HPV type-specific distribution among family members and linen in households of cutaneous wart patients.

BACKGROUND: Common and plantar warts are caused by human papillomaviruses (HPV). Mode of transmission of wart HPVs within families is largely unknown. OBJECTIVE: To demonstrate similarity of HPV type(s) among wart cases, family members and household linen. METHODS: In a cross-sectional study, swabs taken from 123 warts and foreheads of 62 index patients and 157 family members and from 58 kitchen towels and 59 bathroom mats were tested for DNA of 23 cutaneous wart-associated HPV types. Generalized estimating equations (GEE) were used to estimate the chance of detecting the same HPV type as was found in the index patients on the family contacts and on the kitchen towels and bathroom mats. RESULTS: HPV1, HPV2, HPV27 and HPV57 were the most prevalent types in the warts of the index patients. Altogether, 60 (42.3%) of the 142 family members without warts had HPV DNA on their foreheads. When HPV1 and HPV2 were found in the warts, these types were also frequently (>50%) found on the foreheads of index patients and their family members, as well as on the kitchen towels and the bathroom mats. HPV27 and HPV57 were less frequently found (<25%) on foreheads and linen. No associations were found for age, sex and site of HPV DNA presence. CONCLUSION: Dissemination of skin wart-causing HPV types, from wart cases to household contacts and linen, such as kitchen towels and bathroom mats, is more likely for HPV1 and HPV2 than for HPV27 and HPV57. The role of towels and bathroom mats in HPV transmission deserves further investigation.

['When I talk with you about discrimination, I don't feel so small']. / 'Als ik met jou over discriminatie praat, voel ik me niet zo klein'.

Background   In recent years, diversity among therapists in terms of migratory background and openly expressed LGBTQ+ identity has increased. As a result, there are more often dyads in which the patient and therapist belong to the same minority. Aim   To illustrate how having a similar background can influence the therapeutic relationship. These illustrations can help practitioners reflect on how best make use of this similarity. Method   We describe two therapies where therapist and patient shared migratory background and a LGBTQ+ identity. Possible advantages and disadvantages of these similarities are discussed. Finally, we discuss the barriers that therapists can experience to introduce these themes in supervision and intervision. Results   In the case reports, both patients seemed to benefit from having a therapist from the same minority group, partly because he made the similarities in identity open to discussion. They felt that they were understood and were less afraid of negative reactions, which made them feel safe and supported to work on their own conflicts in this dyad. Conclusion   Discussing similarities in identity between therapist and patient can be of added value. With a shared migration background and LGBTQ+ identity, it seems that the same mechanisms often play a role.

[Mental health care in times of corona: experiences of professionals with eHealth]. / Zorgverlening in tijden van corona: ervaringen van behandelaars met zorg-op-afstand.

BACKGROUND: Due to the COVID-19 pandemic, most treatments in mental health care are provided through video calling. AIM: To poll what they think of remote care among 605 care providers of Arkin. METHOD: We surveyed 605 professionals on their experiences. RESULTS: Enthusiasm for remote care was found predominantly among psychologists who worked in curative care. They reported practical benefits for the patient and for the process of care provision. Psychiatrists and clinical psychologists who provided care to patients with complex and/or chronic problems. They feared a deterioration in quality of care and a decline in their job satisfaction. Nurses were also critical, especially those who provided FACT and outreaching care. Their patients often lacked the resources or skills required to access digital care. CONCLUSION: This assessment of remote care was likely adversely affected by the corona measures. Employees were suddenly forced to alter their usual work habits and had not been optimally trained in the new method were more critical. Moreover, they were forced to work from home and lacked informal professional contact with colleagues. Nevertheless, professionals have a nuanced and predominantly positive opinion of video calling: it is not suitable for everyone or appropriate under all circumstances, but remote care is seen as a useful addition to the existing arsenal of treatment modalities.

