bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of lumbar orthoses after posterior lumbar interbody fusion—a prospective randomized study
Authors: Fujiwara Hiroyasu , Makino Takahiro , Yonenobu Kazuo , Moriguchi Yu , Oda Takenori , Kaito Takashi
Published: April 2019

Background:

Lumbosacral orthoses (LSOs) are used as standard care after lumbar fusion surgery though their efficacy is unknown. The purpose of this prospective randomized controlled study was to elucidate the clinical and radiographic efficacies of LSO treatment in patients who underwent posterior lumbar interbody fusion (PLIF) of less than 3 segments.

Methods:

Seventy-three patients who underwent PLIF were randomly allocated to 3 groups: 1 with custom-made LSO with metallic stays (C group); 1 with ready-made LSO without metallic stays (R group), and 1 without LSO (N group). The patients in the C and R groups were instructed to wear LSO postoperatively for 3 months. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) score, JOA-back pain evaluation questionnaire (JOABPEQ), Roland-Morris Disability Questionnaire, and 100-mm visual analog scale for low back pain. Radiographic evaluation included intervertebral fusion rates and loss of correction postoperatively at 2 years.

Results:

A significant difference in the clinical outcomes was observed only for the lumbar dysfunction domain of JOABPEQ postoperatively at 1 month (N vs C groups; 45% vs 10%, P = .03). Radiographic outcomes were not different between the groups.

Conclusions:

No effect of orthosis treatment for less than 3 segments in PLIF was observed on clinical and radiographic outcomes. The type of orthosis also did not influence the outcomes. These results suggest that the use of LSO for PLIF can be simplified or is omissible except in patients with severe osteoporosis.
Laparoscopic approach to an incidentally found pelvic retroperitoneal liposarcoma
Authors: Mandato Vincenzo Dario , Mastrofilippo Valentina , De Marco Loredana , Aguzzoli Lorenzo
Published: April 2019

Rationale:

Well-differentiated liposarcomas (WDLPS) are rare retroperitoneal tumors that can reach significant size as they can grow without constrains before becoming symptomatic. Laparotomic open radical tumor resection represents the most common surgical approach.

Patient concerns:

A mass with “fat fluid level” was found in the right pelvis of an asymptomatic woman undergoing routine transvaginal ultrasound: the preoperative diagnosis was right mature ovarian teratoma.

Diagnosis:

Postoperative histopathology confirmed the diagnosis of WDLPS.

Interventions:

A radical laparoscopic excision of the retroperitoneal mass with bilateral salpingectomy was performed.

Outcomes:

Patient is free of disease at 18 months after surgery.

Lesson:

Despite computed tomography scan is the gold standard technique to identify WDLPS, such neoplasms can be misdiagnosed for mature ovarian teratomas. When a retroperitoneal mass is incidentally discovered during a surgery, an open core-needle biopsy is usually performed, and appropriate treatment planned only after complete staging and final pathology are available. Instead, when tumor margins are identified, resection of an incidentally diagnosed WDLPS would benefit from laparoscopic magnification that could improve distinguishing the disease from the surrounding tissues. Therefore, laparoscopy could represent a safe and effective technique to diagnose and treat retroperitoneal diseases.
Influence of previous corticosteroid treatment on the efficacy and safety of infliximab therapy in Crohn disease
Authors: Liu Ailing , Li Yue , Yang Hong , Lv Hong , Qian Jiaming
Published: April 2019

To determine the effect of prior corticosteroid treatment on the results of infliximab (IFX) therapy in patients with Crohn disease (CD).

Patients with CD treated with at least 3 IFX infusions between March 2009 and April 2017 were divided into steroid group (n = 43) and nonsteroid group (n = 22) and analyzed retrospectively.

The cumulative probabilities of clinical remission and response to IFX at weeks 14, 30, 54, and 78 were higher in the steroid group, though this difference was not statistical significant. At the mean interval of 11.7 months following the initiation of IFX treatment, the mucosal healing rate was significantly higher in the steroid group (71.0% vs 22.2%, P < .01). There was no statistical difference in the incidence of adverse reactions between the 2 groups.

In CD, patients with prior corticosteroid treatment may increase the response rate to IFX therapy.
Decreased catalase expression is associated with ligamentum flavum hypertrophy due to lumbar spinal canal stenosis
Authors: Yücetaş Şeyho Cem , Çakir Tayfun
Published: April 2019

Background:

This is an immunohistologic study of gene expression between patients and controls.

This study aims to evaluate expression of the catalase gene in hypertrophied ligamentum flavum (LF) specimens obtained from patients with lumbar spinal canal stenosis (LSCS).

LSCS is one of the most common spinal disorders. It is well known that LF hypertrophy plays an important role in the onset of LSCS. Although degenerative changes, aging, and mechanical stress are all thought to contribute to hypertrophy and fibrosis of the LF, the precise pathogenesis of LF hypertrophy remains unknown. Previous genetic studies have tried to determine the mechanism of LF hypertrophy. However, the association between catalase gene expression and LF hypertrophy has not yet been explored.

