bluuebunny/crossref_metadata_2025 huggingface dataset:
PENGARUH SUBTITUSI LIMBAH PERUT IKAN TONGKOL (Euthynnus affinis) PADA PAKAN TERHADAP PERTUMBUHAN DAN EFISIENSI PAKAN IKAN NILA (Oreochromis niloticus)
Authors: Karyanto Agoeng , Hadijah Hadijah , Indrawati Erni
Published: February 2021

Penelitian ini bertujuan untuk mengetahui pengaruh substitusi limbah perut ikan Tongkol (Euthynnus affinis) terhadap per-tumbuhan, efisiensi pakan dan konsentrasi yang optimal dalam meningkatkan pertumbuhan ikan Nila (Oreochromis niloticus) dan mengacu pada pemanfaatan bahan baku limbah usus ikan tongkol sebagai bahan alternatif pengganti bahan baku tepung ikan yang mahal. Penelitian ini merupakan jenis penelitian kuantitatif, menggunakan metode eksperimental yang terdiri atas 4 per-lakuan yaitu P0 (Protein 27%), P1 (Protein 20%), P2 (Protein 25%), dan P3 (Protein 30%). Data dianalisis dengan menggunakan analysis of variance (ANOVA). Parameter uji dalam penelitian ini meliputi Laju Pertumbuhan Spesifik, Pertumbuhan Mutlak, dan Efisiensi Pakan. Hasil penelitian menunjukkan rata-rata laju pertumbuhan spesifik  benih ikan Nila (Oreochromis niloticus) berkisar antara 0.65-94%, pertumbuhan mutlak berkisar antara 2-3 gr, efisiensi pakan berkisar antara 4-5%, dan subtitusi tepung usus ikan tongkol (Euthynnus affinis) tidak berpengaruh nyata terhadap laju pertumbuhan spesifik (P>0,05), sedangkan per-tumbuhan mutlak dan efisiensi pakan berpengaruh nyata terhadap subtitusi tepung usus ikan Tongkol (Euthynnus affinis) (p<0,05).
This study aims to determine the effect of substitution of Euthynnus affinis on growth, feed efficiency and optimal concentration in increasing the growth of tilapia (Oreochromis niloticus) and referring to the use of raw materials for tuna intestine waste as an alternative ingredient for the expensive fish flour starch. This study is quantitative research, using an experimental method consisting of 4 treatments, namely P0 (Protein 27%), P1 (Protein 20%), P2 (Protein 25%), and P3 (Protein 30%). Data were analyzed using analysis of variance (ANOVA). Test parameters in this study include Specific Growth Rate, Absolute Growth, and Feed Efficiency. The results showed that the average specific growth rate of tilapia seeds (Oreochromis niloticus) ranged from 0.65% to 0.94%, absolute growth ranged from 2 gr to 3 gr, feed efficiency ranged from 4% to 5%, and substitution of tuna fish intestine flour (Euthynnus affinis) did not significantly affect the specific growth rate (P> 0.05), while absolute growth and feed efficiency significantly affected the substitution of flour of the tuna fish intestine (Euthynnus affinis) (p <0.05).
PENGAYAAN PAKAN BENIH RAJUNGAN (Portunus Pelagicus) STADIA MEGALOPA MELALUI PEMBERIAN BETA KAROTEN
Authors: Yusneri Andi , Budi Sutia , Hadijah Hadijah
Published: February 2021

Penelitian ini bertujuan untuk meningkatkan nilai nutrisi pakan alami rotifer dan artemia melalui penambahan beta karoten yang bersumber dari wortel. Penelitian ini dilaksanakan pada bulan Mei 2020 di unit pembenihan kepiting dan rajungan Balai Pe-rikanan Budidaya Air Payau (BPBAP) Takalar.  Rancangan penelitian yang digunakan adalah rancangan acak lengkap (RAL) sebanyak 4 perlakuan dan 3 ulangan. Hewan uji yang digunakan adalah larva rajungan (Portunus Pelagicus) stadia megalopa yang ditebar dengan kepadatan 5 ekor/l dan dipelihara sampai memasuki stadia crab. Luaran penelitian yang ditargetkan adalah teknologi pengayaan pakan alami rotifer dan artemia menggunakan beta karoten yang berasal dari wortel. Hasil penelitian menunjukkan bahwa Pemberian frekwensi pakan yang tepat setelah dikayakan  dengan beta caroten akan meningkatkan sintasan dan pertumbuhan  pada larva rajungan. Frekwensi pakan yang tepat diberikan pada larva rajungan yang terbaik untuk kelang-sungan hidup larva rajungan adalah pemberian pakan 3 kali/hari.
This study aims to increase the nutritional value of natural rotifer and artemia feed by adding beta carotene from carrots. This research was conducted in May 2020 at the hatchery unit of the Brackish Water Cultivation Fishery Center (BPBAP) Takalar. The research design used was a completely randomized design (CRD) with 4 treatments and 3 replications. The experimental animals used were small crab larvae (Portunus pelagicus) in the megalopa stage which were stocked with a density of 5 individuals/l and they were kept until entering the crab stage. The target output of this research is natural feed enrichment technology for rotifer and artemia using beta carotene derived from carrots. The results showed that giving the right frequency of feed after being enriched with beta carotene would increase survival and growth in small crab larvae. The best frequency of feed given to small crab larvae for the survival of small crab larvae is feeding 3 times/day.
PENGARUH NON PERFORMING LOAN, LOAN DEPOSIT TO RATIO, BEBAN OPERASIONAL PENDAPATAN OPERASIONAL DAN BANK SIZE TERHADAP PROFITABILITAS MELALUI CAPITAL ADEQUACY RATIO
Authors: Dahlan Dahlan , Lewangka Osman , Menne Firman
Published: February 2021

