Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study.

Inflammation is a well-documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C-reactive protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (≥20 µg/L) (OR: 1.29; 95% CI: 1.06-1.56, 1.32; 1.05-1.65 and 1.51; 1.26-1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10-1.74, 1.50; 1.17-1.93 and 1.25; 1.00-1.56, respectively). Albumin was positively associated with Gleason 4 + 3 tumour (1.38; 1.02-1.86) and overall death (HRunit increase in log : 1.60; 95% CI: 1.11-2.30), but inversely associated with high risk PCa and high PSA levels (≥20 µg/L) (0.71; 0.56-0.89 and 0.72; 0.5 9-0.90). WBC was associated with increased odds of T3-T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity.

Low fructosamine and mortality - A long term follow-up of 215,011 non-diabetic subjects in the Swedish AMORIS study.

BACKGROUND AND AIMS: Both high and low fasting glucose has been associated with an increased mortality among individuals without diabetes. This J-shaped association has also been shown for HbA1c in relation to all-cause mortality. High fructosamine is associated with increased mortality. In this study we aim to evaluate if low fructosamine is also associated with increased mortality in non-diabetic subjects. METHODS AND RESULTS: We included 215,011 subjects from the AMORIS cohort undergoing occupational health screening or primary care in Stockholm, Sweden. Cause specific mortality was obtained from the Swedish Cause-of-Death Register by record linkage. Hazard ratios for the lowest decile of fructosamine were estimated by Cox regression for all-cause (n = 41,388 deaths) and cause-specific mortality during 25 years of follow-up. We observed gradually increased mortality with lower fructosamine in a large segment of the population. In the lowest decile of fructosamine the sex, age, social class and calendar adjusted hazard ratio was 1.20 (95% CI; 1.18-1.27) compared to deciles 2-9. This increased mortality was attenuated after adjustment for six other biomarkers (HR = 1.11 (95% CI; 1.07-1.15)). Haptoglobin, an indicator of chronic inflammation, made the greatest difference in the point estimate. In sensitivity analyses we found an association between low fructosamine and smoking and adjustment for smoking further attenuated the association between low fructosamine and mortality. CONCLUSION: Low levels of fructosamine in individuals without diabetes were found to be associated with increased mortality. Smoking and chronic inflammation seem to at least partially explain this association but an independent contribution by low fructosamine cannot be excluded.

Self-perceived oral health and whole salivary immunoglobulin G levels in habitual gutka-chewers and nonchewers.

OBJECTIVE: To assess self-perceived oral health and whole salivary immunoglobulin G (IgG) levels among habitual gutka-chewers and nonchewers (controls). MATERIALS AND METHODS: Fifty gutka-chewers and fifty controls were included. Demographic data and self-perceived oral health status (pain in teeth, pain on chewing, bleeding gums (BG), bad breath, loose teeth and daily oral hygiene protocols) were collected using a questionnaire. Unstimulated whole saliva (UWS) was collected and unstimulated whole salivary flow rate (UWSFR) was determined. Whole salivary IgG levels were determined using standard techniques. Odds ratios were calculated for oral symptoms and group differences in protein levels were compared using one-way analysis of variance (α± <5%). RESULTS: BG was more often reported by gutka-chewers than controls (P < 0.05). There was no significant difference in UWSFR and self-perceived pain in teeth, pain on chewing, bad breath and loose teeth among gutka-chewers and controls. IgG levels were significantly higher among gutka-chewers than controls (P < 0.01). Among gutka-chewers, whole salivary IgG levels were comparable individuals with and without self-perceived oral symptoms. Among controls, IgG levels in UWS were significantly higher among individuals who had BG than those who did not (P < 0.05). CONCLUSIONS: Self-perceived oral health is worse and whole salivary IgG levels are higher in gutka-chewers compared to controls.

Fructosamine is a risk factor for myocardial infarction and all-cause mortality - Longitudinal experience from the AMORIS cohort.