Methods:

LF specimens were surgically obtained from 30 patients with spinal stenosis (LSCS group) and from 30 controls with lumbar disc herniation (LDH group). LF thickness was measured at the thickest point using calipers to an accuracy of 0.01 mm during surgical intervention. The extent of LF elastin degradation and fibrosis were graded (grades 0–4) by hematoxylin and eosin staining and Masson trichrome staining, respectively. The resulting LF measurements, histologic data, and immunohistologic results were then compared between the 2 groups.

Results:

The average LF thickness was significantly higher in the LSCS group than in the LDH group (5.99 and 2.95 mm, respectively, P = .004). Elastin degradation and fibrosis of the LF were significantly more severe in spinal stenosis samples than in the disc herniation samples (3.04 ± 0.50 vs 0.79 ± 0.60, P = .007; 3.01 ± 0.47 vs 0.66 ± 0.42, P = .009, respectively). Significantly lower expression of catalase was observed in the perivascular area of LF samples obtained from patients with LSCS compared with controls (61.80 ± 31.10 vs 152.80 ± 41.13, respectively, P = .009).

Conclusion:

Our findings suggest that decreased expression of catalase is associated with LF hypertrophy in patients with LSCS.
Acupuncture for perioperative care of total hip arthroplasty
Authors: Shin Hee-Ra , Park Kyungtae , Seo Jihye , An Sung-Hu , Yeom Seung-Ryong , Kwon Young-Dal
Published: April 2019

Introduction:

This protocol is intended to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of acupuncture in perioperative care of total hip arthroplasty patients.

Methods and analysis:

The following databases will be searched from their inception to November 2018 without language restrictions: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature, Oriental Medicine Advanced Searching Integrated System, Korean Traditional Knowledge Portal, KoreaMed, DBPIA, Research Information Service System, including the China National Knowledge Infrastructure. Any randomized controlled trials related to perioperative care of total hip arthroplasty will be included. The primary outcomes of this study are dosage of analgesics and pain intensity. For secondary outcomes, Harris hip score, incidence of postoperative cognitive dysfunction, mini-mental state exam score, incidence of deep vein thrombosis, D-dimer and fibrinogen level, adverse events will be assessed. Data analysis and synthesis will be carried out using RevMan version 5.3. The methodological quality will be assessed by the Cochrane Collaboration risk of bias tool.

Systematic review registration:

PROSPERO CRD42018112123.
Cytogenetic and molecular characterization of an oligoasthenozoospermia male carrier of an unbalanced Y;22 translocation
Authors: Jia Chunshu , Li Linlin , Chen Shuang , Li Dejun , Wang Xuan , Liu Ruizhi , Zhang Hongguo
Published: April 2019

Rationale:

Y;autosome translocations are associated with male infertility and azoospermia. Some carriers with a Y:22 translocation can produce offspring and transmit the translocation through generations without phenotypic repercussion. Hence, the clinical features of carriers with certain Y chromosome abnormalities remain uncertain.

Patient concerns:

An apparently healthy 33-year-old man, 175 cm tall and weighing 60 kg had a 6-month history of primary infertility.

Diagnoses:

The patient was diagnosed with oligoasthenozoospermia. A series of examinations have been performed to evaluate possible genetic causes of this diagnosis. Several methods included semen analysis, hormone measurements, cytogenetic analysis, and high-throughput multiplex ligation-dependent probe amplification semiconductor sequencing.

Interventions:

The patient underwent detailed genetic counseling. Cytogenetic analysis was advised for his father. Preimplantation genetic diagnosis was performed to improve potential pregnancy success rate.

Outcomes:

Semen analysis revealed oligoasthenozoospermia. Hormone levels were within the normal limits. The karyotype of the patient and his father was 45,X,der(Y;22). Sequencing results indicated the presence of the sex-determining region on the Y chromosome gene. Y-chromosome microdeletion detection showed the presence of AZF (azoospermic factor)a, AZFb, and AZFc regions, but deletion of b2/b3 and duplication of b3/b4 regions.

Lessons:

A clinical karyotype report involving a Y chromosome abnormality should consider the results of semen analysis, which helps to identify the chromosomal breakpoint. Semiconductor sequencing technology was useful for clarifying AZF gene microdeletions.
Recurrence of papillary thyroid carcinoma from the residual pyramidal lobe: a case report and literature review
Authors: Wang Mingjun , Zou Xiuhe , Li Zhihui , Zhu Jingqiang
Published: April 2019

Rationale:

Recurrence of papillary thyroid carcinoma (PTC) usually requires a second operation, which carries a high complication rate, especially if central neck dissection (CND) is necessary. Recurrent PTC from pyramidal lobe is a rare entity, which is mainly due to non-standardized operation. However, literature on this topic is limited.

Patients concerns:

Here, we present a case of a 46-year-old woman with the recurrence of PTC from the thyroid pyramidal lobe (PL) following two thyroid operations.

Diagnoses:

The final pathological result revealed recurrent PTC from the residual pyramidal lobe tissue.

Interventions:

The resection of the residual PL, the pretracheal nodes and the Delphian nodes plus intraoperative neuromonitoring (IONM) were performed, followed by TSH suppression therapy.

Outcomes:

After two previous operations, the recurrent PTC from the residual pyramidal lobe tissue was completed resected. Until the latest follow-up, the patient had an excellent response to the third intervention.