Tujuan dari penelitian ini adalah untuk mengetahui pengaruh langsung dan tidak langsung Non Performing Loan, Loan to Deposit Ratio, Beban Operasional Pendapatan Operasional dan Bank Size terhadap Profitabilitas melalui Capital Adequacy Ratio pada bank yang terdaftar di BEI periode 2014-2018. Sampel yang digunakan dalam penelitia ini adalah Bank BUMN yang terdiri dari empat Bank dan BUSN Devisa yang terdiri dari 10 Bank. Analisis yang digunakan untuk mengetahui hubungan langsung dan tidak langsung Non Performing Loan, Loan to Deposit Ratio, Beban Operasional Pendapatan Operasional dan Bank Size terhadap Profitabilitas Melalui Capital Adequacy Ratio adalah menggunakan Path Analysis. Berdasarkan hasil penelitian secara parsial Non Performing Loan dan Bank Size tidak terdapat pengaruh secara langsung dan tidak langsung terhadap Profitabilitas. Sedangkan Loan to Deposit Ratio dan Beban Operasional Pendapatan Operasional terdapat pengaruh langsung dan tidak langsung terhadap profitabilitas. Secara simultan dapat dilihat bahwa hasil uji simultan untuk Model 1 diperoleh nilai Fhitung sebesar 229.734 dengan p-value sebesar 0.000 (< 0.05), dan untuk Model 2del 2 diperoleh nilai Fhitung sebesar 11.655 dengan p-value sebesar 0.000 (< 0.05)
The purpose of this study is to determine the direct and indirect effects of Non-Performing Loans, Loan to Deposit Ratio, Operational Expenses of Operational Income and Bank Size on the Profitability through Capital Adequacy Ratio on banks listed on the Indonesia Stock Exchange in the period of 2014-2018. The samples used in this research are BUMN Banks consisting of four Banks and Foreign Exchange BUSN consisting of 10 Banks. The analysis used to determine the direct and indirect relationship of Non-Performing Loans, Loan to Deposit Ratio, Operating Expenses of Operational Income and Bank Size to the Profitability through Capital Adequacy Ratio is Path Analysis. Based on the results of the research in partial analysis, Non-Performing Loans and Bank Size have no direct and indirect effect on the profitability. However, Loan to Deposit Ratio and Operational Expenses of Operational Income have a direct and indirect effect on the profitability. Simultaneously, it can be seen that the simultaneous test results for Model 1 obtained Fcount value of 229,734 with p-value of 0,000 (<0.05), and for the 2del 2 Model obtained Fcount value of 11,655 with p-value of 0,000 (<0.05).
PENGARUH KEPEMIMPINAN, BUDAYA ORGANISASI DAN DISIPLIN KERJA TERHADAP KINERJA PEGAWAI PADA DINAS KESEJAHTERAAN SOSIAL KABUPATEN DEIYAI PROVINSI PAPUA
Authors: Edowai Robert , Abubakar Herminawati , Mane Arifuddin
Published: February 2021

Sumber Daya Manusia (pegawai) merupakan unsur yang strategis   dalam   menentukan   sehat   tidaknya   suatu organisasi. Pengembangan SDM yang terencana dan berkelanjutan merupakan kebutuhan yang mutlak terutama untuk masa depan organisasi. Tujuan penelitian ini adalah untuk mengetahui dan menganalisis pengaruh kepemimpinan, budaya organisasi, dan disiplin kerja terhadap kinerja pengawai pada Dinas Kesejahteraan Sosial  Kabupaten  Deiyai  Kabupaten  Papua.  Teknik pengumpulan data dalam penelitian ini dalam bentuk penyabaran kuesioner. Kemudian jumlah sampel ditetapkan  sebanyak  35  orang.  Pengujian  hipotesis dilakukan dengan menggunakan analisis linier Berganda dan untuk menjelaskan hubungan variabel yang dianalisis menggunakan uji statistik program SPSS 23.0 for windows. Berdasarkan hasil penelitian dapat diketahui bahwa kepemimpinan mempunyai pengaruh positif dan signifikan terhadap kinerja pegawai. Budaya organisasi berpengaruh positif dan signifikan terhadap terhadap kinerja  pegawai.  Disiplin  kerja  mempunyai  pengaruh positif  dan signifikan terhadap kinerja  pegawai  Dinas Kesejahteraan Sosial Kabupaten Deiyai Provinsi Papua. Berdasarkan hasil uji serempak diperoleh hasil bahwa kepemimpinan, budaya organisasi dan disiplin kerja mempunyai pengaruh secara serempak atau bersama-sama terhadap kinerja pegawai pada Dinas Kesejahteraan Sosial Kabupaten Deiyai Provinsi Papua.
Human Resources (employees) are a strategic element in determining whether an organization is healthy or not. Planned and sustainable HR development is an absolutenecessity especially for the future of the organization. The purpose of this study was to determine and analyze the influence of leadership, organizational culture, and work discipline on the performance of employees in the Social Welfare Office of Deiyai Regency, Papua Regency. Data collection techniques in this study were in the form of questionnaires. Then, the number of samples was set at 35 people. Hypothesis testing is carried out using Multiple linear analysis and to explain the relationship of variables, the analysis uses the statistical test program SPSS 23.0 for windows. Based on the research results, it can be seen that leadership has a positive and significant influence on the employee performance. Organizational culture has a positive and significant effect on the employee performance. Work discipline has a positive and significant effect on the performance of employees of the Social Welfare Office of Deiyai Regency, Papua Province. Based on the simultaneous test results obtained that leadership, organizational culture and work discipline have an influence simultaneously or jointly on the performance of employees at the Social Welfare Office of Deiyai Regency, Papua Province.
Intravesical Botulinum Toxin A Injections Do
Not Benefit Patients with Ulcer Type Interstitial
Cystitis
Authors: Kuo Hann-Chorng
Published: February 2021