BACKGROUND AND AIMS: Glycation is linked to microvascular complications of diabetes and also to macrovascular events. Fructosamine is a biomarker of glycation but its associations to macrovascular complications are not well documented. The aim of this study was to evaluate fructosamine as a predictor of myocardial infarction and all-cause mortality in a large population based cohort. METHODS AND RESULTS: Information on glucose and fructosamine was obtained from subjects of the AMORIS cohort (n = 338,443) followed for 19 years on average. Incident cases of myocardial infarction and death from any cause were identified from national patient and cause of death register respectively. The incidence of myocardial infarction (n = 21,526 cases) and all-cause mortality (n = 73,458 deaths) increased at a fructosamine of 2.30 mmol/L or above. For myocardial infarction, the sex-age- fasting- and entry period adjusted hazard ratio in subjects above 2.70 mmol/L vs. reference range subjects was 2.88 (95% CI: 2.70-3.07). The corresponding hazard ratio for all-cause mortality was 2.31 (95% CI: 2.21-2.41). These associations remained basically unchanged after adjustment for total cholesterol, triglycerides, albumin, social class, smoking and hypertension. When additional adjustment for glucose was performed the associations were attenuated but remained. In a sub cohort with simultaneous measurements of fructosamine, HbA1c and fasting glucose respectively similar associations were observed (n = 9746). CONCLUSION: There is a strong association between fructosamine and myocardial infarction and death from any cause when major cardiovascular risk factors are accounted for. In addition, this association could only partly be explained by glucose levels.

Comparison of periodontal inflammatory conditions among habitual gutka chewers and betel quid chewers.

OBJECTIVE: The aim was to compare the periodontal inflammatory conditions among habitual gutka chewers and betel quid (BQ) chewers. MATERIAL AND METHODS: Forty-five gutka chewers, 45 BQ chewers and 50 non-chewers (controls) were included. Demographic data regarding age, gender, duration, and frequency of gutka- and BQ-chewing habits and gingival bleeding were collected using a questionnaire. Clinical periodontal parameters [plaque index (PI), bleeding on probing (BOP), probing depth (PD) and clinical attachment loss (AL)] were recorded. Marginal bone loss (MBL) was measured on digital panoramic radiographs. Group differences in periodontal inflammatory parameters were tested using univariate and multivariable analyses (α < 5%). RESULTS: Periodontal inflammatory parameters [PI, BOP, PD (4-6 and >6 mm), clinical AL and MBL] were significantly high in gutka and BQ chewers than controls. There was no significant difference in periodontal inflammatory parameters among gutka and BQ chewers. The odds for gingival bleeding were six times and 13 times higher in gutka and BQ chewers, respectively, compared to controls. Comparison of gutka and BQ chewers did not significantly increase the odds of gingival bleeding. CONCLUSION: Periodontal inflammatory conditions were comparable among habitual gutka and BQ chewers; which suggests that gutka chewers and BQ chewers are equally susceptible to periodontal disease.

Success, clinical performance and patient satisfaction of direct fibre-reinforced composite fixed partial dentures - a two-year clinical study.

To evaluate the success, clinical performance and patient satisfaction of directly placed fibre-reinforced composite (FRC) fixed partial dentures (FPDs) in 2 years. One hundred sixty-seven FRC FPDs (120 subjects) were directly fabricated to restore a single missing tooth by six Advanced Education in General Dentistry (AEGD) residents. The FRC FPDs recipients were randomised into two groups according to the fibre materials (pre-impregnated glass or polyethylene). Clinical performance was evaluated at baseline (2 weeks), 6, 12 and 24 months by two calibrated evaluators for prosthesis adaptation, colour match, marginal discoloration, surface roughness, caries and post-operative sensitivity using modified United State Public Health Service (USPHS) criteria. Prosthesis appearance, colour, chewing ability and overall satisfaction were evaluated by patients using a visual analogue scale (VAS). Kaplan-Meier estimation was used to estimate the prosthesis success. Ninety-four patients with 137 FRC FPDs returned (21·67% attrition rate for study subjects, 17·94% for FRC FPDs). Seventeen FRC FPDs failed, due to one-end (n = 4) or two-ends (n = 4) debonding or pontic fracture (n = 9). The cumulative 2-year success rate was 84·32% and survival rate was 92·7%; there were no statistically significant differences between the groups according to different missing tooth location, retention type or fibre materials (P > 0·05). Patient satisfaction regarding prosthesis appearance, col-our, chewing ability and overall satisfaction was rated high on the VAS (mean >80 mm) for all criteria at all time points. The FRC FPDs (restoring single tooth) fabricated by AEGD residents achieved acceptable success and survival rates in a 2-year follow-up.

