Health Care Professionals' Experiences With a Mobile Self-Care Solution for Low Complex Orthopedic Injuries: Mixed Methods Study.

BACKGROUND: To cope with the rising number of patients with trauma in an already constrained Dutch health care system, Direct Discharge (DD) has been introduced in over 25 hospitals in the Netherlands since 2019. With DD, no routine follow-up appointments are scheduled after the emergency department (ED) visit, and patients are supported through information leaflets, a smartphone app, and a telephone helpline. DD reduces secondary health care use, with comparable patient satisfaction and primary health care use. Currently, little is known about the experiences of in-hospital health care professionals with DD. OBJECTIVE: The aim of this study was to explore the experiences of health care professionals with the DD protocol to enhance durable adoption and improve the protocol. METHODS: We conducted a mixed methods study parallel to the implementation of DD in 3 hospitals. Data were collected through a preimplementation survey, a postimplementation survey, and semistructured interviews. Quantitative data were reported descriptively, and qualitative data were reported using thematic analysis. Outcomes included the Bowen feasibility parameters: implementation, acceptability, preliminary efficacy, demand, and applicability. Preimplementation expectations were compared with postimplementation experiences. Health care professionals involved in the daily clinical care of patients with low-complex, stable injuries were eligible for this study. RESULTS: Of the 217 eligible health care professionals, 128 started the primary survey, 37 completed both surveys (response rate of 17%), and 15 participated in semistructured interviews. Health care professionals expressed satisfaction with the DD protocol (median 7.8, IQR 6.8-8.9) on a 10-point scale, with 82% (30/37) of participants noting improved information quality and uniformity and 73% (27/37) of patients perceiving reduced outpatient follow-up and imaging. DD was perceived as safe by 79% (28/37) of participants in its current form, but a feedback system to reassure health care professionals that patients had recovered adequately was suggested to improve DD. The introduction of DD had varying effects on workload and job satisfaction among different occupations. Health care professionals expressed intentions to continue using DD due to increased efficiency, patient empowerment, and self-management. CONCLUSIONS: Health care professionals perceive DD as an acceptable, applicable, safe, and efficacious alternative to traditional treatment. A numerical in-app feedback system (eg, in-app communication tools or recovery scores) could alleviate health care professionals' concerns about adequate recovery and further improve DD protocols. DD can reduce health care use, which is important in times of constrained resources. Nonetheless, both advantages and disadvantages should be considered while evaluating this type of treatment. In the future, clinicians and policy makers can use these insights to further optimize and implement DD in clinical practice and guidelines.

Orthopaedic trauma patients' experiences with emergency department care and follow-up through Virtual Fracture Care review: a qualitative study.

OBJECTIVES: This study aimed to identify factors influencing orthopaedic trauma patients' experiences and satisfaction with emergency department (ED) care and follow-up through Virtual Fracture Care (VFC) review workflow. DESIGN: This study employed an explorative, descriptive, qualitative design using individual, semistructured interviews. SETTING: An urban level 2 trauma centre and teaching hospital in Amsterdam, the Netherlands. PARTICIPANTS: Eligible patients were Dutch-speaking or English-speaking orthopaedic trauma patients, aged 18 years or above, who visited the hospital's ED between June and September 2022, and were treated through VFC review workflow. Exclusion criteria were: reason for follow-up other than injury, eye/motor/verbal score <15 at ED admission, follow-up treatment in another hospital, treatment initiated in another hospital, acute hospital admission (<24 hours). Twenty-three patients were invited for participation, of whom 15 participated and were interviewed. RESULTS: Several influential factors contributed to seven generic themes: (1) waiting times, (2) information provision, (3) healthcare professional communication, (4) care expectations, (5) care coordination, (6) care environment and (7) patient condition. Overall, participants were satisfied with received care. Interpersonal skills of healthcare professionals, and timing and content of provided information were specifically valued. Additionally, patients stated that their needs in the ED differed from those after ED discharge, and appreciated the way the VFC review workflow addressed this. Points of improvement included more active involvement of patients in the care process and prevention of inconsistent instructions by different healthcare professionals. CONCLUSIONS: Patient experiences with ED care and VFC review follow-up are influenced by factors categorised into seven themes. The VFC review workflow effectively addresses these factors, leading to positive feedback. Recommendations for healthcare professionals include anticipating evolving post-ED information needs, engaging patients early to provide clarity about the care process, involving them in treatment decisions and expanding information provision across the entire care pathway.