Background: Ulcer type and non-ulcer type interstitial cystitis/bladder pain syndromes (IC/BPS)
are considered different disease entities. Thus, intravesical botulinum toxin A (BoNT-A) treatment
outcomes could differ for each entity.
Objectives: To evaluate and compare the treatment outcomes of BoNT-A injections for treatment
of each IC/BPS type.
Study Design: Prospective interventional study.
Setting: Tertiary medical center affiliated with Buddhist Tzu Chi General Hospital and Tzu Chi
University, Taiwan.
Methods: Forty-four consecutive patients with IC/BPS for whom conventional treatments failed
were prospectively enrolled in this study. Patients were classified as having ulcer (n = 10) or non-ulcer
(n = 30) IC/BPS based on their previous cystoscopic findings.
Intervention: All patients received 4 sets of intravesical BoNT-A injections (100 U in 40 suburothelial
injections) every 6 months. The primary end-point was the global response assessment (GRA) 6 months
after the fourth set of BoNT-A injections. Secondary end-points included the O’Leary-Sant score (OSS)
including symptom indexes (ICSI) and problem indexes (ICPI), visual analog scale (VAS) pain score,
voiding diary, and urodynamics variables.
Results: After 4 sets of BoNT-A injections, 15 patients with non-ulcer IC/BPS had GRA scores ≥ 2,
while the other 15 had GRA scores < 2. All 10 patients with ulcer IC/BPS had GRA scores < 2 at
the study end-point (treatment failure). At baseline, patients with ulcer IC/BPS had significantly higher
daytime frequency, nocturia, smaller functional bladder capacity, smaller voided volume, greater VAS,
smaller maximal bladder capacity, and greater glomerulation grade than did patients with non-ulcer
IC/BPS. After 4 sets of BoNT-A injections, patients with non-ulcer IC/BPS and GRA scores ≥ 2 or <
2 all had significantly decreased ICSI, ICPI, OSS, VAS pain scores, frequency episodes, and increased
functional bladder capacity. However, patients with ulcer IC/BPS showed no significant change in any
clinical or urodynamic variable. After failure of repeated BoNT-A injections, all 10 patients with ulcer IC/
BPS underwent transurethral electrocauterization of their ulcers, which resulted in immediate pain relief.
Limitations: Lack of a control arm in this study.
Conclusion: Repeated intravesical BoNT-A injections provided effective treatment outcomes at the
end-point in half of the patients with non-ulcer IC/BPS, but did not benefit any patient with ulcer type
IC/BPS. Ulcer type IC/BPS should be treated as a different disease than non-ulcer IC/BPS.
Institutional Review: This study was approved by the Institutional Review Board of the Tzu-chi
General Hospital (TCGH 100-06).
Key words: Botulinum toxin, interstitial cystitis, bladder pain syndrome, intravesical treatment,
Hunner’s ulcer
Spinal Cord Stimulation for Radicular Pain
Following Retained Bullet in the Spinal Canal
Authors: Gulur Padma
Published: February 2021

We are reporting on the implantation of a spinal cord stimulator to treat intractable
radicular pain following a retained bullet fragment in the spinal canal. Such retained
fragments are associated with risks including pain, neurological deficit, infection, toxic
effects, and migration. Our patient was a young man with radicular pain and history of
a gunshot entering the abdomen. Computed tomography of the spine had revealed a
nearly complete bullet in the right paracentral canal at L4, partially extending into the
lateral recess. He presented 17 months after his injury with gradually worsening pain
and parasthesias radiating from the back to the whole right leg and foot. There was
no weakness. As the patient had failed conservative therapy, procedural options were
considered. In this case, the potential benefits of epidural steroid injection by any
approach might not have outweighed risks of infection, related to foreign body and
local steroid, or possible migration due to mechanical forces during injection. As he
may well need repeated epidural steroid injections to manage his pain, this increases
his risk for infection. A percutaneous trial spinal cord stimulation lead was placed,
with epidural entry well away from the bullet. After good results, a permanent system
was implanted. There was no evidence of infection or migration, and excellent pain
relief was achieved. Bullets and other foreign bodies retained in the spinal canal
can cause progressive neurologic symptoms through reactive tissue formation and
compression. Spinal cord stimulation can relieve radicular pain while avoiding risks
associated with altering the location of the offending foreign body.
Key words: Spinal cord stimulation, radicular pain, retained bullet, gunshot wound,
spinal canal, spinal injury, lumbar spine
Emergent Intrathecal Baclofen Withdrawal
After Pseudomeningocele Aspiration
Authors: Smith Timothy R.
Published: February 2021

