Restoration of a nonideally placed anterior implant: A clinical report.

This article describes a restorative solution for implants placed at an insufficient depth and in a patient with limited interarch space, making the esthetics, emergence profile, and retention of a cemented restoration problematic. These challenges were overcome by adhesively bonding a pressed lithium disilicate veneer to a custom cast metal abutment veneered with a thin layer of feldspathic porcelain. The ceramic veneer with the attached core engaged a facially located screw-access channel, which increased retention and resistance form and facilitated seating of the veneer. Adhesive bonding via the application of a thin layer of feldspathic porcelain on the custom dental implant abutment was also used to overcome the lack of resistance form with a veneer preparation.

Patients' Attitudes Towards Medical Student Presence in Psychiatric Consultations.

OBJECTIVES: Studies on patient-student relationships have to date largely focused on student attitudes. This study explores attitudes of patients with psychiatric illness in Ireland, towards medical students. Patients' experience of consent for student involvement is an area of concern in previous studies and is also quantified here. METHODS: This was a mixed-methods cross-sectional survey of Irish adult psychiatric patients. Quantitative analysis was carried out using SPSS 22 (Statistical Product and Service Solutions, Version 22, IBM). Differences on Likert score between groups (male/female, hospital site, past experience with students/ no experience) were analysed using ordinal logistic regression with a p-value below 0.05 being significant. Qualitative data were analysed by thematic analysis using OpenCode 4.03. RESULTS: A total of 340 patients completed the survey. The mean age (sd) was 44.8 (16.3). 52.8% were female, 75.2% were outpatients. 24.3% had never met a medical student. Most patients were comfortable seeing students, but preferred students being passive observers. Patients with previous student experience had higher comfort levels and more positive attitudes. Although most patients (63.7%) strongly agreed they had been asked for consent, only 49.3% felt they had been given sufficient information. Qualitative data revealed preference for adequate information and notice of involvement. Patients felt pressured by student presence in certain circumstances. CONCLUSIONS: Psychiatric patients are comfortable with students but many feel inadequately informed. Patients recognise the benefits of interacting with students. More information is needed regarding circumstances in which patients give consent to involvement with students.

How mechanistic in silico modelling can improve our understanding of TB disease and treatment.

TB is one of the top 10 causes of death worldwide and the leading cause of death from a single infectious agent. Decreasing the length of time for TB treatment is an important step towards the goal of reducing mortality. Mechanistic in silico modelling can provide us with the tools to explore gaps in our knowledge, with the opportunity to model the complicated within-host dynamics of the infection, and simulate new treatment strategies. Significant insight has been gained using this form of modelling when applied to other diseases - much can be learned in infection research from these advances.

NAT2 variants and toxicity related to anti-tuberculosis agents: a systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) patients receiving anti-tuberculosis treatment may experience serious adverse drug reactions (ADRs) such as hepatotoxicity. Variants of the N-acetyltransferase 2 (NAT2) gene may increase the risk of experiencing such toxicity events. OBJECTIVE: To provide a comprehensive evaluation of the evidence base for associations between NAT2 variants and anti-tuberculosis drug-related toxicity. METHOD: This was a systematic review and meta-analysis. We searched for studies in Medline, PubMed, EMBASE, BIOSIS and Web of Science. We included data from 41 articles (39 distinct cohorts of patients). We pooled effect estimates for each genotype on each outcome using meta-analyses stratified by country. RESULTS: We assessed the quality of the included studies, which was variable, with many areas of concern. Slow/intermediate NAT2 acetylators were statistically significantly more likely to experience hepatotoxicity than rapid acetylators (OR 1.59, 95%CI 1.26-2.01). Heterogeneity was not detected in the overall pooled analysis (I² = 0%). NAT2 acetylator status was significantly associated with the likelihood of experiencing anti-tuberculosis drug-related hepatotoxicity. CONCLUSION: We encountered several challenges in performing robust syntheses of data from pharmacogenetic studies, and we outline recommendations for the future reporting of pharmacogenetic studies to enable high-quality systematic reviews and meta-analyses to be performed.