[The underrepresentation of complex patient groups in scientific research: ethical considerations]. / De ondervertegenwoordiging van complexe patiëntengroepen in wetenschappelijk onderzoek: ethische overwegingen.

BACKGROUND: Subgroups of patients with severe mental illness are underrepresented in scientific research. One of the possible causes is the fact that in these patient groups barriers may exist to the giving of competent informed consent. AIM: Describing the ethical dilemmas that may occur when conducting research with these patient groups. METHOD: We present an overview of the Dutch legislation and regulation concerning participation in scientific research, and discuss the ethical dilemmas that arise in the mentioned patient groups. We present four directions for solutions. RESULTS: In research with these patient groups more attention is needed for the explicit assessment and enhancement of competence. For the subgroup that is persistently incompetent, the possibilities of doing research with existing patient data without informed consent, need further exploration. CONCLUSION: Further legislative development is needed for research with patients with severe mental illness who are persistently incompetent. Herein, it is crucial to involve ethicists and organizations representing patients' and relatives' perspectives.

Misclassification of stunting, underweight and wasting in children 0-5 years of South Asian and Dutch descent: ethnic-specific v. WHO criteria.

OBJECTIVE: Several authors have questioned the suitability of WHO Child Growth Standards (WHO-CGS) for all ethnic groups. The aim of this study was to identify potential misclassification of stunting, underweight and wasting in children of Surinamese Asian Indian, South Asian (Pakistan/India) and Dutch descent. DESIGN: A series of routine cross-sectional measurements, collected 2012-2015. South Asian-specific normative growth references for weight-for-age and weight-for-length/height were constructed using the LMS method based on historic growth data of Surinamese Asian Indians born between 1974 and 1976. WHO-CGS and ethnic-specific references were applied to calculate z-scores and prevalence of stunting, underweight and wasting. SETTING: Youth HealthCare, providing periodical preventive health check-ups. PARTICIPANTS: 11 935 children aged 0-5 years. RESULTS: Considerable deviations from WHO-CGS were found, with higher-than-expected stunting rates, especially in the first 6 months of life. Surinamese Asian Indian children showed stunting rates up to 16·0 % and high underweight and wasting over the whole age range (up to 7·2 and 6·7 %, respectively). Dutch children consistently had mean WHO-CGS z-scores 0·3-0·5 sd above the WHO baseline (>6 months). The application of ethnic-specific references showed low rates for all studied indicators, although South Asian children were taller and larger than their Surinamese Asian Indian counterparts. CONCLUSIONS: WHO-CGS misclassify a considerable proportion of children from all ethnic groups as stunted in the first 6 months of life. Underweight and wasting are considerably overestimated in Surinamese Asian Indian children. Ethnic-specific growth references are recommended for Surinamese Asian Indian and Dutch children. The considerable differences found between South Asian subpopulations requires further research.

The effect of intrathecal bupivacaine/morphine on quality of recovery in robot-assisted radical prostatectomy: a randomised controlled trial.

