Development and external validation study of a melanoma risk prediction model incorporating clinically assessed naevi and solar lentigines.

BACKGROUND: Melanoma risk prediction models could be useful for matching preventive interventions to patients' risk. OBJECTIVES: To develop and validate a model for incident first-primary cutaneous melanoma using clinically assessed risk factors. METHODS: We used unconditional logistic regression with backward selection from the Australian Melanoma Family Study (461 cases and 329 controls) in which age, sex and city of recruitment were kept in each step, and we externally validated it using the Leeds Melanoma Case-Control Study (960 cases and 513 controls). Candidate predictors included clinically assessed whole-body naevi and solar lentigines, and self-assessed pigmentation phenotype, sun exposure, family history and history of keratinocyte cancer. We evaluated the predictive strength and discrimination of the model risk factors using odds per age- and sex-adjusted SD (OPERA) and the area under curve (AUC), and calibration using the Hosmer-Lemeshow test. RESULTS: The final model included the number of naevi ≥ 2 mm in diameter on the whole body, solar lentigines on the upper back (a six-level scale), hair colour at age 18 years and personal history of keratinocyte cancer. Naevi was the strongest risk factor; the OPERA was 3·51 [95% confidence interval (CI) 2·71-4·54] in the Australian study and 2·56 (95% CI 2·23-2·95) in the Leeds study. The AUC was 0·79 (95% CI 0·76-0·83) in the Australian study and 0·73 (95% CI 0·70-0·75) in the Leeds study. The Hosmer-Lemeshow test P-value was 0·30 in the Australian study and < 0·001 in the Leeds study. CONCLUSIONS: This model had good discrimination and could be used by clinicians to stratify patients by melanoma risk for the targeting of preventive interventions. What's already known about this topic? Melanoma risk prediction models may be useful in prevention by tailoring interventions to personalized risk levels. For reasons of feasibility, time and cost many melanoma prediction models use self-assessed risk factors. However, individuals tend to underestimate their naevus numbers. What does this study add? We present a melanoma risk prediction model, which includes clinically-assessed whole-body naevi and solar lentigines, and self-assessed risk factors including pigmentation phenotype and history of keratinocyte cancer. This model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma, and may assist clinicians to stratify patients by melanoma risk for targeted preventive interventions.

The affect of personality traits and decision-making style on postoperative quality of life and distress in patients undergoing pelvic exenteration.

AIM: Our aim was to identify whether personality traits and decision-making styles affect quality of life (QoL) outcomes and levels of psychological distress following pelvic exenteration (PE). METHOD: Patients undergoing PE between 2008 and 2015 were identified from a prospectively maintained database at a single quaternary referral centre. Patients were invited to complete two validated questionnaires, with the Big Five inventory being used to assess personality traits and the Melbourne Decision Making Questionnaire to determine decision-making style. Data on QoL outcomes and distress from the prospectively established database were utilized. QoL with respect to both physical and mental health components was measured using Short Form 36 version 2 (SF-36v2) and the Functional Assessment of Cancer Therapy - Colorectal (FACT-C). Distress was measured using the Distress Thermometer. Postoperative pain scores were also measured using SF-36v2. RESULTS: Of the 93 patients eligible for participation, 42 returned the study questionnaire. On multivariate analysis, neuroticism was the most significant predictor of poorer QoL and increased levels of distress, consistent across all of the measures utilized and at the different time points used. Other personality traits showed an isolated statistically significant impact upon QoL. There were no significant findings with respect to decision-making style. Apart from neuroticism, the most significant predictor of QoL was the number of major complications for the patient. CONCLUSION: Patients demonstrating neurotic personality traits show poorer QoL outcomes and higher levels of distress following PE. Identification of these patients would allow targeted pre- and postoperative intervention to improve outcomes following PE.

Surgical re-excision vs. observation for histologically dysplastic naevi: a systematic review of associated clinical outcomes.