Equitable tuberculosis care in the North West of England: analysis of tuberculosis cohort review data.

BACKGROUND: In the United Kingdom, tuberculosis (TB) predominantly affects the most deprived populations, yet the extent to which deprivation affects TB care outcomes is unknown. METHODS: Since 2011, the North West TB Cohort Audit collaboration has undertaken quarterly reviews of outcomes against consensus-defined care standard indicators for all individuals notified with TB. We investigated associations between adverse TB care outcomes and Index of Multiple Deprivation (IMD) 2010 scores measured at lower super output area of residence using logistic regression models. RESULTS: Of 1831 individuals notified with TB between 2011 and 2014, 62% (1131/1831) came from the most deprived national quintile areas. In single variable analysis, greater deprivation was significantly associated with increased likelihood of the completion of a standardised risk assessment (OR 2.99, 95%CI 5.27-19.65) and offer of a human immunodeficiency virus test (OR 1.72, 95%CI 1.10-2.62). In multivariable analysis, there were no significant associations. CONCLUSIONS: TB patients in the most deprived areas had similar care indicators across a range of standards to those of individuals living in the more affluent areas, suggesting that the delivery of TB care in the North West of England is equitable. The extent to which the cohort review process contributes to, and sustains, this standard of care deserves further study.

Health professionals' experiences of tuberculosis cohort audit in the North West of England: a qualitative study.

OBJECTIVES: Tuberculosis cohort audit (TBCA) was introduced across the North West (NW) of England in 2012 as an ongoing, multidisciplinary, systematic case review process, designed to improve clinical and public health practice. TBCA has not previously been introduced across such a large and socioeconomically diverse area in England, nor has it undergone formal, qualitative evaluation. This study explored health professionals' experiences of the process after 1515 cases had been reviewed. DESIGN: Qualitative study using semistructured interviews. Respondents were purposively sampled from 3 groups involved in the NW TBCA: (1) TB nurse specialists, (2) consultant physicians and (3) public health practitioners. Data from the 26 respondents were triangulated with further interviews with key informants from the TBCA Steering Group and through observation of TBCA meetings. ANALYSIS: Interview transcripts were analysed thematically using the framework approach. RESULTS: Participants described the evolution of a valuable 'community of practice' where interprofessional exchange of experience and ideas has led to enhanced mutual respect between different roles and a shared sense of purpose. This multidisciplinary, regional approach to TB cohort audit has promoted local and regional team working, exchange of good practices and local initiatives to improve care. There is strong ownership of the process from public health professionals, nurses and clinicians; all groups want it to continue. TBCA is regarded as a tool for quality improvement that improves patient safety. CONCLUSIONS: TBCA provides peer support and learning for management of a relatively rare, but important infectious disease through discussion in a no-blame atmosphere. It is seen as an effective quality improvement strategy which enhances TB care, control and patient safety. Continuing success will require increased engagement of consultant physicians and public health practitioners, a secure and ongoing funding stream and establishment of clear reporting mechanisms within the public health system.

Vitamin D deficiency in Malawian adults with pulmonary tuberculosis: risk factors and treatment outcomes.

SETTING: Vitamin D deficiency is common in African adults with tuberculosis (TB), and may be exacerbated by the metabolic effects of anti-tuberculosis drugs and antiretroviral therapy (ART). It is unclear whether vitamin D deficiency influences response to anti-tuberculosis treatment. OBJECTIVES: To describe risk factors for baseline vitamin D deficiency in Malawian adults with pulmonary TB, assess the relationship between serum 25-hydroxy vitamin D (25[OH]D) concentration and treatment response, and evaluate whether the administration of anti-tuberculosis drugs and ART is deleterious to vitamin D status during treatment. DESIGN: A prospective longitudinal cohort study. RESULTS: The median baseline 25(OH)D concentration of the 169 patients (58% human immunodeficiency virus [HIV] infected) recruited was 57 nmol/l; 47 (28%) had vitamin D deficiency (<50 nmol/l). Baseline 25(OH)D concentrations were lower during the cold season (P < 0.001), with food insecurity (P = 0.034) or in patients who consumed alcohol (P = 0.019). No relationship between vitamin D status and anti-tuberculosis treatment response was found. 25(OH)D concentrations increased during anti-tuberculosis treatment, irrespective of HIV status or use of ART. CONCLUSIONS: Vitamin D deficiency is common among TB patients in Malawi, but this does not influence treatment response. Adverse metabolic effects of drug treatment may be compensated by the positive impact of clinical recovery preventing exacerbation of vitamin D deficiency during anti-tuberculosis treatment.