Lessons:

Complete excision of the PL is mandatory in patients with PTC if thyroid surgery was indicated, considering the potential risk of recurrence from the PL and the high incidence of multifocality of PTC.
Benzbromarone as a possible cause of acute kidney injury in patients with urolithiasis
Authors: Ye Xiaolan , Wu Jian , Tang Kun , Li Wenge , Xiong Cunquan , Zhuo Li
Published: April 2019

Rationale:

Reports of acute kidney injury (AKI) associated with benzbromarone use in patients with hyperuricemia (HUA) are rare so far.

Patient concerns:

We describe 2 unique clinical patterns in which benzbromarone was a possible cause of AKI following self-medication for HUA. In case 1, a 45-year-old man developed AKI after taking 100 mg of benzbromarone. His serum creatinine (Scr) increased to 2.3 mg/dL on day 2 after benzbromarone administration. Ultrasound showed multiple small stones in both kidneys, and the 24-hour urine uric acid level was 3128 mg. In case 2, a 17-year-old male student presented with AKI after self-administration of 50 mg of benzbromarone. His Scr increased to 6.8 mg/dL on day 3 after benzbromarone administration. Ultrasound showed multiple stones in the left kidney.

Diagnosis:

Both patients underwent renal biopsy, with findings of acute tubular interstitial nephropathy in case 1 and acute tubular damage in case 2. Drug-induced AKI was considered.

Interventions:

Both cases were treated supportively with intravenous hydration only. In both patients, the Scr level recovered within 0.5 months and renal function was normal 3 months after discharge.

Lessons:

Oral benzbromarone is widely used in Asian counties to treat HUA and the adverse effects are mostly mild. However, clinicians should be alert for benzbromarone-induced AKI. Moreover, uricosuric drugs should only be used after exclusion of urolithiasis and other contraindications.
Polymer-free drug-eluting stents versus permanent polymer drug-eluting stents
Authors: Chen Yun-lin , Fan Jinqi , Chen Guozhu , Cao Li , Lu Li , Xu Yanping , Yin Yuehui
Published: April 2019

Background:

Polymer-free drug-eluting stents (PF-DES) have been demonstrated comparable to permanent polymer drug-eluting stents (PP-DES) during long-term follow-up. As a critical component of drug-eluting stents, antiproliferative drugs may be a confounding factor for the results. Thus, we sought to compare the outcomes of these stents during long-term follow-up, especially in consideration of different stent platforms with the same drugs.

Methods:

A systemic search was performed to identify the related randomized controlled trials comparing PF-DES with PP-DES. Primary outcomes included short (≤1 year) and long-term (>1 year) target lesion revascularization (TLR), short-term in-stent late luminal loss (LLL) and diameter stenosis (DS). Subgroup analyses stratified by the different platforms with the same proliferative drugs were conducted in TLR, LLL, and DS. Standardized mean differences (SMDs) and risk ratios (RRs) were estimated using fixed /random effects models

Results:

A total of 6927 patients extracted from 12 RCTs were enrolled in the meta-analysis. No differences were observed in clinical outcomes of short-term and long-term overall mortality, myocardial infarction and stent thrombosis and angiographic outcomes of short-term in-stent LLL and DS between PF-DES and PP-DES for patients with coronary artery lesions. Nevertheless, compared with PP-DES coated with the same proliferative drugs, PF-DES had significantly increased risks of in-stent LLL (SMD, 0.49; 95% confidence interval [CI], 0.25–0.72) and DS (SMD, 0.67; 95% CI, 0.27–1.07), and long-term TLR (RR, 1.64; 95% CI 1.13–2.39). There were no significant differences in other outcomes.

Conclusions:

Under the condition of using same antiproliferative drugs (paclitaxel or sirolimus) in different stent systems, PF-DES are associated with the increased risk of restenosis compared to PP-DES.
Acylcarnitine profile in neonatal hypoxic-ischemic encephalopathy
Authors: López-Suárez Olalla , Concheiro-Guisán Ana , Sánchez-Pintos Paula , Cocho Jose A. , Fernández Lorenzo José R. , Couce María L.
Published: April 2019

Optimal prognostic markers evaluating early neuroprotective interventions in neonatal hypoxic-ischemic encephalopathy (HIE) are lacking. This study was designed to assess the prognostic value of acylcarnitines in neonatal HIE.

An observational cohort study was conducted over 10 years in 67 HIE. Variables analyzed included sex, blood cord pH, Apgar score, hypothermia treatment (yes/no), neuron-specific enolase (NSE) levels, and clinical outcome (neurological examination, brain magnetic resonance imaging [MRI], and electroencephalogram) before discharge and at 6 months. Acylcarnitine profiles were analyzed by tandem-mass spectrometry on dried-blood spots collected on day 3 for newborn screening. A cohort of healthy newborns was used as control group.

HIE patients had significantly increased C4, C5, C5:1, C6, C6-OH, C8 levels (all P < .01) and decreased long-chain acylcarnitine levels (P < .03). Hypothermia treatment was associated with a decrease in C4 levels (p = 0.005) and an increase in most long-chain acylcarnitine levels (P < .01). A significant association was found between C4 levels and NSE on day 1 of hypothermia treatment (P = .002) and abnormal brain magnetic resonance imaging (MRI) at discharge (P = .037). In the hypothermia group, C4 levels decreased in patients with favorable outcomes but remained high in those who progressed unfavorably.

