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2.
Ann Fam Med ; 19(6): 547-552, 2021.
Article in English | MEDLINE | ID: mdl-34330714

ABSTRACT

PURPOSE: To examine the psychometric properties and scores of the Person-Centered Primary Care Measure (PCPCM) in 28 languages and 35 Organisation for Economic Co-operation and Development (OECD) countries. METHODS: Using a paid online sampling service, we requested age- and sex-representative samples of 360 adults in each country. We administered the Person-Centered Primary Care Measure-a previously validated 11-item, patient-reported measure that was developed using what patients and clinicians said is most important about primary care. We also assessed construct validity through associations with demographics, the Patient-Enablement Instrument, number of years the person had been with their primary care physician and practice, whether the patient thought the doctor knowing the results would improve their care, and whether it was hard to complete the survey. We assessed the psychometric properties of the PCPCM in each country and report the summative and item-specific PCPCM scores for each country. RESULTS: The PCPCM exhibited solid psychometric properties across all languages and countries, with Cronbach's alphas ranging from 0.88 to 0.95, and corrected item-total correlations ranging from 0.47 to 0.81, with the vast majority of countries ranging from the low 0.50s to the high 0.70s. Multiple analyses showed strong evidence of concurrent validity. With a potential range from a low of 1 to a high of 4, the overall mean score was 2.74, with a standard deviation of 0.19. Mean PCPCM scores ranged from the lowest in Sweden (2.28) to the highest in Turkey (3.08), with Germany ranking second (3.01), and the United States third (2.99). CONCLUSION: The internal consistency and concurrent validity of the PCPCM across multiple countries provides strong evidence of the coherence of the breadth of primary care functions that patients and clinicians say are important. The diversity of total and item-specific scores across countries provokes interesting hypotheses about the influence of each different country's policies, practices, demographics, and culture on primary care, and provides a strong impetus for further ecological and individual data analyses using the Person-Centered Primary Care Measure. Annals "Online First" article.


Subject(s)
Organisation for Economic Co-Operation and Development , Primary Health Care , Adult , Humans , Psychometrics , Reproducibility of Results , Surveys and Questionnaires
3.
J Am Board Fam Med ; 33(5): 728-735, 2020.
Article in English | MEDLINE | ID: mdl-32989067

ABSTRACT

BACKGROUND: Previous research demonstrated that registries are effective for improving clinical guideline adherence for the care of patients with type 2 diabetes. However, registry implementation has typically relied on intensive support (such as practice facilitators) for practice change and care improvement. OBJECTIVE: To determine whether a remotely delivered, low-intensity organizational change intervention supports implementation and use of diabetes registries in primary care. DESIGN: Cluster-randomized controlled effectiveness trial of providing limited external support leveraging internal practice resources and problem-solving capacities for driving diabetes registry implementation in 32 practices in Virginia. INTERVENTION: All practices identified local implementation champions who participated in an in-person education session on the value and use of diabetes registries, while intervention practices were also paired with peer mentors and had access to a physician informaticist, who worked remotely to assist practices with implementation. MAIN MEASURES: Practice champions reported progress on registry implementation milestone achievement, and reported practice-level organizational capacity by using a modified version of the Assessment of Chronic Illness Care (ACIC). KEY RESULTS: Intervention practices were significantly more likely to have implemented a registry (44% vs 6%, P = .04) and to have achieved more implementation milestones (5.5 vs 2.6, P < .0001) than control practices. Baseline ACIC scores indicated room for organizational improvement with regard to chronic illness care (overall median, 6.4; range, 3.8 to 10.8) and clinical information systems use (median, 6.0; range, 0 to 11) with no significant differences between intervention and control practices. CONCLUSIONS: Remotely provided guidance paired with limited in-person assistance can support rapid implementation of diabetes registries in typical primary care practices.