Cytomegalovirus retinitis in the absence of HIV or immunosuppression.

PURPOSE: Cytomegalovirus (CMV) retinitis classically occurs in advanced human immunodeficiencyvirus (HIV) infection but is rare in other forms of immunosuppression. The authors report a case of CMV retinitis in an HIV-negative man with idiopathic CD4 lymphocytopenia (ICL). This is the first such case to be confirmed by polymerase chain reaction (PCR) of aqueous humor. METHODS: Case report. RESULTS: A 69-year-old retired Chinese seaman presented with gradual visual deterioration. He was a diet controlled diabetic on regular steroids for presumed asthma. Examination showed no diabetic eye disease but confirmed acute retinal necrosis (ARN). Anterior chamber tapping of the aqueous humor was PCR positive for CMV. HIV antibody and RNA tests were negative but his full blood count revealed lymphocytopenia, with a low CD4+ subset. He responded to a 3-week course of intravenous ganciclovir therapy followed by suppressiveoral valganciclovir. CONCLUSIONS: CMV is associated with sight-threatening retinitis in HIV infection at CD4+ counts below 50 cells/microL and in transplant recipients or heavily immunosuppressed patients. Systemic steroids are a risk factor for clinical disease in these groups. It is extremely rare to report CMV eye disease in previously healthy individuals. This case illustrates that the condition does occur in association with ICL. Corticosteroids may be implicated in disease reactivation. Molecular METHODS are necessary to confirm the diagnosis.

Maximized virulence in a sterilizing pathogen: the anther-smut fungus and its co-evolved hosts.

Host sterilization is a common feature of sexually transmitted diseases (STDs). Because host reproductive failure may free up resources for pathogen reproduction and transmission, theory predicts that selection on sterilizing pathogens will favour maximum virulence (i.e. complete sterilization). We examined patterns of infection in sexually transmitted anther-smut fungi (Microbotryum) on four of their host species in the Caryophyllaceae. Using controlled fungal matings and experimental inoculations, we compared disease expression in inoculations ranging from host-specific pathogens to hybrids and cross-species treatments. Our data support the existence of host-specific sibling species within the genus Microbotryum based on a low infection rate from cross-inoculations and reduced fitness for hybrid pathogens. These patterns of host specificity and reproductive isolation, however, were not absolute. We did observe some successful cross-species and hybrid infections, but the expression of disease was frequently incomplete, including only partial host sterilization and the failed dehiscence of pathogen spores. The prevalence of these maladapted disease phenotypes may greatly inhibit the emergence of novel host pathogen combinations. Infections by hybrid pathogen genotypes were intermediate, in terms of both infection rate and the normality of disease symptoms, between host-specific and cross-inoculated pathogens. In addition, the frequency with which hybrid and cross-inoculated anther-smut pathogens were able to infect but not sterilize new hosts supports the prediction that sterilizing STDs are under selection to maximize virulence in natural populations.

Measurement of CTL-induced cytotoxicity: the caspase 3 assay.

Cytotoxic T lymphocytes (CTL) are critical effector cells of the immune system. Measurement of target cell damage has historically been an important measure of CTL function. CTL kill their target cells predominantly by inducing programmed cell death, or apoptosis. The gold standard for CTL-mediated cytotoxicity has been the (51)Cr release assay. However, measurement of target cell lysis by (51)Cr release does not provide mechanistic information on the fate of target cells, especially at the single cell level. Given the recent advances in our understanding of programmed cell death, newer assays are required which evaluate the status of the apoptotic pathways in target cells. We have developed a flow cytometry-based assay for CTL-mediated cytotoxicity based on specific binding of antibody to activated caspase 3 in target cells. Our assay is convenient and more sensitive than the (51)Cr release assay. The use of this assay should allow mechanistic studies of the intracellular events resulting from CTL attack.

