909253 on plasma levels of South Indian breast cancer patients

Karuvaje Thriveni, Anisha Raju, Girija Ramaswamy, S Krishnamurthy

Indian Journal of Cancer 2018 55(2):179-183

AIM: Inflammation plays a lead role in the tumor microenvironment and promotes metastasis. Single-nucleotide polymorphism (SNP) in the tumor necrosis factor (TNF) gene locus may alter the expression of genes and proteins. The objective of the study is to find the distribution of genetic polymorphism in the sites of TNF-α −308G>A and TNF- β +252A>G in breast cancer and evaluate polymorphism effects on plasma levels. MATERIALS AND METHODS: The study group consisted of 109 invasive ductal primary breast cancer patients and 75 age-matched healthy female controls. Plasma cytokine concentrations were measured by the MILLIPLEX® MAP Human Cytokine/Chemokine Panel magnetic bead kits. The genotyping procedure for SNP included allele-specific polymerase chain reaction for TNFα and restriction fragment length polymorphism for TNFβ. RESULTS: Odds ratio with 95% confidence interval showed that these polymorphisms were not a causative risk factor, and both polymorphisms were consistent with Hardy–Weinberg equilibrium. Plasma TNFα and TNFβ median concentrations were significantly higher in cases when compared to controls (P < 0.01). When plasma TNFα levels were grouped under polymorphic subtypes, patients with mutant TNF- α −308A allele showed significantly higher values (P < 0.001). In addition, plasma TNFα values were significantly elevated in mutant TNF-β +252G allele (P < 0.01). CONCLUSION: This study demonstrated that there is no significant association between SNPs and breast cancer susceptibility in South Indian population. However, plasma TNFα level is significantly elevated with mutant-recessive TNF-α −308 A and TNF-β +252 G alleles of patients.

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Treatment practices for metastatic pancreatic cancer: Can we deliver an appropriately efficacious and safe regimen in Indian patients?

Anant Ramaswamy, Vikas Ostwal, Alok Goel, Prabhat Bhargava, Sujay Srinivas, Sanyo Dsouza, Shailesh V Shrikhande

Indian Journal of Cancer 2018 55(2):138-143

INTRODUCTION: The median overall survival (mOS) in metastatic pancreatic cancers (PCs) hovers between 6 months to 11 months. MATERIALS AND METHODS: The study is a retrospective analysis of metastatic PC patients who were evaluated from August 2013 to August 2016 in the Department of Gastrointestinal (GI) Medical Oncology, Tata Memorial Hospital (TMH). RESULTS: Out of 218 patients, 24 patients (11%) were not planned for chemotherapy and referred to the Department of Palliative Care for further supportive care. One hundred and fifty-three patients received palliative chemotherapy in TMH with median age of 56 years (range: 23–79), male (60.1%), and nonresident in Maharashtra (60.1%). Regimens used most commonly were gemcitabine–nab-paclitaxel in 60 patients (39.2%), gemcitabine–erlotinib in 25 patients (16.3%), and modified FOLFIRINOX in 21 patients (13.7%). A total of 58 patients (43%; n = 135) had Grade 3/4 toxicities. As of cutoff date for the analysis of outcomes, 139 patients (90.8%) patients had ceased first-line chemotherapy, due to radiologically proven progressive disease (PD) in 89 patients (64%), repeated Grades 3 and 4 adverse events in 26 patients (18.7%), and clinically PD in 18 patients (12.9%). With a median follow-up of 278 days, the mOS was 217 days (95% confidence interval [CI]: 175–258), and the median event-free survival was 125 days (95% CI: 107–122). CONCLUSION: Dose modifications for chemotherapy are required commonly when treating metastatic PC, with common reasons for dose reduction being toxicities, Eastern Cooperative Oncology Group performance status >=2, and low albumin levels. Studies evaluating logistic and financial aspects of treating metastatic PC with chemotherapy in India are warranted.

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Gamna–Gandy bodies in a solid pseudopapillary tumor of the pancreas

Anita Nangia, Shivali Sehgal

Indian Journal of Cancer 2018 55(2):201-202

Gamna gandy bodies are sclerosiderotic granules composed of various amounts of calcium and hemosiderin in hyalinised fibrous tissue. We report a case of an 18 year old girl with solid pseudopapillary tumor of the pancreas in which numerous gamna gandy bodies were present. The pathogenesis of such a finding is unclear. To the best of our knowledge, this is the first report of Gamna Gandy bodies occurring in a solid pesudopapillary tumor of the pancreas.

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Outcomes with second-line chemotherapy in advanced pancreatic cancers: A retrospective study from a tertiary cancer center in India

Anant Ramaswamy, Sangeetha Parthiban, Mridul Malhotra, Rushabh Kothari, Alok Goel, Prabhat Bhargava, Sujay Srinivas, Suyash Kulkarni, Vikas Ostwal