BACKGROUND: The management of histologically dysplastic naevi (HDN) with re-excision vs. observation remains controversial because of lack of evidence about associated melanoma outcomes. OBJECTIVES: To assess published data on the development of biopsy-site primary cutaneous melanoma among biopsy-proven HDN managed with either re-excision or observation. METHODS: A systematic review of all published data: a total of 5293 records were screened, 18 articles were assessed in full text and 12 studies met inclusion criteria. No controlled trials were identified. RESULTS: Most studies (11 of 12, 92%) were retrospective chart reviews, and one was both a cross-sectional and cohort study. Many studies (nine of 12, 75%) had no head-to-head comparison groups and either only reported HDN that were re-excised or observed. A total of 2673 (1535 observed vs. 1138 re-excised) HDN of various grades were included. Follow-up varied between 2 weeks and 30 years. Nine studies reported that no melanomas developed. Eleven biopsy-site melanomas developed across three of the studies, six among observed lesions (0·39%) and five among re-excised lesions (0·44%). CONCLUSIONS: Based upon the available evidence the rates of biopsy-site primary melanoma were similarly low among observed lesions and re-excised lesions. This suggests that HDNs can be observed with minimal adverse melanoma-associated outcomes. However, all included articles were of low quality and further prospective trials could better guide clinical decision making.

The role of multidetector computed tomography in predicting the site of gastroduodenal perforation.

OBJECTIVE: This study aims to evaluate the value of multidetector computed tomography (MDCT) in detecting the location of gastroduodenal perforation. PATIENTS AND METHODS: This cross-sectional descriptive study was conducted with 47 patients who underwent contrast-enhancing MDCT and were diagnosed with gastroduodenal perforation during surgery between July 2021 and June 2022. Radiologic findings included pneumoperitoneum (distribution and quantity) and analyzed the image findings for localizing the site of gastroduodenal perforation. RESULTS: Pneumoperitoneum was the most common finding [95.74% (45 out of 47 patients)]. Regarding air distribution, the sensitivity (Se) and negative predictive value (NPV) of abdominal free air and supramesocolic free air were the highest (100% for both). The accuracy (Acc) of supramesocolic free air was the highest (93.6%), followed by abdominal free air (89.4%). Subphrenic free air also had a high Acc value (89.4%), with Se, specificity (Sp), and positive predictive value (PPV) being 90%, 85,7%, and 97.3%, respectively. The Sp PPV of falciform ligament/ligamentum teres sign, and periportal free air were also high (100% for both). In contrast, retroperitoneal free air was valuable in determining retroperitoneal duodenal perforation with an Sp, Se of 100%, and Acc of 89.4%. The thickness of abdominal free air was ≥5.5 mm, suggesting gastroduodenal perforation with a Se, Sp, PPV, NPV, and Acc of 82.5%, 100%, 100%, 50%, and 85.1%, respectively. CONCLUSIONS: Subphrenic free air, periportal free air, falciform ligament sign, and the air above transverse mesocolon were correlated to gastric and duodenal bulb perforation. Retroperitoneal air indicates the perforation at the retroperitoneal duodenum. The thickness of abdominal free air ≥5.5 mm indicates gastric and duodenal bulb perforation.

Dental safety net providers' experiences with service delivery during the first year of COVID-19 should inform dental pandemic preparedness.

BACKGROUND: COVID-19 disrupted oral health care delivery and revealed gaps in dental public health emergency preparedness and response (PHEPR). Emerging dental PHEPR frameworks can be strengthened by means of understanding the experiences of the discipline's frontline workers-dental safety net providers-during the initial phase of the COVID-19 pandemic. METHODS: Experienced qualitative researchers interviewed dental safety net directors and clinicians (n = 21) in 6 states to understand their experiences delivering care from March 2020 through February 2021. Interview transcriptions were analyzed using iterative codes to identify major and minor themes. Conventional qualitative validity checks were used continuously to ensure impartiality and rigor. RESULTS: Three major themes were identified: unpredictability caused concerns among staff members and patients, while also deepening fulfilling collaborations; care delivery was guided by means of various resources that balanced safety, flexibility, and respect for autonomy; and pandemic-driven changes to oral health care delivery are timely, long-lasting, and can be somewhat fraught. CONCLUSIONS: The human, material, and policy resources that providers used to control infections, serve vulnerable patients, maintain clinic solvency, and address provider burnout during the first year of the COVID-19 pandemic can improve dental PHEPR. PRACTICAL IMPLICATIONS: Dental PHEPR should address concerns beyond infection control within and between practice models, governmental agencies, and professional organizations. Examples of such concerns include, but are not limited to, guideline synchronization, materials exigencies, task shifting, and provider resilience.