C4 appears to be a good prognostic marker in HIE, as blood levels correlated with NSE levels and abnormal MRI findings. Furthermore, hypothermia did not lead to decreased levels in patients with adverse outcomes.
Predictive value of early molecular response for deep molecular response in chronic phase of chronic myeloid leukemia
Authors: Wang Rui , Cong Yue , Li Caili , Zhang Chen , Lin Hai
Published: April 2019

To investigate the association of 3- and 6-month BCR-ABL transcript levels on the international scale (BCR-ABLIS) and other factors with deep molecular response (DMR) achievement in chronic myeloid leukemia (CML)-chronic phase (CP) patients receiving tyrosine kinase inhibitor (TKI) therapy.

We retrospectively analyzed the clinical data of 206 patients enrolled in our hospital between January 2010 and July 2018. These patients were initially diagnosed with CML-CP and received imatinib or nilotinib therapy. Early molecular response (EMR) was assessed based on BCR-ABLIS (IS: on the international scale) transcript level at 3 and 6 months. Potential factors impacting DMR achievement were identified using Cox proportional hazard regression models. The effects of EMR achievement on the cumulative incidence of MR4.0 were investigated via Kaplan–Meier analysis.

Multivariate Cox regression analysis showed that a BCR-ABLIS transcript level at 3 and 6 months of TKI therapy was an independent factor for the achievement of MR4.0, which was nevertheless not related to age, gender, Sokal score, hemoglobin level, or white blood cell (WBC) count at the initial time of diagnosis. Patients achieving an EMR (EMR: 3-month BCR-ABLIS ≤10%, 6-month BCR-ABLIS <1%) were more likely to reach MR4.0 than patients failing to achieve EMR (P
1 <.001, P
2 <.001). Patients who had 3-month BCR-ABLIS ≤1% were more likely to reach MR4.0 than those who had 3-month BCR-ABLIS of 1% to 10% or >10% (P
1 = .001, P
2 <.001). Similarly, patients who had 6-month BCR-ABLIS ≤0.1% were more likely to achieve MR4.0 than those in the 0.1% to 1% and ≥1% groups (P
1 <.001, P
2 <.001). Also, a higher percentage of patients on nilotinib therapy achieved EMR compared with patients on imatinib therapy (93.3% vs 63.6% on 3-month nilotinib therapy, P = .001; 88.9% vs 59.9% on 6-month nilotinib therapy, P = .004).

This study demonstrates that EMR, especially a 3-month BCR-ABLIS ≤1% and 6-month BCR-ABLIS ≤0.1%, have predictive value for DMR achievement. In addition, there is a higher percentage of patients receiving nilotinib therapy achieved EMR than that of those receiving imatinib therapy.
Effects of physical therapy on lung function in children with asthma
Authors: Wang Qiu , Zhang Weijian , Liu Lilong , Yang Wenhao , Liu Hanmin
Published: April 2019

Background:

Morbidity of asthma in children is increasing, which is significantly affecting children's life quality. Despite the medication therapy, physical therapies, including breathing exercises, inspiratory muscle training and physical training, are widely used to improve children's condition. However, the effectiveness of physical therapy remains unclear. This systematic review and meta-analysis is aiming to evaluate the effects of physical therapy on lung function in children with asthma and to assess which physical therapy is more effective.

Methods:

Three main databases (PubMed, Embase, and the Cochrane Library) will be searched from inception to November 30, 2018 for randomized controlled trials investigating the effects of physical therapy on lung function in children (age < 18 years old) with asthma published in English. In addition, a manual search of the references of relevant published studies in English will also be considered.

Two independent reviewers will conduct studies selection, data extraction, and risk of bias assessment. Outcome measures will be the Peak Expiratory Flow (PEF), the Forced Expiratory Volume in the first second (FEV1), and the Forced Vital Capacity (FVC). Subgroup analyses will be performed according to the physical therapy (breathing exercises, inspiratory muscle training, and physical training) and the outcome (PEF, FEV1, FVC).

Results:

The results will provide useful information about the effect of physical therapy on lung function in children with asthma and demonstrate which physical therapy is more effective.

Conclusion:

The findings of this study will be published in a peer-reviewed journal.

Prospero registration number:

CRD42019121627
A systematic review and meta-analysis of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) versus traditional staged hepatectomy
Authors: Liu Yanmo , Yang Yingxin , Gu Shenglong , Tang Kezhong
Published: April 2019

It is still controversial whether associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or traditional staged hepatectomy such as portal vein embolization (PVE) and 2-staged hepatectomy (TSH) is better. The aim of this study was to compare these 3 available strategies in extended hepatectomy.

Trials were identified by searching MEDLINE, PubMed, the Cochrane Library, and Embase and additional articles were identified by hand searching. Comparative clinical studies reporting volumetric changes, mortality, morbidity, and feasibility of the second stage about ALPPS versus PVE or ALPPS versus TSH were included.