Indian Journal of Cancer 2018 55(2):144-147

INTRODUCTION: Approximately 40% of patients receiving first-line chemotherapy (CT1) for advanced pancreatic adenocarcinomas (PDACs) receive second-line chemotherapy (CT2). The most appropriate regimen to be used has not been identified, and data regarding CT2 in advanced PDAC from India are scarce. MATERIALS AND METHODS: A retrospective analysis of advanced PDAC patients who were evaluated during the period of August 2013 to August 2016 in the Department of GI medical Oncology, at Tata Memorial Hospital was conducted. Patients with histologically proven PDAC and started on CT2 postprogression or recurrence after CT1 were included for analysis. RESULTS: A total of 237 patients received CT1 in the period of study, of which 76 patients (39.66%) received CT2. The median age of patients was 59.5 years (range: 38–82), majority were male (69.7%), and 14 patients (18.4%) had undergone curative pancreatic resection at baseline. The common regimens used as CT2 were modified 5 fluorouracil/leucovorin/irinotecan (mFOLFIRI) (35.5%), gemcitabine-nab paclitaxel (18.4%), and gemcitabine-erlotinib (11.8%). Common grade 3/4 toxicities noted were fatigue (10.3%), anemia (10.3%), neutropenia (7.4%), and vomiting (7.4%). Dose reductions were required in 32.9% of patients. RR, DCR, median event free survival, and median overall survival were 21.1%, 48.7%, and 5.94 months (95% confidence intervals [CI]: 4.68–7.20) and 8.08 months (95% CI: 7.11–9.07) respectively. CONCLUSIONS: CT2 in advanced PDAC appears feasible in the Indian setting if the patients are appropriately selected and they can be treated with acceptable toxicities and reasonable outcomes.

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Compliance to radiotherapy: A tertiary care center experience

Shivani Gupta, Kartick Rastogi, Aseem Rai Bhatnagar, Daleep Singh, Kampra Gupta, Ajay Singh Choudhary

Indian Journal of Cancer 2018 55(2):166-169

CONTEXT: The most commonly prescribed conventional fractionation radiotherapy uses 1.8–2.2 Gy per fraction for five fractions in a week. Many times, unwanted interruptions are encountered, which ultimately affect the local control and overall survival. AIMS: The present retrospective study was carried out to study the compliance to radiotherapy at our institute and to determine various factors related to it. PATIENTS AND METHODS: The present retrospective study was carried out at the department of Radiotherapy, SMS Medical College and attached group of hospitals, Jaipur; in patients who were treated with curative intent with conventional fractionation radiotherapy over telecobalt machine from January 2017 to April 2017. Noncompliance was studied for association with various factors such as age, sex, site of primary disease, stage of tumor, distance patients had to travel to receive treatment, administration of concurrent chemotherapy, and financial burden of the treatment. RESULTS: Of 203 patients, 138 were of head-and-neck cancer, 42 of cervical cancer, and 23 of breast cancer. The cumulative incidence of noncompliance was 12.8% (15.9% for head-and-neck cancer, 7.2% for cervical cancer, and 4.4% for breast cancer). Statistically significant association was found between noncompliance and higher age of the patients (P = 0.07), male gender (P = 0.002), advanced stage (P = 0.004), administration of concurrent chemoradiotherapy (CCRT) (P < 0.001), and greater distance patients had to travel for radiotherapy (P = 0.03). CONCLUSIONS: The factors with which noncompliance is significantly associated in the present study are higher age, male gender, advanced stage of tumor, administration of CCRT, and greater distance patients had to travel to avail radiotherapy.

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A comparative study of the effects of medical versus surgical androgen deprivation therapy on health-related quality of life in patients with metastatic carcinoma prostate

Prabhjot Singh, Tapan Agrawal, Siddharth Yadav, Brusabhanu Nayak, Amlesh Seth, Prem Nath Dogra

Indian Journal of Cancer 2018 55(2):148-153

INTRODUCTION: Androgen deprivation therapy (ADT) is known to adversely affect the quality of life (QoL). One may choose between surgical and medical forms depending on his economic status, education status, and taboos. The aim of this study was to assess the impact of medical versus surgical ADT on health-related quality of life (HRQoL) in patients with metastatic cancer prostate in Indian population. MATERIALS AND METHODS: From July 2012 to December 2014, 50 patients (10 medical castration and 40 surgical castration) of hormone-naïve metastatic prostate cancer who were started on combined ADT were included in this study. Before starting therapy, baseline data and QoL score (short form [SF-36] scale) were noted and all patients were followed up at 3 months, 6 months, and 1 year. Baseline data and HRQoL at all time intervals between surgical and medical castration groups were compared. RESULTS: All patients, except two, completed the 1-year follow-up period. Patients who opted for medical castration were more educated and belonged to higher socioeconomic status. For all the domains of SF-36 QoL questionnaire, a similar improvement in the score was noted at first 3-month follow-up which deteriorated in the next follow-up at 6 months and then further at 1 year. There was no difference in HRQoL after medical or surgical castration. CONCLUSIONS: In patients with metastatic cancer, prostate initiation of ADT, irrespective of method, causes an initial improvement in HRQoL followed later by a more gradual decline below the baseline.

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Clinical outcomes of limb salvage surgery with postoperative intensity-modulated radiation therapy for soft-tissue sarcoma and metastasis

Katsuhisa Kawanami, Toshihiro Matsuo, Shintaro Yuki, Shoji Shimose, Ryosuke Takahashi, Masataka Deie

Indian Journal of Cancer 2018 55(2):176-178

OBJECTIVE: The primary aim of intensity-modulated radiation therapy (IMRT) for treating soft tissue sarcoma of an extremity is the reduction of morbidity and maintenance of local control. METHODS: We evaluated the outcomes and toxicity of adjuvant IMRT following function-preserving surgery to treat patients with soft tissue sarcoma and metastasis of the extremities. We retrospectively reviewed prospective databases at Kure Medical Center and Aichi Medical University between 2013 and 2016 and identified 10 patients with lower extremity soft tissue sarcoma who underwent both limb-sparing surgery and postoperative IMRT at one of our institutions. RESULTS: There were 7 men and 3 women (mean age, 67.2 years; range, 48–87 years) included in the study. Of these, four patients were continuously disease-free, two showed no evidence of disease, and four died due to disease. The average functional score was 82% (range, 53–100%). Among the 10 patients, 2 (22%) had grade 1–2 edema and 1 (11%) had grade 2 joint stiffness. Another patient developed grade 2 acute dermatitis. There were no severe complications such as infection, tissue necrosis, fracture, or nerve palsy. CONCLUSION: Although the number of patients in this study was small, our results show that adjuvant IMRT following function-preserving surgery for soft tissue sarcoma of the extremity can be valuable for treating unmanageable tumors.