Diminished response to pleasant stimuli by depressed women.

This study examined the self-report and facial expressions of emotional response to pictorial stimuli and the incidental learning of pleasant and unpleasant words by depressed (n = 20) and nondepressed (n = 20) women. Depression was associated with reports of diminished emotional response and reduced frequency and intensity of facial expressions only to pleasant stimuli. The 2 groups did not differ in response to hedonically unpleasant stimuli, even those specifically relevant to the emotion of sadness. In a similar vein, depressed and nondepressed participants showed differences in incidental recall for only pleasant self-referential terms. There was no difference in recall of unpleasant words. These findings suggest the importance of hedonic deficits on psychological processes in clinical depression.

High-dose intra-arterial cisplatin boost with hyperfractionated radiation therapy for advanced squamous cell carcinoma of the head and neck.

PURPOSE: To evaluate the tolerance and efficacy of intra-arterial (IA) cisplatin boost with hyperfractionated radiation therapy (HFX-RT) in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Forty-two patients with locally advanced primary SCCHN were treated on consecutive phase I/II studies of HFX-RT (receiving a total of 76.8 to 81.6 Gy, given at 1.2 Gy bid) and IA cisplatin (150 mg/m(2) received at the start of and during RT boost treatment). RESULTS: Acute grade 3 to 4 toxicities were as follows: grade 4 and grade 3 mucosal toxicity occurred in three (7%) and 31 patients (69%), respectively, and grade 3 hematologic, infectious, and skin events occurred in one patient each. Eight of 24 patients (33%) were unable to receive a second planned dose of IA cisplatin because of general anxiety (n = 5), nausea and/or emesis (n = 2), or asymptomatic occlusion of an external carotid artery (n = 1). Thirty-seven patients (88%) experienced complete response (CR) at primary site. Twenty-nine (85%) of 34 patients presenting with nodal disease experienced CR. The actuarial 2-year rates of locoregional control and disease-specific and overall survival are 73%, 63%, and 57%, respectively, with a median active follow-up of 30 months. CONCLUSION: In this highly unfavorable subset of patients, these results seem superior to previously reported chemoradiation regimens in more favorable patients. Use of a second dose of IA cisplatin boost was associated with increased toxicity without obvious therapeutic gain. This novel strategy allows for an incremental increase in the treatment intensity of the HFX-RT regimen recently established as superior to once-a-day RT.

Lymphoscintigraphy of melanoma: lymphatic channel activity guides localization of sentinel lymph nodes, and gamma camera imaging/counting confirms presence of radiotracer in excised nodes.

UNLABELLED: Lymphoscintigraphy has become a standard preoperative procedure to map the cutaneous lymphatic channel for progression of nodal metastasis of melanoma of the skin. Lymphoscintigraphy was employed to visualize lymphatic channels as a guide to identify sentinel lymph nodes (SLNs). Excised tissue was imaged with a gamma camera to verify the findings of presurgical lymphoscintigraphy. Percent counts of SLN(s) among the total counts of the excised melanoma tumor or scar tissue and SLN(s) were calculated. METHODS: Eleven patients with cutaneous melanoma received four to ten intradermal injections of Tc-99m sulfur colloid at elual distances around the melanoma site. Images were made immediately after injection: 1 minute per image for 15 min; and then 5 minutes or 1,000,000 counts per image for 30 min. After surgery, the excised melanoma tumor or scar and SLN(s) were imaged/counted with a gamma camera. Percent counts of SLNs among the total counts of the excised melanoma tumor or scar tissue and SLNs were calculated. To validate the specimen count accuracy, an experimental phantom study was done. RESULTS: Linear lymphatic channels were identified between the injected sites and the SLNs in each patient. Gamma camera images demonstrated radioactivity in the SLNs of all patients, verifying the lymphoscintigraphy findings. Uptake in the SLNs of ten of the eleven patients ranged from 0.4 to 7.2% (mean 2.2%) of the total counts in excised tissue. We noted that a node with lower uptake should not be ignored because a lower percent of SLN activity does not necessarily rule out existing metastasis. In two of eleven patients, histopathologic showed metastases. One patient's melanoma on the middle back had lymphatic channel activity directed to both axillae. The results of the phantom study validated accuracy of our specimen counts. CONCLUSIONS: Because linear lymphatic channels existed between lymph nodes and the injected sites in all eleven patients, these lymphatic channels could be used as a guide for localizing SLNs. The SLNs indicated by presurgical lymphoscintigraphy were verified by postoperative gamma camera imaging, and radiotracer localization in the SLNs averaged 2.2%.