Nine studies involving 557 patients met the inclusion criteria. Five studies reported on comparison of ALPPS and PVE, and the other 4 reported about ALPPS and TSH. In the comparison of ALPPS versus traditional staged hepatectomy (PVE and TSH), ALPPS was associated with a greater increase in the future liver remnant (FLR) (RR: 4.87; 95%CI, 3.41–6.33) and more frequent completion of stage 2 resection (RR: 1.32; 95%CI, 1.21–1.44). Compared with the traditional staged hepatectomy, ALPPS had a trend toward higher morbidity (RR: 1.19, 95%CI, 0.96–1.47) and mortality (RR: 2.11, 95%CI, 1.02–4.33) after stage 2 resection.

ALPPS is associated with greater future liver remnant hypertrophy and a higher rate of completion of stage 2, but this may be at the price of greater morbidity and mortality.
Calcineurin B1 subunit in human peripheral blood mononuclear cells and its role in idiopathic membranous nephropathy
Authors: Zhu Ying , Zhang Min , Wang Fan , Sun Jing , Lu Jianda , Chen Ruiying , Xie Qionghong , Xue Jun , Hao Chuanming , Lin Shanyan
Published: April 2019

The immune responses involved in the pathogenesis of idiopathic membranous nephropathy (IMN) have not been fully understood. Calcineurin, a key signaling enzyme in T-cell activation, may be implicated in IMN. The present study aimed to investigate the role of calcineurin B1 subunit (CnB1) in IMN and the potential mechanism.

A total of 59 biopsy-proven IMN patients and 28 healthy controls were recruited. The CnB1 expression in human peripheral blood mononuclear cells (PBMCs) was assessed by Western blotting. Knockdown and overexpression of CnB1 in Jurkat T cell line were achieved by small interference RNA (siRNA) transfection and lentiviral transduction, respectively.

It was found that PBMCs CnB1 expression was significantly increased in IMN patients (P = .002), but unrelated to the severity and prognosis of IMN. Knockdown of CnB1 in Jurkat cells inhibited the nuclear factor of activated T cells (NFAT)-regulated gene expression required for T-cell activation.

Our study suggested the potential role of CnB1 in the occurrence of IMN. The mechanism maybe involved the effect of CnB1 on the T-cell activation mediated by calcineurin-NFAT signaling.
Solitary adrenal metastasis from advanced gastric cancer invading duodenal bulb with situs inversus totalis
Authors: Xue Wangsheng , Li Yongbo , Zhao Zeyun , Li Wei , Wang Shuang , Zhang Mingwei , Liu Tongjun , Wang Min
Published: April 2019

Rationale:

Situs invsersus totalis (SIT) is a rare anomaly featured by complete inversion of abdominal and thoracic organs. Adrenal metastasis is often encountered as part of advanced systemic dissemination, which is usually unresectable. Few published cases reported the adrenal metastasis from gastric cancer with SIT and the treatment of gastrectomy combined with adrenalectomy, especially with intraoperative radiotherapy (IORT).

Patient concerns:

A 61-year-old SIT man found a mass on the right clavicle and the biopsy revealed a metastatic cancer. Around 14 years ago, he had a rectal cancer resection surgery and no sign of occurrence. Five months later, the patient had a pain in his right low abdomen and abdominal CT found a right adrenal mass.

Diagnoses:

Gastroscopy and the pathology revealed the gastric antrum cancer invading the duodenal bulb. Abdominal enhanced CT suspected the adrenal mass as a hematoma, but positron emission tomography computed tomography suspected it as the metastases of gastric cancer which is consistent with the pathology results. Finally, the SIT patient was diagnosed with primary gastric cancer invading duodenal bulb with solitary right adrenal metastasis.

Interventions:

The patient was treated with curative distal gastrectomy and Billroth-II anastomosis with D2 lymphadenectomy. A total 18 Gy intraoperative radiotherapy (IORT) using low energy x-rays by Intrabeam were given after resection.

Outcomes:

The patient had liver metastasis in the seventh month after surgery but there is no sign of local recurrence until now.

Lessons:

Gastric cancer with adrenal metastasis, especially with SIT is rare and intractable. The result suggested that active surgical treatment for resectable gastric cancer and solitary adrenal metastatic tumor, especially in combination with IORT may be an option in controlling local relapse and prolonging survival in selected patients.
Efficacy of acyclovir for herpes simplex encephalitis
Authors: Wang Wei , Ji Meng
Published: April 2019

Background:

Clinical researches indicate that acyclovir can be used to herpes simplex encephalitis (HSE). However, no systematic review has explored its efficacy for the treatment of HSE. Therefore, this study systematically will investigate the efficacy and safety of acyclovir for patients with HSE.

Methods:

We will search the following databases from inceptions to March 1, 2019 without any language restrictions: Cochrane Library, Embase, MEDICINE, PsycINFO, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. This study will include randomized controlled trials that assess the efficacy and safety of acyclovir for patients with HSE. Two authors will independently carry out the study selection, data extraction, and risk of bias assessment. Cochrane risk of bias tool will be used to assess the risk of bias assessment.

Results:

This study will systematically assess the efficacy and safety of acyclovir for HSE. The primary outcome is mortality rate, which is measured by Glasgow coma score, or other instruments. The secondary outcomes include quality of life, as assessed by 36-Item Short Form Health Survey or relevant scales; overall survival, the number of patient who died; the number of patient who had severe sequelae, and adverse events.

