Trends of Buprenorphine Prescribing for Opioid Dependence Before, and During the Early and Later Part of the COVID-19: A Study from a Large Publicly-Funded Opioid Agonist Treatment Services in India.

BACKGROUND: The COVID-19 pandemic has affected the availability and access to medications for opioid dependence (OD). We examined the monthly trends in new buprenorphine/naloxone (BNX) treatment episodes, number of clinical visits for BNX, BNX dispensed per person, and BNX prescription over 56-month, which included pre-pandemic, during early, and later part of pandemic (Jan 2017 - Aug 2022). METHODS: Research data were collected from the pharmacy database of a large publicly funded treatment center in India. A flexible, low-threshold service was adopted in April 2020 in response to the lockdown implemented on 25 March 2020. Change Point analyses were performed to examine monthly trends visually and statistically. We used Autoregressive integrated moving averages to forecast trends from April to Aug 2020 and March to August 2022, using Jan 2017 to March 2020 and March 2020 to February 2022 as training datasets. RESULTS: 993 patients were started on BNX treatment, 40452 BNX clinic attendances were made, 1401393 BNX tablets were dispensed, and 6795 new patients with OD were registered. The observed data for clinic attendance for BNX was significantly lower than the projected estimates in April -Aug 2020; however, observed new treatment episodes and monthly BNX prescriptions were within the 95% projected estimates; BNX dispensed per person was significantly more than the projected estimate. In contrast, observed BNX prescription trends surpassed the upper limit of 95% CI in March-Aug 2022. CONCLUSION: A low-threshold and flexible treatment service could mitigate the unintended consequences of pandemic-induced restrictions.

Does Prescription Length of Buprenorphine Influence Treatment Outcomes in Opioid Use Disorder? A Retrospective Cohort Study from North India.

OBJECTIVE: Buprenorphine (BUP) effectively suppresses non-prescription opioid use and increases treatment retention in opioid use disorder (OUD). However, short prescription length may interfere with treatment retention and recovery. We wanted to examine whether the outcomes of BUP treatment differ in high (HPL up to 4 wk) and low-prescription (LPL 1-2 wk) length groups. METHODS: We compared time to treatment discontinuation (TD), non-prescription opioid-positive urine screen, buprenorphine-negative urine screen, and self-reported non-prescription opioid use between two different cohorts of LPL (case record: June 2018 to August 2019; n = 105; observation endpoint: 31 October 2019) and HPL groups (case record: June 2020 to Aug 2021; n = 133; observation endpoint: 31 October 2021). We used Kaplan-Meier survival analysis and log-rank tests for between-group comparisons. We used Cox regression analysis to adjust for age, opioid potency, comorbidities, family income, and marital status. RESULTS: Subjects' age and buprenorphine dose were significantly lower, and the percentage of high-potency opioid users was significantly higher in the LPL group. In the unadjusted survival analysis, the median time to BUP discontinuation in the HPL was longer than that of the LPL [LPL= 22.4 ± 4.3 wk; HPL = 33.1 ± 8.5 wk; χ2(1)= 5.7; p=.02]. The survival distributions of other outcomes did not differ between groups. When adjusted for covariates, neither the prescription length nor other covariates independently predicted any treatment outcome. CONCLUSION: Higher prescription length might be associated with longer treatment retention. We provide preliminary evidence to support greater flexibility in BUP treatment, enhancing its scalability and attractiveness.

Effectiveness of buprenorphine (naloxone) for opioid dependence does not differ across opioid categories: a retrospective cohort study from India.

We aimed to examine whether treatment retention, abstinence, and adherence to buprenorphine-naloxone (BNX) differ among individuals with opioid dependence (OD) across three common categories of opioids- heroin, opium, and low-potency pharmaceutical. In a retrospective cohort study, we analyzed outpatient treatment records from March 2020 through February 2022. Opioid category was determined by lifetime and current opioid use. We defined treatment retention as weeks of uninterrupted clinic attendance. Abstinence and BNX adherence were calculated by weeks of extra-medical opioid-negative and buprenorphine-positive urine screening from treatment initiation. Four-hundred-thirteen patients were eligible; 406 (98.3%) were included in the final analysis. Two-hundred-ninety (71.4%) patients were dependent on heroin; 66 (16.3%) were natural opioid dependent, and 50 (12.3%) were dependent on low-potency pharmaceutical opioids. BNX effectiveness in treatment retention, abstinence, and adherence did not differ in patients dependent on heroin, natural, and low-potency pharmaceutical opioids. Patients on ≥8 mg daily BNX had better retention and adherence than those on <8 mg daily. Patients from lower socioeconomic status (SES) had higher odds of retention, abstinence, and adherence than those from upper/middle SES. Treatment outcomes on BNX did not differ across opioid categories. However, BNX should be dosed adequately.

