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CONTEXT: On October 6, 2014, the United States Drug Enforcement Administration (DEA) implemented a regulatory change for hydrocodone combination products (HCPs), moving them from Schedule III to II, in an effort to decrease drug overdoses. Existing research suggests this regulatory action reduced HCP prescribing and dispensing; however, there is limited research assessing its possible effects on overdoses and accidental exposures. OBJECTIVE: To analyze the changes in opioid exposures reported to the California Poison Control System (CPCS) before and after DEA rescheduling of HCPs. METHODS: We collected monthly exposure data reported to CPCS from 2012–2019 and conducted interrupted time series analyses to assess changes in exposures after rescheduling for HCPs, tramadol, oxycodone, morphine, codeine, fentanyl, and heroin. Additional analyses were done to assess any changes in exposures resulting in severe outcomes (moderate or major health effects). For HCPs, we also conducted logistic regressions to identify characteristics of exposures resulting in severe outcomes before and after rescheduling. RESULTS: Overall monthly opioid exposures reported to CPCS decreased after DEA rescheduling of HCPs. These decreases were significant for HCP, tramadol, and morphine (p

Buprenorphine is a Schedule III opioid with unique pharmacodynamic and pharmacokinetic properties that contribute to effective analgesia and fewer safety risks than other opioids. This review article focuses on the buccal film formulation, which is preferable to other buprenorphine formulations on the basis of bioavailability, safety and efficacy. The clinical studies reviewed here confirm that buprenorphine buccal film offers effective and continuous pain relief that is generally well tolerated, with no cases of respiratory depression reported in any of the studies. On the basis of these clinical data and individual patient risk/benefit assessments, clinicians should consider utilizing buprenorphine buccal film as a first-line opioid treatment for chronic pain over other buprenorphine formulations or other opioids.

This study aimed to evaluate the rescheduling of hydrocodone combination products (HCPs) from schedule III (CIII) to schedule II (CII) in patients receiving chronic HCP therapy.This study was a retrospective cohort analysis of administrative pharmacy data from 118 statewide pharmacies from a retail chain in Tennessee. HCP filling histories were analyzed on patients meeting enrollment criteria from July 1, 2014, to October 1, 2015. The average number of tablets dispensed, daily average of the number of tablets dispensed, and monthly average of morphine milligram equivalents (MME) dispensed were compared for the periods of July 1, 2014, to October 5, 2014 (enrollment period before schedule change) and October 6, 2014, to October 1, 2015 (period following schedule change) using a pooled t test.A total of 4536 patients met the inclusion criteria. Of these 4536 patients, 60.6% were female, and 40.4% were male, with an average age of 58 years (patients included in this study were between the ages of 18 and 99 years). The total number of hydrocodone tablets dispensed in the 12 periods after the schedule change dropped from 467,217 to 259,327, a 45.5% reduction (P0.001). Total MME decreased from 4.11 to 2.29 million, a 45.3% reduction (P0.001). The number of study participants still receiving an HCP at the end of the study decreased to an average of 2736 across the 12 periods following the schedule change, a 40% reduction.HCP dispensing and use decreased among patients receiving chronic opioid treatment from a large corporate statewide community pharmacy in Tennessee after a schedule change from CIII to CII. Monthly sums of total tablets dispensed, average daily tablets dispensed, MME, and average daily MME calculated from July 1, 2014, to October 1, 2015, all experienced statistically significant reductions.

The main objective of a Physical Protection System (PPS) in a nuclear facility is to protect against possible malevolent human attack. Failures of that PPS could lead to radiological consequences, so that, radiation dose calculations have been performed for a radiological sabotage event in a Hypothetical Research Reactor Facility using an atmospheric dispersion modeling (HotSpot code) and compared with the annual regulatory limits for the public as set in Schedule III in IAEA Safety Report Series (GSR part 3). To mitigate those effects, a PPS for a hypothetical research reactor facility has been designed and evaluated, before upgrading the PPS, the Probability of Effectiveness (PE) is for a regular PPS, thus a high values of risk are associated, however after modification of the PPS, the security system becomes high since the probability of effectiveness is greater than 90% which is by far excellent in order to interrupt and deter any adversary.