Conclusions:

The findings of this study may provide the existing evidence on the efficacy and safety of acyclovir for HSE.

PROSPERO registration number:

PROSPERO CRD42019125999.
Options for the Interpretation of and Recommendations for Acting on Different PROMs in Daily Clinical Practice Using KLIK
Authors: Haverman Lotte , van Oers Hedy A. , van Muilekom Maud M. , Grootenhuis Martha A.
Published: April 2019

Introduction:

This paper describes the different ways in which information is being fed back to health care providers (HCPs) using the Dutch evidence-based KLIK Patient-Reported Outcome Measures (PROMs) portal (www.hetklikt.nu). KLIK was initially developed for children with a chronic illness and their parents, and recently expanded for use in adult health care. Patients complete online PROMs at home about their health-related quality of life (HRQOL), symptoms and/or psychosocial functioning before an outpatient consultation with their HCP. PROMs are subsequently converted into an individual KLIK electronic (e)PROfile and discussed during the consultation to facilitate systematic attention for HRQOL.

Methods for PRO Score Interpretation:

KLIK includes a variety of different PROMs. The KLIK ePROfile initially consisted of literal representations of the individual PROM items in the European traffic light colors (red, orange, green) and only one graph. Over the years, the KLIK ePROfile evolved into a broader spectrum of feedback options; (1) literal representation of individual items, (2) summary scores, and (3) graphic representations (4 options).

Developing Recommendations for Acting on PRO Results:

The primary goal of KLIK is to longitudinally monitor patient and parent self-reported or proxy-reported health outcomes, which means that the focus of KLIK is not mainly on recommending actions for PRO results. However, there are several aids that help interpretation of the KLIK ePROfile and recommendations are given for actions based on PROM scores. The main aid is the KLIK training, which includes a theoretical and a practical part. In the training, 2 tools—a decision tree and a summary of information about the KLIK ePROfile—are given to the HCPs to assist them in using KLIK.

Discussion:

Customization of a PROM portal is needed for each different patient group and clinical setting. Because the KLIK website is flexible, every PROM (with good psychometric qualities and permission of the publisher) can be built in. However, implementing and feeding back PROMs in pediatric health care encompasses different challenges, because different versions of the same PROM are needed for children of different ages, as well as proxy and self-report versions.
A Decade in Review
Authors: Barbera Lisa , Moody Lesley
Published: April 2019

Background:

In 2007 Cancer Care Ontario (CCO) implemented standardized systematic symptom evaluation in all cancer patients in Ontario using the Edmonton Symptom Assessment System. The initial implementation did not include symptom management guidance and this limited the success of the implementation. Within a short time, the need for guidance on how to respond to symptoms became apparent.

Objective:

To describe how CCO has approached electronic symptom monitoring and related clinical response to symptom scores.

Results:

CCO’s approach to symptom management includes acknowledgment, assessment, and intervention steps. In partnership with the Program in Evidence Based Care, CCO developed guidance documents for management of each of the symptoms assessed with Edmonton Symptom Assessment System. These materials included an in-depth document similar to the full guidelines created by Program in Evidence Based Care for cancer treatment topics, a shorter pocket guide, and a 1-page algorithm. The guidance was aligned with symptom score severity. The 1-page algorithm was the most popular format of these materials. When time for revisions came, only this document was revised. When additional PRO measures were implemented, the plan ensured that the launch included a bundle of clinician-facing and patient-facing guidance materials together with the measure. All resources are accessible from a mobile-friendly website.

Conclusions:

Providing clear guidance for symptom management is an important part of successful PRO measure implementation. Involving a wide range of stakeholders early in the creation of such resources facilitates implementation and team building.
Interpreting and Acting on PRO Results in Clinical Practice
Authors: Blackford Amanda L. , Wu Albert W. , Snyder Claire
Published: April 2019

Introduction:

We have used several methods to aid in the interpretation of patient-reported outcome (PRO) scores, and to suggest recommendations for acting on them, both within the PatientViewpoint system and in work done since.

Methods for Interpreting PRO Scores:

For identifying possibly concerning change scores, PatientViewpoint uses questionnaires’ minimally important differences or score worsening >½ SD. For poor scores in absolute terms, PatientViewpoint primarily uses distributions based on normative data (eg, worst quartile, >2 SD from the mean). To advance methods for score interpretation, we explored using needs assessments to identify health-related quality-of-life scores associated with unmet needs and requiring follow-up. We also investigated the ability of PRO scores to predict patients’ most bothersome issues.

Methods for Addressing PRO Results:

To develop suggestions for addressing issues identified by PRO questionnaires, we conducted a targeted literature review, interviewed experts from different disciplines, developed draft recommendations based on the literature and interviews, and finalized the recommendations in a consensus meeting with all experts.

Discussion:

The needs assessment method requires strongly correlated content in the needs assessment and health-related quality-of-life questionnaire. Additional research is needed to explore using the worst scores in absolute terms to identify patients’ most bothersome issues. The approach described for developing suggestions for addressing PRO results focuses on local resources and is best-suited for a local context.