Predictors of Five-year Readmission to an Inpatient Service among Patients with Opioid Use Disorders.

Background Opioid use disorder (OUD), a relapsing-remitting chronic medical disease, accounts for a sizable proportion of all-cause adult inpatient stays. We evaluated the incidence and predictors of any and multiple readmissions to inpatient care for OUD. Methods This retrospective, register-based cohort study assessed consecutive patients with OUD admitted to a federally-funded inpatient service of an addiction treatment center in North India between January 2007 and December 2014. Binary logistic regression was used to determine independent readmission predictors based on demographic, clinical, and treatment variables that significantly differed in bivariate analysis. Results Among 908 patients, 306 (33.7%) and 106 (11.7%) had any and multiple readmissions, respectively. Injection drug use (Odds ratio [OR] 2.92, 95% confidence interval [CI] 1.90-4.49), comorbid severe mental illness (OR 2.80, 95% CI 1.42-5.55) and common mental disorder (OR 3.4 95% CI 1.65-6.95), antagonist treatment (OR 1.6 95% CI 1.14-2.27), and urban residence (OR 1.38 95% CI 1.01-1.90) increased odds of readmission. 'Improved' discharge status (OR 0.48 95% CI 0.34-0.70) in first admissions reduced odds of any readmission. Similar risk factors also influenced multiple readmissions with higher odds ratios. Conclusions Identification and adequate treatment of risk factors may reduce the chances of readmission.

Predictors of Treatment Completion in an Inpatient Substance Use Treatment Service in India.

INTRODUCTION: Treatment completion is associated with a better outcome in substance use disorders. We examined the rates of treatment completion and its predictors in patients admitted to specialized addiction treatment settings over a 13-year period. METHODS: Ours was a retrospective cohort study. We included consecutive 2850 patients admitted to the inpatient treatment between January 2007 and December 2019. We divided the patients into 2 groups: completed versus premature discontinuation of treatment. The predictor variables were based on previous research, clinical experience, and availability of the digital record. RESULTS: The number of patients who completed and discontinued treatments was 1873 (72.6%) and 707 (27.4%), respectively. The inpatient treatment discontinuation rate varied widely during the study period (18% in 2007 and 41% in 2012). The average rate of treatment discontinuation was 27%. The change-point analysis showed 5 statistically significant change points in the years 2008, 2010, 2012, 2014, and 2016. Patients who were prescribed medications for alcohol and opioid dependence and those who were on opioid agonist treatment had 4.7 and 6.3 higher odds of completing inpatient treatment than those who were not on medication. Patients with physical and psychiatric comorbidities had higher odds of treatment completion. Patients with a primary diagnosis of opioid dependence had lower odds of treatment completion than those with alcohol dependence. CONCLUSIONS: The rates of discontinuation may vary with concurrent changes in the treatment policies. Awareness of the risk factors and policy measures that may improve treatment completion must aid in informed decision making.

Does Online Newsmedia Portrayal of Substance Use and Persons with Substance Misuse Endorse Stigma? A Qualitative Study from India.

Media provides and shapes public knowledge, perceptions, and attitude towards people with substance misuse. We aimed to explore the content and specific themes of Indian online news articles on substance use or persons with substance misuse. We followed an exploratory qualitative design to analyze online news media reports published between July 1 2020 and June 30 2021. Hundred articles met the selection criteria. Our content analysis was based on a checklist. Thematic analysis was done by the coding, categorization, and theme generation after meticulous data immersion and triangulation. Sixty percent of articles had pessimistic headlines and portrayed substance use or persons with substance use negatively. Fifty-one percent articles were on alcohol. Twenty-seven percent articles focussed supply reduction, whereas only 5% positively discussed the role of treatment. We identified seven themes. Most frequent themes were legal-criminal aspects of substance use (n = 39), psychosocial and health hazards of substance use (n = 30), and propagation of public stigma (n = 25). Two other prevalent themes were the business and marketing of alcohol (n = 20) and sociocultural aspects of substance use (n = 9). The theme, treatment strategy, appeared in only five articles. There is an urgent need for media guidelines for responsible reporting of substance misuse. We suggested a set of recommendations for media reporting.