Intrathecal baclofen (ITB) infusion has become a common treatment for severe spasticity.
Many complications of these drug delivery systems have been reported such as those
related to improper dosing, mechanical failure of the implanted pump or catheter, or postoperative wound issues. We report a case of ITB withdrawal after pseudomeningocele
aspiration. A 21 year-old male with spastic quadriparesis due to traumatic brian injury (TBI)
presented with a pseudomeningocele surrounding an ITB pump (215 mcg/day, continuous)
implanted in the abdomen. The pseudomeningocele was percutaneously aspirated and
approximately 15 hours later the patient developed signs and symptoms of acute baclofen
withdrawal. As a result, the patient underwent an exploration of the ITB infusion system
with an intraoperative epidural blood patch. The symptoms of ITB withdrawal improved over
the next 18 hours. The subcutaneous cerebrospinal fluid (CSF) collection partially recurred
48 hours later, but this resolved after a second epidural blood patch. The case illustrates a
unique presentation of a serious complication of ITB infusion. This underscores that timely
diagnosis and treatment of acute baclofen withdrawal is key to optimal outcomes.
Key words: Intrathecal baclofen, baclofen withdrawal, intrathecal baclofen pump
complications, pseudomeningocele, cerebrospinal fluid leak, case report
Long-Term Neuropsychological Effects of
Opioid Use in Children: A Descriptive Literature
Review
Authors: Jain Gaurav
Published: February 2021

Background: Use of opioids in the management of pain and its consequences in children
presents a substantial challenge. A significant concern in pediatric pain management is the longterm neuropsychological consequences of opioids.
Objectives: The authors aim to provide a descriptive review of the current literature surrounding
the neuropsychological impact of opioid use in children, along with possible extrapolations from
their use in adults and animal models.
Study Design: Systematic review of published literature.
Setting: Various universities in the United States.
Methods: The electronic review for papers published between January 1992 and December 2012
was conducted using Medline/Pubmed, PsychInfo, CINAHL, the Cochrane Library database, and
Google Scholar.
Results: Findings assessing pediatric pain patients treated with opioids demonstrated no
significant differences in intelligence, behavior, vocabulary, or motor skills. One study reported a
decrease in a visuo-constructional ability, which measured higher order executive function. Studies
from prenatal illicit opioid exposure found poorer performance on measures of language, verbal
ability, mathematics, reading, impulse control, and school readiness skills. The literature from adult
prescribed opioid users has mixed results. Some showed impairment in the neuropsychological
domains of memory, decision-making, attention, concentration, information processing, psychomotor speed, visual special skills, and hand-eye coordination, while others found no differences or
revealed improved perceptual-cognitive status, possibly due to the removal of pain as a stressor.
Limitations: Very few studies looked into the long term neuropsychological and cognitive effects
of the opioids in pediatric population. In an attempt to extrapolate from other groups, this review
also included literature from adult patients, prenatal opioid exposure, and animal studies.
Conclusion: Opioid medications have the potential to produce long-lasting neuropsychological
side effects. However, given the negative consequences of untreated pain, the potential benefit
may offset their risk. More studies are needed to clarify this complex interaction.
Key words: Chronic pain management, infants, children, pediatrics, long term neurocognitive
effects, opioid medication
Acquiring the Optimal Time for Hyperbaric
Therapy in the Rat Model of CFA Induced
Arthritis
Authors: Lee Chang-Hyung
Published: February 2021

Background: We previously published an article about the pressure effect using a rheumatoid
animal model. Hyperbaric therapy appears to be beneficial in treating rheumatoid arthritis (RA)
by reducing the inflammatory process in an animal model. In this sense, acquiring the optimal
pressure-treatment time parameter for RA is important and no optimal hyperbaric therapy time
has been suggested up to now.
Objective: The purpose of our study was to acquire the optimal time for hyperbaric therapy
in the RA rat model.
Study Design: Controlled animal study.
Methods: Following injection of complete Freund’s adjuvant (CFA) into one side of the knee
joint, 32 rats were randomly assigned to 3 different time groups (1, 3, 5 hours a day) under
1.5 atmospheres absolute (ATA) hyperbaric chamber for 12 days. The pain levels were assessed
daily for 2 weeks by weight bearing force (WBF) of the affected limb. In addition, the levels of
gelatinase, MMP-2, and MMP-9 expression in the synovial fluids of the knees were analyzed.
Results: The reduction of WBF was high at 2 days after injection and then it was spontaneously
increased up to 14 days in all 3 groups. There were significant differences of WBF between 5
hours and control during the third through twelfth days, between 3 hours and control during
the third through fifth and tenth through twelfth days, and between 3 hours and 5 hours
during the third through seventh days (P < 0.05). The MMP-9/MMP-2 ratio increased at 14
days after the CFA injection in all groups compared to the initial findings, however, the 3 hour
group showed a smaller MMP-9/MMP-2 ratio than the control group.
Limitation: Although enough samples were used for the study to support our hypothesis,
more samples will be needed to raise the validity and reliability.
Conclusion: The effect of hyperbaric treatment appears to be dependent upon the elevated
therapy time under 1.5 ATA pressure for a short period of time; however, the long-term effects
were similar in all pressure groups. Further study will be needed to acquire the optimal pressuretreatment parameter relationship in various conditions for clinical application.
Key words: Pressure effect, arthritic knee, arthritic pain, long-term effect of pressure,
biophysiologic assessment, pain behavior assessment, arthritis treatment
KIMS, CEDIA, and HS-CEDIA Immunoassays
Are Inadequately Sensitive for Detection of
Benzodiazepines in Urine from Patients Treated
for Chronic Pain
Authors: Melanson Stacy
Published: February 2021