The Opioid Analgesic Reduction Study (OARS) Pilot: A Double-Blind Randomized Multicenter Trial.

BACKGROUND: With addiction rates and opioid deaths increasing, health care providers are obligated to help stem the opioid crisis. As limited studies examine the comparative effectiveness of fixed-dose combination nonopioid analgesia to opioid-containing analgesia, a comparative effectiveness study was planned and refined by conducting a pilot study. METHODS: The Opioid Analgesic Reduction Study (OARS) pilot, a stratified, randomized, multisite, double-blind clinical trial, was designed to test technology and procedures to be used in the full OARS trial. Participants engaged in the full protocol, enabling the collection of OARS outcome data. Eligible participants reporting to 1 of 5 sites for partial or full bony impacted mandibular third molar extraction were stratified by biologic sex and randomized to 1 of 2 treatment groups, OPIOID or NONOPIOID. OPIOID participants were provided 20 doses of hydrocodone 5 mg/acetaminophen 300 mg. NONOPIOID participants were provided 20 doses of ibuprofen 400 mg/acetaminophen 500 mg. OARS outcomes data, including pain experience, adverse effects, sleep quality, pain interference, overall satisfaction, and remaining opioid tablets available for diversion, were collected via surveys, electronic medication bottles, eDiary, and activity/sleep monitor. RESULTS: Fifty-three participants were randomized with 50 completing the OARS pilot protocol. Across all outcome pain domains, in all but 1 time period, NONOPIOID was better in managing pain than OPIOID (P < 0.05 level). Other outcomes suggest less pain interference, less adverse events, better sleep quality, better overall satisfaction, and fewer opioid-containing tablets available for diversion. DISCUSSION: Results suggest patients requiring impacted mandibular third molar extraction would benefit from fixed-dose combination nonopioid analgesia. KNOWLEDGE TRANSFER STATEMENT: Study results suggest fixed-dose nonopioid combination ibuprofen 400 mg/acetaminophen 500 mg is superior to opioid-containing analgesic (hydrocodone 5 mg/acetaminophen 500 mg). This knowledge should inform surgeons and patients in the selection of postsurgical analgesia.

Early Childhood Caries Experience Associated with Upper Respiratory Infection in US Children: Findings from a Retrospective Cohort Study.

INTRODUCTION: Both Early Childhood Caries (ECC) and Upper Respiratory Infection (URI) are infectious diseases. The oral cavity is considered a potential reservoir of respiratory pathogens due to the anatomical proximity between the oral cavity and respiratory system, which implies a potential association between ECC and URI. Hence, this study aimed to evaluate the association between ECC experience and URI incidence in preschool children. METHODS: This retrospective cohort study collected data via electronic health records. The exposure was ECC before 3 years of age. The dependent variable was the incidence of URI between 4-6 years of age. To analyze the factors associated with the time-to-event of URI, we used log-rank tests and Cox regression models to compare the survival of URI between the ECC and Caries-Free (CF) groups, adjusting factors including demographic-socioeconomic characteristics and medical conditions. To analyze factors associated with the number of URI episodes, we used negative binomial regression models adjusting for factors mentioned above. RESULTS: A total of 497 US preschool children were included, with 117 ECC and 380 CF children. More children with ECC (58.1%) developed URI than the CF group (47.6%) during the follow-up period (4-6 years of age) (p=0.04). The ECC children were at 1.6 times higher risk to develop URI than the CF children even after accounting for other URI risk factors (Hazard Ratio 1.57 (1.13, 2.10), p=0.007). CONCLUSIONS: Our study suggests a potential association between ECC and URI, with an inference that early life ECC experience could be used as a predictor for developing URI in preschool age. The causal relationship between ECC and URI incidence in young children needs to be investigated through future studies.