Subject(s)
Diabetes Mellitus, Type 2 , Primary Health Care , Registries , Ambulatory Care , Diabetes Mellitus, Type 2/therapy , Humans , Outcome Assessment, Health Care , Primary Health Care/organization & administration , Virginia
4.
Crit Care Med ; 48(6): 847-853, 2020 06.
Article in English | MEDLINE | ID: mdl-32317595

ABSTRACT

OBJECTIVES: To determine the number of top-ranked U.S. academic institutions that require ethics consultation for specific adult clinical circumstances (e.g., family requests for potentially inappropriate treatment) and to detail those circumstances and the specific clinical scenarios for which consultations are mandated. DESIGN: Cross-sectional survey study, conducted online or over the phone between July 2016 and October 2017. SETTING: We identified the top 50 research medical schools through the 2016 U.S. News and World Report rankings. The primary teaching hospital for each medical school was included. SUBJECTS: The chair/director of each hospital's adult clinical ethics committee, or a suitable alternate representative familiar with ethics consultation services, was identified for study recruitment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A representative from the adult ethics consultation service at each of the 50 target hospitals was identified. Thirty-six of 50 sites (72%) consented to participate in the study, and 18 (50%) reported having at least one current mandatory consultation policy. Of the 17 sites that completed the survey and listed their triggers for mandatory ethics consultations, 20 trigger scenarios were provided, with three sites listing two distinct clinical situations. The majority of these triggers addressed family requests for potentially inappropriate treatment (9/20, 45%) or medical decision-making for unrepresented patients lacking decision-making capacity (7/20, 35%). Other triggers included organ donation after circulatory death, initiation of extracorporeal membrane oxygenation, denial of valve replacement in patients with subacute bacterial endocarditis, and posthumous donation of sperm. Twelve (67%) of the 18 sites with mandatory policies reported that their protocol(s) was formally documented in writing. CONCLUSIONS: Among top-ranked academic medical centers, the existence and content of official policies regarding situations that mandate ethics consultations are variable. This finding suggests that, despite recent critical care consensus guidelines recommending institutional review as standard practice in particular scenarios, formal adoption of such policies has yet to become widespread and uniform.


Subject(s)
Ethics Consultation/organization & administration , Hospitals, Teaching/ethics , Cross-Sectional Studies , Ethics Consultation/standards , Health Services Misuse , Humans , United States
5.
Ann Fam Med ; 17(3): 221-230, 2019 05.
Article in English | MEDLINE | ID: mdl-31085526

ABSTRACT

PURPOSE: To develop and evaluate a concise measure of primary care that is grounded in the experience of patients, clinicians, and health care payers. METHODS: We asked crowd-sourced samples of 412 patients, 525 primary care clinicians, and 85 health care payers to describe what provides value in primary care, then asked 70 primary care and health services experts in a 2½ day international conference to provide additional insights. A multidisciplinary team conducted a qualitative analysis of the combined data to develop a parsimonious set of patient-reported items. We evaluated items using factor analysis, Rasch modeling, and association analyses among 2 online samples and 4 clinical samples from diverse patient populations. RESULTS: The resulting person-centered primary care measure parsimoniously represents the broad scope of primary care, with 11 domains each represented by a single item: accessibility, advocacy, community context, comprehensiveness, continuity, coordination, family context, goal-oriented care, health promotion, integration, and relationship. Principal axes factor analysis identified a single factor. Factor loadings and corrected item-total correlations were >0.6 in online samples (n = 2,229) and >0.5 in clinical samples (n = 323). Factor scores were fairly normally distributed in online patient samples, and skewed toward higher ratings in point-of-care patient samples. Rasch models showed a broad spread of person and item scores, acceptable item-fit statistics, and little item redundancy. Preliminary concurrent validity analyses supported hypothesized associations. CONCLUSIONS: The person-centered primary care measure reliably, comprehensively, and parsimoniously assesses the aspects of care thought to represent high-value primary care by patients, clinicians, and payers. The measure is ready for further validation and outcome analyses, and for use in focusing attention on what matters about primary care, while reducing measurement burden.