Direct discharge for children with a greenstick or torus fracture of the wrist is a non-inferior satisfactory solution to traditional treatment.

PURPOSE: Direct Discharge protocols (DD) can alleviate strain on healthcare systems by reducing routine outpatient follow-up. These protocols include low-complex musculoskeletal injuries, such as isolated greenstick fractures or torus fractures of the wrist in children. While there is consensus on the effectiveness of DD, there is a lack of injury-specific powered studies. This study compares treatment satisfaction between DD and traditional treatment in children with a greenstick fracture or torus fractures of the wrist. METHODS: Children with isolated torus or greenstick fractures of the distal radius or ulna were eligible for inclusion before (pre-DD cohort) and after (DD cohort) the implementation of DD in four hospitals. Traditionally, patients receive a (soft) cast and minimally one routine outpatient follow-up appointment. With DD, patients are discharged directly from the ED after receiving a brace and information, summarized in a smartphone app and a helpline for questions during recovery. The primary outcome was patient or proxy treatment satisfaction (0 to 10), and a power analysis was performed to assess non-inferiority. Secondary outcomes included complications, functional outcomes measured in Patient-Reported Outcomes Measurement Information System Upper Extremity (PROMIS UE), primary healthcare utilisation, and secondary healthcare utilisation (follow-up appointments and imaging). RESULTS: In total, 274 consecutive children were included to analyse the primary endpoint. Of these, 160 (58%) were male with a median age of 11 years (IQR 8 to 12). Pre-DD and DD treatment satisfaction did not vary statistically significantly for greenstick fractures (p = 0.09) and torus fractures (p = 0.93). No complications were observed. PROMIS UE showed no statistically significant differences before and after implementation of direct discharge protocol for torus (p = 0.99) or greenstick (p = 0.45) fractures. Secondary healthcare utilisation regarding follow-up was significantly lower in the DD-torus cohort compared to the pre-DD torus cohort, with a mean difference (MD) of - 1.00 follow-up appointments (95% Confidence Interval (CI) - 0.92 to - 1.13). Similar results were found in the pre DD-greenstick cohort compared to the pre-DD-greenstick cohort (MD): - 1.17 follow-up appointments, 95% CI - 1.09 to - 1.26). CONCLUSION: Direct Discharge is non-inferior to traditional treatment in terms of treatment satisfaction for paediatric patients with greenstick or torus fractures of the wrist compared to children treated with rigid immobilisation and routine follow-up. Furthermore, the results demonstrate no complications, comparable functional outcomes, and a statistically significant reduction of secondary healthcare utilisation, making DD a good solution to cope with strained resources for children with an isolated greenstick fracture or torus fracture of the wrist.

Efficiency of a virtual fracture care protocol in non-operative treatment of adult patients with a distal radial fracture.

This study aimed to determine the effects of virtual fracture care (VFC) on secondary healthcare utilization in non-operative treatment of adult patients with a distal radial fracture. A retrospective cohort study was performed, including those who received non-operative treatment without VFC (pre-VFC) and with VFC (VFC). Outcomes included secondary healthcare utilization, calculated treatment costs, emergency department (ED) reattendances and complication rates. In total, 88 pre-VFC and 99 VFC patients were included. Pre-VFC patients had more follow-up appointments, with a median of 4 (IQR: 3) versus a median of 4 (IQR: 1) in VFC patients. In addition, 3% of follow-up appointments for pre-VFC patients were performed remotely compared to 18% for VFC patients. Complications and ED reattendances were comparable between groups. In this study, non-operative treatment of adult patients with a distal radial fracture through VFC reduced secondary healthcare utilization, with similar reported complication and ED reattendance rates compared with treatment without VFC.Level of evidence: III.