Ventilation Assessment by Carbon Dioxide Levels in Dental Treatment Rooms.

It is important for dental care professionals to reliably assess carbon dioxide (CO2) levels and ventilation rates in their offices in the era of frequent infectious disease pandemics. This study was to evaluate CO2 levels in dental operatories and determine the accuracy of using CO2 levels to assess ventilation rate in dental clinics. Mechanical ventilation rate in air change per hour (ACHVENT) was measured with an air velocity sensor and airflow balancing hood. CO2 levels were measured in these rooms to analyze factors that contributed to CO2 accumulation. Ventilation rates were estimated using natural steady-state CO2 levels during dental treatments and experimental CO2 concentration decays by dry ice or mixing baking soda and vinegar. We compared the differences and assessed the correlations between ACHVENT and ventilation rates estimated by the steady-state CO2 model with low (0.3 L/min, ACHSS30) or high (0.46 L/min, ACHSS46) CO2 generation rates, by CO2 decay constants using dry ice (ACHDI) or baking soda (ACHBV), and by time needed to remove 63% of excess CO2 generated by dry ice (ACHDI63%) or baking soda (ACHBV63%). We found that ACHVENT varied from 3.9 to 35.0 in dental operatories. CO2 accumulation occurred in rooms with low ventilation (ACHVENT ≤6) and overcrowding but not in those with higher ventilation. ACHSS30 and ACHSS46 correlated well with ACHVENT (r = 0.83, P = 0.003), but ACHSS30 was more accurate for rooms with low ACHVENT. Ventilation rates could be reliably estimated using CO2 released from dry ice or baking soda. ACHVENT was highly correlated with ACHDI (r = 0.99), ACHBV (r = 0.98), ACHDI63% (r = 0.98), and ACHBV63% (r = 0.98). There were no statistically significant differences between ACHVENT and ACHDI63% or ACHBV63%. We conclude that ventilation rates could be conveniently and accurately assessed by observing the changes in CO2 levels after a simple mixing of household baking soda and vinegar in dental settings.

Removable Denture Wearing as a Risk Predictor for Pneumonia Incidence and Time to Event in Older Adults.

INTRODUCTION: Older adults are more susceptible to a common respiratory infection: pneumonia. Nearly 1 million older adults per year are hospitalized for community-acquired pneumonia in the United States. OBJECTIVE: To examine whether wearing removable dentures are associated with an increased risk of pneumonia incidence in a geriatric population. METHODS: We conducted a retrospective cohort study among patients >65 y of age within a large academic health system (University of Rochester Medical Center). The medical and dental electronic records from 2010 to 2018 were reviewed and used for data collection. The exposure was removable denture wearing. The main outcome variables were the incidence of pneumonia and time to event of pneumonia. A Cox proportional hazards regression was used to examine the association between pneumonia onset and wearing removable dentures, adjusting for demographics, socioeconomic status, and medical and dental conditions. RESULTS: A total of 2,364 patients were included, with 1,189 (50.29%) in the denture-wearing group and 1,175 (49.70%) in the non-denture wearing group. The annual pneumonia incidence rate per 100,000 persons was 1,191 in the denture-wearing group and 128 per 100,000 persons in the non-denture wearing group, with a crude incidence rate ratio of 9.33 (95% CI, 5.41 to 18.81; P < 0.0001). The mean ± SD age of the pneumonia onset was 78.0 ± 10.0 and 78.6 ± 9.0 y among denture-wearing and nonwearing groups (P = 0.84). The time to event of pneumonia was associated with removable denture wearing (yes/no; hazard ratio, 7.68 [95% CI, 3.91 to 15.08]; P < 0.001) after adjusting for covariates. CONCLUSIONS: Wearing removable dentures was found to be a risk predictor for pneumonia incidence among the geriatric population even after accounting for other risk factors. KNOWLEDGE TRANSFER STATEMENT: Wearing removable dentures was found to be a risk predictor of pneumonia incidence among older adults. Although the current study does not imply a causal relationship between denture wearing and pneumonia, clinicians and older patients could reference the study results when choosing dental prostheses to restore missing teeth.