Robot-assisted radical prostatectomy causes discomfort in the immediate postoperative period. This randomised controlled trial investigated if intrathecal bupivacaine/morphine, in addition to general anaesthesia, could be beneficial for the postoperative quality of recovery. One hundred and fifty-five patients were randomly allocated to an intervention group that received intrathecal 12.5 mg bupivacaine/300 µg morphine (20% dose reduction in patients > 75 years) or a control group receiving a subcutaneous sham injection and an intravenous loading dose of 0.1 mg.kg-1 morphine. Both groups received standardised general anaesthesia and the same postoperative analgesic regimen. The primary outcome was a decrease in the Quality of Recovery-15 (QoR-15) questionnaire score on postoperative day 1. The intervention group (n = 76) had less reduction in QoR-15 on postoperative day 1; median (IQR [range]) 10% (1-8 [-60% to 50%]) vs. 13% (5-24 [-6% to 50%]), p = 0.019, and used less morphine during the admission; 2 mg (1-7 [0-41 mg]) vs. 15 mg (12-20 [8-61 mg]), p < 0.001. Furthermore, they perceived lower pain scores during exertion; numeric rating scale (NRS) 3 (1-6 [0-9]) vs. 5 (3-7 [0-9]), p = 0.001; less bladder spasms (NRS 1 (0-2 [0-10]) vs. 2 (0-5 [0-10]), p = 0.001 and less sedation; NRS 2 (0-3 [0-10]) vs. 3 (2-6 [0-10]), p = 0.005. Moreover, the intervention group used less rescue medication. Pruritus was more severe in the intervention group; NRS 4 (1-7 [0-10]) vs. 0 (0-1 [0-10]), p = 0.000. We conclude that despite a modest increase in the incidence of pruritus, multimodal pain management with intrathecal bupivacaine/morphine remains a viable option for robot-assisted radical prostatectomy.

Performance improvement of wastewater treatment processes by application of machine learning.

Improving wastewater treatment processes is becoming increasingly important, due to more stringent effluent quality requirements, the need to reduce energy consumption and chemical dosing. This can be achieved by applying artificial intelligence. Machine learning is implemented in two domains: (1) predictive control and (2) advanced analytics. This is currently being piloted at the integrated validation plant of PUB, Singapore's National Water Agency. (1) Primarily, predictive control is applied for optimised nutrient removal. This is obtained by application of a self-learning feedforward algorithm, which uses load prediction and machine learning, fine-tuned with feedback on ammonium effluent. Operational results with predictive control show that the load prediction has an accuracy of ≈88%. It is also shown that an up to ≈15% reduction of aeration amount is achieved compared to conventional control. It is proven that this load prediction-based control leads to stable operation and meeting effluent quality requirements as an autopilot system. (2) Additionally, advanced analytics are being developed for operational support. This is obtained by application of quantile regression neural network modelling for anomaly detection. Preliminary results illustrate the ability to autodetect process and instrument anomalies. These can be used as early warnings to deliver data-driven operational support to process operators.

A randomized controlled proof-of-concept trial of digoxin and furosemide in adults with cutaneous warts.

BACKGROUND: Topical ionic contraviral therapy (ICVT) with digoxin and furosemide inhibits the potassium influx on which DNA viruses rely for replication. Therefore, ICVT was hypothesized to be a potential novel treatment for cutaneous warts. OBJECTIVES: To assess the clinical efficacy, safety and tolerability of ICVT in adults with cutaneous warts. The secondary objective was to gain insight into the underlying working mechanism of ICVT. METHODS: Treatment with ICVT was assessed for efficacy, safety and tolerability in a single- centre, randomized, double-blind, placebo-controlled phase IIA trial. Eighty adult patients with at least two cutaneous warts (plantar or common) were randomized to one of four treatments: digoxin + furosemide (0·125%), digoxin (0·125%), furosemide (0·125%) or placebo. The gel was administered once daily for 42 consecutive days. Predefined statistical analysis was performed with a mixed-model ancova. The trial was registered at ClinicalTrials.gov with number NCT02333643. RESULTS: Wart size and human papillomavirus (HPV) load reduction was achieved in all active treatment groups. A statistically significant reduction in wart diameter of all treated warts was shown in the digoxin + furosemide treatment group vs. placebo (-3·0 mm, 95% confidence interval -4·9 to -1·1, P = 0·002). There was a statistically significant reduction in the HPV load of all treated warts in the digoxin + furosemide group vs. placebo (-94%, 95% confidence interval -100 to -19, P = 0·03). With wart size reduction, histologically and immunohistochemically defined viral characteristics disappeared from partial and total responding warts. CONCLUSIONS: This study demonstrates the proof of concept for the efficacy of topical ICVT in adults with cutaneous warts.

Evaluation of bony fusion after anterior cervical discectomy: a systematic literature review.