A bio-inventory of herpetofauna occurring in Amchang wildlife sanctuary was made along with identification of perceived threats, the herpetofauna faces in the sanctuary. During the study period 22 species of amphibians representing seven families and 41 species of reptiles representing eleven families were encountered. According to conservation concern based on categorization by IUCN redlist, amongst amphibians a single species was vulnerable, four species were data deficient and the rest were least concern and amongst reptiles, two species were vulnerable, 13 species were least concern and the rest of 26 species were yet to be evaluated. According to India’s Wildlife (Protection) Act, 1972, 13 species of amphibians fall under Schedule IV; five, three and twenty species of reptile come under Schedule I, schedule II and Schedule III respectively. The remaining species are non-scheduled. The major threats in the sanctuary includes habitat degradation, encroachment of forest land and lack of people awareness regarding herpetofauna.

Designer steroids contain chemical structures “derived from, or substantially similar to” anabolic steroids, which became Schedule III controlled substances in the United States in 1990. Chemists create designer steroids by reverse engineering existing drugs, altering their chemical structures, and creating new compounds. Seeking to help curtail problems with steroid-spiked dietary supplements, the Designer Anabolic Steroid Control Act of 2014 classified 25 designer steroids, many contained in supplements, as controlled substances. Previous versions of the 2014 legislation, introduced in 2010 and 2012, had failed to become law despite consistent news accounts of supplements contaminated with conventional and designer steroids, as well as steroid precursors. Guided conceptually by a streams-of-influence model, the present article examines regulatory processes involving designer steroids and discusses limitations on the capacity of news outlets to build policy agendas.

The U.S. consumes about 99% of the world's supply of hydrocodone, primarily in hydrocodone combination products (HCPs). The Drug Enforcement Administration's (DEA) rescheduling of HCPs from Schedule III to the more restrictive Schedule II has changed prescribing patterns. The purpose of our article was to revisit HCP rescheduling to determine the impact this change had and its related consequences. Before 2014, DEA drug classification (scheduling) caused the ＂Vicodin loophole＂ which allowed HCP products to be prescribed under less restrictive conditions than single-entity hydrocodone products or oxycodone combination products. The rescheduling of HCPs to the more restrictive Schedule II has resulted in a decrease in HCP use but increased use of other analgesics. Unintended consequences of the rescheduling may include additional healthcare provider work, the potential for added costs, and patient inconvenience. For some patients, the rescheduling of HCPs may mean that they no longer have access to their preferred or effective analgesic or that they have been switched to another possibly less effective or tolerable analgesic. While the rescheduling has reduced the prescribing of hydrocodone, it is not apparent that it resulted in a net decrease in opioid use.

It has been four years since the National Food Security Act, 2013 (NFSA) was passed, ample time for us to assess its impact on the food insecurity in India. The Act was initiated as an ambitious attempt to provide food security through a life-cycle approach, but over the years it has remained restricted to merely converting four schemes into legal entitlements. It has lost sight of its ultimate goal of providing „food security‟ and remains largely over occupied by food distribution. Additionally, core aspects of food production and management have been placed under schedule III, to be progressively realized, in other words "not imperative".The present paper shall critically analyze the concept of food security against the national Act. An attempt shall be made at highlighting the lacunae within the provisions of the Act, implementation gaps and operational inadequacies. Moreover, the interaction between the national law and the individual state rules and the impact of diverse state-specific factors on rule-making and ground-level implementation shall also be considered. The paper introduces the concept of food security and gives an overview of the NFSA. It also critically analyzes the provisions of the Act and highlights the gaps in food security therein. The paper concludes with recommendations as to how food security can be implemented in an effective way.

Due to rising misuse, the Drug Enforcement Administration (DEA) moved hydrocodone combination products (HCPs) from DEA Schedule III to DEA Schedule II in October 2014. Aside from increasing regulatory scrutiny, rescheduling may have increased the administrative burden surrounding HCP prescribing. This study explored how HCP rescheduling and associated administrative barriers may have affected physician treatment of acute (aNCP) and chronic (cNCP) noncancer pain. To this end, physician members of the Texas Medical Association completed a self-administered online questionnaire. Pharmacotherapy treatment plan was measured with two questions asking physicians whether they were more likely to recommend HCPs, acetaminophen/codeine (APAP/codeine), nonsteroidal anti-inflammatory drugs (NSAIDs), tramadol, or other agents for the treatment of aNCP and cNCP. Two Likert-scaled items were used to assess administrative burden. In total, 1365 physicians responded (response rate = 15.39%). Physicians more frequently selected APAP/codeine (37%) for aNCP and tramadol (44%) for cNCP. A majority (78.8%) of physicians agreed that rescheduling led to modified prescribing, and those in agreement were significantly less likely than those who disagreed to prescribe HCPs for aNCP (24.2% vs. 56.4%; χ