Audit of Molecular Mechanisms of Primary and Secondary Resistance to Various Generations of Tyrosine Kinase Inhibitors in Known Epidermal Growth Factor Receptor-Mutant Non-small Cell Lung Cancer Patients in a Tertiary Centre.

AIMS: Presently, three generations of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are approved against oncogene addicted EGFR-mutant non-small cell lung cancer (NSCLC). Patients with actionable EGFR mutations invariably develop resistance. This resistance can be intrinsic (primary) or acquired (secondary). MATERIALS AND METHODS: This was a retrospective study carried out between January 2016 and April 2021 analysing 486 samples of NSCLC for primary and secondary resistance to first- (erlotinib, gefitinb), second- (afatinib) and/or third-generation (osimertinib) TKIs in EGFR-mutant NSCLCs by next generation sequencing (NGS). Tissue NGS was carried out using the Thermofischer Ion Torrent™ Oncomine™ Focus 52 gene assay; liquid biopsy NGS was carried out using the Oncomine Lung Cell-Free Total Nucleic Acid assay. All cases were previously tested for a single EGFR gene with the Therascreen® EGFR RGQ PCR kit. RESULTS: The results were divided into four groups: (i) group 1: primary resistance to first- and/or second-generation TKIs. This group, with 21 cases, showed EGFR exon 20 insertions, dual, complex mutations and variant of unknown significance, de novo MET gene amplification besides other mutations. (ii) Group 2: primary resistance to third-generation TKIs. This group showed two cases, with one showing dual EGFR mutation (L858R and E709A) and EGFR gene amplification. (iii) Group 3: secondary resistance to first- and second-generation TKIs. This group had 27 cases, which were previously reported negative for EGFR T790M by single gene testing. Significant findings were MET gene amplification in four cases, with one also showing MET exon 14 skipping mutation. Three cases showed small cell change and one showed loss of primary mutation. (iv) Group 4: secondary resistance to third-generation TKIs. The latter group was further subgrouped into group 4A: secondary resistance to osimertinib (third-generation TKI) when offered as second-line therapy after first- and second-generation TKIs on detection of T790M mutation. This group had 15 cases. EGFR T790M mutation was lost in 10 (10/15; 67%) cases and was retained in five cases. Patients with T790M loss experienced early resistance (6.9 months versus 12.6 months mean, P = 0.0024) compared with cases that retained T790M. Two cases gained MET amplification as the resistance mechanisms. Other mutations that were found when EGFR T790M was lost were in FGFR3, KRAS, PIK3CA, CTNNB1, BRAF genes. One case had EML4-ALK translocation. Two cases showed driver EGFR deletion 19, retained T790M and C797S mutation in Cis form. Group 4B: secondary resistance to osimertinib (when given as first-line therapy) in EGFR-mutant NSCLC. This group had three cases. The duration of osimertinib treatment ranged from 11 to 17 months. Two patients showed additional C797S mutation along with primary EGFR mutation. CONCLUSION: This study shows the wide spectrum of primary and secondary EGFR resistance mechanisms to first, second and third generation of TKIs and helps us to identify newer therapeutic targets that could carry forward the initial advantage offered by EGFR TKIs.

Course and Correlates of Stigma in Patients on Opioid Agonist Treatment: A Prospective Study from an Outpatient Treatment Program in India.