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Superficial incisional surgical site infections in emergency surgery in cancer patients: A tertiary cancer care center experience

Rexeena Bhargavan, Paul Augustine

Indian Journal of Cancer 2018 55(2):154-156

OBJECTIVE: The objective of this study is to review the superficial incisional surgical site infections (SISSIs) in emergency surgery in cancer patients. MATERIAL AND METHODS: The microbiological culture and sensitivity reports of patients undergoing emergency surgery for cancer of 1 year (April 2016 to March 2017) were analyzed along with the clinical factors associated with it from a surgeon's perspective. RESULTS: Of the 308 patients who underwent surgery, SISSI rate was 11.7%. The most common organism was Escherichia coli (27%) followed by enterococci (21%). Prolongation of hospital stay was average 2 days. Mortality rate among SISSI patients was 7.9%. Concordance among ongoing antibiotic and culture was 72%. CONCLUSION: Regular review of the current microbial spectrum and its antibiotic spectrum is required, especially in immunocompromized cancer patients.

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Breast cancer-related lymphedema in postmastectomy patients receiving adjuvant irradiation: A prospective study

Kartick Rastogi, Sandeep Jain, Aseem-Rai Bhatnagar, Shivani Gupta, Sandeep Bhaskar, RK Spartacus

Indian Journal of Cancer 2018 55(2):184-189

CONTEXT: In India, most breast cancer patients present with advanced stage requiring postmastectomy radiotherapy. Lymphedema is a long-term side effect that causes both physical and psychological distresses. AIMS: The present prospective study was carried out to study various factors affecting breast cancer-related lymphedema (BCRL). SUBJECTS AND METHODS: From January 2015 to March 2016, 100 postmastectomy patients who received adjuvant irradiation to chest wall were selected prospectively. Circumference of both arms was measured before surgery, at start, and at end of radiotherapy followed by 3 monthly intervals till last follow-up. Lymphedema was defined as a difference of ≥2 cm from the baseline in the arm circumference on the side of surgery. RESULTS: At a median follow-up of 24 months, the cumulative incidence of BCRL was 13%. On multivariate analysis, risk of BCRL was significantly associated with higher body mass index (BMI) (P = 0.004), greater number of lymph nodes (LNs) dissected (P = 0.005), higher nodal ratio (P = 0.006), and regional LN radiation (RLNR) (P = 0.048) but not with the type of fractionation (P = 0.094). CONCLUSIONS: Adjuvant RLNR, higher BMI, greater number of LNs dissected, and higher nodal ratio significantly increases the risk of development of BCRL. There was no significant difference in the lymphedema with the type of fractionation. Females receiving RLNR should be prospectively monitored for lymphedema to ensure early detection and possible intervention.

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The efficacy and tolerability of scalp cooling in preventing chemotherapy-induced alopecia in patients with breast cancer receiving anthracycline and taxane-based chemotherapy in an Asian setting

Marniza Saad, Flora Li Tze Chong, Anita Zarina Bustam, Gwo Fuang Ho, Rozita Abdul Malik, Wan Zamaniah Wan Ishak, Vincent Chee Ee Phua, Mastura Md Yusof, Ning Yi Yap, Adlinda Alip

Indian Journal of Cancer 2018 55(2):157-161

BACKGROUND: Scalp cooling has been shown in several studies to be an effective method in preventing chemotherapy-induced alopecia (CIA). Data on the use of scalp cooling in Asian countries are limited, and evidence for its use and efficacy among our patients are not available. OBJECTIVE: The aim of this study was to assess the effectiveness and tolerability of scalp cooling among breast cancer patients in our study population. METHODS: Consecutive breast cancer patients receiving FE75C, FE100C, FE100C-D, docetaxel75 or docetaxel, and cyclophosphamide (TC) at our treatment center were recruited and allocated to the treatment (scalp cooling, DigniCapTM system) or control group in this prospective nonrandomized controlled study. The assessment of alopecia was carried out using the World Health Organization grading system and clinical photographs. RESULTS: Seventy patients were recruited, but only 25 completed the study and were evaluable for analysis. Five of 12 patients (42%) in the scalp cooling group managed to preserve hair. Two of three patients who received FE75C and TC regimens had minimal hair loss. All patients treated with FE100C had severe hair loss. Half of all patients who received scalp cooling throughout chemotherapy rated the treatment as reasonably well tolerated. The most common reason for discontinuing scalp cooling was intolerance to its side effects. CONCLUSION: Scalp cooling is potentially effective in reducing CIA caused by docetaxel, TC, and FE75C chemotherapy regimen. However, it was not well tolerated by our study population. The dropout rate was high, and this needs to be taken into consideration when pursuing further trials in a similar setting.