PURPOSE: Anterior cervical discectomy and fusion (ACDF) has proven effective in treating radicular arm pain. Post-operatively, cervical spine stability is temporarily challenged, but data on bony fusion and speed of fusion are ambiguous; optimum evaluation method and criteria are debated. AIM: To study bony fusion accomplishment and to obtain an overview of methods to evaluate fusion. METHODS: A literature search was performed in PubMed and Embase. Included studies had to report original data concerning 1- or 2-level ACDF with intervertebral device or bone graft, where bony fusion was assessed using CT scans or X-rays. RESULTS: A total of 146 articles comprising 10,208 patients were included. Bony fusion was generally defined as "the presence of trabecular bridging" and/or "the absence of motion". Fusion was accomplished in 90.1% of patients at the final follow-up. No gold standard for assessment could be derived from the results. Addition of plates and/or cages with screws resulted in slightly higher accomplishment of fusion, but differences were not clinically relevant. Eighteen studies correlated clinical outcome with bony fusion, and 3 found a significant correlation between accomplishment and better clinical outcome. CONCLUSIONS: In approximately 90% of patients, bony fusion is accomplished one year after ACDF. As there is no generally accepted definition of bony fusion, different measuring techniques cannot be compared to a gold standard and it is impossible to determine the most accurate method. Variations in study design hamper conclusions on optimising the rate of bony fusion by choice of material and/or additives. Insufficient attention is paid to correlation between bony fusion and clinical outcome. These slides can be retrieved from electronic supplementary material.

Developing and validating the Cutaneous WARTS (CWARTS) diagnostic tool: a novel clinical assessment and classification system for cutaneous warts.

BACKGROUND: The clinical appearance of cutaneous warts is highly variable and not standardized. OBJECTIVES: To develop and validate a reproducible clinical tool for the standardized assessment of cutaneous warts to distinguish these lesions accurately. METHODS: Nine morphological characteristics were defined and validated regarding intra- and interobserver agreement. Based on literature and semistructured interviews, a systematic dichotomous assessment tool, the Cutaneous WARTS (CWARTS) diagnostic tool was developed. The validation consisted of two independent parts performed with photographs from the recent WARTS-2 trial. In part A, the CWARTS diagnostic tool was tested by 28 experienced physicians who assessed photographs of 10 different warts to investigate interobserver concordance. In part B, morphological characteristics were validated by masked and independent scoring of 299 photographs by six different observers. Part B also entailed reassessment of the photographs after at least 1 week. The primary outcome measurement was the intraclass correlation coefficient (ICC). RESULTS: Presence of black dots (capillary thrombosis) had the greatest ICC (0·85) for interobserver agreement in part A, followed by arrangement (0·65), presence of border erythema (0·64) and sharpness of the border (0·60). In part B, results were similar for interobserver agreement with presence of black dots having the highest ICC (0·68), followed by border erythema (0·64), arrangement (0·58) and colour (0·55). For intraobserver agreement, presence of black dots had the highest agreement (0·70), followed by presence of border erythema (0·694) and colour (0·59). CONCLUSIONS: Wart phenotype can be reliably assessed using the CWARTS diagnostic tool.

Morphological characteristics and human papillomavirus genotype predict the treatment response in cutaneous warts.