The impact of underutilization of preventive dental care by adult Medicaid participants.

OBJECTIVE: To ascertain the financial impact associated with the underutilization of preventive dental care for adults enrolled in Medicaid. METHODS: We used adult claims data for patients aged 21-64 in the IBM Watson Marketscan Medicaid database. Enrollees were included if they had at least one dental claim in 2019 and were continuously enrolled between 2014 and 2019. We then evaluated the costs of their dental care in 2019, based on the number of years of preventive dental care they received between 2014 and 2018. We also assessed Emergency Department (ED) utilization for dental conditions, oral surgeries, and dental-related opioid prescriptions. RESULTS: The average Medicaid enrollee with five continuous years of preventive care prior to 2019 experienced 43% lower costs than an individual who received no preventive dental care at all. Most of the savings were a result of fewer oral surgeries. A Medicaid enrollee with no preventive dental visits was eight times more likely to have an ED visit for a nontraumatic dental condition (NTDC), seven times more likely to have oral surgery and six times more likely to receive a dental-related opioid prescription compared to those who had a dental prevention visit every year in the 5-year lookback period. CONCLUSIONS: Regular preventive dental care in the lookback period was associated with significant savings in overall dental care costs when compared to dental care costs for those individuals who received no or few preventive visits. Prior preventive dental care was also associated with lower rates of ED-NTDC utilization, oral surgery, and dental-related opioid prescriptions.

A systematic review of dental-related emergency department among Medicaid beneficiaries.

OBJECTIVES: Dental-related emergency department (ED) visits are a growing public health concern. Dental insurance coverage is a strong predictor of dental service access. The objective of this study was to conduct a systematic review to assess the incidence of dental-related ED visits for Medicaid dental enrollees compared to those with other insurances. METHODS: PubMed, EMBASE, and Google Scholar were searched for surveillance and observational data published in English from January 1999 to April 2020 to address the following PECOT question: Do patients with nontraumatic dental conditions (NTDC) (P1), or patients with any dental condition (P2) who have Medicaid (E) compared to other insurance status (private insurance, Medicare, no insurance) (C) have a differential incidence of single dental-related ED visits (O) in the literature search results from 1999 to April 2020 (T)? A critical appraisal was performed using a combination of the AXIS tool (for cross-sectional studies with observational data and MetaQAT (for public health evidence). RESULTS: This systematic review included 32 studies. Overall, risk of bias was low. Due to significant statistical heterogeneity, a synthesis without meta-analysis was conducted. NTDC ED visits ranged from 16.0 percent to 79.8 percent for Medicaid patients and 0.9 percent to 57.2 percent for uninsured patients. The range for any dental visit to the ED was 2.2-63.8 percent for Medicaid patients and 2.9-40.8 percent for uninsured patients. CONCLUSIONS: The results of this study support expanding insurance coverage in Medicaid programs to reduce ED use for NTDC visits in the United States.

Restless legs syndrome in monozygotic twins: clinical correlates.

To better understand genetic characteristics of restless legs syndrome (RLS) and identify nongenetic factors that may influence phenotype, the authors studied 12 identical twins in which at least one member expressed RLS. Ten of the 12 twin pairs were concordant for RLS symptoms. Despite the high concordance rate, the disease severity, age at onset, and symptom descriptions often varied between twins. Birth order, birth weight, and serum ferritin levels did not predict RLS severity or age at onset.