Subject(s)
Patient Reported Outcome Measures , Primary Health Care/standards , Adolescent , Adult , Female , Humans , Male , Middle Aged , Patient-Centered Care/standards , Qualitative Research , Reproducibility of Results , Young Adult
7.
J Neurosurg Anesthesiol ; 31(3): 273-284, 2019 Jul.
Article in English | MEDLINE | ID: mdl-29952815

ABSTRACT

OBJECTIVE: Despite clinical use spanning 50+ years, questions remain concerning the optimal use of mannitol. The published reviews with meta-analysis frequently focused on mannitol's effects on a specific physiological aspect such as intracranial pressure (ICP) in sometimes heterogeneous patient populations. A comprehensive review of mannitol's effects, as well as side effects, is needed. METHODS: The databases Medline (OvidSP), Embase (OvidSP), and NLM PubMed were systematically searched for randomized controlled trials (RCTs) comparing mannitol to a control therapy in either the critical care or perioperative setting. Meta-analysis was performed when feasible to examine mannitol's effects on outcomes, including ICP, cerebral perfusion pressure, mean arterial pressure (MAP), brain relaxation, fluid intake, urine output, and serum sodium. Systematic literature search was also performed to understand mannitol-related complications. RESULTS: In total 55 RCTs were identified and 7 meta-analyses were performed. In traumatic brain injury, mannitol did not lead to significantly different MAP (SMD [95% confidence interval (CI)] =-3.3 [-7.9, 1.3] mm Hg; P=0.16) but caused significantly different serum sodium concentrations (SMD [95% CI]=-8.0 [-11.0, -4.9] mmol/L; P<0.00001) compared with hypertonic saline. In elective craniotomy, mannitol was less likely to lead to satisfactory brain relaxation (RR [95% CI]=0.89 [0.81, 0.98]; P=0.02), but was associated with increased fluid intake (SMD [95% CI]=0.67 [0.21, 1.13] L; P=0.004), increased urine output (SMD [95% CI]=485 [211, 759] mL; P=0.0005), decreased serum sodium concentration (SMD [95% CI]=-6.2 [-9.6, -2.9] mmol/L; P=0.0002), and a slightly higher MAP (SMD [95% CI]=3.3 [0.08, 6.5] mm Hg; P=0.04) compared with hypertonic saline. Mannitol could lead to complications in different organ systems, most often including hyponatremia, hyperkalemia, and acute kidney injury. These complications appeared dose dependent and had no long-term consequences. CONCLUSIONS: Mannitol is effective in accomplishing short-term clinical goals, although hypertonic saline is associated with improved brain relaxation during craniotomy. Mannitol has a favorable safety profile although it can cause electrolyte abnormality and renal impairment. More research is needed to determine its impacts on long-term outcomes.


Subject(s)
Critical Care/methods , Diuretics, Osmotic/therapeutic use , Mannitol/therapeutic use , Neurosurgery/methods , Humans , Neurosurgical Procedures/methods , Randomized Controlled Trials as Topic
8.
J Contin Educ Health Prof ; 37(4): 223-229, 2017.
Article in English | MEDLINE | ID: mdl-29189493

ABSTRACT

INTRODUCTION: This study examines how improving curricular content and technical interface issues could make maintenance of certification activities more meaningful to American Board of Family Medicine diplomates completing Maintenance of Certification for Family Physicians (MC-FP) Program self-assessment modules (SAMs). METHODS: We used a sequential exploratory design to analyze quantitative and qualitative data from 320,500 surveys of family physicians who completed a SAM between January 2004 and April 2013. This included numeric rating scales and free text comments. Basic statistical rankings, template-based automated coding, and emergent coding were used to analyze SAM experience and identify thematic content. RESULTS: Across SAMs, numeric ratings were universally high and positive free text comments outnumbered negative comments two to one. When comparing feedback on the knowledge assessment and clinical simulation (CS) activities, SAMs were rated less favorably when the frequency of ideas identified by participants as most prevalent in one activity mismatched those identified as most prevalent in the companion activity. Participants were also critical of navigation issues, technical issues, and a lack of realness in the CS activity. DISCUSSION: Whether analyzed through quantitative data, qualitative data, or mixed methods, a large majority of participants rated their experience with SAMs highly. When individual SAMs were rated poorly, it seemed to be due to discordance in ideas emphasized between the knowledge assessment and CS components, or an opinion regarding the SAM topic that existed independent of the SAM process.