Secondary hyperparathyroidism: evidence for an association with papillary thyroid cancer.

The association between primary hyperparathyroidism and nonmedullary thyroid malignancies is well known. There is also, however, some evidence for an association between secondary hyperparathyroidism (SHPT) and thyroid cancer. We report three patients in whom invasive papillary thyroid carcinoma (PTC) was diagnosed before (one case) or at the time of (two cases) parathyroidectomy for SHPT. Three women (ages 23, 54, and 64 years) presented with bone pain and pruritus typical of SHPT. All three patients had biopsy-proven parathyroid bone disease and elevated parathormone levels (664, 1674, and 2051 pg/mL). All underwent subtotal parathyroidectomy and total thyroidectomy without complications. Pathology revealed diffuse parathyroid hyperplasia with multifocal invasive papillary thyroid carcinoma (two cases) and follicular variant of papillary thyroid carcinoma (one case). Two cases were associated with metastatic disease to local lymph nodes. The patients received adjuvant radioactive 131I, and remained tumor free 24 to 36 months after surgery with complete resolution of SHPT. We conclude: 1) PTC may accompany SHPT, 2) PTCs associated with SHPT may be locally aggressive although usually they are early tumors, 3) surgeons need to have an index of suspicion for thyroid tumor when operating on patients with SHPT, and 4) routine removal of the thymus as part of the operation for SHPT may have a secondary benefit in diagnosing PTC in the occasional patient.

Cancer pain management skills among medical students: the development of a Cancer Pain Objective Structured Clinical Examination.

Recent surveys suggest that most physicians have inadequate knowledge to assess and manage cancer pain; however, the important domain of clinical performance has not yet been clearly evaluated. The Objective Structured Clinical Examination (OSCE) has become a widely- used and accepted method to evaluate the clinical abilities of medical students. The purpose of this study was to develop and test a Cancer Pain OSCE for medical students evaluating their clinical competence in the area of cancer pain management. A four-component Cancer Pain OSCE was developed and presented to 34 third-year medical students during a sixteen-week combined medicine/surgery clerkship. The content of the objective criteria for each component of the OSCE was developed by a multidisciplinary group of pain experts. The OSCE was designed to assess the students' cancer pain management skills of pain history-taking, focused physical examination, analgesic management of cancer pain, and communication of opioid analgesia myths. Actual cancer survivors were used in the five-minute individual stations. The students were asked to complete a cancer pain history, physical examination, manage cancer pain using analgesics, and communicate with a family member regarding opioid myths. Clinical performance was evaluated using pre-defined checklists. Results showed the student's average performance for the history component was the highest of all four components of the examination. Out of 34 points possible on this clinical skills item, students on average (SD) scored 24.5 (5.2), or 72%. For the short-answer analgesic management component of the Cancer Pain OSCE, the overall score was 32%. Most students managed cancer pain with opioids, however, very few prescribed regular opioid use, and the use of adjuvant analgesics was uncommon. Student performance on the focused cancer pain physical examination was, in general, poor. On average students scored 61% on the musculoskeletal system, but only 31% on both the neurological and lymphathic examination. The overall percent score for the cancer pain OSCE was 48%. We conclude that the Cancer Pain OSCE is a useful performance-based tool to test individual skills in the essential components of cancer pain assessment and management. Of the four components of the Cancer Pain OSCE, medical students performed best on the cancer pain history and performed poorly on the cancer pain physical examination. Information gained from this study will provide a foundation on which future small-group medical student structured teaching will be based.