Daytime sleepiness and other sleep disorders in Parkinson's disease.

BACKGROUND: PD is associated with a variety of sleep problems. The dopamine agonists (DA) pramipexole and ropinirole were recently implicated in causing "sleep attacks" and motor vehicle accidents. METHODS: In order to determine the overall rate of subjective sleep problems in PD and to determine if any factors, including specific medications, correlate with sleep pathology, the authors surveyed consecutive patients with PD seen over a 3-month period in a Movement Disorders Clinic. The authors collected demographic and medication data, and the patients completed the Epworth Sleepiness Scale (ESS), questions assessing the presence of restless legs syndrome (RLS), a modified National Sleep Foundation sleep survey, and specific questions regarding falling asleep while driving. RESULTS: A total of 320 patients completed the questionnaire. The authors eliminated 17, six for incomplete data and 11 for having a primary diagnosis other than PD. The mean age of the remaining 303 patients was 67.1 +/- 10.7 years, and the mean duration of PD was 9.1 +/- 5.7 years. The ESS scores averaged 11.1 +/- 5.9, and in 50.2% of patients the score was abnormally high (>10). Stepwise regression analysis found that sleepiness correlated with longer duration of PD (p < 0.001), more advanced PD (p < 0.004), male sex (p < 0.001), and the use of any DA (p < 0.003). The soporific effects of the three most common DA (pramipexole, ropinirole, and pergolide) were similar. Falling asleep while driving was reported by 63/279 (22.6%) of current drivers and correlated with higher ESS scores (p < 0.05). Other sleep disorders, including RLS, were also frequently reported. CONCLUSION: Daytime sleepiness is common in PD and correlates with more advanced and longer duration of PD, and male sex. The DA were also independently associated with daytime sleepiness, but in this group, no single DA was more culpable than the others.

The effects of physical treatment on induced fever in humans.

PURPOSE: Initial treatments for fever include the amelioration of underlying causes and administration of antipyretic medications. However, patients who fail these treatments are often actively cooled, which may be counterproductive because decreasing skin temperature increases the thermoregulatory core target temperature. Cooling may also provoke metabolic and autonomic stress and thermal discomfort. SUBJECTS AND METHODS: We studied 9 subjects, each on 3 days. Fever was induced each day with 100,000 IU/kg of interleukin-2 administered intravenously (elapsed time zero). Randomly assigned treatments were 1) control (a cotton blanket), 2) cooling (forced air at 15 degrees C), or 3) self-adjust (forced-air warming adjusted to comfort). Treatments were maintained for 3 to 8 elapsed hours. RESULTS: Peak core temperatures (mean +/- SD) were 38.4 +/- 0.5 degrees C on the control day, 38.1 +/- 0.5 degrees C on the cooling day, and 38.5 +/- 0.4 degrees C on the self-adjust day. Integrated core temperatures were 6.0 +/- 1.6 degrees C x h on the control day, 5.7 +/- 2.2 degrees C x h on the cooling day, and 6.4 +/- 1.2 degrees C x h on the self-adjust day. Neither peak nor integrated core temperatures differed significantly on the 3 days. Shivering was common on the cooling day but otherwise rare. Oxygen consumption was normal on the control and self-adjust days but increased 35% to 40% during cooling (P = 0.0001). Mean arterial pressure and plasma norepinephrine and epinephrine concentrations were significantly greater during cooling (P <0.05). On a self-reported thermal comfort scale, the subjects were miserable during cooling and significantly more comfortable on the self-adjust than control day (P <0.05). CONCLUSION: We conclude that active cooling should be avoided in unsedated patients with moderate fever, because it does not reduce core temperature but does increase metabolic rate, activate the autonomic nervous system, and provoke thermal discomfort.

Botulinum toxin A for chronic daily headache: a randomized, placebo-controlled, parallel design study.