Subject(s)
Certification/methods , Education, Medical, Continuing/standards , Physicians, Family/psychology , Adult , Education, Medical, Continuing/methods , Feedback , Female , Humans , Male , Middle Aged , Qualitative Research , Self-Assessment , Surveys and Questionnaires
9.
Epilepsy Res ; 122: 37-43, 2016 May.
Article in English | MEDLINE | ID: mdl-26921855

ABSTRACT

OBJECTIVE: No standard, widely accepted criteria exist to determine who should be referred for an epilepsy surgical evaluation. As a result, indications for epilepsy surgery evaluation vary significantly between centers. We review the literature to assess what criteria have been used to select patients for resective epilepsy surgery and examine whether these have changed since the publication of the first epilepsy surgery randomized controlled trial in 2001. METHODS: A systematic review was conducted using PubMed and EMBASE, bibliographies of reviews and book chapters identifying focal epilepsy resective series. Abstract, full text review and data abstraction (i.e. indications for surgery) were performed independently by two reviewers. Descriptive historical analysis was done to examine indications over time. RESULTS: Out of 5061 articles related to epilepsy surgery, 384 articles met all eligibility criteria. Most common criteria for selecting patients for evaluation for resective surgery were: AED resistance (n=303, most commonly >2 AEDs=46), epilepsy duration (n=53, most commonly >1 year=42) and seizure frequency (most commonly at least one seizure/month, n=29). Out of the prospective studies the most notable change over time (pre-2000 vs. post-2000) was failure of ≥2 AEDs (8% vs. 43% respectively, p<0.001). CONCLUSIONS: Important variations between studies make it difficult to identify consistent criteria to guide surgical candidacy or changes in indications over time. With increasing evidence that earlier surgery is associated with better outcomes, it is recommended that patients be evaluated as soon as they have failed two AEDs, consistent with the new definition of drug resistant epilepsy. Furthermore, low seizure frequency should not be a barrier to epilepsy surgery. Anyone with drug resistant epilepsy should be promptly evaluated for possible surgery, regardless of seizure frequency.


Subject(s)
Epilepsies, Partial/surgery , Neurosurgical Procedures/methods , Humans , Patient Selection
10.
J Clin Neurosci ; 21(9): 1599-602, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24836298

ABSTRACT

Calcified lesions described within the neural axis are classified as either an ossification of the posterior longitudinal ligament, diffuse idiopathic skeletal hyperostosis, or ossification of the ligamentum flavum. We aim to describe a unique pathologic entity: the giant thoracic osteophyte. We identified four patients who were surgically treated at the Massachusetts General Hospital from 2006 to 2012 with unusual calcified lesions in the ventral aspect of the spinal canal. In order to differentiate giant thoracic osteophytes from calcified extruded disc material, disc volumetrics were performed on actual and simulated disc spaces. All patients underwent operative resection of the calcific lesion as they had signs and/or symptoms of spinal cord compression. The lesions were found to be isolated, large calcific masses that originated from the posterior aspect of adjacent thoracic vertebral bodies. Pathological examination was negative for tumor. Adjacent disc volumes were not significantly different from the index disc (p=0.91). A simulated calculation hypothesizing that the calcific mass was extruded disc material demonstrated a significant difference (p=0.01), making this scenario unlikely. In conclusion, giant thoracic osteophyte is a unique and rare entity that can be found in the thoracic spine. The central tenant of surgical treatment is resection to relieve spinal cord compression.