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Cetuximab in combination with chemoradiotherapy for nasopharyngeal carcinoma: A meta-analysis

Na Wang, Kai Wang, Feixue Song, Yating Liu

Indian Journal of Cancer 2018 55(2):196-200

AIMS AND OBJECTIVES: The aims and objectives of this study are to investigate the efficacy and safety of chemoradiotherapy (CCRT) with or without cetuximab in nasopharyngeal carcinoma (NPC). METHODS: We searched the Cochrane Library, PubMed, Embase, CNKI, VIP, Chinese biomedicine literature database, and WANFANG database for relevant articles. The methodological quality of included studies was evaluated, and data were analyzed using RevMan 5.0 software. RESULTS: Ten relevant articles (783 patients) were identified. The results were complete response rate; the response rate was significantly better in the cetuximab plus CCRT (C225+CCRT) group than the CCRT group. The partial response and 3-year-overall survival rates were not significantly different between the two groups. Regarding adverse effects, myelosuppression was observed in the CRRT group and the C225+CCRT group; the main toxicity was mucositis and rash, but no significant statistical difference was observed. CONCLUSION: The combination of cetuximab and CCRT was more effective for NPC than CCRT alone and had no serious side effects.

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An evaluation of early-onset fatigue and the related coping strategies in patients with gastrointestinal cancer: A prospective pilot study

Anita D'souza, Richa Kamboj, Sarika Mandavkar, Neeta Chavan, Anant Ramaswamy, Vikas Ostwal

Indian Journal of Cancer 2018 55(2):162-165

BACKGROUND: Cancer related fatigue (CRF) has been studied extensively and it has the worse impact as compared to pain on quality of life (QOL) of cancer patients. MATERIAL AND METHODS: Prospective study was conducted at Tata Memorial center in Gastrointestinal (GI) cancer patients to assess fatigue with FACIT and PIPER scales. This was also to assess qualitative data on coping strategies in these patients. RESULTS: Severe to moderate fatigue was commonly associated with sedentary to moderate activities (P = 0.049) whereas it was less common as education level increases (P = 0.031). Baseline pain was significantly associated with increase in fatigue (P = 0.033). This study also suggests that fatigue increases with as number of chemotherapy cycles increase. Qualitative data analysis revealed that majority of the patients used resting and energy conservation in the form of sitting, lying down. Most of them were following high protein diet (with or without supplementary protein powder) and little exercise such as walking. CONCLUSION: Patients with GI cancer receiving chemotherapy were found to have fatigue, which increased during the subsequent cycles. Patients with sedentary lifestyle and experiencing pain at baseline were found to have more fatigue. Coping strategies adopted by majority of patients were resting and a high-protein diet.

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Cervical cancer in Bihar: Time to revisit the shortcomings

Sangeeta Pankaj, Anita Kumari, Vijayanand Choudhary, Babban Jee

Indian Journal of Cancer 2018 55(2):203-204



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Limitations and Misinterpretations of E-Values for Sensitivity Analyses of Observational Studies

The E-value was recently introduced on the basis of earlier work as "the minimum strength of association…that an unmeasured confounder would need to have with both the treatment and the outcome to fully explain away a specific treatment–outcome association, conditional on the measured covariates." E-values have been proposed for wide application in observational studies evaluating causality. However, they have limitations and are prone to misinterpretation. E-values have a monotonic, almost linear relationship with effect estimates and thus offer no additional information beyond what effect estimates can convey. Whereas effect estimates are based on real data, E-values may make unrealistic assumptions. No general rule can exist about what is a "small enough" E-value, and users of the biomedical literature are not familiar with how to interpret a range of E-values. Problems arise for any measure dependent on effect estimates and their CIs—for example, bias due to selective reporting and dependence on choice of exposure contrast and level of confidence. The automation of E-values may give an excuse not to think seriously about confounding. Moreover, biases other than confounding may still undermine results. Instead of misused or misinterpreted E-values, the authors recommend judicious use of existing methods for sensitivity analyses with careful assumptions; systematic assessments of whether and how known confounders have been handled, along with consideration of their prevalence and magnitude; thorough discussion of the potential for unknown confounders considering the study design and field of application; and explicit caution in making causal claims from observational studies.

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Reassessment of Risk for Stroke During Follow-up of Patients With Atrial Fibrillation

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A Pound of Prevention? Assessing the Value of New Cholesterol-Lowering Drugs

Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors substantially reduce cholesterol levels, but the U.S. Food and Drug Administration–approved PCSK9 inhibitors, alirocumab and evolocumab, came to market priced at $14 000 per year—more than 100 times the cost of a generic statin. Kazi and colleagues performed a cost-effectiveness analysis of alirocumab in secondary prevention based on new trial results and updated pricing. The editorialist discusses the findings and what it takes for preventive therapies to be cost-effective.

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Pharmacovigilance in the Real World

In this issue, Fralick and colleagues use real-world observational data to clarify discrepant findings from clinical trials on whether canagliflozin, a sodium–glucose cotransporter-2 inhibitor, increases risk for fracture. The editorialists discuss the findings and why they believe that real-world data are critical to pharmacovigilance.

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Cost-Effectiveness of Alirocumab A Just-in-Time Analysis Based on the ODYSSEY Outcomes Trial

Background:

The ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial included participants with a recent acute coronary syndrome. Compared with participants receiving statins alone, those receiving a statin plus alirocumab had lower rates of a composite outcome including myocardial infarction (MI), stroke, and death.

Objective:

To determine the cost-effectiveness of alirocumab in these circumstances.

Design:

Decision analysis using the Cardiovascular Disease Policy Model.