Background: Patients treated for chronic pain may frequently undergo urine drug testing to monitor
medication compliance and detect undisclosed prescribed or illicit drug use. Due to the increasing use
and abuse of benzodiazepines, this class of medications is often included in drug screening panels.
However, immunoassay-based methods lack the requisite sensitivity for detecting benzodiazepine use
in this population primarily due to their poor cross-reactivity with several major urinary benzodiazepine
metabolites. A High Sensitivity Cloned Enzyme Donor Immunoassay (HS-CEDIA), in which betaglucuronidase is added to the reagent, has been shown to perform better than traditional assays, but
its performance in patients treated for chronic pain is not well characterized.
Objectives: To determine the diagnostic accuracy of HS-CEDIA, as compared to the Cloned Enzyme
Donor Immunoassay (CEDIA) and Kinetic Interaction of Microparticles in Solution (KIMS) screening
immunoassays and liquid chromatography-tandem mass spectrometry (LC-MS/MS), for monitoring
benzodiazepine use in patients treated for chronic pain.
Study Design: A study of the diagnostic accuracy of urine benzodiazepine immunoassays.
Setting: The study was conducted at an academic tertiary care hospital with a clinical laboratory that
performs urine drug testing for monitoring medication compliance in pain management.
Methods: A total of 299 urine specimens from patients treated for chronic pain were screened
for the presence of benzodiazepines using the HS-CEDIA, CEDIA, and KIMS assays. The sensitivity
and specificity of the screening assays were determined using the LC-MS/MS results as the reference
method.
Results: Of the 299 urine specimens tested, 141 (47%) confirmed positive for one or more of the
benzodiazepines/metabolites by LC-MS/MS. All 3 screens were 100% specific with no false-positive
results. The CEDIA and KIMS sensitivities were 55% (78/141) and 47% (66/141), respectively. Despite
the relatively higher sensitivity of the HS-CEDIA screening assay (78%; 110/141), primarily due to
increased detection of lorazepam, it still missed 22% (31/141) of benzodiazepine-positive urines.
The KIMS, CEDIA, and HS-CEDIA assays yielded accuracies of 75%, 79%, and 90%, respectively, in
comparison with LC-MS/MS.
Limitations: This study was limited by its single-site location and the modest size of the urine
samples utilized.
Conclusions: While the HS-CEDIA provides higher sensitivity than the KIMS and CEDIA assays, it still
missed an unacceptably high percentage of benzodiazepine-positive samples from patients treated for
chronic pain. LC-MS/MS quantification with enzymatic sample pretreatment offers superior sensitivity
and specificity for monitoring benzodiazepines in patients treated for chronic pain.
Key words: High sensitivty immunoassay, benzodiazepine, beta-glucoronidase, pain management,
compliance, LC-MS/MS, screening
A Review of the Role of Genetic Testing in Pain
Medicine
Authors: Trescot Andrea M.
Published: February 2021

Background: Pain clinicians have always been challenged by the variability of response to pain
treatment. Differences in the degree of pain stimulation and pain sensitivity, weight and age
differences, prior opioid use and tolerance, as well as the differences in bioavailability of various
opioid formulations have been cited as causes for the wide variability in analgesia seen with
opioids. Genetics may explain the variability of responses and help to predict more effective (or
less dangerous) medication choices and doses. Genetics may also help to predict the response to
specific opioids and antidepressants.
Objectives: In this review article, we discuss the genetic influence of nociception, analgesia, and
hyoanalgesia. The CYP450 enzymes involved in the metabolism and activity of opioids and adjuvant
analgesics are genetically controlled, as are the opioid receptors and a variety of brain chemistries.
Methods: This article discusses the specific pain implications of genetic variations in CYP1A2,
CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A7, OPRM1, OPRK1, OPRD1,
COMT, GABA, UGT, MC1R, GCH1, ABCB1, P-glycoprotein, 5HTR1A, 5HTR2A, MTHFR, CACNA2D2,
and 5-HTTLPR.
Results: Recent research findings suggest the relationship between genetic predisposition and
clinical behavior, including the risk of opioid misuse and addiction. While urine drug testing may hint
at genetic issues regarding opioid metabolism, cheek swab DNA testing has become economically
viable, and we review the current and future genetic pain issues that may influence the decisions
that pain clinicians make every day.
Conclusion: Genetic testing may explain and predict many of the clinical responses seen with
opioids and adjuvant medications, and may help the clinician identify those patients at genetic risk
of opioid misuse and addiction.
Key words: Genetics, genetic testing, opioid metabolism, drug interactions, urine drug testing,
opioid risk evaluation, opioid receptors
Utility of Oral Fluid in Compliance Monitoring
of Opioid Medications
Authors: Conermann Till
Published: February 2021