Subject(s)
Osteophyte/pathology , Osteophyte/surgery , Adult , Female , Humans , Imaging, Three-Dimensional , Intervertebral Disc/pathology , Middle Aged , Osteophyte/complications , Retrospective Studies , Spinal Cord Compression/etiology , Spinal Cord Compression/surgery , Thoracic Vertebrae/pathology , Tomography, X-Ray Computed
11.
J Neurosurg ; 120(1): 278-84, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24032702

ABSTRACT

OBJECT: Dural closure with synthetic grafts has been suggested to contribute to the incidence of infection and CSF leak. The objective of this study was to assess the contribution of choice of dural closure material, as well as other factors, to the incidence of infection and CSF leak. METHODS: A retrospective, consecutive cohort study of adult patients undergoing elective craniotomy was established between April 2010 and March 2011 at a single center. Exclusion criteria consisted of trauma, bur hole placement alone, and temporary CSF fluid diversion. RESULTS: Three hundred ninety-nine patients were included (mean follow-up 396.6 days). Nonautologous (synthetic) dural substitute was more likely to be used (n = 106) in cases of reoperation (p = 0.001). Seventeen patients developed a surgical site infection and 12 patients developed a CSF leak. Multivariate logistic regression modeling identified estimated blood loss (OR 1.002, 95% CI 1.001-1.003; p < 0.001) and cigarette smoking (OR 2.198, 95% CI 1.109-4.238; p = 0.019) as significant predictors of infection. Synthetic dural graft was not a predictor of infection in multivariate analysis. Infratentorial surgery (OR 4.348, 95% CI 1.234-16.722; p = 0.024) and more than 8 days of postoperative corticosteroid treatment (OR 3.886, 95% CI 1.052-16.607; p = 0.048) were significant predictors for the development of CSF leak. Synthetic dural graft was associated with a lower likelihood of CSF leak (OR 0.072, 95% CI 0.003-0.552; p = 0.036). CONCLUSIONS: The use of synthetic dural closure material is not associated with surgical site infection and is associated with a reduced incidence of CSF leak. Modifiable risk factors exist for craniotomy complications that warrant vigilance and further study.


Subject(s)
Craniotomy/adverse effects , Dura Mater/surgery , Elective Surgical Procedures/adverse effects , Postoperative Complications/epidemiology , Craniotomy/methods , Female , Humans , Incidence , Male , Middle Aged , Postoperative Complications/etiology , Retrospective Studies
12.
Clin Neurol Neurosurg ; 115(11): 2377-81, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24075713

ABSTRACT

OBJECTIVE: Symptomatic supratentorial cavernous malformations may present with seizure, headache, neurological deficit, or a combination thereof. Factors that contribute to treatment algorithms commonly include patient age, lesion size and location, lesion multiplicity, hemorrhage history, and the ability to control seizure activity with medication. A better appreciation of the impact of patient and lesion characteristics on post-operative seizure control may provide insight into management strategies. To determine long-term seizure outcomes following surgical resection of supratentorial cavernous malformations, the predictive value of characteristics including seizure duration and number, presence of generalized seizures, and lesion multiplicity and size on seizure control rate was evaluated. METHODS: We performed a single institution retrospective review of consecutive patients with supratentorial cavernous malformations presenting with at least one seizure between 1995 and 2008. Univariate and multivariate analyses were used to determine the influence of patient and lesion characteristics on postoperative seizure control. RESULTS: Fifty-six patients met inclusion criteria. Mean follow-up duration was 87.9 months. At last follow-up there were 46 patients (82.1%) that were free from impairing seizures (Engel Class 1). Ten patients (17.9%) were classified as Engel Class 2-4. Univariate analysis demonstrated that only the presence of multiple cavernomas was associated with worse post-operative seizure outcome (p=0.006). Multivariate analysis demonstrated that multiple cavernomas remained a significant predictor for development of worse seizure outcome controlling for number and duration of seizures prior to operation, presence of generalized tonic-clonic seizures, and size (odds ratio, 0.17; 95% confidence interval, 0.03, 0.99). CONCLUSION: Resection of supratentorial cavernomas is associated with a high rate of postoperative seizure freedom. The presence of multiple cavernomas is predictive of seizure persistence following surgery.


