SKINNY LABELS: CHANGING SCENARIO OF INDUCED INFRINGEMENT AND PUBLIC POLICY

A patent is an exclusive right granted for an invention to the inventor. However, when it comes to life-sustaining products, these exclusive rights have a negative impact on people’s lives. The government has tried to develop initiatives, such as the Hatch-Waxman Act, to compensate and speed up the entry of affordable medicines into the market. But when one patent addressing one medical condition (indication) blocks the entry of the generic, the use of skinny labels makes it possible for the generic players to carve out the label and enter the market only with indications that are off-patent. This helps bring these unaffordable medical products within reach of the common person who could not otherwise afford them. This note will examine how the generic players navigate the drug approval system, the strategies of the innovators to ward off competition, and the public policy surrounding the availability of affordable medical products. It will also discuss the impact and implications of skinny labels on the market entry of affordable life- sustaining products and the landmark case that is changing the scenario altogether. Finally, this note will propose possible alternative methods to increase the affordability and availability of life-sustaining products by making it a win-win situation for innovators, generics, and the public

Tibial Cut Strategy for Mitigating Workspace Limit Risk for Surgical Robots

A method for mitigating workspace limit risk for surgical robots is described herein. A surgical robot may execute a cut-file having two or more cut-paths on a bone. The cut-path that is closest to the edge of the robot\u27s workspace is executed last in the cut-file to reduce the amount of time the robot is fully extended. This pushes the highest risk of cutting to the very end of the surgical procedure making the process more manageable in the event the workspace is exceeded when cutting this region of the bone

Use of off-label drugs in the neonatal intensive care unit in India

Background: Off-label use of drugs is widespread in pediatrics and almost all neonates hospitalized in NICU are affected by the use of off-label drugs regardless of gestational age and birth weight. This is because of the lack of regulation for medications in the neonatal population and the delays in updating drug instructions. This is mainly due to the ethical difficulty in the research and difficulties in conducting clinical trials in this vulnerable population. Hence, the study was planned to assess the extent of the use of off-label drugs in the NICU. Methods: An observational study was carried out in the NICU of a tertiary care center from May 2021 to Oct 2022 and case records of neonates admitted to the NICU were evaluated. Results: Among 1745 drug prescriptions in 360 neonates, 1208 (69.22%) were off-label. Anti-infectives were the most commonly used off-label class of drug, Piperacillin+tazobactam was the most commonly used off-label drug and most common reason for off-label prescriptions was indication and administration. It was found that 79.44% of neonates received at least one off-label drug. Conclusions: Off-label use of drugs, specifically anti-infective drugs, is common in NICUs of India as in other countries. So, more research should be done to generate evidence-based guidelines for the rational use of drugs in neonates

Frequency format diagram and probability chart for breast cancer risk communication: a prospective, randomized trial

<p>Abstract</p> <p>Background</p> <p>Breast cancer risk education enables women make informed decisions regarding their options for screening and risk reduction. We aimed to determine whether patient education regarding breast cancer risk using a bar graph, with or without a frequency format diagram, improved the accuracy of risk perception.</p> <p>Methods</p> <p>We conducted a prospective, randomized trial among women at increased risk for breast cancer. The main outcome measurement was patients' estimation of their breast cancer risk before and after education with a bar graph (BG group) or bar graph plus a frequency format diagram (BG+FF group), which was assessed by previsit and postvisit questionnaires.</p> <p>Results</p> <p>Of 150 women in the study, 74 were assigned to the BG group and 76 to the BG+FF group. Overall, 72% of women overestimated their risk of breast cancer. The improvement in accuracy of risk perception from the previsit to the postvisit questionnaire (BG group, 19% to 61%; BG+FF group, 13% to 67%) was not significantly different between the 2 groups (<it>P </it>= .10). Among women who inaccurately perceived very high risk (≥ 50% risk), inaccurate risk perception decreased significantly in the BG+FF group (22% to 3%) compared with the BG group (28% to 19%) (<it>P </it>= .004).</p> <p>Conclusion</p> <p>Breast cancer risk communication using a bar graph plus a frequency format diagram can improve the short-term accuracy of risk perception among women perceiving inaccurately high risk.</p

Effect of Body Mass Index on work related musculoskeletal discomfort and occupational stress of computer workers in a developed ergonomic setup

<p>Abstract</p> <p>Background</p> <p>Work urgency, accuracy and demands compel the computer professionals to spend longer hours before computers without giving importance to their health, especially body weight. Increase of body weight leads to improper Body Mass Index (BMI) may aggravate work related musculoskeletal discomfort and occupational-psychosocial stress. The objective of the study was to find out the effect of BMI on work related musculoskeletal discomforts and occupational stress of computer workers in a developed ergonomic setup.</p> <p>Methods</p> <p>A descriptive inferential study has been taken to analyze the effect of BMI on work related musculoskeletal discomfort and occupational-psychosocial stress. A total of 100 computer workers, aged 25-35 years randomly selected on convenience from software and BPO companies in Bangalore city, India for the participation in this study. BMI was calculated by taking the ratio of the subject's height (in meter) and weight (in kilogram). Work related musculoskeletal discomfort and occupational stress of the subjects was assessed by Cornell University's musculoskeletal discomfort questionnaire (CMDQ) and occupational stress index (OSI) respectively as well as a relationship was checked with their BMI.</p> <p>Results</p> <p>A significant association (p < 0.001) was seen among high BMI subjects with their increase scores of musculoskeletal discomfort and occupational stress.</p> <p>Conclusion</p> <p>From this study, it has been concluded that, there is a significant effect of BMI in increasing of work related musculoskeletal discomfort and occupational-psychosocial stress among computer workers in a developed ergonomic setup.</p

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2):a multicentre observational cohort study

Background: Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Methods: Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Findings: Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively). Interpretation: In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation. Funding: The Stroke Association and the British Heart Foundation

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707