Association between Dental Anomalies and Orofacial Clefts: A Meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis to assess whether individuals with nonsyndromic orofacial clefts (OCs) display a higher frequency of dental anomalies (DAs) when compared with individuals without OCs. METHODS: A literature search of indexed databases (PubMed, Cochrane, Web of Science, Embase, Scopus, and LILACS) was conducted without language restriction up to and including February 1, 2020. Cross-referencing was used to further identify articles. Several cleft teams across the United States and Europe were contacted to obtain unpublished data. The eligibility criteria were observational studies with original data that statistically compared individuals with OC without syndromes and those without OC on any type of DA in primary and/or permanent dentition. Random effects meta-analysis through the Mantel-Haenszel estimator was used to evaluate the association between OC and DA based on odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The literature search generated 933 records, and 75 full-text articles were reviewed. Twenty-six studies encompassing 15,213 individuals met the inclusion criteria. The meta-analysis revealed statistically significant associations between OC and agenesis (OR, 14.2; 95% CI, 9.4 to 21.3), supernumerary teeth (OR, 5.7; 95% CI, 3.3 to 9.7), developmental enamel defects (OR, 5.6; 95% CI, 3.5 to 9.0), microdontia (OR, 14.8; 95% CI, 4.0 to 54.6), peg-shaped anterior teeth (OR, 12.2; 95% CI, 3.6 to 41.2), taurodontism (OR, 1.7; 95% CI, 1.0 to 2.7), tooth malposition and/or transposition (OR, 5.6; 95% CI, 2.8 to 11.5), tooth rotation (OR, 3.2; 95% CI, 1.3 to 8.2), and tooth impaction (OR, 3.6; 95% CI, 1.1 to 12.2). The OR estimates of the reviewed studies exhibited significant heterogeneity (P < 0.0001). No association was observed between OC and fusion and/or gemination. CONCLUSION: Within the limitations of this study, the available evidence suggests that individuals with OCs are more likely to present with a range of DAs than their unaffected peers. KNOWLEDGE TRANSFER STATEMENT: The findings of the current review suggest that individuals with orofacial clefts (OCs) are more likely to present with a range of dental anomalies than their unaffected peers. Understanding the association between OCs and dental anomalies is essential in guiding clinicians during treatment-planning procedures and is important in raising our awareness of the possible need for future dental treatment for patients with OCs.

Dental Care and Oral Health under the Clouds of COVID-19.

KNOWLEDGE TRANSFER STATEMENT: This commentary provides a timely evidence-based overview on the impact of COVID-19 on dental care and oral health and identifies gaps in protection of patients and staff in dental settings. Oral symptoms are prominent before fever and cough occur. Dental professionals may play an important role in early identification and diagnosis of patients with COVID-19.

Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: an European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874).