Data Sources:

Data sources representative of the United States combined with data from the ODYSSEY Outcomes trial.

Target Population:

U.S. adults with a recent first MI and a baseline low-density lipoprotein cholesterol level of 1.81 mmol/L (70 mg/dL) or greater.

Time Horizon:

Lifetime.

Perspective:

U.S. health system.

Intervention:

Alirocumab or ezetimibe added to statin therapy.

Outcome Measures:

Incremental cost-effectiveness ratio in 2018 U.S. dollars per quality-adjusted life-year (QALY) gained.

Results of Base-Case Analysis:

Compared with a statin alone, the addition of ezetimibe cost $81 000 (95% uncertainty interval [UI], $51 000 to $215 000) per QALY. Compared with a statin alone, the addition of alirocumab cost $308 000 (UI, $197 000 to $678 000) per QALY. Compared with the combination of statin and ezetimibe, replacing ezetimibe with alirocumab cost $997 000 (UI, $254 000 to dominated) per QALY.

Results of Sensitivity Analysis:

The price of alirocumab would have to decrease from its original cost of $14 560 to $1974 annually to be cost-effective relative to ezetimibe.

Limitation:

Effectiveness estimates were based on a single randomized trial with a median follow-up of 2.8 years and should not be extrapolated to patients with stable coronary heart disease.

Conclusion:

The price of alirocumab would have to be reduced considerably to be cost-effective. Because substantial reductions already have occurred, we believe that timely, independent cost-effectiveness analyses can inform clinical and policy discussions of new drugs as they enter the market.

Primary Funding Source:

University of California, San Francisco, and Institute for Clinical and Economic Review.

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Correcting Misinterpretations of the E-Value

In their article, Ioannidis and colleagues raise several important issues concerning the potential misuse and misinterpretation of the E-value, a metric related to the robustness of associations to potential unmeasured or residual confounding. The editorialists discuss the usefulness of the E-value in practice in response to practical objections sometimes raised to other sensitivity analysis techniques that they are too complicated to describe in papers, are too difficult to present, take up too much space, and are difficult to understand.

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Fracture Risk After Initiation of Use of Canagliflozin A Cohort Study

Background:

Sodium–glucose cotransporter-2 inhibitors promote glycosuria, resulting in possible effects on calcium, phosphate, and vitamin D homeostasis. Canagliflozin is associated with decreased bone mineral density and a potential increased risk for fracture.

Objective:

To estimate risk for nonvertebral fracture among new users of canagliflozin compared with a glucagon-like peptide-1 (GLP-1) agonist.

Design:

Population-based new-user cohort study.

Setting:

Two U.S. commercial health care databases providing data on more than 70 million patients from March 2013 to October 2015.

Patients:

Persons with type 2 diabetes who initiated use of canagliflozin were propensity score–matched in a 1:1 ratio to those initiating use of a GLP-1 agonist.

Measurements:

The primary outcome was a composite end point of humerus, forearm, pelvis, or hip fracture requiring intervention. Secondary outcomes included fractures at other sites. A fixed-effects meta-analysis that pooled results from the 2 databases provided an overall hazard ratio (HR).

Results:

79 964 patients initiating use of canagliflozin were identified and matched to 79 964 patients initiating use of a GLP-1 agonist. Mean age was 55 years, 48% were female, average baseline hemoglobin A_1c level was 8.7%, and 27% were prescribed insulin. The rate of the primary outcome was similar for canagliflozin (2.2 events per 1000 person-years) and GLP-1 agonists (2.3 events per 1000 person-years), with an overall HR of 0.98 (95% CI, 0.75 to 1.26). Risk for pelvic, hip, humerus, radius, ulna, carpal, metacarpal, metatarsal, or ankle fracture was also similar for canagliflozin (14.5 events per 1000 person-years) and GLP-1 agonists (16.1 events per 1000 person-years) (overall HR, 0.92 [CI, 0.83 to 1.02]).

Limitation:

Unmeasured confounding, measurement error, and low fracture rate.

Conclusion:

In this study of middle-aged patients with type 2 diabetes and relatively low fracture risk, canagliflozin was not associated with increased risk for fracture compared with GLP-1 agonists.

Primary Funding Source:

Brigham and Women's Hospital, Division of Pharmacoepidemiology and Pharmacoeconomics.

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E-Cigarette Use Without a History of Combustible Cigarette Smoking Among U.S. Adults: Behavioral Risk Factor Surveillance System, 2016

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Learning From Temporal Relationships: Childbirth and Breast Cancer Risk

In their article, Nichols and colleagues report the results of a large and sophisticated analysis of the relationship between childbirth and breast cancer risk. The editorial discusses the insight the study provides into this complex relationship. Although the clinical implications of these findings are limited, the temporal relationship between childbirth and breast cancer risk offers an important clue for the ongoing effort to identify the mechanisms linking reproductive history and breast cancer risk.

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The Apocalypse

"You must not tell them or anyone until I am dead what I will tell you now. Promise?"

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The Burden of Candidate Pathogenic Variants for Kidney and Genitourinary Disorders Emerging From Exome Sequencing

Background:

Exome sequencing is increasingly being used for clinical diagnostics, with an impetus to expand reporting of incidental findings across a wide range of disorders. Analysis of population cohorts can help reduce risk for genetic variant misclassification and resultant unnecessary referrals to subspecialists.

Objective:

To examine the burden of candidate pathogenic variants for kidney and genitourinary disorders emerging from exome sequencing.

Design:

Secondary analysis of genetic data.

Setting:

A tertiary care academic medical center.