Sixty patients with headaches of more than 15 days per month were recruited for this double-blind, placebo-controlled, parallel study of botulinum toxin type A (BTX) for chronic tension type and chronic migraine headaches. The primary efficacy point was the number of headache-free days as assessed by diary for 12 weeks after BTX injection. Secondary efficacy points included global impressions, the use of abortive headache medications, and palpation. After recruitment, subjects kept diaries for 4 weeks prior to randomization, at which time they received either 200 U of BTX or matching placebo and were followed. After the week-12 evaluation, patients were offered 200 U of BTX (open label), and were similarly followed for another 12 weeks. The mean days with headache of the 60 subjects (49 female, mean age 47 +/- 11 years) was 23 +/- 7 out of 30. Both groups were demographically similar (58 completed). Over a 12-week period after injections, headache-free days had improved in the BTX group from week 8 to 12 (P < 0.05), and strongly tended to improve over the entire 12-week period, 33 +/- 23 vs. 24 +/- 16 days without headache (P = 0.07), but did not meet the a priori significance criteria. The subject global impressions (P < 0.05), subject change in headache impressions (P < 0.005), and investigator global impressions (P < 0.001) all improved in the BTX group compared with placebo. Adverse events were mild and did not differ between groups. At week 24 (open label), headache-free days were less in the twice BTX injected group compared with the once injected group, 40 +/- 26 vs. 26 +/- 19 (P < 0.05). BTX may help chronic daily headache and appears to have a cumulative effect with subsequent injections. The treatment was very well tolerated.

Comparison of efficacy and immunogenicity of original versus current botulinum toxin in cervical dystonia.

The authors compared 130 patients treated for cervical dystonia with original botulinum toxin (BTX) type A (Botox; Allergan, Inc., Irvine, CA), 42 of whom were exposed only to the original BTX type A used before 1998 (25 ng protein/100 units), and 119 treated only with the current BTX type A (5 ng of protein/100 units). Blocking antibodies were detected in 4 of 42 (9.5%) patients treated only with original BTX type A but in none of the 119 patients treated exclusively with current BTX type A (p < 0.004). The current preparation decreased the risk of antibody formation by a factor of six. The authors conclude that the low risk of antibody formation after current BTX type A treatment is related to lower protein load.

Gabapentin for essential tremor: a multiple-dose, double-blind, placebo-controlled trial.

Essential tremor (ET) is a common movement disorder that often becomes refractory to conventional pharmacologic management. Open-label studies suggest that gabapentin is efficacious for ET, but the results of controlled trials have been mixed. To determine the efficacy and tolerability of gabapentin in ET, we conducted a double-blind, placebo-controlled, cross-over trial evaluating two doses (1800 mg per day and 3600 mg per day; N = 25). Patients on other ET medications were maintained on their concurrent medications for 3 months prior to study initiation and throughout the study. Twenty patients (mean age, 69.9 +/- 6.1 yrs) completed the study. Overall, patient global assessments (p <0.05), observed tremor scores (p <0.005), water pouring scores (p <0.05), and activities of daily living scores (p <0.005) significantly improved. Accelerometry scores, spirographs, and investigator global impression scores did not improve. The results were similar for high and low doses. Statistical regression models did not demonstrate any significant predictors for response. Gabapentin may be effective in some cases of ET.

Hearing impairment in essential tremor.

OBJECTIVE: To assess hearing in patients with essential tremor (ET) vs patients with Parkinson disease (PD) and normal controls. METHODS: The authors assessed demographic and clinical information including use of hearing aids in 250 patients with ET, 127 patients with PD, and 127 normal controls. The authors administered the Nursing Home Hearing Handicap Index (NHHI), a validated measure of hearing disability. Regression techniques were used to adjust for factors such as age and sex. The authors assessed a complete audiologic evaluation in a subset of patients with ET. RESULTS: Patients with ET had worse adjusted NHHI scores when compared to patients with PD (p < 0.001), controls (p < 0.001), and both (p < 0.001). A higher percentage of patients with ET also used hearing aids (p < 0.0001). In the ET group, hearing loss was associated with tremor severity (p = 0.02) and tended to be associated with older age (p = 0.06), male sex (p = 0.06), and the absence of dystonia (p = 0.18). Audiology testing was consistent with high-frequency sensorineural hearing loss. Central processing was not disproportionally greater than peripheral loss. CONCLUSION: Patients with ET have increased hearing disability compared to patients with PD and normal controls, which correlates with tremor severity.