The management of uterine sarcomas continues to present many difficulties. Primary surgery is the optimal treatment but the role of post-operative radiation remains uncertain. In the mid-1980s, the European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study proposed a trial to evaluate adjuvant radiotherapy, as previous non-randomised studies had suggested a survival advantage and improved local control when post-operative radiation was administered. The study opened in 1987 taking 13 years to accrue 224 patients. All uterine sarcoma subtypes were permitted. Patients were required to have undergone as a minimum, TAH and BSO and wahsings (166 patients) but nodal sampling was optional. There were 103 leiomyosarcomas (LMS), 91 carcinosarcomas (CS) and 28 endometrial stromal sarcomas (ESS). Patients were randomised to either observation or pelvic radiation, 51 Gy in 28 fractions over 5 weeks. Hundred and twelve were recruited to each arm. The initial analysis has shown a reduction in local relapse (14 versus 24, p=0.004) but no effect on either OS or PFS. No unexpected toxicity was seen in the radiation arm. No difference in either overall or disease-free survival was demonstrated but there is an increased local control for the CS patients receiving radiation but without any benefit for LMS. Prognostic factor analysis shows that stage, age and histological subtype were important predictors of behaviour which may explain differences between CS and LMS. CS appears to show more kinship to poorly differentiated endometrial carcinomas in behaviour. LMS did not show the same benefit from radiation. These results will help shape future management and clinical trials in uterine sarcomas.

Role of local alendronate delivery on the osseointegration of implants: a systematic review and meta-analysis.

There is controversy regarding whether locally delivered alendronate enhances osseointegration. The aim of this systematic review was to assess the role of local alendronate delivery (topical, or as a coating on implant surfaces) in the osseointegration of implants. The focused question was, "Does the local delivery of alendronate affect osseointegration around implants?". To address this question, indexed databases were searched, without time or language restriction, up to and including January 2017. Various combinations of the following key words were used: "alendronate", "bisphosphonates", "osseointegration", and "topical administration". letters to the editor, historic reviews, commentaries, case series, and case reports were excluded. In total, 18 experimental studies were included: alendronate-coated implants were used in 13 of these studies and local delivery in five studies. The results of 11 of the studies showed that alendronate coating increased new bone formation, the bone volume fraction, or bone-to-implant contact (BIC) and biomechanical properties. Results from two studies in which alendronate was administered topically indicated impaired BIC and/or biomechanical fixation around implants. On experimental grounds, local alendronate delivery seems to promote osseointegration. From a clinical perspective, the results in animal models support phase 1 studies in healthy humans (without co-morbidities other than edentulism).

Association between periodontal disease and polycystic ovary syndrome: a systematic review.

The purpose of the present study was to review systematically the association between periodontal diseases (PDs) and polycystic ovary syndrome (PCOS). To address the focused question, 'Is there a relationship between PD and PCOS?' indexed databases were searched up to October 2016 without time or language restrictions using different combinations of the following key words: PCOS, ovarian cysts, PD, periodontitis, gingival diseases and gingivitis. Letters to the Editor, commentaries, historic reviews, case-report, unpublished articles and animal/experimental studies were excluded. Seven case-control studies were included. The number of study participants ranged between 52 and 196 females aged between 15 and 45 years. In three and three studies, proinflammatory cytokines were assessed in gingival crevicular fluid and saliva samples, respectively. In one study, salivary microbes were investigated. All studies reported that a positive association exists between PD and PCOS. In conclusion, there is a positive association between PD and PCOS; however, further well-designed longitudinal controlled clinical trials are needed in this regard. It is recommended that physicians should refer patients with PCOS to oral health-care providers for comprehensive oral evaluation and treatment.

Cancer in twins: genetic and nongenetic familial risk factors.