Subject(s)
Hemangioma, Cavernous, Central Nervous System/surgery , Neurosurgical Procedures , Postoperative Complications/etiology , Seizures/etiology , Adolescent , Adult , Child , Female , Follow-Up Studies , Hemangioma, Cavernous, Central Nervous System/complications , Hemangioma, Cavernous, Central Nervous System/diagnosis , Humans , Male , Middle Aged , Multivariate Analysis , Neurosurgical Procedures/adverse effects , Neurosurgical Procedures/methods , Postoperative Complications/diagnosis , Retrospective Studies , Seizures/diagnosis , Time , Treatment Outcome , Young Adult
13.
Neurosurgery ; 72(2): 196-202; discussion 202, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23147780

ABSTRACT

BACKGROUND: Anterior cingulotomy (AC) can be an effective therapy for patients with severe obsessive-compulsive disorder who are refractory to traditional medical therapy. For patients who do not respond to AC, the benefit of additional lesion procedures vs continued medical management remains unknown. OBJECTIVE: To determine whether a second lesion procedure is beneficial after unsuccessful initial AC. METHODS: In this retrospective cohort study, we reviewed the records of 31 patients who were nonresponders to initial AC. Full response was defined as at least a 35% decrease and partial response as a 25% to 34% decrease in Yale-Brown Obsessive-Compulsive Scale scores. Yale-Brown Obsessive-Compulsive Scale change was compared between patients who underwent additional surgery and those treated nonsurgically. In addition, for patients who underwent additional surgery, we compared the benefit of subcaudate tractotomy with repeat AC (extension of the initial lesion) as the second procedure. RESULTS: Nineteen patients underwent a second surgery and 12 patients continued nonsurgical therapy. Fifty-three percent of patients who received additional surgery were full responders and 21% were partial responders at the most recent follow-up compared with 17% full responders and 25% partial responders among those who continued conventional therapy (P = .02). Of the patients who underwent an additional surgery, there were 64% full and 9% partial responders in the subcaudate tractotomy group compared with 38% full and 38% partial responders in the repeat AC group (P = .04). CONCLUSION: Second lesion surgery can be a safe and effective therapy for patients who do not respond to initial AC. Subcaudate tractotomy may confer a higher response rate than repeat cingulotomy.


Subject(s)
Catheter Ablation/methods , Gyrus Cinguli/surgery , Obsessive-Compulsive Disorder/surgery , Psychosurgery/methods , Adult , Chi-Square Distribution , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Postoperative Complications , Psychiatric Status Rating Scales , Retrospective Studies , Severity of Illness Index , Treatment Outcome
14.
J Neurosurg ; 118(3): 491-7, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23240700

ABSTRACT

OBJECT: Obsessive-compulsive disorder (OCD) is a common and disabling psychiatric illness, and in a significant proportion of patients with OCD the disease is refractory to conventional pharmacotherapy and psychotherapy. For more than half a century, patients with severe, treatment-resistant OCD have been treated with stereotactic limbic system lesions, including dorsal anterior cingulotomy. The authors present their results describing the efficacy and durability of limbic system surgery for OCD, characterizing a large cohort of patients treated at a single institution with a mean follow-up of more than 5 years. METHODS: The authors identified 64 consecutive patients undergoing cingulotomy for refractory OCD at the Massachusetts General Hospital between 1989 and 2009. Changes in OCD and major depressive disorder symptom severity were assessed at both the initial and most recent postoperative follow-up by using the Yale-Brown Obsessive Compulsive Scale and the Beck Depression Inventory, respectively. Full and partial OCD symptom responses were defined as Yale-Brown Obsessive Compulsive Scale score reductions of ≥ 35% and 25%-34%, respectively. RESULTS: Regarding OCD symptom improvement, at the first postoperative follow-up (mean 10.7 months), 35% of patients demonstrated a full response and 7% were partial responders. Thirty patients had a subsequent procedure (repeat cingulotomy or subcaudate tractotomy). By the most recent follow-up (mean 63.8 months), rates climbed to 47% and 22% for full and partial responses, respectively. Of the 24 patients with at least a partial response at initial follow-up, 20 (83%) retained at least a partial response at final follow-up. Comorbid major depressive disorder severity decreased by 17% at the most recent follow-up. CONCLUSIONS: Limbic system surgery based on initial cingulotomy offers a durable and effective treatment option for appropriately selected patients with severe OCD who have not responded to conventional pharmacotherapy or psychotherapy.