Background: Prescription drug abuse is the fastest growing drug problem in the United States, and
the increase in unintentional drug overdose deaths has been driven by the increase in opioid analgesic
use. Given the epidemic of non-medical prescription pain reliever use and the current medico-legal
climate, it is increasingly important for the prescriber to monitor for medication compliance.
Objectives: The purpose of this IRB approved study is to compare the results of oral fluid (OF)
and routine urinalysis for monitoring compliance in a single academic pain management program
in an urban setting in order to evaluate the utility of OF analysis in compliance monitoring when
prescribing opioid medications.
Study Design: Outcomes analysis of prospective, consecutive, paired comparison study with
clinical implications.
Setting: Single academic interventional pain management center in the United States.
Methods: Paired OF and urine specimens were collected for each patient with signed informed
consent, at the Institute for Pain Medicine, Western Pennsylvania Hospital, from patients who
routinely donated urine on a random basis for compliance testing. A total of 153 paired specimens
were analyzed. Demographic and prescription data were made available. Specimens were screened
using immunoassay and presumptive positive findings were confirmed with liquid-chromatography
and mass spectrometry. Although both matrices were tested for a wider range of medications, the
data presented here are representative of analgesic opioids and benzodiazepine drug classes only.
Results: Following exclusion criteria, of the 132 remaining specimen pairs that were positive for
opioids or benzodiazepines in at least one matrix, 101 pairs showed exact drug class matches (76.5%).
In an additional 21 pairs, at least one drug class was positive in both matrices (15.9%), giving an
overall agreement of 92.4%. Overall, 191 positive results were found in urine averaging 1.4 drugs per
specimen; 176 positives were detected using OF for an average of 1.3 drugs per specimen.
Conclusions: In the setting of stable dosing of prescription opioids and/or concomitant illicit
drug use, given comparable detection rates between urine and OF matrix qualitative results, the
OF matrix for drug testing for compliance monitoring may serve as a useful and valid testing tool.
The authors conclude that overall OF analysis produces comparable results to urine sample analysis
with detection rates differing primarily due to differences in windows of detection for different drug
classes.
Limitations: The limitations include the study was performed in a single academic center in
an urban community. Also, there is a paucity of literature regarding windows of detection for OF
analysis compared to urine.
IRB: APPROVED - Allegheny-Singer Research Institute West Penn Allegheny Heath System (ASRIWPAHS) - IRB Study #FWA00015120
Key Words: Urine drug testing, oral fluid drug testing, saliva, opioids, drug abuse, compliance,
chronic pain, diversion
The Science of Conventional and Water-Cooled
Monopolar Lumbar Radiofrequency Rhizotomy:
An Electrical Engineering Point of View
Authors: Ball Richard D.
Published: February 2021

Radiofrequency ablation (RFA) is a safe and effective pain therapy used to create sensory
dysfunction in appropriate nerves via thermal damage. While commonly viewed as a simple
process, RF heating is actually quite complex from an electrical engineering standpoint,
and it is difficult for the non-electrical engineer to achieve a thorough understanding of
the events that occur. RFA is highly influenced by the configuration and properties of the
peri-electrode tissues. To rationally discuss the science of RFA requires that examples be
procedure-specific, and lumbar RFA is the procedure selected for this review. Adequate
heating of the lumbar medial branch has many potential failure points, and the underlying
science is discussed with recommendations to reduce the frequency of failure in heating
target tissues. Important technical details of the procedure that are not generally appreciated
are discussed, and the status quo is challenged on several aspects of accepted technique. The
rationale underlying electrode placement and the limitations of RF heating are, for the most
part, commonly misunderstood, and there may even need to be significant changes in how
lumbar radiofrequency rhizotomy (RFR) is performed. A new paradigm for heating target
tissue may be of value. Foremost in developing best practices for this procedure is avoiding
pitfalls. Good RF heating and medial branch lesioning are the rewards for understanding how
the process functions, attention to detail, and meticulous attention to electrode positioning.
Key words: Electrical equipment and supplies, zygapophyseal joint, catheter ablation,
lumbar vertebrae, low back pain, lumbar vertebrae/innervation, radiofrequency ablation,
water-cooled radiofrequency ablation, conventional radiofrequency ablation, radiofrequency
electrode behavior
Opioid Induced Hyperalgesia Altered with
Propofol Infusion
Authors: Kaye Alan D.
Published: February 2021

Propofol is a common induction agent that is utilized worldwide in the field of
anesthesiology. In recent years, its potential therapeutic role in a variety of patient states
has been demonstrated. Controversy exists regarding Propofol mediated analgesic
and antihyperalgesic properties. Recent studies have suggested a variety of different
mechanisms of action, including modulation of N-Methyl-D- Aspartate receptors and the
endocannabinoid system. The N-Methyl-D- Aspartate receptor is part of a larger family of
glutamate receptors and is an important mediator of excitatory neurotransmission. In the
case presented, the pain experienced by the patient was not well-controlled, in spite of
increasing doses of opioids, potentially due to superimposed opioid induced hyperalgesia.
In the present case, we demonstrate a cycle of opioid induced hyperalgesia which was
successfully affected with a Propofol infusion. Controversial reports exist in animal studies
on the analgesic properties of Propofol. Randomized controlled studies in animal models
studying the effect of Propofol on pain sensation have shown that Propofol possesses
an analgesic effect. This clinical case demonstrates that Propofol could possibly have
antihyperalgesic effects on opioid induced hyperalgesia caused by high-doses of chronic
opioids and worsened by fentanyl. We postulate that a probable mechanism of complete
pain relief after the procedure could be the inhibition of activity of the N-Methyl-DAspartate receptor by Propofol because it was the only agent the patient received during
the procedure, causing a break of the cycle of opioid induced hyperalgesia. Additional
research is required to clarify Propofol mediated or modulated analgesic properties in
humans.
Key words: Analgesia, hyperalgesia, opioids, propofol, antihyperalgesia, anesthesia
Economic Impact of Converting an Interventional
Pain Medicine Physician Office-Based Practice
into a Provider-Based Ambulatory Pain Practice
Authors: Grider Jay S.
Published: February 2021