Patients:

A convenience sample of exome sequence data from 7974 self-declared healthy adults.

Measurements:

Assessment of the prevalence of candidate pathogenic variants in 625 genes associated with Mendelian kidney and genitourinary disorders.

Results:

Of all participants, 23.3% carried a candidate pathogenic variant, most of which were attributable to previously reported variants that had implausibly high allele frequencies. In particular, 25 genes (discovered before the creation of the Exome Aggregation Consortium, a genetic database comprising data from a large control population) accounted for 67.7% of persons with candidate pathogenic variants. After stringent filtering based on allele frequency, 1.4% of persons still had a candidate pathogenic variant, an excessive rate given the prevalence of monogenic kidney and genitourinary disorders. Manual annotation of a subset of variants showed that the majority would be classified as nonbenign under current guidelines for clinical sequence interpretation and could prompt subspecialty referrals if returned.

Limitation:

Limited access to health record data prevented comprehensive assessment of the phenotypic concordance with genetic diagnoses.

Conclusion:

Widespread reporting of incidental genetic findings related to kidney and genitourinary disorders will require stringent curation of clinical variant databases and detailed case-level review to avoid genetic misdiagnosis and unnecessary referrals. These findings motivate similar analyses for genes relevant to other medical subspecialties.

Primary Funding Source:

National Institute of Diabetes and Digestive and Kidney Diseases and National Human Genome Research Institute.

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The Talking Cure

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Weighing the Harms and Benefits of Using Statins for Primary Prevention: Raising the Risk Threshold

In this issue, Yebyo and colleagues challenge the risk thresholds in current guidelines for use of statins for primary prevention of cardiovascular disease. The editorialists discuss how the findings can support patient-centered decision making, particularly for older adults or those who are more concerned about harms of treatment.

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PROBAST: A Tool to Assess Risk of Bias and Applicability of Prediction Model Studies: Explanation and Elaboration

Prediction models in health care use predictors to estimate for an individual the probability that a condition or disease is already present (diagnostic model) or will occur in the future (prognostic model).Publications on prediction models have become more common in recent years, and competing prediction models frequently exist for the same outcome or target population. Health care providers, guideline developers, and policymakers are often unsure which model to use or recommend, and in which persons or settings. Hence, systematic reviews of these studies are increasingly demanded, required, and performed.A key part of a systematic review of prediction models is examination of risk of bias and applicability to the intended population and setting. To help reviewers with this process, the authors developed PROBAST (Prediction model Risk Of Bias ASsessment Tool) for studies developing, validating, or updating (for example, extending) prediction models, both diagnostic and prognostic.PROBAST was developed through a consensus process involving a group of experts in the field. It includes 20 signaling questions across 4 domains (participants, predictors, outcome, and analysis). This explanation and elaboration document describes the rationale for including each domain and signaling question and guides researchers, reviewers, readers, and guideline developers in how to use them to assess risk of bias and applicability concerns. All concepts are illustrated with published examples across different topics. The latest version of the PROBAST checklist, accompanying documents, and filled-in examples can be downloaded from www.probast.org.

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Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a common systemic inflammatory autoimmune disease characterized by painful, swollen joints that can severely impair physical function and quality of life. The presenting symptoms of musculoskeletal pain, swelling, and stiffness are common in clinical practice, so familiarity with diagnosing and managing RA is crucial. Patients with RA are at greater risk for serious infection, respiratory disease, osteoporosis, cardiovascular disease, cancer, and mortality than the general population. In recent years, early diagnosis, aggressive treatment, and expanded therapeutic options of disease-modifying antirheumatic drugs have markedly improved both the management and long-term prognosis of RA.

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PROBAST: A Tool to Assess the Risk of Bias and Applicability of Prediction Model Studies

Clinical prediction models combine multiple predictors to estimate risk for the presence of a particular condition (diagnostic models) or the occurrence of a certain event in the future (prognostic models).PROBAST (Prediction model Risk Of Bias ASsessment Tool), a tool for assessing the risk of bias (ROB) and applicability of diagnostic and prognostic prediction model studies, was developed by a steering group that considered existing ROB tools and reporting guidelines. The tool was informed by a Delphi procedure involving 38 experts and was refined through piloting.PROBAST is organized into the following 4 domains: participants, predictors, outcome, and analysis. These domains contain a total of 20 signaling questions to facilitate structured judgment of ROB, which was defined to occur when shortcomings in study design, conduct, or analysis lead to systematically distorted estimates of model predictive performance. PROBAST enables a focused and transparent approach to assessing the ROB and applicability of studies that develop, validate, or update prediction models for individualized predictions.Although PROBAST was designed for systematic reviews, it can be used more generally in critical appraisal of prediction model studies. Potential users include organizations supporting decision making, researchers and clinicians who are interested in evidence-based medicine or involved in guideline development, journal editors, and manuscript reviewers.

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Finding the Balance Between Benefits and Harms When Using Statins for Primary Prevention of Cardiovascular Disease A Modeling Study

Background:

Many guidelines use expected risk for cardiovascular disease (CVD) during the next 10 years as a basis for recommendations on use of statins for primary prevention of CVD. However, how harms were considered and weighed against benefits is often unclear.

Objective:

To identify the expected risk above which statins provide net benefit.

Design:

Quantitative benefit–harm balance modeling study.

Data Sources:

Network meta-analysis of primary prevention trials, a preference survey, and selected observational studies.

Target Population:

Persons aged 40 to 75 years with no history of CVD.

Time Horizon:

10 years.