Objective: To compare the differences in physical, mental, and spiritual health among Schedule I and II with III and IV controlled drugs users.Methods: A cross-sectional comparison design was used. A convenience sample of 479 drugs users was recruited in Taiwan.Results: The results showed that Schedule I and II drug-users had less perceptions of their overall body-mental-spirit health than Schedule III and IV drug-users (52.72 vs. 55.40, t = -3.00, p < .01).Conclusions: The health professionals could design drug rehabilitation programs for all Schedules of drug-users, especially for Schedule I and II drug-users.

Purpose This research examines the direct and interactive effects of defendant race and sex on judicial decisions to utilize mitigating departures in cases involving felony drug convictions in Virginia. Methodology/approach Logistic regression models are used to examine judicial decisions to depart downward in Schedule I & II, and Other (Schedule III, VI, and V), drug cases. The direct and interactive effects of race and sex on departure decisions are modeled separately for Schedule I & II and Other drug offenses. Findings Defendant race and sex exert both direct and interactive effects on decisions to sentence offenders below the guidelines for both drug categories. Cases involving Black and male defendants, relative to white and female defendants, are significantly less likely to result in mitigating departures for Schedule I & II, and Other drug, violations. The interaction models indicate that cases involving Black male defendants are less likely to result in mitigating departures than other cases, while cases involving white females have higher odds of receiving mitigating departures than other cases. Originality/value This chapter adds to the current literature on sentencing disparity by examining unwarranted sentencing disparity in Virginia, where scant research has been conducted. Furthermore, this research models decisions separately by drug category and examines both the direct and interactive effects of race and sex.

Background Clandestine laboratory operators commonly extract ephedrine and pseudoephedrine—precursor chemicals used to synthesize methamphetamine—from over-the-counter cold/allergy/sinus products. To prevent this activity, two states, Oregon in 07/2006 and Mississippi in 07/2010, implemented regulations classifying ephedrine and pseudoephedrine as Schedule III substances, making products containing them available by prescription only. Using simple pre-regulation versus post-regulation comparisons, reports claim that the regulations have substantially reduced clandestine laboratory seizures (an indicator of laboratory prevalence) in both states, motivating efforts to implement similar regulation nationally. This study uses ARIMA-intervention time-series analysis to more rigorously evaluate the regulations’ impacts on laboratory seizures. Methods Monthly counts of methamphetamine clandestine laboratory seizures were extracted from the Clandestine Laboratory Seizure System (2000—early 2011) for Oregon, Mississippi and selected nearby states (for quasi-control). Findings Seizures in Oregon and nearby western states largely bottomed out months before Oregon's regulation, and changed little thereafter. No significant impact for Oregon's regulation was found. Mississippi and nearby states generally had elevated seizures before Mississippi's regulation. Mississippi experienced a regulation-associated drop of 28.9 seizures (50.2%) in the series level ( p Conclusions Oregon's regulation encountered a floor effect, making any sizable impact infeasible. Mississippi, however, realized a substantial impact, suggesting that laboratories, if sufficiently extant, can be meaningfully impacted by prescription precursor regulation. It follows that national prescription precursor regulation would have little impact in western states with low indicated laboratory prevalence, but may be of significant use in regions facing higher indicated prevalence.

Twenty years after policy makers passed the Anabolic Steroid Control Act of 1990, adding steroids to the list of Schedule III Controlled Substances in the United States, illicit use of the drugs continues among both adolescents and adults in American society. Some of the men and women who use steroids seek enhanced athletic performance, whereas others simply want to appear more muscular. But what, exactly, is a “steroid”? The present article examines legislation surrounding actual anabolic-androgenic steroids, steroid precursors, and associated “dietary supplements,” exploring how the political interests of policy actors and the economic interests of industry lobbies have compromised regulatory efforts. Among the issues addressed are the arbitrary assignment of substances to (and exemption from) the Omnibus Controlled Substances Act and the retailing of “dietary supplements” that contain widely varying amounts of active ingredients and, in some cases, synthetic steroids. Conceptually, the article draws on the “garbage can” model of policy processes as well as the broader public arenas model of social problems, focusing on subjective issue constructions and symbolic appeals.