Subject(s)
Limbic System/surgery , Obsessive-Compulsive Disorder/psychology , Obsessive-Compulsive Disorder/surgery , Psychosurgery/methods , Adolescent , Adult , Aged , Female , Follow-Up Studies , Humans , Limbic System/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Obsessive-Compulsive Disorder/diagnosis , Obsessive-Compulsive Disorder/therapy , Prospective Studies , Psychiatric Status Rating Scales , Severity of Illness Index , Time Factors , Treatment Outcome
15.
Neurosurgery ; 71(1): 14-22, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22353796

ABSTRACT

BACKGROUND: Inferior petrosal sinus sampling (IPSS) is a useful technique for confirming a pituitary source of adrenocorticotropic hormone (ACTH) overproduction in Cushing disease. Uncertainty remains regarding the appropriate course of therapy when an ectopic tumor is predicted by IPSS but none can be found and in circumstances when the procedure cannot be successfully completed owing to technical or anatomic limitations. OBJECTIVE: To determine an appropriate course of action after nondiagnostic IPSS. METHODS: We reviewed 288 IPSS procedures in 283 patients between 1986 and 2010 at our center. An IPS:peripheral ACTH ratio ≥ 2 at baseline or ≥ 3 after corticotrophin-releasing hormone was considered predictive of a pituitary source of ACTH. A procedure was considered nondiagnostic if the procedure was successfully performed and the results predicted an ectopic source but none could be found despite extensive imaging or if the IPS could not be bilaterally cannulated because of technical difficulties or anatomic variants. RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value of IPSS for detecting a pituitary source in Cushing disease were 94%, 50%, 98%, and 29%, respectively. We identified 3 categories of nondiagnostic IPSS comprising 44 of the total procedures. These patients underwent exploratory transsphenoidal surgery, and in 42 of these patients (95%), a pituitary source was surgically proven, with a remission rate of 83%. CONCLUSION: Transsphenoidal surgery should be considered in cases of ACTH-dependent Cushing disease and noncentralized or technically unsuccessful IPSS without evidence of ectopic tumor.


Subject(s)
Nose/surgery , Petrosal Sinus Sampling/methods , Pituitary ACTH Hypersecretion/diagnosis , Pituitary ACTH Hypersecretion/surgery , Adolescent , Adrenocorticotropic Hormone/metabolism , Adult , Aged , Aged, 80 and over , Child , Corticotropin-Releasing Hormone/metabolism , Female , Humans , Hydrocortisone/metabolism , Male , Middle Aged , Pituitary Gland/surgery , Predictive Value of Tests , Retrospective Studies , Sensitivity and Specificity , Statistics, Nonparametric , Treatment Outcome , Young Adult
16.
Proc Natl Acad Sci U S A ; 104(6): 1889-94, 2007 Feb 06.
Article in English | MEDLINE | ID: mdl-17261812

ABSTRACT

Herbivorous insect species are constantly challenged with reactive oxygen species (ROS) generated from endogenous and exogenous sources. ROS produced within insects because of stress and prooxidant allelochemicals produced by host plants in response to herbivory require a complex mode of antioxidant defense during insect/plant interactions. Some insect herbivores have a midgut-based defense against the suite of ROS encountered. Because the Hessian fly (Mayetiola destructor) is the major insect pest of wheat worldwide, and an emerging model for all gall midges, we investigated its antioxidant responses during interaction with its host plant. Quantitative data for two phospholipid glutathione peroxidases (MdesPHGPX-1 and MdesPHGPX-2), two catalases (MdesCAT-1 and MdesCAT-2), and two superoxide dismutases (MdesSOD-1 and MdesSOD-2) revealed high levels of all of the mRNAs in the midgut of larvae on susceptible wheat (compatible interaction). During development of the Hessian fly on susceptible wheat, a differential expression pattern was observed for all six genes. Analysis of larvae on resistant wheat (incompatible interaction) compared with larvae on susceptible wheat showed increased levels of mRNAs in larvae on resistant wheat for all of the antioxidant genes except MdesSOD-1 and MdesSOD-2. We postulate that the increased mRNA levels of MdesPHGPX-1, MdesPHGPX-2, MdesCAT-1, and MdesCAT-2 reflect responses to ROS encountered by larvae while feeding on resistant wheat seedlings and/or ROS generated endogenously in larvae because of stress/starvation. These results provide an opportunity to understand the cooperative antioxidant defense responses in the Hessian fly/wheat interaction and may be applicable to other insect/plant interactions.