BACKGROUND: Familial clustering has been observed for cancers that occur at specific sites. Most findings, which leave little doubt about the involvement of a heritable (i.e., genetic) component in the development of some cancers, are based on data from "cancer-prone" families or interviews with subjects who have cancer. The study of twins should be of value in cancer epidemiology because twins either are genetically identical or share half of their segregating genes. PURPOSE: We linked the Swedish Twin Registry to the Swedish Cancer Registry, thereby identifying cases of cancer diagnosed from 1959 through 1992 in twins born in the period from 1886 through 1958, to assess the importance of both genetic and nongenetic (i.e., environmental) familial factors in determining cancer risk. METHODS: Same-sex twin pairs with both individuals alive and living in Sweden in 1959-1961 or 1970-1972 were identified in the old cohort (born from 1886 through 1925) or the young cohort (born from 1926 through 1958), respectively, of the Swedish Twin Registry; pairs for whom zygosity (i.e., the number of eggs that gave rise to the twins) could be determined were considered further. The association of cancer with combined genetic and nongenetic familial factors was tested by comparing all twin pairs (regardless of zygosity) in which at least one member of the pair had been diagnosed with cancer at one of several specific sites with pairs in which neither twin had that cancer. Heritable effects alone were tested by comparing monozygotic (one egg) and dizygotic (two eggs) twin pairs. Statistical methods used in quantitative genetics and standard methods for epidemiologic research were used in parallel to analyze the data. RESULTS AND CONCLUSIONS: In the 10503 twin pairs from the old cohort, 361.7 cases of malignant cancer were identified; 918 malignant cancers were identified in the 12883 twin pairs from the young cohort. When cancer sites with a total number of at least 200 cases and at least one twin pair concordant (i.e., both twins affected) for the site were evaluated, namely, cancers of the stomach, colon and rectum, lung, female breast, and prostate, as well as total cancer, profound genetic and/or nongenetic familial effects were identified in twins from the old cohort. Similar findings were obtained for twins in the young cohort for cancers of the prostate and female breast, as well as for total cancer. Genetic and nongenetic familial effects were also identified in twins from both cohorts for in situ cancer of the cervix. The increase in risk of colon and rectum, breast, cervical, and especially prostate cancer, but not stomach or lung cancer, tended to be greater if a monozygotic rather than a dizygotic twin were affected. IMPLICATIONS: The identification of familial effects for total cancer in this study is consistent with the idea that individuals may possess a genetic susceptibility to cancer in general.

Prevalence of dental problems in recreational SCUBA divers: a pilot survey.

Objective To determine the prevalence of dental symptoms in recreational scuba divers and describe the distribution of these symptoms on the basis of diver demographics, diving qualifications and dive conditions during the episode of dental pain.Design A survey was designed and distributed through online social media platforms dedicated to scuba diving. A convenience sample of 100 recreational divers was obtained by this method.Main outcome measures The outcome measures of interest were: diver demographics, diving characteristics (level of certification, number of dives completed), occurrence of dental problems during a dive, and details of the episode.Results Forty-one percent of the respondents experienced dental symptoms during a dive. Barodontalgia was the most frequently experienced dental symptom during a dive.Conclusion Within the limits of the small sample size and online method of recruitment, the findings of this study suggest that a high proportion of recreational divers may experience dental symptoms during a dive. It would be meaningful to ensure that dental decay and damaged restorations are addressed before a dive and that the mouthpiece design be evaluated in case of complaints of temporomandibular discomfort during a dive.

Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel.

PURPOSE: Topotecan, a topoisomerase I inhibitor, was evaluated in a multicenter, phase II study of women with epithelial ovarian carcinoma who relapsed after one or two prior regimens that included platinum and paclitaxel. PATIENTS AND METHODS: Topotecan 1.5 mg/m2 daily was administered as a 30-minute infusion for 5 consecutive days on a 21-day cycle. Eligibility criteria included bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of 2 or less, and adequate bone marrow, liver, and renal function. Efficacy was assessed by independent radiologic review. RESULTS: One hundred thirty-nine patients were treated; 81% were platinum resistant. Sixty-two patients had received one prior regimen and 77 patients had received two prior regimens. Nine patients were not assessable for response; however, all patients were included in the response analysis. The overall response rate was 13.7%; 12.4% in platinum-resistant and 19.2% in platinum-sensitive patients. Stable disease lasted at least 8 weeks in 27.3% of the patients. The median duration of response and time to progression were 18.1 and 12.1 weeks, respectively. The median survival was 47.0 weeks. Grade 4 neutropenia occurred in 82% of the patients (34% of the courses) and thrombocytopenia in 30% of the patients (9% of the courses). Infectious complications occurred in 6% of the courses. Nonhematologic toxicities were mild. There were no drug-related toxic deaths. CONCLUSION: As a single agent, topotecan has modest activity in women with advanced epithelial ovarian carcinoma who have progressed or not responded after one or two prior regimens with platinum and paclitaxel. Further investigation of combination regimens is indicated in the primary therapy for ovarian cancer based on the mechanism of action and tolerability.

Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer.

PURPOSE: Topotecan and paclitaxel were evaluated in a randomized, multicenter study of patients with advanced epithelial ovarian carcinoma who had progressed during or after one platinum-based regimen. PATIENTS AND METHODS: Patients received either topotecan (1.5 mg/m2) as a 30-minute infusion daily for 5 days every 21 days (n = 112) or paclitaxel (175 mg/m2) infused over 3 hours every 21 days (n = 114). Patients had bidimensionally measurable disease and were assessed for efficacy and toxicity. RESULTS: Response rate was 23 of 112 (20.5%) in topotecan-treated patients and 15 of 114 (13.2%) in paclitaxel-treated patients (P = .138). Disease stabilization for at least 8 weeks was noted in 30% of patients with topotecan and 33% of patients with paclitaxel. Median durations of response to topotecan and paclitaxel were 32 and 20 weeks, respectively (P = .222) and median times to progression were 23 and 14 weeks, respectively (P = .002). Median survival was 61 weeks for topotecan and 43 weeks for paclitaxel (P = .515). Response rates for topotecan and paclitaxel were 13.3% versus 6.7% (P = .303) in resistant patients (not responded to prior platinum-based therapy or progressed within 6 months of an initial response) and 28.8% versus 20.0% (P = .213) in sensitive patients (progressed > 6 months after response). Neutropenia was significantly more frequent on the topotecan arm 79% versus paclitaxel arm 23% (P < .01). It was short-lasting and noncumulative in both arms. Nonhematologic toxicities were generally mild (grades 1 to 2) for both agents. CONCLUSION: Topotecan has efficacy at least equivalent to paclitaxel manifested by the higher response rate and significantly longer time to progression.

Clinical evidence for topotecan-paclitaxel non--cross-resistance in ovarian cancer.

PURPOSE: A large, randomized study comparing the efficacy and safety of topotecan versus paclitaxel in patients with relapsed epithelial ovarian cancer showed that these two compounds have similar activity. In this study, a number of patients crossed over to the alternative drug as third-line therapy, ie, from paclitaxel to topotecan and vice versa. We therefore were able to assess the degree of non-cross-resistance between these two compounds. PATIENTS AND METHODS: Patients who had progressed after one platinum-based regimen were randomized to either topotecan (1.5 mg/m(2)/d) x 5 every 21 days (n = 112) or paclitaxel (175 mg/m(2) over 3 hours) every 21 days (n = 114). A total of 110 patients received cross-over therapy with the alternative drug (61 topotecan, 49 paclitaxel) as third-line therapy. RESULTS: Response rates to third-line cross-over therapy were 13.1% (8 of 61 topotecan) and 10.2% (5 of 49 paclitaxel; P =.638). Seven patients who responded to third-line topotecan and four patients who responded to paclitaxel had failed to respond to their second-line treatment. Median time to progression (from the start of third-line therapy) was 9 weeks in both groups, and median survival was 40 and 48 weeks for patients who were receiving topotecan or paclitaxel, respectively. The principal toxicity was myelosuppression; grade 4 neutropenia was more frequent with topotecan (81.4% of patients) than with paclitaxel (22.9% of patients). CONCLUSION: Topotecan and paclitaxel have similar activity as second-line therapies with regard to response rates and progression-free and overall survival. We demonstrated that the two drugs have a degree of non-cross-resistance. Thus, there is a good rationale for incorporating these drugs into future first-line regimens.