Patient perceptions after the operative and nonoperative treatment of shoulder instability: A qualitative focus group study.

Background: Little evidence is available regarding patient perceptions of the treatment of shoulder instability. The aim of this study is to investigate patient perceptions regarding the operative and nonoperative treatment of anterior shoulder instability. Methods: Patients who presented to the emergency department or outpatient clinic between 2016 and 2020 were retrospectively selected using diagnosis and procedure codes. Online focus groups and semistructured interviews were conducted, systematically recorded and subsequently transcribed to MaxQDA 2007 for qualitative analysis. Coded transcripts of all focus groups were subjected to a grounded theory-based analysis. Results: Six focus groups and two semistructured interviews were hosted with 35 included patients. The mean age of included patients was 34.1 years (±11.5). Eight patients were female (23%), and 27 patients were male (77%). Fear of (recurrent) dislocation, preoperative counseling, communication between surgeon and physiotherapists and need for a consistent postoperative rehab protocol turned out to be important patient perceptions. The most crucial factor for discontent was a lack of communication from the surgeon. Discussion: This patient-centered focus group study revealed that fear of (recurrent) dislocation, preoperative counseling, communication between surgeons and physiotherapists and the need for a consistent postoperative rehabilitation protocol was the most frequently discussed themes.

Healthcare utilization and satisfaction with treatment before and after direct discharge from the Emergency Department of simple stable musculoskeletal injuries in the Netherlands.

PURPOSE: To evaluate healthcare utilization and satisfaction with treatment before and after implementing direct discharge (DD) from the Emergency Department (ED) of patients with simple, stable musculoskeletal injuries. METHODS: Patients with simple, stable musculoskeletal injuries were included in two Dutch hospitals, both level-2 trauma centers: OLVG and Sint Antonius (SA), before (pre-DD-cohort) and after implementing DD (DD-cohort). With DD, no routine follow-up appointments are scheduled after the ED visit, supported by information leaflets, a smartphone application and a telephone helpline. Outcomes included: secondary healthcare utilization (follow-up appointments and X-ray/CT/MRI); satisfaction with treatment (scale 1-10); primary healthcare utilization (general practitioner (GP) or physiotherapist visited, yes/no). Linear regression was used to compare secondary healthcare utilization for all patients and per injury subgroup. Satisfaction and primary healthcare utilization were analyzed descriptively. RESULTS: A total of 2033 (OLVG = 1686; SA = 347) and 1616 (OLVG = 1396; SA = 220) patients were included in the pre-DD-cohort and DD-cohort, respectively. After DD, the mean number of follow-up appointments per patient reduced by 1.06 (1.13-0.99; p < 0.001) in OLVG and 1.07 (1.02-0.93; p < 0.001) in SA. Follow-up appointments reduced significantly for all injury subgroups. Mean number of follow-up X-rays per patient reduced by 0.17 in OLVG (p < 0.001) and 0.18 in SA (p < 0.001). Numbers of CT/MRI scans were low and comparable. In OLVG, mean satisfaction with treatment was 8.1 (pre-DD-cohort) versus 7.95 (DD-cohort), versus 7.75 in SA (DD-cohort only). In OLVG, 23.6% of pre-DD-cohort patients visited their GP, versus 26.1% in the DD-cohort, versus 13.3% in SA (DD-cohort only). Physiotherapist use was comparable. CONCLUSION: This study performed in a large population and additional hospital confirms earlier pilot results, i.e., that DD has the potential to effectively reduce healthcare utilization, while maintaining high levels of satisfaction. LEVEL OF EVIDENCE: II.

Effect of Antibiotic Prophylaxis on Surgical Site Infections Following Removal of Orthopedic Implants Used for Treatment of Foot, Ankle, and Lower Leg Fractures: A Randomized Clinical Trial.