Thalamic deep brain stimulation: effects on the nontarget limbs.

Unilateral thalamic ventral intermediate (VIM) deep brain stimulation (DBS) is now accepted as an effective treatment for essential tremor (ET) and tremor related to Parkinson's disease (PD). The effects of unilateral placement on the side ipsilateral to the surgical site have not been carefully evaluated. To systematically assess the effects ipsilateral to the surgical side and to determine the effects of device inactivation on the baseline tremor, we evaluated tremor in 73 patients approximately 3 months after their unilateral thalamic placement. Assessment included blinded and unblinded ratings using the Unified Parkinson's Disease Rating Scale for PD patients and a modified Tremor Rating Scale in ET patients. All measures of tremor contralateral to the implantation site improved significantly and robustly in both PD and ET. Implantation did not worsen tremor by any measure on the ipsilateral side. There was mild ipsilateral improvement as measured by lower observed tremor scores in ET (6.0 +/- 1.8 to 5.0 +/- 1.9, P < 0.005), but not PD. There was no rebound augmentation of tremor in either hand after the devices were deactivated in either group. We conclude that VIM DBS may mildly improve ipsilateral ET, and that concerns about meaningful ipsilateral tremor augmentation after device deactivation are not warranted.

Alfentanil reduces the febrile response to interleukin-2 in humans.

OBJECTIVE: Manifestation of intraoperative fever is impaired by volatile anesthetics and muscle relaxants. Opioids are common anesthetic adjuvants and remain the dominant treatment for postoperative surgical pain and sedation of critically ill patients. The effect of opioids on normal thermoregulatory control is well established. However, the extent to which these drugs might inhibit fever remains unknown. Accordingly, we tested the hypothesis that relatively low plasma concentrations of the mu-receptor agonist alfentanil reduce fever magnitude. DESIGN: Prospective, randomized, crossover study. SETTING: Outcomes Research Laboratory, at the Department of Anesthesia and Perioperative Care, University of California, San Francisco. PATIENTS: Eight healthy male volunteers, aged 25-31 yrs, each studied on three separate days. INTERVENTION: Each volunteer was given an intravenous injection of 30 IU/g interleukin (IL)-2, followed 2 hrs later by 70 IU/g. One hour after the second dose, the volunteers were randomly assigned to three doses of alfentanil: a) none (control); b) a target plasma concentration of 100 ng/mL; and c) a target concentration of 200 ng/mL. Opioid administration continued for 5 hrs. METHODS AND MAIN RESULTS: Alfentanil significantly reduced the febrile response to pyrogen, decreasing integrated tympanic membrane temperatures from 7.5+/-2.2 degrees C x hr on the control day, to 4.9+/-1.5 degrees C x hr with 100 ng/mL alfentanil, and to 5.1+/-1.7 degrees C x hr with 200 ng/mL alfentanil (p = .011). Peak temperatures were also significantly reduced from 38.5+/-0.4 degrees C on the control day, to 38.0+/-0.4 degrees C on the 100 ng/mL-alfentanil day and 38.0+/-0.6 degrees C on the 200-ng/mL day (p = .019). Plasma cytokine concentrations increased after IL-2 administration, roughly in proportion to the elevation in core temperature. However, cytokine concentrations did not differ significantly among the treatment groups. CONCLUSION: Alfentanil significantly reduced the febrile response to IL-2 administration. However, the reduction was comparable at plasma concentrations near 100 and 200 ng/mL. These data indicate that concentrations of opioids commonly observed in critical care patients significantly inhibit the manifestation of fever.