Perspective:

Clinicians and guideline developers.

Intervention:

Low- or moderate-dose statin versus no statin.

Outcome Measures:

The 10-year risk for CVD at which statins provide at least a 60% probability of net benefit, with baseline risk, frequencies of and preferences for statin benefits and harms, and competing risk for non-CVD death taken into account.

Results of Base-Case Analysis:

Younger men had net benefit at a lower 10-year risk for CVD than older men (14% for ages 40 to 44 years vs. 21% for ages 70 to 75 years). In women, the risk required for net benefit was higher (17% for ages 40 to 44 years vs. 22% for ages 70 to 75 years). Atorvastatin and rosuvastatin provided net benefit at lower 10-year risks than simvastatin and pravastatin.

Results of Sensitivity Analysis:

Most alternative assumptions led to similar findings.

Limitation:

Age-specific data for some harms were not available.

Conclusion:

Statins provide net benefits at higher 10-year risks for CVD than are reflected in most current guidelines. In addition, the level of risk at which net benefit occurs varies considerably by age, sex, and statin type.

Primary Funding Source:

Swiss Government Excellence Scholarship Office, Béatrice Ederer-Weber Foundation, and North-South Cooperation at the University of Zurich.

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Correction: Mechanisms That Contribute to a Profound Reduction of the HIV-1 Reservoir After Allogeneic Stem Cell Transplant

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Trends in Drug Use–Associated Infective Endocarditis and Heart Valve Surgery, 2007 to 2017 A Study of Statewide Discharge Data

Background:

Drug use–associated infective endocarditis (DUA-IE) is increasing as a result of the opioid epidemic. Infective endocarditis may require valve surgery, but surgical treatment of DUA-IE has invoked controversy, and the extent of its use is unknown.

Objective:

To examine hospitalization trends for DUA-IE, the proportion of hospitalizations with surgery, patient characteristics, length of stay, and charges.

Design:

10-year analysis of a statewide hospital discharge database.

Setting:

North Carolina hospitals, 2007 to 2017.

Patients:

All patients aged 18 years or older hospitalized for IE.

Measurements:

Annual trends in all IE admissions and in IE hospitalizations with valve surgery, stratified by patients' drug use status. Characteristics of DUA-IE surgical hospitalizations, including patient demographic characteristics, length of stay, disposition, and charges.

Results:

Of 22 825 IE hospitalizations, 2602 (11%) were for DUA-IE. Valve surgery was performed in 1655 IE hospitalizations (7%), including 285 (17%) for DUA-IE. Annual DUA-IE hospitalizations increased from 0.92 to 10.95 and DUA-IE hospitalizations with surgery from 0.10 to 1.38 per 100 000 persons. In the final year, 42% of IE valve surgeries were performed in patients with DUA-IE. Compared with other surgical patients with IE, those with DUA-IE were younger (median age, 33 vs. 56 years), were more commonly female (47% vs. 33%) and white (89% vs. 63%), and were primarily insured by Medicaid (38%) or uninsured (35%). Hospital stays for DUA-IE were longer (median, 27 vs. 17 days), with higher median charges ($250 994 vs. $198 764). Charges for 282 DUA-IE hospitalizations exceeded $78 million.

Limitation:

Reliance on administrative data and billing codes.

Conclusion:

DUA-IE hospitalizations and valve surgeries increased more than 12-fold, and nearly half of all IE valve surgeries were performed in patients with DUA-IE. The swell of patients with DUA-IE is reshaping the scope, type, and financing of health care resources needed to effectively treat IE.

Primary Funding Source:

National Institutes of Health.

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Statistical Code for Clinical Research Papers

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Statistical Code for Clinical Research Papers

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Breast Cancer Risk After Childbirth

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Correction: Preventability of Early Versus Late Hospital Readmissions in a National Cohort of General Medicine Patients

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Breast Cancer Risk After Recent Childbirth A Pooled Analysis of 15 Prospective Studies

Background:

Parity is widely recognized as protective for breast cancer, but breast cancer risk may be increased shortly after childbirth. Whether this risk varies with breastfeeding, family history of breast cancer, or specific tumor subtype has rarely been evaluated.

Objective:

To characterize breast cancer risk in relation to recent childbirth.

Design:

Pooled analysis of individual-level data from 15 prospective cohort studies.

Setting:

The international Premenopausal Breast Cancer Collaborative Group.

Participants:

Women younger than 55 years.

Measurements:

During 9.6 million person-years of follow-up, 18 826 incident cases of breast cancer were diagnosed. Hazard ratios (HRs) and 95% CIs for breast cancer were calculated using Cox proportional hazards regression.

Results:

Compared with nulliparous women, parous women had an HR for breast cancer that peaked about 5 years after birth (HR, 1.80 [95% CI, 1.63 to 1.99]) before decreasing to 0.77 (CI, 0.67 to 0.88) after 34 years. The association crossed over from positive to negative about 24 years after birth. The overall pattern was driven by estrogen receptor (ER)–positive breast cancer; no crossover was seen for ER-negative cancer. Increases in breast cancer risk after childbirth were pronounced when combined with a family history of breast cancer and were greater for women who were older at first birth or who had more births. Breastfeeding did not modify overall risk patterns.

Limitations:

Breast cancer diagnoses during pregnancy were not uniformly distinguishable from early postpartum diagnoses. Data on human epidermal growth factor receptor 2 (HER2) oncogene overexpression were limited.