Importance: Following clean (class I, not contaminated) surgical procedures, the rate of surgical site infection (SSI) should be less than approximately 2%. However, an infection rate of 12.2% has been reported following removal of orthopedic implants used for treatment of fractures below the knee. Objective: To evaluate the effect of a single dose of preoperative antibiotic prophylaxis on the incidence of SSIs following removal of orthopedic implants used for treatment of fractures below the knee. Design, Setting, and Participants: Multicenter, double-blind, randomized clinical trial including 500 patients aged 18 to 75 years with previous surgical treatment for fractures below the knee who were undergoing removal of orthopedic implants from 19 hospitals (17 teaching and 2 academic) in the Netherlands (November 2014-September 2016), with a follow-up of 6 months (final follow-up, March 28, 2017). Exclusion criteria were an active infection or fistula, antibiotic treatment, reimplantation of osteosynthesis material in the same session, allergy for cephalosporins, known kidney disease, immunosuppressant use, or pregnancy. Interventions: A single preoperative intravenous dose of 1000 mg of cefazolin (cefazolin group, n = 228) or sodium chloride (0.9%; saline group, n = 242). Main Outcomes and Measures: Primary outcome was SSI within 30 days as measured by the criteria from the US Centers for Disease Control and Prevention. Secondary outcome measures were functional outcome, health-related quality of life, and patient satisfaction. Results: Among 477 randomized patients (mean age, 44 years [SD, 15]; women, 274 [57%]; median time from orthopedic implant placement, 11 months [interquartile range, 7-16]), 470 patients completed the study. Sixty-six patients developed an SSI (14.0%): 30 patients (13.2%) in the cefazolin group vs 36 in the saline group (14.9%) (absolute risk difference, -1.7 [95% CI, -8.0 to 4.6], P = .60). Conclusions and Relevance: Among patients undergoing surgery for removal of orthopedic implants used for treatment of fractures below the knee, a single preoperative dose of intravenous cefazolin compared with saline did not reduce the risk of surgical site infection within 30 days following implant removal. Trial Registration: clinicaltrials.gov Identifier: NCT02225821.

Trauma surgery by general surgeons: Still an option for proximal femoral fractures?

INTRODUCTION: Surgery for proximal femoral fractures in the Netherlands is performed by trauma surgeons, general surgeons and orthopaedic surgeons. The aim of this study was to assess whether there is a difference in outcome for patients with proximal femoral fractures operated by trauma surgeons versus general surgeons. Secondly, the relation between hospital and surgeon volume and postoperative complications was explored. METHODS: Patients of 18 years and older were included if operated for a proximal femoral fracture by a trauma surgeon or a general surgeon in two academic, eight teaching and two non-teaching hospitals in the Netherlands from January 2010 until December 2013. The combined endpoint was defined as reoperation or surgical site infection. Multivariate analysis was used to adjust for patient and fracture characteristics and hospital and surgeon volume. Categories for hospital volume were>170/year (high volume), 96-170/year (medium volume) and <96/year (low volume). RESULTS: In 4552 included patients 2382 (52.3%) had surgery by a trauma surgeon. Postoperative complications occurred in 276 (11.6%) patients operated by a trauma surgeon and in 258 (11.9%) operated by a general surgeon (p=0.751). When considering confounders in a multivariate analysis, surgery by trauma surgeons was associated with less postoperative complications (OR 0.746; 95%CI 0.580-0.958; p=0.022). Surgery in high volume hospitals was also associated with less complications (OR 0.997; 95%CI 0.995-0.999; p=0.012). Surgeon volume was not associated with complications (OR 1.008; 95%CI 0.997-1.018; p=0.175). CONCLUSION: Surgery by trauma surgeons and high hospital volume are associated with less reoperations and surgical site infections for patients with proximal femoral fractures.

Wound Infections Following Implant removal below the knee: the effect of antibiotic prophylaxis; the WIFI-trial, a multi-centre randomized controlled trial.