Background: Individuals with opioid dependence experience stigma and discrimination. Stigma can potentially reduce treatment-seeking and negatively affect treatment outcomes. We aimed to study the course of stigma and its correlates among patients receiving opioid agonist treatment (OAT). Methods: We recruited 51 subjects (aged between 18 and 45 years) registered in the OAT clinic from February to September 2019. We excluded subjects dependent on alcohol and other drugs (except for cannabis and tobacco), with severe mental illness, intellectual disability, and organic brain disease. We assessed the internalized and enacted stigma and quality of life at the treatment entry and after 3 months. Relationship of stigma with quality of life, socio-demographic, and other clinical variables were examined at the treatment entry. Results: Mean age of the subjects was 26.7 (± 5) years. At the end of three months, 33 (64.7%) patients were retained in the treatment. Internalized stigma correlated negatively with the social and environmental domains of quality of life. The strength of the correlations was modest. No significant correlation was found between demographic and clinical variables and internalized stigma and enacted stigma scores. Both internalized and enacted stigma scores reduced significantly at 3 months follow-up. The significance levels were retained even after controlling for the baseline quality of life scores. Stigma at the treatment entry did not predict early dropout. Conclusion: Despite higher severity at the treatment entry, the level of internalized and enacted stigma reduced significantly within three months of an outpatient-based OAT program.

Predictors of Five-Year Readmission to an Inpatient Service among Patients with Alcohol Use Disorders: Report from a Low-Middle Income Country.

BACKGROUND: Alcohol use disorder (AUD) is a relapsing-remitting disease that accounted for a sizable proportion of all-cause adult inpatient stays. OBJECTIVES: To determine the predictors of any and multiple readmissions to inpatient care for AUD within 5 years of the index admission. METHODS: This retrospective, register-based cohort study assessed consecutive patients with AUD admitted to a publicly-funded inpatient service between January 2007 and December 2014. Binary logistic regression was used to determine independent predictors for readmissions based on relevant demographic, clinical, and treatment variables that showed significant differences (p < 0.05) on univariate analysis. RESULTS: Among 938 patients (age 35.9 ± 10.3 years; duration of alcohol use 159.6 ± 104.5 months; dual diagnosis 19%; comorbidity of substance use disorder 49.3%; medical disorder 34.8%, 299 (31.9%) and 115 (12.3%) had any and multiple readmissions, respectively. Comorbid "severe mental illness" (Odds ratio [OR] 1.99, 95% confidence interval [CI] 1.11-3.57) and urban residence (OR 1.58, 95% CI 1.13-2.18) increased the odds of any readmission; "Improved" status at discharge (OR 0.51, 95% CI 0.35-0.72) during index hospitalization reduced odds of readmission. Additionally, any medical or psychiatric comorbidities increased (OR 2.23, 95% CI 1.26-3.97), and comorbid substance use disorder decreased (OR 0.41, 95% CI 0.19-0.89) risk of multiple readmissions. CONCLUSIONS: Clinicians could identify patients at-risk for any and multiple readmissions during the index hospitalization. A policy aimed at reducing the risk of rehospitalization, healthcare cost, and stigma should pay attention to the predictors of readmission. Such policy should further benefit resource-limited settings.

Telemedicine-assisted stepwise approach of service delivery for substance use disorders in India.

Restricted access to healthcare during COVID-19 pandemic warranted an urgent adaptation of telemedicine practice. We describe a synchronous, stepwise (telephonic, video, and in-person consultation) direct-care model. From 18th May to 31st August 2020, 128 new and 198 follow-up patients received consultation. Eighty-nine percent of new patients required video-consultation. Sixty-eight percent of follow-up cases were managed by telephonic consultation. A third of new and a fifth of the follow-up patients had to be called for physical consultation. Limited access to and understanding of the technologies, potential breach in privacy, and restrictions imposed on online prescription of medications posed significant challenges.

Role of postoperative intact serum PTH as an early predictor of severe post-thyroidectomy hypocalcemia: a prospective study.

BACKGROUND: Post thyroidectomy hypocalcemia is a major sequel of thyroidectomy and continues to trouble the endocrinologists and the endocrine surgeons as there is no ideal predictive marker of hypocalcemia which has the potential to develop into a life-threatening complication. The role of early serum intact parathormone (iPTH) to predict post thyroidectomy hypocalcemia is becoming useful but the literature is still unclear regarding the optimal time of testing and the optimal cut-off value of serum iPTH. PATIENTS AND METHODS: This is a prospective cohort study of 111 patients who underwent total thyroidectomy in a tertiary care endocrine surgery referral unit. Serum iPTH was measured after 20 min and 4 h of surgery. Receiver-Operator characteristic Curve (ROC) was used to find out of the best cut-off value of S. iPTH 20 min and 4 h after surgery in predicting hypocalcemia. RESULTS: Hypocalcemia was noted in 60 (54%) out of 111 subjects who underwent total thyroidectomy. The best cut-off values of Serum iPTH to predict hypocalcemia was found to be 4.28 pmol/l at 20 min post total thyroidectomy with a sensitivity and specificity of 81.7% and 51%, respectively. In addition, patients with malignancy or central lymph nodal dissection were significantly over-represented in the hypocalcemia group with serum iPTH above the threshold level of 4.28 pmol/l. Below the cut off level, parenteral calcium supplementation was required in 23% (17/74) subjects while the rate was only 5.4% (2/37) patients when serum iPTH was above the cut-off level. CONCLUSIONS: The decline of serum iPTH below a specific level after surgery has predictive value together with other factors strictly related to patient, the thyroid disease itself and surgery. The risk of development of hypocalcemia and consequent need for calcium supplementation should be evaluated by clinical assessment along with serum PTH measurement.