Background: One consequence of the shifting economic health care landscape is the growing
trend of physician employment and practice acquisition by hospitals. These acquired practices
are often converted into hospital- or provider-based clinics. This designation brings the increased
services of the hospital, the accreditation of the hospital, and a new billing structure verses the
private clinic (the combination of the facility and professional fee billing). One potential concern
with moving to a provider-based designation is that this new structure might make the practice
less competitive in a marketplace that may still be dominated by private physician office-based
practices. The aim of the current study was to evaluate the impact of the provider-based/hospital
fee structure on clinical volume.
Objective: Determine the effect of transition to a hospital- or provider-based practice setting
(with concomitant cost implications) on patient volume in the current practice milieu.
Setting: Community hospital-based academic interventional pain medicine practice.
Study Design: Economic analysis of effect of change in price structure on clinical volumes.
Methods: The current study evaluates the effect of a change in designation with price implications
on the demand for clinical services that accompany the transition to a hospital-based practice
setting from a physician office setting in an academic community hospital.
Results: Clinical volumes of both procedures and clinic volumes increased in a mature practice
setting following transition to a provider-based designation and the accompanying facility and
professional fee structure. Following transition to a provider-based designation clinic visits were
increased 24% while procedural volume demand did not change.
Limitations: Single practice entity and single geographic location in southeastern United States.
Conclusions: The conversion to a hospital- or provider-based setting does not negatively impact
clinical volume and referrals to community-based pain medicine practice. These results imply that
factors other than price are a driver of patient choice.
Key words: Economics of interventional pain medicine, hospital-based ambulatory practice,
provider-based ambulatory practice, physician-office based practice, price in-elasticity of health
care
Anti-Tumor Necrosis Factor Antagonists in the
Treatment of Low Back Pain and Radiculopathy:
A Systematic Review and Meta-analysis
Authors: Amadera Joao E. D.
Published: February 2021

Background: Low back pain, with or without radiculopathy, is an important cause of disability
and economic expenditure. However, many patients are not achieving optimal pain control with
existing medications. Tumor necrosis factor antagonists (anti-TNFα) could be an alternative drug
treatment.
Objectives: Systematic review the efficacy and safety of anti-TNFα in the treatment of low back
pain with or without radiculopathy.
Study Design: Inclusion criteria were observational studies with safety as an outcome, and
randomized or nonrandomized controlled trial (RCT) studies on efficacy and/or safety of antiTNFα drugs on low back pain. Exclusion criteria included patients with auto-immune conditions or
osteoporosis.
Results: Studies were assessed independently by 2 authors regarding inclusion/exclusion criteria,
risk of bias, clinical relevance, quality, and strength of evidence (GRADE approach). Of the 1,179
studies retreived,all duplicates were excluded and then the inclusion/exclusion criteria was applied.
One observational study (n = 143) and 11 RCTs remained (n = 539): 8 for etanercept (n = 304), one
for adalimumab (n = 61), one for adalimumab and etanercept (n = 60), one for infliximab (n = 40)
and one for REN-1654 (n = 74). Only 3 etanercept and 2 adalimumab studies showed statistically
significant pain relief when compared to placebo. There was no difference in the overall incidence
of adverse effects when comparing anti-TNF-α and placebo.
Limitations: Despite the statistically significant effect, this meta-analysis has important limitations,
such as high heterogeneity and high use of outcome imputation.
Conclusions: There is low evidence that epidural etanercept has a low-to-moderate effect size
when compared to placebo for pain due to discogenic lumbar radiculopathy (5 studies, n=185),
with a standardized mean difference = -0.43 (95% confidence interval [CI] -0.84 to -0.02).
There is moderate evidence that epidural etanercept does not have a higher adverse effects incidence
rate when compared to placebo for discogenic lumbar radiculopathy (5 studies, n = 185) with a
relative risk (RR) = 0.84 (95% CI 0.53 to 1.34).
There is moderate evidence that anti-TNFα does not have a higher adverse effects incidence rate
when compared to placebo for low back pain (10 studies, n= 343) with an RR = 0.93 (95% CI 0.56
to 1.55).
We strongly suggest that anti-TNFα continue to be studied in experimental settings for the treatment
of low back pain. We cannot currently recommend this therapy in clinical practice. New research
could shed some light on the efficacy of anti-TNFα and change this recommendation in the future.
Key words: Low back pain, systematic review, meta-analysis, tumor necrosis factor-alpha, TNF,
biologics, tumor necrosis factor-alpha antagonists, anti-TNF, etanercept, adalimumab, discogenic
lumbar radiculopathy, sciatica.
Development of an Interventional Pain
Management Specific Instrument for Methodologic
Quality Assessment of Nonrandomized Studies of
Interventional Techniques
Authors: Manchikanti Laxmaiah
Published: February 2021