BACKGROUND: In the Netherlands about 18,000 procedures with implant removal are performed annually following open or closed reduction and fixation of fractures, of which 30-80% concern the foot, ankle and lower leg region. For clean surgical procedures, the rate of postoperative wound infections (POWI) should be less than ~2%. However, rates of 10-12% following implant removal have been reported, specifically after foot, ankle and lower leg fractures. Currently, surgeons individually decide if antibiotics prophylaxis is given, since no guideline exists. This leads to undesirable practice variation. The aim of the study is to assess the (cost-)effectiveness of a single intravenous gift of Cefazolin prior to implant removal following surgical fixation of foot, ankle and/or lower leg fractures. METHODS: This is a double-blind randomized controlled trial in patients scheduled for implant removal following a foot, ankle or lower leg fracture. Primary outcome is a POWI within 30 days after implant removal. Secondary outcomes are quality of life, functional outcome and costs at 30 days and 6 months after implant removal. With 2 x 250 patients a decrease in POWI rate from 10% to 3.3% (expected rate in clean-contaminated elective orthopaedic trauma procedures) can be detected (Power = 80%, 2-sided alpha = 5%, including 15% lost to follow up). DISCUSSION: If administration of prophylactic antibiotics prior to implant removal reduces the infectious complication rate, this will offer a strong argument to adopt this as standard practice of care. This will consequently lead to less physical and social disabilities and health care use. A preliminary, conservative estimation suggests yearly cost savings in the Netherlands of € 3.5 million per year. TRIAL REGISTRATION: This study is registered at Clinicaltrials.gov ( NCT02225821 ) and the Netherlands Trial Register ( NTR4393 ) and was granted permission by the Medical Ethical Review Committee of the Academic Medical Centre on October 7 2014.

Differences between sporadic and MEN related primary hyperparathyroidism; clinical expression, preoperative workup, operative strategy and follow-up.

BACKGROUND: Primary hyperparathyroidism (PHPT) is most commonly sporadic (sPHPT). However, sometimes PHPT develops as part of multiple endocrine neoplasia (MEN) type 1 or 2A. In all, parathyroidectomy is the only curative treatment. Nevertheless, there are important differences in clinical expression and treatment. METHODS: We analyzed a consecutive cohort of patients treated for sporadic, MEN1-related, and MEN2A-related PHPT and compared them regarding clinical and biochemical parameters, differences in preoperative workup, operative strategies, findings, and outcome. RESULTS: A total of 467 patients with sPHPT, 52 with MEN1- and 16 with MEN2A-related PHPT were analyzed. Patients with sPHPT were older, more often female and had higher preoperative calcium and parathyroid hormone levels, when compared with MEN1 and MEN2A patients. Minimally invasive parathyroidectomy (MIP) was performed in 367 of 467 sPHPT patients (79%). One abnormal parathyroid was found in 426 patients (91%). Two or more in 35 patients (7%). In six patients (1%) no abnormal parathyroid gland was retrieved. Of 52 MEN1 patients, eight (15%) underwent a MIP and 44 patients (85%) underwent conventional neck exploration (CNE); with resection of fewer than 3½ enlarged glands in 21 patients (40%), subtotal parathyroidectomy (SPTX, 3-3½ glands) in seventeen (33%) and total parathyroidectomy with autotransplantation (TPTX) in six (12%). Eleven patients (21%) had persistent disease, 29 (56%) recurrent PHPT and nine (17%) permanent hypoparathyroidism, mostly after TPTX. Of 16 MEN2A patients, six (38%) underwent MIP, four (25%) CNE and six (38%) selective resection of the enlarged gland(s) during total thyroidectomy. Three patients (19%) suffered from persistent PHPT and two (13%) developed recurrent disease. CONCLUSIONS: Sporadic PHPT, MEN1- and MEN2A-related PHPT are three distinct entities as is reflected preoperatively by differences in gender, age at diagnosis and calcium and PTH levels. MEN2A patients are very similar to sPHPT with respect to operative approach and findings. MIP is the treatment of choice for both. MIP has low rates of persistent and recurrent PHPT and a low complication rate. The percentage of multiglandular disease and recurrences are significantly higher in MEN1 patients, demonstrating the need for a different approach. We advocate treating these patients with CNE and SPTX.