BACKGROUND: Cutaneous warts have a cure rate after therapy of no more than approximately 50%. Recently, we developed and validated a standard assessment tool for warts (Cutaneous WARTS diagnostic tool, CWARTS) based on phenotypical characteristics. OBJECTIVES: To assess whether patient and morphological wart characteristics predict the human papillomavirus (HPV) type in a specific wart and whether these characteristics as well as the HPV type predict a favourable treatment response. METHODS: Photographs were used to score nine morphological wart characteristics using the newly developed CWARTS tool. Genotyping of 23 wart-associated HPV types was performed using the hyperkeratotic skin lesion-polymerase chain reaction/multiplex genotyping assay. The results were correlated with a favourable response to treatment with monochloroacetic acid, cryotherapy or a combination of cryotherapy and salicylic acid. Odds ratios were calculated using logistic regression in a generalized estimating equations model. RESULTS: Black dots (capillary thrombosis) strongly predicted the presence of any HPV type in a wart. From all characteristics tested, the HPV type most strongly predicted the treatment response when the warts were treated with monochloroacetic acid or a combination of cryotherapy and salicylic acid with a significantly decreased treatment response if the warts contained HPVs of the alpha genus (HPV2, HPV27 or HPV57). When cryotherapy alone was used for common warts, HPV type did not play a role, but cryotherapy was less effective in the presence of callus and when the wart was located deeper in the skin. CONCLUSIONS: Morphological characteristics of the warts and the HPV genotype influence treatment outcome and thus potentially influence future treatment decisions for common and plantar warts.

From 'miserable minority' to the 'fortunate few': the other end of the mild traumatic brain injury spectrum.

OBJECTIVES: This study, as part of the UPFRONT-study, aimed to study the patients that report zero complaints early after injury, a group that we named the 'fortunate few'. We focused on their demographic, clinical and premorbid characteristics, and examined whether they would remain asymptomatic. Moreover, we investigated the influence of anxiety and depression (HADS), and determined outcome (GOS-E) and quality of life (WHOQOL-BREF) 1 year after injury. METHODS: Patients with MTBI (Glasgow Coma Scale score 13-15), without complaints 2 weeks after injury were included. Follow-up took place at 3, 6 and 12 months after injury. RESULTS: Of the entire UPFRONT-cohort (n = 1151), 10% (n = 119) reported zero complaints 2 weeks after injury. More than half of these patients (57%) developed complaints at a later stage (M = 2, p < .001). Patients with secondary complaints had higher anxiety (p = .004) and depression (p = .002) scores, leading to less favourable outcome (p = .014) and a lower quality of life (p = .006) 1 year after injury compared to patients that remained asymptomatic. CONCLUSION: One in 10 patients with mTBI report zero complaints early after injury. Although they seem fully recovered early after injury, a substantial part may develop secondary complaints leading to less favourable outcome and lower quality of life, warranting further research of this interesting group.

HPV testing in first-void urine provides sensitivity for CIN2+ detection comparable with a smear taken by a clinician or a brush-based self-sample: cross-sectional data from a triage population.

OBJECTIVE: To compare the sensitivity of high-risk human papillomavirus (hrHPV) and genotype detection in self-collected urine samples in the morning (U1), and later on (U2), brush-based self-samples (SS), and clinician-taken smears (CTS) for detecting cervical intraepithelial neoplasia grade 2+ (CIN2+) in a colposcopic referral population. DESIGN: Cross-sectional single-centre study. SETTING: A colposcopy clinic in Spain. POPULATION: A cohort of 113 women referred for colposcopy after an abnormal Pap smear. METHODS: Women undergoing colposcopy with biopsy for abnormal Pap smears were sent a device (Colli-Pee™, Novosanis, Wijnegem, Belgium) to collect U1 on the morning of colposcopy. U2, CTS, and SS (Evalyn brush™, Rovers Medical Devices B.V., Oss, the Netherlands) were also analysed. All samples were tested for HPV DNA using the analytically sensitive SPF10-DEIA-LiPA25 assay and the clinically validated GP5+/6+-EIA-LMNX. MAIN OUTCOME MEASURES: Histologically confirmed CIN2+ and hrHPV positivity for 14 high-risk HPV types. RESULTS: Samples from 91 patients were analysed. All CIN3 cases (n = 6) tested positive for hrHPV in CTS, SS, U1, and U2 with both HPV assays. Sensitivity for CIN2+ with the SPF10 system was 100, 100, 95, and 100%, respectively. With the GP5+/6+ assay, sensitivity was 95% in all sample types. The sensitivities and specificities for both tests on each of the sample types did not significantly differ. There was 10-14% discordance on hrHPV genotype. CONCLUSIONS: CIN2+ detection using HPV testing of U1 shows a sensitivity similar to that of CTS or brush-based SS, and is convenient. There was substantial to almost excellent agreement between all samples on genotype with both hrHPV assays. There was no advantage in testing U1 compared with U2 samples. TWEETABLE ABSTRACT: Similar CIN2+ sensitivity for HPV testing in first-void urine, physician-taken smear and brush-based self-sample.