Disulfiram Ethanol Reaction with Alcohol-Based Hand Sanitizer: An Exploratory Study.

AIMS: We conducted a cross-sectional survey to estimate the prevalence and clinical manifestation of disulfiram ethanol reaction (DER) and isopropanol toxicity (IT) in patients with alcohol use disorders, on disulfiram. Alcohol-based hand rub contains either ethanol or isopropanol or both. COVID-19 pandemic has led to wide scale usage of sanitizers. Patients with alcohol use disorders, on disulfiram, might experience disulfiram ethanol like reactions with alcohol-based sanitizers. METHODS: We telephonically contacted 339 patients, prescribed disulfiram between January 2014 and March 2020. The assessment pertained to the last 3 months (i.e. third week of March to third week of June 2020). RESULT: The sample consisted of middle-aged men with a mean 16 years of alcohol dependence. Among the 82 (24%) patients adherent to disulfiram, 42 (12.3%) were using alcohol-based hand rubs. Out of these, a total of eight patients (19%; 95% CI 9-33) had features suggestive of DER; four of whom also had features indicative of IT. Five patients (62.5%) had mild and self-limiting symptoms. Severe systemic reactions were experienced by three (37.5%). Severe reactions were observed with exposure to sanitizers in greater amounts, on moist skin or through inhalation. CONCLUSION: Patients on disulfiram should be advised to use alternate methods of hand hygiene.

Extended lockdown and India's alcohol policy: a qualitative analysis of newspaper articles.

OBJECTIVES: Since 25th March 2020 India went into a complete and extended lockdown. Alcohol production, sales, and purchase were barred with this overnight prohibition order. We conducted a qualitative analysis of the media reports published within the first month of the nationwide lockdown with the objectives (a) using the media reports as indications of possible public health impact and population response of a sudden alcohol prohibition in India, (b) suggesting areas for future research. METHODS: We performed thematic and content analysis of 350 articles published online in national newspapers between the 26th March, 2020 and 25th April, 2020. Initial inductive, followed by deductive coding was done in this exploratory thematic analysis. RESULTS: The thematic analysis revealed four main themes: the beneficial aspects of the policy, the harmful aspects of the policy, non-compliance and attempts to change and / or subvert the policy, popularity and level of public buy-in of the policy. We generated relevant sub-themes under main themes. Two additional themes, not directly related to the sudden prohibition, were use of stigmatizing language and ethical concerns. The content analysis showed the frequency of the appearance of the main themes and proportions of sub-themes and codes under those main themes. CONCLUSION: The harms, perceived from the media reports, should be balanced against the potential benefits. Absence of a national-level alcohol policy was made apparent by the reflexive, disconnected, and conflictual measures. Future research could systematically examine the potential ramifications of alcohol prohibition on public health, social, and economic aspects.

Opioid substitution therapy with buprenorphine-naloxone during COVID-19 outbreak in India: Sharing our experience and interim standard operating procedure.