Conclusion:

Compared with nulliparous women, parous women have an increased risk for breast cancer for more than 20 years after childbirth. Health care providers should consider recent childbirth a risk factor for breast cancer in young women.

Primary Funding Source:

The Avon Foundation, the National Institute of Environmental Health Sciences, Breast Cancer Now and the UK National Health Service, and the Institute of Cancer Research.

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Annals Graphic Medicine - Caring for Dying Patients: Visual Narratives From the Intensive Care Unit

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Benefits and Harms of Using Statins to Prevent Cardiovascular Disease

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Annals On Call - Diverticulitis: Myth Versus Evidence

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[ASAP] Kinetic Resolution of Allylic Alcohol with Chiral BINOL-Based Alkoxides: A Combination of Experimental and Theoretical Studies

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b12796

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[ASAP] Toward Anion-p Interactions Directed Self-Assembly with Predesigned Dual Macrocyclic Receptors and Dianions

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b12018

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[ASAP] Tuning P2-Structured Cathode Material by Na-Site Mg Substitution for Na-Ion Batteries

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b08638

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[ASAP] Pressure-Engineered Structural and Optical Properties of Two-Dimensional (C4H9NH3)2PbI4 Perovskite Exfoliated nm-Thin Flakes

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b07765

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[ASAP] Tip-Enhanced Raman Imaging of Single-Stranded DNA with Single Base Resolution

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b11506

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[ASAP] Dynamic Carbon Isotope Exchange of Pharmaceuticals with Labeled CO2

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b12140

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[ASAP] Deconvoluting Surface-Bound Quinone Proton Coupled Electron Transfer in Unbuffered Solutions: Toward a Universal Voltammetric pH Electrode

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b11518

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[ASAP] Correction to “Bismuth as a New Chloride-Storage Electrode Enabling the Construction of a Practical High Capacity Desalination Battery”

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b13455

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A warped disk around an infant protostar

A warped disk around an infant protostar

A warped disk around an infant protostar, Published online: 31 December 2018; doi:10.1038/s41586-018-0819-2

Observations at millimetre wavelengths reveal a young protostar surrounded by a disk with two differently tilted regions.

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Structural basis of Notch recognition by human γ-secretase

Structural basis of Notch recognition by human γ-secretase

Structural basis of Notch recognition by human γ-secretase, Published online: 31 December 2018; doi:10.1038/s41586-018-0813-8

The cryo-electron microscopy structure of human γ-secretase in complex with its substrate Notch reveals pronounced structural rearrangements compared to the apo enzyme, including formation of a β-sheet involving residues from both enzyme and substrate.

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Tissue-resident memory CD8+ T cells promote melanoma–immune equilibrium in skin

Tissue-resident memory CD8⁺ T cells promote melanoma–immune equilibrium in skin

Tissue-resident memory CD8⁺ T cells promote melanoma–immune equilibrium in skin, Published online: 31 December 2018; doi:10.1038/s41586-018-0812-9

A transplantable mouse model of persistent cutaneous melanoma shows that immune-mediated tumour suppression can result in a state of melanoma–immune equilibrium, and that tissue-resident memory T cells are essential drivers of this equilibrium state.

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Structure of the post-translational protein translocation machinery of the ER membrane

Structure of the post-translational protein translocation machinery of the ER membrane

Structure of the post-translational protein translocation machinery of the ER membrane, Published online: 31 December 2018; doi:10.1038/s41586-018-0856-x

Structure of the post-translational protein translocation machinery of the ER membrane

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A nationwide follow-up study of occupational organic dust exposure and risk of chronic obstructive pulmonary disease (COPD)

Objectives

To study exposure-response relations between cumulative organic dust exposure and incident chronic obstructive pulmonary disease (COPD) among subjects employed in the Danish farming and wood industry.

Methods

We studied exposure-response relations between cumulative organic dust exposure and incident COPD (1997–2013) among individuals born during 1950–1977 in Denmark ever employed in the farming or wood industry (n=1 75 409). Industry-specific employment history (1964–2007), combined with time-dependent farming and wood industry-specific exposure matrices defined cumulative exposure. We used logistic regression analysis with discrete survival function adjusting for age, sex and calendar year. Adjustment for smoking status was explored in a subgroup of 4023 with smoking information available.

Results

Cumulative organic dust exposure was inversely associated with COPD (adjusted rate ratios (RR_adj (95% CIs) of 0.90 (0.82 to 0.99), 0.76 (0.69 to 0.84) and 0.52 (0.47 to 0.58) for intermediate-low, intermediate-high and high exposure quartiles, respectively, compared with the lowest exposure quartile). Lagging exposure 10 years was not consistently suggestive of an association between cumulative exposure and COPD; RR_adj (95% CI): 1.05 (0.94 to 1.16), 0.92 (0.83 to 1.02) and 0.63 (0.56 to 0.70). Additional stratification by duration of employment showed no clear association between organic dust exposure and COPD except for the longer exposed (15–40 years) where an inverse association was indicated. Subgroup analyses showed that smoking had no impact on exposure-response estimates.

Conclusions

Our findings show no increased risk of COPD with increasing occupational exposure to organic dust in the farming or wood industry.

Potential residual confounding by smoking can, however, not be ruled out.

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[ASAP] Realizing High Thermoelectric Performance in p-Type SnSe through Crystal Structure Modification

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b12450

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[ASAP] Well-Designed Phosphine–Urea Ligand for Highly Diastereo- and Enantioselective 1,3-Dipolar Cycloaddition of Methacrylonitrile: A Combined Experimental and Theoretical Study

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b10939

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