The Drug Enforcement Administration (DEA) in late August successfully concluded its 10-year campaign to move hydrocodone-containing combination products from Schedule III of the Controlled Substances Act to the more tightly regulated Schedule II. DEA stated that the change affects several hundred

Office-based treatment of opioid dependence with buprenorphine has the potential to expand treatment capacity in the United States. However, nationally, little is known about the number, characteristics, and experiences of physicians certified to prescribe buprenorphine. Moreover, little is known about the impact of easing federal regulations on the number of patients a physician is allowed to treat concurrently. To address these questions, surveys of national samples of physicians certified to prescribe buprenorphine (2004-2008) were analyzed (N = 6,892). There has been a continual increase in the number of physicians certified to prescribe buprenorphine, increase in the mean number of patients treated by physicians, and decrease in patients turned away, coinciding temporally with easing of federal regulations. In addition, most physicians prescribed buprenorphine outside of traditional treatment settings. The U.S. experiment in expanding Schedule III-V medications for opioid dependence to physicians outside of formal substance abuse treatment facilities appears to have resulted in expanded capacity.

Advanced practice nurses play significant roles in providing care to patients with advanced disease. Their roles are enhanced when they can prescribe controlled substances, especially opioid analgesics essential for the management of moderate to severe pain in persons at the end of life. A review of state laws and regulations shows that although advanced practice nurses have some degree of prescriptive authority in all 50 states and the District of Columbia, there are restrictions on their prescribing of controlled substances. In 40 states, advanced practice nurses have differing authorities to prescribe schedule II-V controlled substances; in eight states they can prescribe only schedule III-V drugs. Three states do not allow advanced practice nurses to prescribe controlled substances. Inappropriate restrictions on the ability of advanced practice nurses to prescribe the full range of controlled substances needed to control pain and other symptoms may negatively affect quality of care, especially in persons at the end of life.

In October 2014, the Drug Enforcement Administration in the U.S. reclassified hydrocodone combination products (HCPs) from Schedule III to Schedule II, initiating one of the most significant and controversial regulatory changes for opioids in recent national history. The aim of the present study was to determine community pharmacist opinions on the effect of the rescheduling of HCPs on their personal practice. A web-based pilot survey was emailed to a convenience sample through online newsletters of professional pharmacy organizations in Pennsylvania, Kentucky and West Virginia in April/May 2015. A total of 62 surveys were initiated, yielding 56 complete responses. More than 75% of respondents noted increases in their workload as a result of the rescheduling of HCPs. Opinions regarding the intended outcomes of rescheduling were only weakly positive, with only 37.5% of respondents believing it has increased safety and 44.6% of respondents believing it has lessened abuse/diversion. For overall attitudes regarding the rescheduling, respondents were split between positive (26.8%), neutral (26.8%) and negative (46.4%). These initial data suggest that pharmacists have encountered barriers in practice resulting from the rescheduling. Further expanded work is necessary to verify these results from the small sample, and to assess the intended effects of the rescheduling upon the safe and effective use of hydrocodone.

To develop a suitable treatment strategy for patients with cleidocranial dysplasia (CCD) who miss the optimal early treatment stage.This study enrolled 15 patients with CCD who had all missed the optimal treatment stage and were diagnosed with CCD through clinical examinations and genetic tests. Based on the chief complaints and requirements of the patients, three different therapeutic schedules were devised for these patients. Schedules I (periodontal and endodontic treatments) and II (periodontal, endodontic and prosthodontic treatments) were used for patients with low requirements, whereas Schedule III (multidisciplinary strategy, including periodontal, endodontic, surgical, orthodontic and prosthodontic treatments) was used for patients with high requirements.Schedules I, II and III were used in five, seven and three patients, respectively. Schedule III treatments produced the best outcomes in terms of occlusion and esthetics.Schedule III based on a comprehensive multidisciplinary therapy is an ideal restorative therapeutic strategy and can achieve good outcomes for patients with CCD who missed the optimal treatment stage.