Background: The major component of a systematic review is assessment of the methodologic
quality and bias of randomized and nonrandomized trials. While there are multiple instruments
available to assess the methodologic quality and bias for randomized controlled trials (RCTs),
there is a lack of extensively utilized instruments for observational studies, specifically for
interventional pain management (IPM) techniques. Even Cochrane review criteria for randomized
trials is considered not to be a “gold standard,” but merely an indication of the current state of
the art review methodology. Recently a specific instrument to assess the methodologic quality
of randomized trials has been developed for interventional techniques.
Objectives: Our objective was to develop an IPM specific instrument to assess the
methodological quality of nonrandomized trials or observational studies of interventional
techniques.
Methods: The item generation for the instrument was based on a definition of quality, to
the extent to which the design and conduct of the trial were congruent with the objectives of
the study. Applicability was defined as the extent to which procedures produced by the study
could be applied using contemporary IPM techniques. Multiple items based on Cochrane review
criteria and Interventional Pain Management Techniques – Quality Appraisal of Reliability and
Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR) were utilized.
Results: A total of 16 items were developed which formed the IPM-QRBNR tool.
The assessment was performed in multiple stages. The final assessment was 4 nonrandomized
studies. The inter-rater agreement was moderate to good for IPM-QRBNR criteria.
Limitations: Limited validity or accuracy assessment of the instrument and the large number
of items to be scored were limitations.
Conclusion: We have developed a new comprehensive instrument to assess the
methodological quality of nonrandomized studies of interventional techniques. This instrument
provides extensive information specific to interventional techniques is useful in assessing the
methodological quality and bias of observational studies of interventional techniques.
Key words: Methodological quality assessment, evidence-based medicine, comparative
effectiveness research, Cochrane Reviews, interventional techniques, risk of bias assessment,
nonrandomized trials, observational studies
Spontaneous C1-2 Cerebrospinal Fluid Leak
Treated with a Targeted Cervical Epidural Blood
Patch Using a Cervical Epidural Racz Catheter
Authors: Kim Dr. Yong-Shin
Published: February 2021

A 39-year-old woman with no history of trauma or meningitis presented to the neurology
department of our hospital with an occipital headache, neck pain, nausea, and dizziness
that had worsened during the previous month. The headache worsened when sitting or
standing and partially regressed when lying down. She was diagnosed with spontaneous
intracranial hypotension (SIH) and received conservative management. After failing to
respond to conservative management, she underwent an autologous epidural blood
patch (EBP) at the T7-8 level. The headache and associated symptoms did not improve
after the procedure. Magnetic resonance (MR) myelography suggested a cerebrospinal
fluid leakage at the C1-2 level resulting in intracranial hypotension. An 18-gauge Tuohy
needle was inserted at the T1-2 interlaminal level using a paramedian approach under
fluoroscopic guidance. The cervical epidural Racz catheter was threaded through the
Tuohy needle up to the cervical spine and the catheter tip was confirmed to be at the
right cervical 1-2 site on an anteroposterior (AP) view. Five mL of autologous blood was
injected into the epidural space through the cervical epidural Racz catheter.
Her occipital headache and associated symptoms gradually disappeared after the
procedure. Seven days later the headache was largely resolved and she was discharged.
Follow-up magnetic resonance imaging (MRI) showed the disappearance of abnormal
radiological features associated with intracranial hypotension. She currently remains
symptom free for 9 months. Delivery of autologous blood patch via a cervical epidural
Racz catheter inserted from the upper thoracic spine can be a safe and effective method
for patients with SIH due to cerebrospinal fluid (CSF) leakage in the upper cervical spine.
Key words: Cerebrospinal fluid leakage, epidural blood patch, intracranial hypotension,
myelography, occipital headache
Transforaminal Epidural Injections in Chronic
Lumbar Disc Herniation: A Randomized,
Double-Blind, Active-Control Trial
Authors: Manchikanti Laxmaiah
Published: February 2021

Background: The estimated prevalence of lumbar radiculopathy has been described as
9.8 per 1,000 cases of low back pain. There are various surgical and nonsurgical modalities
for treating lumbar disc herniation or radicular pain, including epidural injections. Epidural
injection administration routes include transforaminal, interlaminar, and caudal approaches. The
transforaminal approach requires the smallest volume to reach the primary site of pathology.
Systematic reviews have yielded highly variable results, but a recent systematic review showed
no significant difference among the 3 approaches.
Study Design: A randomized, controlled, double blind, active control trial.
Setting: An interventional pain management practice, a private specialty referral center in the
United States.
Objectives: To assess the effectiveness of transforaminal epidural injections of local anesthetic
with or without steroids in managing chronic low back and lower extremity pain in patients with
disc herniation and radiculitis.
Methods: One hundred twenty patients were randomly assigned to 2 groups: Group I received
1.5 mL of 1% preservative-free lidocaine, followed by 0.5 mL of sodium chloride solution.
Group II received 1% lidocaine, followed by 3 mg, or 0.5 mL of betamethasone. The sodium
chloride solution and betamethasone were either clear liquids or were provided in opaquecovered syringes.
Outcomes Assessment: The primary outcome measure was significant improvement (at
least 50%) measured by the average Numeric Rating Scale (NRS) and the Oswestry Disability
Index 2.0 (ODI). Secondary outcome measures were employment status and opioid intake.
Results: At 2 years there was significant improvement in all participants in 65% who received
local anesthetic alone and 57% who received local anesthetic and steroid. When separated
into non-responsive and responsive categories based on initial relief of at least 3 weeks with 2
procedures, significant improvement (at least 50% improvement in pain and function) was seen
in 80% in the local anesthetic group and 73% in the local anesthetic with steroid group.
Limitations: Presumed limitations of this evaluation include the lack of a placebo group.
Conclusion: Transforaminal epidural injections of local anesthetic with or without steroids
might be an effective therapy for patients with disc herniation or radiculitis. The present evidence
illustrates the lack of superiority of steroids compared with local anesthetic at 2-year follow-up.
Key words: Chronic low back pain, transforaminal epidural injections, disc herniation,
radiculitis, lower extremity pain, local anesthetic, steroids