Subject(s)
Antioxidants/metabolism , Diptera/physiology , Reactive Oxygen Species/metabolism , Triticum/physiology , Triticum/parasitology , Animals , Diptera/genetics , Gene Expression Regulation/physiology , Molecular Sequence Data
17.
J Insect Sci ; 7: 1-13, 2007.
Article in English | MEDLINE | ID: mdl-20307234

ABSTRACT

Two new Delta and Sigma glutathione S-transferases (GSTs) in the Hessian fly, Mayetiola destructor (Diptera: Cecidomyiidae), were characterized and transcription profiles described. The deduced amino acid sequences for the two M. destructor Delta GSTs (MdesGST-1 and MdesGST-3) showed high similarity with other insect Delta GSTs including the conserved catalytic serine residue. The deduced amino acid sequence for the M. destructor Sigma GST (MdesGST-2) showed high similarity with other insect Sigma GSTs including the conserved glutathione and substrate binding sites. Quantitative tissue expression analysis showed that mRNA levels for MdesGST-1 were predominant in fat body, whereas for MdesGST-2 and MdesGST-3 expression was predominant in the midgut. Temporal expression during development showed peak mRNA levels for MdesGST-1 during larval development, but in the pupal stage for MdesGST-2. MdesGST-3 showed a constitutive expression pattern throughout development. M. destructor feeds on wheat, and expression analysis after feeding indicated that mRNA levels for MdesGST-1 were significantly higher in incompatible interactions in which larvae fed on resistant wheat, while MdesGST-3 was significantly higher in compatible interactions when larvae fed on susceptible wheat. MdesGST-2 showed an equivalent expression pattern during both interactions. These results suggest that the M. destructor Delta GSTs are important in detoxifying wheat allelochemicals during feeding, while Sigma GST participates in metabolism of endogenous substrates.


Subject(s)
Diptera/enzymology , Gene Expression Regulation, Enzymologic , Glutathione Transferase/metabolism , Life Cycle Stages/physiology , Amino Acid Sequence , Animals , Diptera/growth & development , Gene Expression Regulation, Developmental , Glutathione Transferase/chemistry , Glutathione Transferase/genetics , Host-Parasite Interactions , Larva , Molecular Sequence Data , Sequence Alignment , Sequence Homology, Amino Acid , Triticum/chemistry , Triticum/parasitology
18.
Insect Biochem Mol Biol ; 35(9): 981-9, 2005 Sep.
Article in English | MEDLINE | ID: mdl-15978999

ABSTRACT

We have recovered two Hessian fly cytochrome P450 cDNAs from an ongoing midgut EST project. CYP6AZ1 and CYP6BA1 represent two new subfamilies within the CYP6 family. The deduced amino acid sequences for CYP6AZ1 and CYP6BA1 show conserved structural and functional domains of insect P450s. Expression analysis with reverse transcription-polymerase chain reaction (RT-PCR) indicated that CYP6AZ1 is midgut specific and induced during active larval feeding, whereas CYP6BA1 was expressed in all tissues and developmental stages examined. Further expression analysis of CYP6AZ1 with RT-PCR in compatible and incompatible Hessian fly/wheat interactions suggested that CYP6AZ1 may be required for larval feeding in compatible interactions. These results should lead to a better understanding of the Hessian fly/wheat interaction with emphasis on the larval midgut as a critical interface with its host plant.


Subject(s)
Cytochrome P-450 Enzyme System/genetics , Diptera/enzymology , Triticum/parasitology , Amino Acid Sequence , Animals , Base Sequence , Cytochrome P-450 Enzyme System/biosynthesis , Diptera/genetics , Gene Expression Regulation, Enzymologic , Host-Parasite Interactions , Larva/enzymology , Molecular Sequence Data , Sequence Homology, Amino Acid
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