Anabolic steroids, which are Schedule III controlled substances, can be prescribed for a narrow field of legitimate medical conditions. Typically, they are prescribed one at a time, and by a single physician that is closely monitoring both dosage and side effects. These prescriptions do not result in dramatically elevated anabolic steroid levels, and they are generally not long term because of the potential for addiction and other harmful side effects. Because of the growing performance and image enhancement market, roid mills have sprung up all over the United States and the illegal importation of anabolic steroids from foreign countries is at an all-time high. This means that what appears to be a legitimate prescription for anabolic steroids may be obtained illegally by falsifying information, by visiting a “clinic” that is operating in an unlawful fashion, or by getting what may be an unlawful prescription from an online source. It is not difficult to determine when anabolic steroids are being prescribed or used unlawfully. It does, however, require thoughtful observation and basic inquiry by public safety personnel. To that end, they must be aware of, and respond to, red flags associated with illegal steroid procurement, prescriptions, and abuse.

This article examines the processes by which the Anabolic Steroid Control Act of 2004, an act that added steroid precursors such as androstenedione to the list of Schedule III Controlled Substances in the United States, came to pass in both the House of Representatives and the Senate. Grounded theoretically in political economy, the article addresses, in the abstract, how the interplay of political pressures and economic influences stands to affect the actions of public officials, and how "tougher" drug policies-those touted to be more substantive and efficacious than existing regulations-often fail to effect change. The article concludes with implications for those involved in the regulation of anabolic steroids and steroid precursors.

A multiyear Drug Enforcement Administration (DEA) effort to stem the abuse of hydrocodone-containing combination products received a boost in January when FDA advisers voted 19–10 in favor of reclassifying these products from Schedule III to Schedule II. The vote followed two days of sometimes

Increasing and inappropriate use of opioid analgesics (OA) have been declared a public health concern in the United States. There are no epidemiologic studies of OA use in skin disorders. We examined OA use in a nationally representative sample of US patient visits with only physician-diagnosed skin disorders.Retrospective cross-sectional study of 56 751 patient visits from 1995 to 2010 (International Classification of Diseases, 9th Revision, Clinical Modification codes 680-709 denoting "Diseases of the Skin and Subcutaneous Tissue"; 172, 173, 216 and 232 denoting malignant and benign skin neoplasms).An estimated 3.1% ± 0.2% of skin disorders visits were associated with OA use; 52.7% ± 5.4% were Schedule III opioids; 11.4% ± 1.4% of OA visits involved skin neoplasms and 45.4% ± 2.3% cellulitis and abscess. OA use increased from 1995 to 2010 (adjusted OR = 1.82, 95% CI: 1.49-2.22), even after controlling for increase in the frequency of skin infections from 1995 to 2010.The most frequent use OA for cellulitis and abscess is entirely consistent with their Food and Drug Administration (FDA)-approved indications for pain management. The almost two-fold increase in OA use in skin disorders from 1995 to 2010 may suggest that OA are being considered for pain management earlier in therapy.Only a minority of patient visits with OA had primary dermatologic disease. OA are being used in dermatology primarily for FDA-approved indications.

Background Midlevel providers, including physician assistants (PA), have been recommended by some to fill the current inadequate supply of providers nationally, including in emergency medicine. Objective PA practice is governed by state law. We described the differences in qualifications, scope of practice, prescriptive authority, and physician supervision required by individual states for PA practice and describe the impact this may have on emergency medicine. Methods A cross-sectional analysis of United States laws governing PA practice by abstraction from each state’s public website. State characteristics were collected from the American Academy of Physician Assistants and United States Census websites and dichotomized by median values. Results Only six states (12%), all of which were larger-population states, required physician review of medical records within 1 week of a PA-only patient encounter. However, one state (Virginia) explicitly required onsite physician presence for PA practice in the emergency department. All states allowed PAs to assist in invasive procedures, but 13 (25%) restricted independent performance. Restriction of this practice was more likely in states with a higher population (38%), lower rural proportion (40%), and lower number of PAs per population (40%). Eleven (22%) states restricted performance of sedation or general anesthesia. An expanded scope of practice for disaster situations was allowed by 24 (47%) states and was more likely in larger population states (62%). All but two states (Florida and Kentucky) allowed PA prescribing of schedule III–V medications, and 37 (73%) allowed prescribing of schedule II medications. Conclusions Laws governing PA practice in emergency departments differ by state, but generally allow for a broad scope of practice and limited direct supervision. Smaller, rural states were less likely to have tighter restrictions or oversight.