Key Points:

A combination of pragmatic solutions and exploratory research can inform interpreting and acting on PRO scores.
Turning Feed-forward and Feedback Processes on Patient-reported Data into Intelligent Action and Informed Decision-making
Authors: Oliver Brant J. , Nelson Eugene C. , Kerrigan Carolyn L.
Published: April 2019

Introduction:

The collection of patient-reported outcomes (PROs) in routine clinical practice provides opportunities to “feed-forward” the patient’s perspective to his/her clinical team to inform planning and management. This data can also be aggregated to “feedback” population-level analytics that can inform treatment decision-making, predictive modeling, population-based care, and system-level quality improvement efforts.

Methods Aiding Interpretation and Acting on Results:

Three case studies demonstrate a number of system-level features which aid effective PRO interpretation: (1) feed-forward and feedback information flows; (2) score interpretation aids; (3) cascading measurement; (4) registry-enabled learning health care systems; and (5) the maturational development of information systems.

Discussion:

The case studies describe the developmental span of feed-forward PRO programs—from simple to mature applications. The Concord Hospital (CH) Multiple Sclerosis Neurobehavioral Clinic exemplifies a simple application in which PRO data are used before and during clinic visits by patients and clinicians to inform care. The Dartmouth-Hitchcock (D-H) Spine Center exemplifies a mature program which utilizes population-level analytics to provide decision support by predicting outcomes for different treatment options. The Swedish Rheumatology Quality (SRQ) Registry epitomizes an exceptional application which has spread to multiple systems across an entire country.

Key Points:

Feed-forward and feedback PRO information systems can better inform, involve, and support clinicians, patients and families, and allow health systems to monitor and improve system performance and population health outcomes. Ideal systems have the capability for multilevel analyses at patient, system, and population levels, and an information technology infrastructure that is linked to associated workflows and a supportive practice culture. As systems mature, they progress beyond the ability to describe and inform towards higher level capabilities including prediction and decision support. Finally, there is additional promise for the integration of patient-reported information that is adjusted (or weighted) by preferences and values to guide shared decision-making and inform individualized precision health care in the future.
A PRO-cision Medicine Methods Toolkit to Address the Challenges of Personalizing Cancer Care Using Patient-Reported Outcomes
Authors: Snyder Claire , Brundage Michael , Rivera Yonaira M. , Wu Albert W.
Published: April 2019

Patients are increasingly being asked to complete standardized, validated questionnaires with regard to their symptoms, functioning, and well-being [ie, patient-reported outcomes (PROs)] as part of routine care. These PROs can be used to inform patients’ care and management, which we refer to as “PRO-cision Medicine.” For PRO-cision Medicine to be most effective, clinicians and patients need to be able to understand what the PRO scores mean and how to act on the PRO results. The papers in this supplement to Medical Care describe various methods that have been used to address these issues. Specifically, the supplement includes 14 papers: 6 describe different methods for interpreting PROs and 8 describe how different PRO systems have addressed interpreting PRO scores and/or acting on PRO results. As such, this “Methods Toolkit” can inform clinicians and researchers aiming to implement routine PRO reporting into clinical practice by providing methodological fundamentals and real-world examples to promote personalized patient care.
Interpreting and Acting on the PRO Scores From the Patient-reported Outcomes for Personalized Treatment and Care (PROMPT-Care) eHealth System
Authors: Girgis Afaf , Durcinoska Ivana , Arnold Anthony , Delaney Geoff P.
Published: April 2019

Introduction:

Patient-reported Outcomes for Personalized Treatment and Care (PROMPT-Care) is the first eHealth system in Australia that is fully electronically integrated into hospital oncology information systems, enabling real-time, routine collection of patient-reported outcomes (PROs) to support and enable cancer patients to achieve and maintain improved health, well-being, and cancer outcomes. Five previously published papers detail the impetus for developing this eHealth system, its development, and testing of its acceptability and feasibility, the development of algorithms to standardize the cancer care pathways which underpin patient care, and the protocol for evaluating the efficacy of PROMPT-Care.

Methods:

This manuscript provides “how-to” guidance to inform future system development, focusing on selecting relevant PROs and measuring them in cancer patients, score interpretation, and determining recommended care in response to scores which are above the predetermined threshold.

Discussion:

Electronic PRO systems are increasingly used in cancer clinical care settings, with the potential to support timely patient-centered care when implemented appropriately.

Key Points:

PRO selection should consider patient response burden, and prioritizing PROs that are amenable to clinical intervention. Having clear, evidence-based, care pathways, and actionable recommendations in response to above-threshold PRO scores facilitate PRO integration into the clinical workflow. Centers should determine thresholds for clinical action for each PRO which provide an acceptable balance between false positives and false negatives; and develop care pathway recommendations which consider the availability of local services and resources, are feasible in the clinical setting, clear, concise, manageable, based on evidence-based guidelines, and adaptable to local environments.
Using Stakeholder Engagement to Overcome Barriers to Implementing Patient-reported Outcomes (PROs) in Cancer Care Delivery
Authors: Stover Angela M. , Tompkins Stricker Carrie , Hammelef Karen , Henson Sydney , Carr Philip , Jansen Jennifer , Deal Allison M. , Bennett Antonia V. , Basch Ethan M.
Published: April 2019

Introduction:

Patient-reported outcome (PRO) measures used during cancer care delivery improve communication about symptoms between patients and clinicians and reduce service utilization for uncontrolled symptoms. However, uptake of PROs in routine cancer care has been slow. In this paper, we describe stakeholder engagement activities used to overcome barriers to implementing PROs. Implementation occurred in 2 study settings: PROs completed in the waiting room and reviewed during clinical visits to guide symptom management for multiple myeloma (visit-based PROs); and weekly PROs completed by cancer patients between chemotherapy visits to monitor symptoms at home (remote PROs).