Type C distal radial fractures treated with conventional AO plates: an easy and cost-saving solution in a locking plate era.

PURPOSE: C-type distal radial fractures remain challenging fractures. Currently locking plates are very popular because of their length preserving, stability. A considerable drawback is the high cost. Since 2003 we have been using mini AO plates (2.7 mm) as an alternative. We analysed our results and performed a cost analysis. METHODS: Retrospective analysis was performed of all patients operated upon between 2003 and 2008 for C type distal radius fractures. Reduction was achieved with mini AO plates, applied in a buttress fashion, with ligamentotaxis. Rehabilitation consisted of immediate mobilisation. Pre- and postoperative X-rays, operative results and patient charts were reviewed. Furthermore, we prospectively evaluated the functional results using VAS, DASH and Mayo wrist scores. Lastly, we assessed the implant costs and compared them to locking plates. RESULTS: Thirty-four patients were treated with a mean age of 49 years. Mean radial shortening improved 2 mm; dorsal and radial angulation improved 23 and 4°, respectively. At consolidation (eight weeks) the average radial shortening was 0.75 mm, a volar angulation of 3°, and 21° of radial angulation. Functional results were excellent, demonstrated by a mean VAS score less than 1, a DASH score of 12 and a Mayo wrist score of 87. Compared to locking plates, there was an overall reduction in material costs of 15,300 Euro. CONCLUSIONS: Our technique has excellent biomechanical stability, enabling immediate functional rehabilitation, good anatomical and functional outcome with significantly lower costs.

Hypercalcemia in patients with bipolar disorder treated with lithium: a cross-sectional study.

BACKGROUND: Lithium-induced hyperparathyroidism (LIH) is a relative underrecognized complication of long-term lithium treatment. Hypercalcemia may be the first, but often overlooked, sign of LIH. Symptoms of LIH can be similar to the underlying psychiatric illness, which may cause a significant doctor's delay in diagnosing LIH. The aim of this study was to determine the prevalence of hypercalcemia in a cohort of psychiatric patients. METHODS: In this cross-sectional study, we collected data from 314 patients treated with lithium in an outpatient clinic for bipolar disorder. Patients with bipolar disorder from the same clinics, who had never been treated with lithium and of whom serum calcium levels were available, were included as controls (n = 15). Patient characteristics and laboratory results were collected during the period of June 2010 till June 2011. RESULTS: The mean serum calcium level was 2.49 (SD 0.11) mmol/l. The point prevalence of hypercalcemia (>2.60 mmol/l) was 15.6%. In a comparable group of psychiatric patients not using lithium, the mean serum calcium level was 2.37 mmol/l, and none of these patients had hypercalcemia (p = 0.001). The duration of lithium treatment was the only significant predictor for the development of hypercalcemia (p = 0.002). DISCUSSION: The prevalence of hypercalcemia in lithium-treated patients was significantly higher than that in non-lithium treated controls and correlated to the cumulative time lithium was used in this cross-sectional study. We recommend that serum calcium levels should be routinely tested in patients using lithium for timely detection of LIH or hypercalcemia due to other causes.

[Lithium-induced hyperparathyroidism]. / Lithium-geïnduceerde hyperparathyreoïdie.

Lithium is a medication successfully being used for the treatment of bipolar disorder. Lithium-induced hyperparathyroidism (LIH) is a little known complication that may arise due to the use of lithium. Symptoms of LIH are often similar to the underlying psychiatric illness for which lithium was indicated. It is thus difficult to differentiate between these, resulting in significant 'doctors' delay' in the diagnosis of LIH. The authors present three cases in this article. In the first case concerning a 51-year-old woman, they illustrate that LIH and subsequent hypercalcaemia are often diagnosed by coincidence. In the second case concerning a 47-year-old woman, they show that it can be quite complicated to locate the underlying aberration of the parathyroid and that medication may be an eligible alternative to surgery. In the third case, a 56-year-old woman, they show the need for cogency regarding appropriate surgical strategy as recurrences are quite common.