Multiple Copy Prescription Programs (MCPPs) are state initiatives intended to monitor the prescribing, dispensing, and consumption patterns of potent and abusable prescription drugs which are controlled substances. This analysis examines the impact of MCPPs on opioid and non-opioid analgesic use while considering the influence of patient and physician variables. Using cross-sectional data from the National Ambulatory Medical Care Survey, a hierarchical choice model is used to predict the probability of a patient receiving a Schedule II, Schedule III, or Schedule IV opioid analgesic versus a non-scheduled analgesic. MCPPs have a negative influence (t = − 5.01) on Schedule II opioid use and a positive influence (t = 6.30) on Schedule III opioid use. These patterns suggest that less potent drugs are substituted for Schedule II analgesics in MCPP states. This study finds that MCPPs alter analgesic utilization patterns, which has implications for physician practice patterns and patient access to analgesic therapy.

Prescriptions for combination analgesics containing the opiate hydrocodone have fallen by 22% since the US government imposed tougher prescribing rules in 2014, a study has found.1 Hydrocodone bitartrate, which is often formulated with a non-opioid analgesic such as paracetamol, is one of the most commonly misused prescription opioids in the United States. In October 2014, in response to a growing opioid use epidemic, the US Drug Enforcement Administration tightened prescribing requirements for hydrocodone combination products by moving them from schedule III of the Controlled Substances Act to the more restrictive designation of schedule II. Under schedule …

The proposed analysis and evaluation of the data elements in the OPP and other similar regulatory programs will support the following potential impact on the patients and physicians in Michigan and other states: Reduced rates of addictive use of prescriptions of Schedule II medications. Reduced rates of addictive patterns of prescribing of Schedule II medications. Improved the prescribing of Schedule II medication for pain disorders. Improved the prescribing of Schedule II medications in addictive disorders. Establish the need and direction for development of curriculum for Schedule II drugs for undergraduate medical education and continuing medical education. Establish the need and direction for development of curriculum for use of Schedule II medications in patients with addictive and pain disorders. Explore the need and direction for development of the monitoring system medical curriculum for Schedule III, IV, and V drugs. Demonstrate link between diversion and adverse effects on health caused by an addictive pattern of use and prescribing of Schedule II drugs

On October 6, the DEA final rule moving hydrocodone combination products (HCPs) from Schedule III to the stricter Schedule II went into effect. A top question on community pharmacists' minds was likely whether they would honor refills of prescriptions for HCPs written before October 6.

On August 22, DEA published a final rule moving hydrocodone combination products (HCPs) from Schedule III to Schedule II, effective October 6, 2014. APhA and most pharmacy groups strongly opposed the move.

In opposing DEA's proposal to reschedule hydrocodone combination products from Schedule III to Schedule II, APhA's government affairs team led the development and submission of a joint pharmacy stakeholder comment letter to the agency.

On October 25, FDA approved hydrocodone bitartrate extendedrelease capsules (Zohydro ER—Zogenix), a single-ingredient opioid product with no abuse-deterrent features. The decision to approve Zohydro ER without such controls goes against the 2012 recommendation of the agency’s own advisory committee and came just a day after FDA announced its intent to recommend that DEA move combination hydrocodone products from Schedule III to Schedule II (see page 72).

In January, FDA’s Drug Safety and Risk Management Committee voted 19–10 in favor of moving hydrocodone-containing medications from Schedule III to Schedule II. In March, the Safe Prescribing Act of 2013 was introduced to reclassify hydrocodone-containing drugs to Schedule II. The prospect of rescheduling these medications is stirring up a conversation among clinicians, especially physicians and pain management specialists.

Sens. Joe Manchin (D-WV) and Mark Kirk (R-IL) and Reps. Vern Buchanan (R-FL) and Ed Markey (D-MA) introduced hydrocodone rescheduling legislation on March 20. The Safe Prescribing Act of 2013 (S. 621) would reclassify hydrocodone products such as Vicodin and Lortab from a Schedule III to a Schedule II controlled substance. “Under the new restrictions, a written prescription would be required in order to receive hydrocodone painkillers except in cases of emergency,” according to Manchin’s

FDA's Drug Safety and Risk Management Advisory Committee has voted to recommend rescheduling of hydrocodone from Schedule III (C-III) to Schedule II (C-II). The January 25 vote was 19–10 in favor of the change.