Methods:

PRO implementation steps across studies included: (1) clinician and patient input on key symptoms, PRO measures, and identifying which PRO responses are clinically concerning to better target nursing actions; (2) developing PRO-based clinical decision support (CDS) for responding to concerning PROs; (3) training clinicians and clinical research assistants to interpret PROs and use software; and (4) describing implementation impact (frequency of concerning PRO responses and nursing actions).

Discussion:

Clinician and patient input was critical for identifying key symptoms, PRO measures, and clinically concerning response options. For the visit-based PRO observational study, all symptom scores appeared on a clinician dashboard, and those rated ≥1 by patients (on a 0–4 or 0–10 scale) had PRO-based CDS available for access. For the 2 remote PROs trials, stakeholders recommended that the 2 “worst” response options (eg, PRO responses of “often”/“always” or “severe”/“very severe”) would trigger an automated email alert to a nurse along with PRO-based CDS. In each study, PRO-based CDS was tailored based on clinician input. Across studies, the most common nursing response to concerning PROs was counseling patients on (or providing care plans for) self-management of symptoms. In the trials, the percentage of weekly remote PROs generating an alert to a nurse ranged from 13% at an academic center to 36% in community oncology practices.

Key Points:

Across 3 prospective studies, PROs implemented into cancer care enabled tailored care based on issues identified on PROs. Stakeholder engagement was critical for successful implementation. This paper assists in addressing important PRO implementation challenges by describing a stakeholder-driven approach.
Can Methods Developed for Interpreting Group-level Patient-reported Outcome Data be Applied to Individual Patient Management?
Authors: King Madeleine T. , Dueck Amylou C. , Revicki Dennis A.
Published: April 2019

Background:

Patient-reported outcome (PRO) data may be used at 2 levels: to evaluate impacts of disease and treatment aggregated across individuals (group-level) and to screen/monitor individual patients to inform their management (individual-level). For PRO data to be useful at either level, we need to understand their clinical relevance.

Purpose:

To provide clarity on whether and how methods historically developed to interpret group-based PRO research results might be applied in clinical settings to enable PRO data from individual patients to inform their clinical management and decision-making.

Methods:

We first differentiate PRO-based decision-making required at group versus individual levels. We then summarize established group-based approaches to interpretation (anchor-based and distribution based), and more recent methods that draw on item calibrations and qualitative research methods. We then assess the applicability of these methods to individual patient data and individual-level decision-making.

Findings:

Group-based methods provide a range of thresholds that are useful in clinical care: some provide screening thresholds for patients who need additional clinical assessment and/or intervention, some provide thresholds for classifying an individual’s level of severity of symptoms or problems with function, and others provide thresholds for meaningful change when monitoring symptoms and functioning over time during or after interventions. Availability of established cut-points for screening and symptom severity, and normative/reference values, may play into choice of PRO measures for use in clinical care. Translatability of thresholds for meaningful change is more problematic because of the greater reliability needed at the individual-level versus group-level, but group-based methods may provide lower bound estimates. Caution is needed to set thresholds above bounds of measurement error to avoid “false-positive changes” triggering unwarranted alerts and action in clinic.

Conclusions:

While there are some challenges in applying available methods for interpreting group-based PRO results to individual patient data and clinical care—including myriad contextual factors that may influence an individual patient’s management and decision-making—they provide a useful starting point, and should be used pragmatically.
Applying PRO Reference Values to Communicate Clinically Relevant Information at the Point-of-care
Authors: Jensen Roxanne E. , Bjorner Jakob B.
Published: April 2019

Introduction:

The inclusion of reference values for common patient-reported outcomes (PROs) measures in clinical care settings provides a clinically relevant context for an individual patient’s PRO scores. PRO reference values are currently not reported in clinical care settings. This is a missed opportunity, as clinicians are familiar with the presence and interpretation of reference values, commonly provided alongside laboratory test results. Incorporating PRO reference values into clinical PRO reporting requires: an understanding of the clinical purpose, the availability of an appropriate reference value, and graphical representation.

Methods for PRO Score Interpretation:

We present reference value terminology adapted for PROs and discuss important differences between using reference values in the PRO score interpretation compared to other types of clinical measures from clinical chemistry. We outline the basic methodological approaches in obtaining a PRO reference sample and calculating reference intervals. Lastly, we provide recommendations on how to present and use PRO reference values in clinical care settings.

Discussion:

There is a strong, long-standing discipline behind reference value development and application in psychology and medicine, allowing for both providers and patients to understand comparisons and identify what is “out of range.” PRO reference values can be communicated in a wide range of ways within clinical care settings and are adaptable as required to different patient populations or clinical care situations. However, a notable adoption barrier is the expense and methodological expertise needed to establish and apply PRO reference values effectively in clinical encounters.