Coronavirus disease 2019 (COVID-19) has been declared as a pandemic by the World Health Organization on March 11, 2020. It has affected most countries of the world, including India. Both the disease and the unavoidable national response to it have posed unique challenges to our health-care system. A particular vulnerable group of patients is those with opioid dependence maintained on opioid substitution therapy (OST). These patients are pharmacologically dependent on the OST medication (buprenorphine, buprenorphine-naloxone combination [BNX], and methadone) for their healthy functioning and recovery. COVID-19 outbreak, lock-down, and difficult access to medical care, all are likely to induce stress and withdrawal, which is a potential risk for relapse among individuals with opioid dependence, who are anyway more vulnerable due to social, housing, living, and medical conditions. In this context, it is essential to re-strategize the existing OST services to adapt to the challenging circumstances. In this communication, we share our experience and formulate interim standard operating procedures (SOPs) for running a hospital-based OST service utilizing take-home BNX. The challenges, principles to meet the challenges, and interim SOPs are shared as being currently practiced in our center. Individual institutes, agencies, hospitals, and clinics running OST service with BNX can adapt these SOPs according to their characteristics, needs, demand, and resources; so long as, the basic principles are adhered to.

Does Cannabis Dependence Add on to the Neurocognitive Impairment Among Patients With Opioid Dependence? A Cross-Sectional Comparative Study.

BACKGROUND AND OBJECTIVES: Chronic opioid exposure has been linked with neurocognitive impairments. Evidence of residual impairment with cannabis use is less consistent. We investigated whether patients with opioid and cannabis dependence perform poorly compared with those with opioid dependence alone. METHODS: We recruited three groups of participants aged 18 to 55 years: opioid and cannabis dependence (OCaD; n = 21), only opioid dependence (OD; n = 19), and a control group (HC; n = 20). Subjects with other substance use, human immunodeficiency virus, head injury, epilepsy, and severe mental illness were excluded. Cognitive tests, performed after at least 1 week of abstinence, consisted of the Wisconsin card sorting test (WCST), Iowa gambling task (IGT), trail making tests A and B (TMT-A and B), verbal and visual N-back test (NBT), and standard progressive matrices for intelligence quotient (IQ). The general linear model was used to compare the groups with age and years of education as covariates. RESULTS: IQ and severity of opioid dependence were comparable in the three groups. The mean duration of cannabis use was 76.2 (±39.4) months. Compared with the HC, both OD and OCaD had significant impairment on the IGT, WCST, TMTs, and NBT. No significant group difference was observed between the OD and OCaD groups. DISCUSSION AND CONCLUSIONS: Opioid dependence is associated with impairments in decision making, executive function, working memory, and attention. Co-morbid cannabis dependence had similar profiles of cognitive impairments. SCIENTIFIC SIGNIFICANCE: Co-morbid cannabis dependence might not add on to the existing cognitive dysfunction in opioid dependence. Further studies should be done with a larger sample. (Am J Addict 2020;29:120-128).

Tapentadol, the new kid on the block in India: Is it time to worry?

BACKGROUND AND OBJECTIVES: Large-scale prospective case series of tapentadol abuse or dependence in India is not available. Hence, we aimed to study the prevalence and profile of tapentadol users in a treatment-seeking population. MATERIALS AND METHODS: The study had prospective and retrospective arms. We collected 8-month prospective data by face-to-face interviews (n = 70) and 8-year retrospective data from case notes (n = 26) with either tapentadol misuse/abuse or dependence in patients attending a de-addiction center. RESULTS: The prevalence of tapentadol abuse or dependence was 25% among the pharmaceutical opioid users. Concurrent use of other opioids was seen in >80% of participants of both the arms. Major sources of tapentadol were chemists (without a prescription) (53%) and doctors (prescriptions) (40%). Patients in the tapentadol dependence group had a significantly higher dose, duration, and pharmaceutical opioid use. CONCLUSION: India needs awareness promotion, training, availability restriction, and provision of treatment for tapentadol abuse or dependence.

A 5 kA pulsed power supply for inductive and plasma loads in large volume plasma device.

This paper describes 5 kA, 12 ms pulsed power supply for inductive load of Electron Energy Filter (EEF) in large volume plasma device. The power supply is based upon the principle of rapid sourcing of energy from the capacitor bank (2.8 F/200 V) by using a static switch, comprising of ten Insulated Gate Bipolar Transistors (IGBTs). A suitable mechanism is developed to ensure equal sharing of current and uniform power distribution during the operation of these IGBTs. Safe commutation of power to the EEF is ensured by the proper optimization of its components and by the introduction of over voltage protection (>6 kV) using an indigenously designed snubber circuit. Various time sequences relevant to different actions of power supply, viz., pulse width control and repetition rate, are realized through optically isolated computer controlled interface.