An advisory panel of the US Food and Drug Administration has recommended that the FDA reclassify hydrocodone combination products as schedule II drugs, defined as those having a high potential for abuse and severe threat of dependence. These products include the popular combination of hydrocodone and acetaminophen (paracetamol), such under brands such as Vicodin. The panel, which met on 24-25 January, voted 19 to 10 in favor of rescheduling. Although such recommendations are considered only advisory, the FDA usually follows its advisory panels’ guidance. Hydrocodone combination products are currently classified as schedule III drugs, recognizing that they pose a “moderate” risk of dependence. But …

Ninety-six patients with stage III and stage IV chronic lymphocytic leukemia (CLL) were randomized into one of three treatment schedules. Prednisone was common to all three schedules and was given daily in an initial dosage of 0.8 mg/kg for the first 14 days, with successive halving of the daily dose on days 15 and 29 for a total 6-wk course. Prednisone was then given once a month at 0.8 mg/kg once a day for each of 7 consecutive days. Schedule I was prednisone plus chlorambucil (CLB) given as a once-a-month dose of 0.4–0.8 mg/kg; schedule II was both drugs, but the CLB was given as a daily dose of 0.08 mg/kg; schedule III was prednisone alone. Complete and partial remission (CR + PR) was 47% for schedule I, 38% for schedule II, and 11% for schedule III. Patients who responded (CR + PR) in each of the treatment schedules survived longer than the nonresponders. Complete remission was obtained in both CLB treatment schedules, but not with the prednisone alone regimen. Although overall survival was best in the intermittent CLB arm, there was no significant difference in survival time between the three treatment schedules. Toxicity was minimal in all three regimens. Augmentation of the intermittent monthly CLB, even to 1.5 and 2.0 mg/kg, was tolerated without undue marrow toxicity. About 22% of these patients either had diabetes mellitus at the time of entry on the study or manifested hyperglycemia during the course of treatment and observation.

A surface area of 5 m2, a QB of 500 ml/min and a QD of 1000 ml/min reduces the time of hemodialysis to just 6 hours per week. All the patients had been in a conventional dialysis program for at least 2 years. These patients have now been in LSH for a period of between 2 and 3 years. Most patients have no appreciable residual function, they follow a free diet, living a normal life, and weigh between 51 and 88 Kg, ranging in ages from between 26 and 69 years. We use this technique with 3 schedules: Schedule I) 2 hours/3 days/week; Schedule II) 3 hours/2 days/week; Schedule III) 6 hours/1 day/week. In the 3 schedules the clinical and biochemical results have been the same as with conventional dialysis. With this technique the patients have greater freedom and comfort because they avoid 312 hours per year connected to the artificial kidney. The patients in Schedule II also avoid 52 dialysis sessions and 104 trips to the dialysis center per year. And the patients in Schedule III also avoid 104 dialysis sessions and 208 trips to the center per year. Furthermore, the cost savings in Schedule II is $2,500 per year/patient and in Schedule III $8,500 per patient/year.

An attempt was made to reduce a loud high-pitched respiratory stridor in a 52-year-old male hospitalized for paranoid schizophrenia. Four consecutive schedules of electric shock were employed over a period of 68 days. Each treatment session lasted 15 min per day and consisted of ninety 10-sec intervals. In Schedule I (10 days), the subject was shocked every 10 sec if he emitted four or more stridors. In Schedule II (28 days), the subject was shocked if he emitted three or more stridors during each 10-sec interval. In Schedule III (15 days) shock was delivered immediately after the emission of a stridor, and in schedule IV (15 days) the shock switch was depressed immediately after the subject emitted a stridor but no shock was delivered. While the first schedule yielded a reduction in the subject's stridor, a greater decrease was found during Schedule II, wherein almost complete elimination of the behavior occurred. Schedules III and IV both had deleterious effects, with the former schedule showing the greater increase in the stridor. The differential effects of these aversive schedules are discussed.

Three groups of albino rats were trained under a free-operant avoidance (Sidman) procedure with equal shock-shock and response-shock intervals. After stable performance was achieved, the animals were concurrently exposed to a brief electric shock after each response. The procedures were as follows: Punishment Schedule I: punishment shock was introduced at an intensity approximately one quarter that of avoidance shock; increments of nearly this same size were made as stable performance was achieved at succeeding punishment shock intensities. Punishment Schedule II: punishment shock was introduced at approximately one-half the intensity of avoidance shock; after stable performance, punishment shock was increased to the same intensity as avoidance shock. Punishment Schedule III: punishment shock was introduced and maintained at the same intensity as avoidance shock. Punishment was continued for all groups until one of two suppression criteria was attained. All animals made fewer responses and received more avoidance shocks as a function of increasing punishment shock. Half of the animals under Punishment Schedule I required punishment shock higher than avoidance shock to meet their assigned suppression criterion. A comparison of all procedures showed that suppression was greater when punishment shock was initially at high intensity.