Randomized clinical trial of LigaSure versus conventional suture ligation in thyroid surgery.

BACKGROUND: In thyroid surgery vessel division and haemostasis make up an important and time consuming part of the operation. While the presence of the recurrent laryngeal nerve limits the liberal use of diathermia, the many arterial and venous branches to and from the thyroid gland necessitates the use of numerous conventional suture ligatures.This study evaluates the effect of using a vessel sealing system on operation time during thyroid surgery. METHODS: A randomized clinical trial was performed between September 2005 and October 2008 in a teaching hospital. Forty patients undergoing total hemithyroidectomy participated in the trial. Twenty were randomized to the intraoperative use of the LigaSure Precise™ vessel sealing system, and twenty to the use of conventional suture ligatures. RESULTS: The total median operation time was 10 minutes shorter in the LigaSure group (56 versus 66 minutes, P = 0.001). No significant differences in complications were noticed. CONCLUSION: Using an electrothermal vessel sealing system during thyroid surgery is time saving. TRIAL REGISTRATION: This trial was registered in the international standard randomized controlled trials number register (ISRCTNR) under number ISRCTNR82389535.

Topical diltiazem cream versus botulinum toxin a for the treatment of chronic anal fissure: a double-blind randomized clinical trial.

OBJECTIVE: A double-blind randomized clinical trial to compare topical diltiazem with botulinum toxin A (BTA) in the treatment of chronic anal fissure. BACKGROUND: Chronic anal fissures remain a challenging condition. Topical diltiazem and BTA are promising agents in the treatment of anal fissure. As to date diltiazem and BTA were never compared in a solid randomized trial, which is the purpose of this study. METHODS: One hundred thirty-four patients were randomized to receive either diltiazem cream and placebo injection or BTA injection and placebo cream. The primary end point was fissure healing after 3 months. RESULTS: After 3 months healing of the fissure was noted in 32 of 74 (43%) patients in the diltiazem group and 26 of 60 (43%) patients in the BTA group. Reduction >50% in mean pain score was noted in 58 of 74 (78%) patients in the diltiazem group and 49 of 60 (82%) patients in the BTA group. Perianal itching was the only side effect reported and was noted in 15% of patients in the diltiazem group, and this difference was statistically significant (P = 0.012). CONCLUSIONS: BTA yields higher healing rates in the short term, though after 3 months diltiazem and BTA resulted in equal healing rates. Also no significant difference in pain reduction was observed for both treatments. This study shows no significant advantage of one treatment compared to the other. This randomized clinical trial is registered by the Dutch Trial Register as NTR1012.

The additional value of intraoperative parathyroid hormone assessment is marginal in patients with nonfamilial primary hyperparathyroidism: a prospective cohort study.

BACKGROUND: The success of minimally invasive parathyroidectomy is attributed to evolving preoperative imaging techniques and intraoperative parathyroid hormone (IOPTH) measurement. The additional value of IOPTH measurement in patients undergoing surgery for primary hyperparathyroidism (pHPT) was evaluated. METHODS: Between 1999 and 2010 there were 119 patients who underwent surgery for pHPT at our institutions. In all patients, preoperative imaging was performed and IOPTH samples were collected prospectively but the results were not disclosed during surgery. RESULTS: Postoperative calcium level normalized in 114 patients (96%). The 5 surgical failures represented the maximum yield of IOPTH sampling. Three of these patients would have been identified intraoperatively by an inadequate IOPTH decrease, whereas IOPTH decreased inaccurately in the other 2 patients. In addition, in 1 of these 3 patients no abnormal gland was found during minimally invasive parathyroidectomy and subsequent conventional neck exploration. Therefore, only 2 reoperations would have been prevented (1.7%). CONCLUSIONS: IOPTH would have changed the outcome in 2 patients, increasing the biochemical cure rate from 96% to 98%. We believe that although it can be helpful in certain cases, it may not be necessary routinely in patients treated for pHPT.

Shifting incidence of solitary adenomas in the era of minimally invasive parathyroidectomy. A multi-institutional study.