Topical ionic contra-viral therapy comprised of digoxin and furosemide as a potential novel treatment approach for common warts.

BACKGROUND: DNA viruses such as HPV rely on K+ influx for replication. Both digoxin and furosemide inhibit the K+ influx by interacting with cell membrane ion co-transporters (Na+ /K+ -ATPase and Na+ -K+ -2Cl- co-transporter-1, respectively). We therefore hypothesized that these two compounds in a topical formulation may be valuable in the treatment of HPV-induced warts. This new approach is called Ionic Contra-Viral Therapy (ICVT). OBJECTIVE: To evaluate systemic exposure, safety and tolerability of ICVT with a combination of furosemide and digoxin after repeated topical application in subjects with common warts. Furthermore, we aimed to evaluate pharmacodynamics effects of ICVT. METHODS: Twelve healthy subjects with at least four common warts on their hands were included in the study and treated with a fixed dose of 980 mg topical gel containing 0.125% (w/w) digoxin and 0.125% (w/w) furosemide for 7 consecutive days on their lower back to assess safety and systemic exposure. Two warts were treated with 10 mg each and two served as negative controls to obtain preliminary evidence of treatment effect. RESULTS: ICVT was well tolerated topically, and there was no evidence of systemic exposure of digoxin or furosemide. There were no clinical relevant safety findings and no serious adverse events (SAEs). A rapid and statistically significant reduction in diameter, height and volume of the warts was already observed at day 14. CONCLUSION: ICVT was found to be safe for administration to humans and 7 days of active treatment showed a statistical significant wart reduction compared to untreated control lesions, clearly indicating pharmacological activity.

Outpatient follow-up after mild traumatic brain injury: Results of the UPFRONT-study.

OBJECTIVE: To investigate outpatient follow-up after mild traumatic brain injury (mTBI) by various medical specialists, for both hospitalized and non-hospitalized patients, and to study guideline adherence regarding hospital admission. METHODS: Patients (n = 1151) with mTBI recruited from the emergency department received questionnaires 2 weeks (n = 879), 3 months (n = 780) and 6 months (n = 668) after injury comprising outpatient follow-up by various health care providers, and outcome defined by the Glasgow Outcome Scale Extended (GOS-E) after 6 months. RESULTS: Hospitalized patients (60%) were older (46.6 ± 19.9 vs. 40.6 ± 18.5 years), more severely injured (GCS <15, 50% vs. 13%) with more Computed Tomography (CT) abnormalities on admission (21% vs. 2%) compared to non-hospitalized patients (p < 0.01) . Almost half of the patients visited a neurologist at the outpatient clinic within six months (60% of the hospitalized and 25% of the non-hospitalized patients (χ2 = 67.10, p < 0.01)), and approximately ten per cent consulted a psychiatrist/psychologist. Outcome was unfavourable (GOS-E <7) in 34% of hospitalized and 21% of non-hospitalized patients (χ2 = 11.89, p < 0.01). CONCLUSION: Two-thirds of all mTBI patients consult one or more specialists within six months after injury, with 30% having an unfavourable outcome. A quarter of non-hospitalized patients was seen at the outpatient neurology clinic, underling the importance of regular follow-up of mTBI patients irrespective of hospital admittance.