Rhesus monkeys were trained to complete three multiple schedules. The schedules consisted of three components: a fixed interval (component 1), a variable interval (component 2), and a fixed ratio (component 3). During components 1 and 2, pressing lever 1 was always reinforced by food delivery. During component 3, pressing lever 2 resulted in either food delivery or intravenous infusions of saline solution, solutions of cocaine, of d-amphetamine, of phenmetrazine, or fenetylline. In schedule I, animals were presented with all three components independent of key-pressing behavior during components 1 and 2. In schedule II the availability of component 2 was dependent on completion of component 1. Component 3 was made available only on completion of component 2. Noncompletion of components 1 or 2 resulted in timeoutperiods of 15 and 10 min, respectively. Schedule III was identical with schedule II, except that in schedule III the completion of components was indicated only by a change in the lever lights. The influence of self-administered drugs on behavior in all three components was evaluated. Self-administration of psychomotor stimulants impaired the performance of animals and delayed completion of components 1 and 2 of schedules I, II, and III. The effects on behavior were similar with low drug intake in schedule III, moderate intake in schedule II, and high drug intake in schedule I. These effects were strong with self-administration of phenmetrazine, moderate with self-administration of cocaine and d-amphetamine, and weak with self-administration of fenetylline.

Three experiments which utilized an ultrashort sleep-waking cycle were conducted to investigate the 24 h structure of sleepiness after 1 night of sleep deprivation under 2 experimental conditions: instructing subjects to attempt to fall asleep or instructing subjects to attempt to resist sleep. Six subjects participated in experiment 1. At 19.00 h they started a 13 min waking-7 min sleep attempt, or 13 min waking-7 min resisting sleep, until 19.00 h on the next day. Eight subjects were tested in a similar way in experiment 2, which started at 07.00 h after a night of sleep deprivation and lasted for 24 h. Eight subjects were similarly tested in experiment 3 which started at 11.00 h after a night of sleep deprivation and lasted for 36 h until 23.00 h on the next day. The results showed that in spite of the significant between-group differences in total sleep, the temporal structure of sleepiness was very similar in the 3 experiments. In each there was a bimodal distribution of sleepiness: a major nocturnal sleepiness crest and a secondary mid-afternoon sleepiness peak. These were separated by a 'forbidden zone' for sleep centred at around 20.00-22.00 h. The onset of the nocturnal sleep period (the sleep gate) was found to be a discrete event occurring as an 'all or none' phenomenon. Its timing was stable over a 2 week period, and independent of the specific experimental demands; there were no significant differences between the AS and RS conditions with respect to total sleep time or any of the sleep stages. These results, which demonstrate structured variations in sleepiness across the nycthemeron are discussed in the light of the recent modelling of sleep along homeostatic principles.

Manufacture of drugs by the Parties to the Single Convention is allowed only under licence except where such manufacture is carried out by a state enterprise or state enterprises.1 Such licences are required for two purposes: (a)for authorization to engage in the manufacture of drugs; and (b) for the use of establishments and premises in which such manufacture may take place.2 Manufacture of drugs under licence, includes basic drugs, their salts and preparations,3 including preparations in Schedule III. The state enterprises will not, for obvious reasons, need a formal licence in this regard, yet they are not allowed to manufacture drugs, salts and preparations, other than those for which permission may be given to a private manufacturer.4 However, a licence will detail the names of drugs, their quantities and the period for which the manufacturer concerned will be allowed to use it, and similarly, where a state enterprise is authorized to manufacture drugs, the aforementioned procedure shall also be observed, in order to ensure that the manufacture of a particular drug in a given country or territory does not exceed the limit permitted by the Single Convention. The licensing authority will enjoy the discretionary power to revoke or amend the licence, both in respect of a private manufacturer and a state enterprise, although in the former case such discretionary power would have “to be limited to the extent necessary to facilitate the economical conduct of business by a law-abiding manufacturer.”5