BACKGROUND: Previously, when a conventional neck exploration (CNE) without preceding diagnostic imaging was the surgical treatment for patients with primary hyperparathyroidism (pHPT) solitary adenomas were observed in 69-88% of patients. The advent of minimally invasive parathyroidectomy (MIP), aiming at a preoperatively identified parathyroid abnormality may be associated with a different incidence of solitary and multiglandular parathyroid disease. MATERIALS AND METHODS: In a cohort of 467 patients with sporadic pHPT who preferentially underwent MIP in four hospitals in the same geographical region, the incidence of solitary adenomas, multiple adenomas, and multiglandular hyperplasia (MGD) was evaluated. RESULTS: A total of 367 patients were scheduled for MIP; 100 patients underwent a planned CNE. The overall surgical success rate of the first operation was 93%, and the cumulative success rate, including a second operative procedure, was 99%. Normocalcemia resulted from removing 1 abnormal PG in 426 patients (91%) and more than one abnormal gland in 35 patients (8%). A parathyroid carcinoma was diagnosed in four of the 426 patients with a single abnormal gland. Four gland hyperplasia was observed in 1 patient. In hospitals where diagnostic workup usually consisted of ultrasound (US) and computed tomography (CT) the incidence of solitary adenomas was 88%, compared with 96% in hospitals where MIBI, US, and CT were used preoperatively (P = 0.007). CONCLUSIONS: A higher frequency of solitary adenomas was observed than historically reported. The extent of the preoperative workup influences the number of observed solitary adenomas.

Identifying candidate Hirschsprung disease-associated RET variants.

Patients with sporadic Hirschsprung disease (HSCR) show increased allele sharing at markers in the 5' region of the RET locus, indicating the presence of a common ancestral RET mutation. In a previous study, we found a haplotype of six SNPs that was transmitted to 55.6% of our patients, whereas it was present in only 16.2% of the controls we used. Among the patients with that haplotype, 90.8% had it on both chromosomes, which led to a much higher risk of developing HSCR than when the haplotype occurred heterozygously. To more precisely define the HSCR-associated region and to identify candidate disease-associated variant(s), we sequenced the shared common haplotype region from 10 kb upstream of the RET gene through intron 1 and exon 2 (in total, 33 kb) in a patient homozygous for the common risk haplotype and in a control individual homozygous for the most common nonrisk haplotype. A comparison of these sequences revealed 86 sequence differences. Of these 86 variations, 8 proved to be in regions highly conserved among different vertebrates and within putative transcription factor binding sites. We therefore considered these as candidate disease-associated variants. Subsequent genotyping of these eight variants revealed a strong disease association for six of the eight markers. These six markers also showed the largest distortions in allele transmission. Interspecies comparison showed that only one of the six variations was located in a region also conserved in a nonmammalian species, making it the most likely candidate HSCR-associated variant.

Localizing a putative mutation as the major contributor to the development of sporadic Hirschsprung disease to the RET genomic sequence between the promoter region and exon 2.

Hirschsprung disease (HSCR), a congenital disorder characterized by intestinal obstruction due to absence of enteric ganglia along variable lengths of the intestinal tract, occurs both in familial and sporadic cases. RET mutations have been found in approximately 50% of the families, but explains only a minority of sporadic cases. This study aims at investigating a possible role of RET in sporadic HSCR patients. Haplotypes of 13 DNA markers, within and flanking RET, have been determined for 117 sporadic HSCR patients and their parents. Strong association was observed for six markers in the 5' region of RET. The largest distortions in allele transmission were found at the same markers. One single haplotype composed of these six markers was present in 55.6% of patients versus 16.2% of controls. Odds ratios (ORs) revealed a highly increased risk of homozygotes for this haplotype to develop HSCR (OR>20). These results allowed us to conclude that RET plays a crucial role in HSCR even when no RET mutations are found. An unknown functional disease variant(s) with a dosage-dependent effect in HSCR is likely located between the promoter region and exon 2 of RET.